how to make a conclusion in a research

Get science-backed answers as you write with Paperpal's Research feature

How to Write a Conclusion for Research Papers (with Examples)

The conclusion of a research paper is a crucial section that plays a significant role in the overall impact and effectiveness of your research paper. However, this is also the section that typically receives less attention compared to the introduction and the body of the paper. The conclusion serves to provide a concise summary of the key findings, their significance, their implications, and a sense of closure to the study. Discussing how can the findings be applied in real-world scenarios or inform policy, practice, or decision-making is especially valuable to practitioners and policymakers. The research paper conclusion also provides researchers with clear insights and valuable information for their own work, which they can then build on and contribute to the advancement of knowledge in the field.

The research paper conclusion should explain the significance of your findings within the broader context of your field. It restates how your results contribute to the existing body of knowledge and whether they confirm or challenge existing theories or hypotheses. Also, by identifying unanswered questions or areas requiring further investigation, your awareness of the broader research landscape can be demonstrated.

Remember to tailor the research paper conclusion to the specific needs and interests of your intended audience, which may include researchers, practitioners, policymakers, or a combination of these.

Table of Contents

What is a conclusion in a research paper, summarizing conclusion, editorial conclusion, externalizing conclusion, importance of a good research paper conclusion, how to write a conclusion for your research paper, research paper conclusion examples.

• How to write a research paper conclusion with Paperpal? 

Frequently Asked Questions

A conclusion in a research paper is the final section where you summarize and wrap up your research, presenting the key findings and insights derived from your study. The research paper conclusion is not the place to introduce new information or data that was not discussed in the main body of the paper. When working on how to conclude a research paper, remember to stick to summarizing and interpreting existing content. The research paper conclusion serves the following purposes: 1

• Warn readers of the possible consequences of not attending to the problem.
• Recommend specific course(s) of action.
• Restate key ideas to drive home the ultimate point of your research paper.
• Provide a “take-home” message that you want the readers to remember about your study.

Types of conclusions for research papers

In research papers, the conclusion provides closure to the reader. The type of research paper conclusion you choose depends on the nature of your study, your goals, and your target audience. I provide you with three common types of conclusions:

A summarizing conclusion is the most common type of conclusion in research papers. It involves summarizing the main points, reiterating the research question, and restating the significance of the findings. This common type of research paper conclusion is used across different disciplines.

An editorial conclusion is less common but can be used in research papers that are focused on proposing or advocating for a particular viewpoint or policy. It involves presenting a strong editorial or opinion based on the research findings and offering recommendations or calls to action.

An externalizing conclusion is a type of conclusion that extends the research beyond the scope of the paper by suggesting potential future research directions or discussing the broader implications of the findings. This type of conclusion is often used in more theoretical or exploratory research papers.

Align your conclusion’s tone with the rest of your research paper. Start Writing with Paperpal Now!  

The conclusion in a research paper serves several important purposes:

• Offers Implications and Recommendations : Your research paper conclusion is an excellent place to discuss the broader implications of your research and suggest potential areas for further study. It’s also an opportunity to offer practical recommendations based on your findings.
• Provides Closure : A good research paper conclusion provides a sense of closure to your paper. It should leave the reader with a feeling that they have reached the end of a well-structured and thought-provoking research project.
• Leaves a Lasting Impression : Writing a well-crafted research paper conclusion leaves a lasting impression on your readers. It’s your final opportunity to leave them with a new idea, a call to action, or a memorable quote.

Writing a strong conclusion for your research paper is essential to leave a lasting impression on your readers. Here’s a step-by-step process to help you create and know what to put in the conclusion of a research paper: 2

• Research Statement : Begin your research paper conclusion by restating your research statement. This reminds the reader of the main point you’ve been trying to prove throughout your paper. Keep it concise and clear.
• Key Points : Summarize the main arguments and key points you’ve made in your paper. Avoid introducing new information in the research paper conclusion. Instead, provide a concise overview of what you’ve discussed in the body of your paper.
• Address the Research Questions : If your research paper is based on specific research questions or hypotheses, briefly address whether you’ve answered them or achieved your research goals. Discuss the significance of your findings in this context.
• Significance : Highlight the importance of your research and its relevance in the broader context. Explain why your findings matter and how they contribute to the existing knowledge in your field.
• Implications : Explore the practical or theoretical implications of your research. How might your findings impact future research, policy, or real-world applications? Consider the “so what?” question.
• Future Research : Offer suggestions for future research in your area. What questions or aspects remain unanswered or warrant further investigation? This shows that your work opens the door for future exploration.
• Closing Thought : Conclude your research paper conclusion with a thought-provoking or memorable statement. This can leave a lasting impression on your readers and wrap up your paper effectively. Avoid introducing new information or arguments here.
• Proofread and Revise : Carefully proofread your conclusion for grammar, spelling, and clarity. Ensure that your ideas flow smoothly and that your conclusion is coherent and well-structured.

Write your research paper conclusion 2x faster with Paperpal. Try it now!

Remember that a well-crafted research paper conclusion is a reflection of the strength of your research and your ability to communicate its significance effectively. It should leave a lasting impression on your readers and tie together all the threads of your paper. Now you know how to start the conclusion of a research paper and what elements to include to make it impactful, let’s look at a research paper conclusion sample.

How to write a research paper conclusion with Paperpal?

A research paper conclusion is not just a summary of your study, but a synthesis of the key findings that ties the research together and places it in a broader context. A research paper conclusion should be concise, typically around one paragraph in length. However, some complex topics may require a longer conclusion to ensure the reader is left with a clear understanding of the study’s significance. Paperpal, an AI writing assistant trusted by over 800,000 academics globally, can help you write a well-structured conclusion for your research paper. 

• Sign Up or Log In: Create a new Paperpal account or login with your details.  
• Navigate to Features : Once logged in, head over to the features’ side navigation pane. Click on Templates and you’ll find a suite of generative AI features to help you write better, faster.  
• Generate an outline: Under Templates, select ‘Outlines’. Choose ‘Research article’ as your document type.  
• Select your section: Since you’re focusing on the conclusion, select this section when prompted.  
• Choose your field of study: Identifying your field of study allows Paperpal to provide more targeted suggestions, ensuring the relevance of your conclusion to your specific area of research. 
• Provide a brief description of your study: Enter details about your research topic and findings. This information helps Paperpal generate a tailored outline that aligns with your paper’s content. 
• Generate the conclusion outline: After entering all necessary details, click on ‘generate’. Paperpal will then create a structured outline for your conclusion, to help you start writing and build upon the outline.  
• Write your conclusion: Use the generated outline to build your conclusion. The outline serves as a guide, ensuring you cover all critical aspects of a strong conclusion, from summarizing key findings to highlighting the research’s implications. 
• Refine and enhance: Paperpal’s ‘Make Academic’ feature can be particularly useful in the final stages. Select any paragraph of your conclusion and use this feature to elevate the academic tone, ensuring your writing is aligned to the academic journal standards. 

By following these steps, Paperpal not only simplifies the process of writing a research paper conclusion but also ensures it is impactful, concise, and aligned with academic standards. Sign up with Paperpal today and write your research paper conclusion 2x faster .  

The research paper conclusion is a crucial part of your paper as it provides the final opportunity to leave a strong impression on your readers. In the research paper conclusion, summarize the main points of your research paper by restating your research statement, highlighting the most important findings, addressing the research questions or objectives, explaining the broader context of the study, discussing the significance of your findings, providing recommendations if applicable, and emphasizing the takeaway message. The main purpose of the conclusion is to remind the reader of the main point or argument of your paper and to provide a clear and concise summary of the key findings and their implications. All these elements should feature on your list of what to put in the conclusion of a research paper to create a strong final statement for your work.

A strong conclusion is a critical component of a research paper, as it provides an opportunity to wrap up your arguments, reiterate your main points, and leave a lasting impression on your readers. Here are the key elements of a strong research paper conclusion: 1. Conciseness : A research paper conclusion should be concise and to the point. It should not introduce new information or ideas that were not discussed in the body of the paper. 2. Summarization : The research paper conclusion should be comprehensive enough to give the reader a clear understanding of the research’s main contributions. 3 . Relevance : Ensure that the information included in the research paper conclusion is directly relevant to the research paper’s main topic and objectives; avoid unnecessary details. 4 . Connection to the Introduction : A well-structured research paper conclusion often revisits the key points made in the introduction and shows how the research has addressed the initial questions or objectives. 5. Emphasis : Highlight the significance and implications of your research. Why is your study important? What are the broader implications or applications of your findings? 6 . Call to Action : Include a call to action or a recommendation for future research or action based on your findings.

The length of a research paper conclusion can vary depending on several factors, including the overall length of the paper, the complexity of the research, and the specific journal requirements. While there is no strict rule for the length of a conclusion, but it’s generally advisable to keep it relatively short. A typical research paper conclusion might be around 5-10% of the paper’s total length. For example, if your paper is 10 pages long, the conclusion might be roughly half a page to one page in length.

In general, you do not need to include citations in the research paper conclusion. Citations are typically reserved for the body of the paper to support your arguments and provide evidence for your claims. However, there may be some exceptions to this rule: 1. If you are drawing a direct quote or paraphrasing a specific source in your research paper conclusion, you should include a citation to give proper credit to the original author. 2. If your conclusion refers to or discusses specific research, data, or sources that are crucial to the overall argument, citations can be included to reinforce your conclusion’s validity.

The conclusion of a research paper serves several important purposes: 1. Summarize the Key Points 2. Reinforce the Main Argument 3. Provide Closure 4. Offer Insights or Implications 5. Engage the Reader. 6. Reflect on Limitations

Remember that the primary purpose of the research paper conclusion is to leave a lasting impression on the reader, reinforcing the key points and providing closure to your research. It’s often the last part of the paper that the reader will see, so it should be strong and well-crafted.

• Makar, G., Foltz, C., Lendner, M., & Vaccaro, A. R. (2018). How to write effective discussion and conclusion sections. Clinical spine surgery, 31(8), 345-346.
• Bunton, D. (2005). The structure of PhD conclusion chapters.  Journal of English for academic purposes ,  4 (3), 207-224.

Paperpal is a comprehensive AI writing toolkit that helps students and researchers achieve 2x the writing in half the time. It leverages 21+ years of STM experience and insights from millions of research articles to provide in-depth academic writing, language editing, and submission readiness support to help you write better, faster.  

Get accurate academic translations, rewriting support, grammar checks, vocabulary suggestions, and generative AI assistance that delivers human precision at machine speed. Try for free or upgrade to Paperpal Prime starting at US$19 a month to access premium features, including consistency, plagiarism, and 30+ submission readiness checks to help you succeed.  

Experience the future of academic writing – Sign up to Paperpal and start writing for free!  

Related Reads:

• 5 Reasons for Rejection After Peer Review
• Ethical Research Practices For Research with Human Subjects

7 Ways to Improve Your Academic Writing Process

• Paraphrasing in Academic Writing: Answering Top Author Queries

Preflight For Editorial Desk: The Perfect Hybrid (AI + Human) Assistance Against Compromised Manuscripts

You may also like, how to write an abstract in research papers..., how to write the first draft of a..., mla works cited page: format, template & examples, how to write a high-quality conference paper, academic editing: how to self-edit academic text with..., measuring academic success: definition & strategies for excellence, phd qualifying exam: tips for success , ai in education: it’s time to change the..., is it ethical to use ai-generated abstracts without..., what are journal guidelines on using generative ai....

In a short paper—even a research paper—you don’t need to provide an exhaustive summary as part of your conclusion. But you do need to make some kind of transition between your final body paragraph and your concluding paragraph. This may come in the form of a few sentences of summary. Or it may come in the form of a sentence that brings your readers back to your thesis or main idea and reminds your readers where you began and how far you have traveled.

So, for example, in a paper about the relationship between ADHD and rejection sensitivity, Vanessa Roser begins by introducing readers to the fact that researchers have studied the relationship between the two conditions and then provides her explanation of that relationship. Here’s her thesis: “While socialization may indeed be an important factor in RS, I argue that individuals with ADHD may also possess a neurological predisposition to RS that is exacerbated by the differing executive and emotional regulation characteristic of ADHD.”

In her final paragraph, Roser reminds us of where she started by echoing her thesis: “This literature demonstrates that, as with many other conditions, ADHD and RS share a delicately intertwined pattern of neurological similarities that is rooted in the innate biology of an individual’s mind, a connection that cannot be explained in full by the behavioral mediation hypothesis.”  

Highlight the “so what”  

At the beginning of your paper, you explain to your readers what’s at stake—why they should care about the argument you’re making. In your conclusion, you can bring readers back to those stakes by reminding them why your argument is important in the first place. You can also draft a few sentences that put those stakes into a new or broader context.

In the conclusion to her paper about ADHD and RS, Roser echoes the stakes she established in her introduction—that research into connections between ADHD and RS has led to contradictory results, raising questions about the “behavioral mediation hypothesis.”

She writes, “as with many other conditions, ADHD and RS share a delicately intertwined pattern of neurological similarities that is rooted in the innate biology of an individual’s mind, a connection that cannot be explained in full by the behavioral mediation hypothesis.”  

Leave your readers with the “now what”  

After the “what” and the “so what,” you should leave your reader with some final thoughts. If you have written a strong introduction, your readers will know why you have been arguing what you have been arguing—and why they should care. And if you’ve made a good case for your thesis, then your readers should be in a position to see things in a new way, understand new questions, or be ready for something that they weren’t ready for before they read your paper.

In her conclusion, Roser offers two “now what” statements. First, she explains that it is important to recognize that the flawed behavioral mediation hypothesis “seems to place a degree of fault on the individual. It implies that individuals with ADHD must have elicited such frequent or intense rejection by virtue of their inadequate social skills, erasing the possibility that they may simply possess a natural sensitivity to emotion.” She then highlights the broader implications for treatment of people with ADHD, noting that recognizing the actual connection between rejection sensitivity and ADHD “has profound implications for understanding how individuals with ADHD might best be treated in educational settings, by counselors, family, peers, or even society as a whole.”

To find your own “now what” for your essay’s conclusion, try asking yourself these questions:

• What can my readers now understand, see in a new light, or grapple with that they would not have understood in the same way before reading my paper? Are we a step closer to understanding a larger phenomenon or to understanding why what was at stake is so important?  
• What questions can I now raise that would not have made sense at the beginning of my paper? Questions for further research? Other ways that this topic could be approached?  
• Are there other applications for my research? Could my questions be asked about different data in a different context? Could I use my methods to answer a different question?  
• What action should be taken in light of this argument? What action do I predict will be taken or could lead to a solution?  
• What larger context might my argument be a part of?  

What to avoid in your conclusion  

• a complete restatement of all that you have said in your paper.  
• a substantial counterargument that you do not have space to refute; you should introduce counterarguments before your conclusion.  
• an apology for what you have not said. If you need to explain the scope of your paper, you should do this sooner—but don’t apologize for what you have not discussed in your paper.  
• fake transitions like “in conclusion” that are followed by sentences that aren’t actually conclusions. (“In conclusion, I have now demonstrated that my thesis is correct.”)
• picture_as_pdf Conclusions

• Privacy Policy

Home » Research Paper Conclusion – Writing Guide and Examples

Research Paper Conclusion – Writing Guide and Examples

Table of Contents

Research Paper Conclusion

Definition:

A research paper conclusion is the final section of a research paper that summarizes the key findings, significance, and implications of the research. It is the writer’s opportunity to synthesize the information presented in the paper, draw conclusions, and make recommendations for future research or actions.

The conclusion should provide a clear and concise summary of the research paper, reiterating the research question or problem, the main results, and the significance of the findings. It should also discuss the limitations of the study and suggest areas for further research.

Parts of Research Paper Conclusion

The parts of a research paper conclusion typically include:

Restatement of the Thesis

The conclusion should begin by restating the thesis statement from the introduction in a different way. This helps to remind the reader of the main argument or purpose of the research.

Summary of Key Findings

The conclusion should summarize the main findings of the research, highlighting the most important results and conclusions. This section should be brief and to the point.

Implications and Significance

In this section, the researcher should explain the implications and significance of the research findings. This may include discussing the potential impact on the field or industry, highlighting new insights or knowledge gained, or pointing out areas for future research.

Limitations and Recommendations

It is important to acknowledge any limitations or weaknesses of the research and to make recommendations for how these could be addressed in future studies. This shows that the researcher is aware of the potential limitations of their work and is committed to improving the quality of research in their field.

Concluding Statement

The conclusion should end with a strong concluding statement that leaves a lasting impression on the reader. This could be a call to action, a recommendation for further research, or a final thought on the topic.

How to Write Research Paper Conclusion

Here are some steps you can follow to write an effective research paper conclusion:

• Restate the research problem or question: Begin by restating the research problem or question that you aimed to answer in your research. This will remind the reader of the purpose of your study.
• Summarize the main points: Summarize the key findings and results of your research. This can be done by highlighting the most important aspects of your research and the evidence that supports them.
• Discuss the implications: Discuss the implications of your findings for the research area and any potential applications of your research. You should also mention any limitations of your research that may affect the interpretation of your findings.
• Provide a conclusion : Provide a concise conclusion that summarizes the main points of your paper and emphasizes the significance of your research. This should be a strong and clear statement that leaves a lasting impression on the reader.
• Offer suggestions for future research: Lastly, offer suggestions for future research that could build on your findings and contribute to further advancements in the field.

Remember that the conclusion should be brief and to the point, while still effectively summarizing the key findings and implications of your research.

Example of Research Paper Conclusion

Here’s an example of a research paper conclusion:

Conclusion :

In conclusion, our study aimed to investigate the relationship between social media use and mental health among college students. Our findings suggest that there is a significant association between social media use and increased levels of anxiety and depression among college students. This highlights the need for increased awareness and education about the potential negative effects of social media use on mental health, particularly among college students.

Despite the limitations of our study, such as the small sample size and self-reported data, our findings have important implications for future research and practice. Future studies should aim to replicate our findings in larger, more diverse samples, and investigate the potential mechanisms underlying the association between social media use and mental health. In addition, interventions should be developed to promote healthy social media use among college students, such as mindfulness-based approaches and social media detox programs.

Overall, our study contributes to the growing body of research on the impact of social media on mental health, and highlights the importance of addressing this issue in the context of higher education. By raising awareness and promoting healthy social media use among college students, we can help to reduce the negative impact of social media on mental health and improve the well-being of young adults.

Purpose of Research Paper Conclusion

The purpose of a research paper conclusion is to provide a summary and synthesis of the key findings, significance, and implications of the research presented in the paper. The conclusion serves as the final opportunity for the writer to convey their message and leave a lasting impression on the reader.

The conclusion should restate the research problem or question, summarize the main results of the research, and explain their significance. It should also acknowledge the limitations of the study and suggest areas for future research or action.

Overall, the purpose of the conclusion is to provide a sense of closure to the research paper and to emphasize the importance of the research and its potential impact. It should leave the reader with a clear understanding of the main findings and why they matter. The conclusion serves as the writer’s opportunity to showcase their contribution to the field and to inspire further research and action.

When to Write Research Paper Conclusion

The conclusion of a research paper should be written after the body of the paper has been completed. It should not be written until the writer has thoroughly analyzed and interpreted their findings and has written a complete and cohesive discussion of the research.

Before writing the conclusion, the writer should review their research paper and consider the key points that they want to convey to the reader. They should also review the research question, hypotheses, and methodology to ensure that they have addressed all of the necessary components of the research.

Once the writer has a clear understanding of the main findings and their significance, they can begin writing the conclusion. The conclusion should be written in a clear and concise manner, and should reiterate the main points of the research while also providing insights and recommendations for future research or action.

Characteristics of Research Paper Conclusion

The characteristics of a research paper conclusion include:

• Clear and concise: The conclusion should be written in a clear and concise manner, summarizing the key findings and their significance.
• Comprehensive: The conclusion should address all of the main points of the research paper, including the research question or problem, the methodology, the main results, and their implications.
• Future-oriented : The conclusion should provide insights and recommendations for future research or action, based on the findings of the research.
• Impressive : The conclusion should leave a lasting impression on the reader, emphasizing the importance of the research and its potential impact.
• Objective : The conclusion should be based on the evidence presented in the research paper, and should avoid personal biases or opinions.
• Unique : The conclusion should be unique to the research paper and should not simply repeat information from the introduction or body of the paper.

Advantages of Research Paper Conclusion

The advantages of a research paper conclusion include:

• Summarizing the key findings : The conclusion provides a summary of the main findings of the research, making it easier for the reader to understand the key points of the study.
• Emphasizing the significance of the research: The conclusion emphasizes the importance of the research and its potential impact, making it more likely that readers will take the research seriously and consider its implications.
• Providing recommendations for future research or action : The conclusion suggests practical recommendations for future research or action, based on the findings of the study.
• Providing closure to the research paper : The conclusion provides a sense of closure to the research paper, tying together the different sections of the paper and leaving a lasting impression on the reader.
• Demonstrating the writer’s contribution to the field : The conclusion provides the writer with an opportunity to showcase their contribution to the field and to inspire further research and action.

Limitations of Research Paper Conclusion

While the conclusion of a research paper has many advantages, it also has some limitations that should be considered, including:

• I nability to address all aspects of the research: Due to the limited space available in the conclusion, it may not be possible to address all aspects of the research in detail.
• Subjectivity : While the conclusion should be objective, it may be influenced by the writer’s personal biases or opinions.
• Lack of new information: The conclusion should not introduce new information that has not been discussed in the body of the research paper.
• Lack of generalizability: The conclusions drawn from the research may not be applicable to other contexts or populations, limiting the generalizability of the study.
• Misinterpretation by the reader: The reader may misinterpret the conclusions drawn from the research, leading to a misunderstanding of the findings.

About the author

Muhammad Hassan

Researcher, Academic Writer, Web developer

You may also like

Background of The Study – Examples and Writing...

Research Gap – Types, Examples and How to...

Research Results Section – Writing Guide and...

Research Paper Outline – Types, Example, Template

Ethical Considerations – Types, Examples and...

Data Verification – Process, Types and Examples

• PRO Courses Guides New Tech Help Pro Expert Videos About wikiHow Pro Upgrade Sign In
• EDIT Edit this Article
• EXPLORE Tech Help Pro About Us Random Article Quizzes Request a New Article Community Dashboard This Or That Game Popular Categories Arts and Entertainment Artwork Books Movies Computers and Electronics Computers Phone Skills Technology Hacks Health Men's Health Mental Health Women's Health Relationships Dating Love Relationship Issues Hobbies and Crafts Crafts Drawing Games Education & Communication Communication Skills Personal Development Studying Personal Care and Style Fashion Hair Care Personal Hygiene Youth Personal Care School Stuff Dating All Categories Arts and Entertainment Finance and Business Home and Garden Relationship Quizzes Cars & Other Vehicles Food and Entertaining Personal Care and Style Sports and Fitness Computers and Electronics Health Pets and Animals Travel Education & Communication Hobbies and Crafts Philosophy and Religion Work World Family Life Holidays and Traditions Relationships Youth
• Browse Articles
• Learn Something New
• Quizzes Hot
• This Or That Game
• Train Your Brain
• Explore More
• Support wikiHow
• About wikiHow
• Log in / Sign up
• Education and Communications
• College University and Postgraduate
• Academic Writing
• Research Papers

How to Write a Conclusion for a Research Paper

Last Updated: May 8, 2024 Approved

This article was co-authored by Christopher Taylor, PhD . Christopher Taylor is an Adjunct Assistant Professor of English at Austin Community College in Texas. He received his PhD in English Literature and Medieval Studies from the University of Texas at Austin in 2014. wikiHow marks an article as reader-approved once it receives enough positive feedback. This article received 43 testimonials and 83% of readers who voted found it helpful, earning it our reader-approved status. This article has been viewed 2,261,417 times.

The conclusion of a research paper needs to summarize the content and purpose of the paper without seeming too wooden or dry. Every basic conclusion must share several key elements, but there are also several tactics you can play around with to craft a more effective conclusion and several you should avoid to prevent yourself from weakening your paper's conclusion. Here are some writing tips to keep in mind when creating a conclusion for your next research paper.

Sample Conclusions

Writing a basic conclusion.

• Do not spend a great amount of time or space restating your topic.
• A good research paper will make the importance of your topic apparent, so you do not need to write an elaborate defense of your topic in the conclusion.
• Usually a single sentence is all you need to restate your topic.
• An example would be if you were writing a paper on the epidemiology of infectious disease, you might say something like "Tuberculosis is a widespread infectious disease that affects millions of people worldwide every year."
• Yet another example from the humanities would be a paper about the Italian Renaissance: "The Italian Renaissance was an explosion of art and ideas centered around artists, writers, and thinkers in Florence."

• A thesis is a narrowed, focused view on the topic at hand.
• This statement should be rephrased from the thesis you included in your introduction. It should not be identical or too similar to the sentence you originally used.
• Try re-wording your thesis statement in a way that complements your summary of the topic of your paper in your first sentence of your conclusion.
• An example of a good thesis statement, going back to the paper on tuberculosis, would be "Tuberculosis is a widespread disease that affects millions of people worldwide every year. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease ."

• A good way to go about this is to re-read the topic sentence of each major paragraph or section in the body of your paper.
• Find a way to briefly restate each point mentioned in each topic sentence in your conclusion. Do not repeat any of the supporting details used within your body paragraphs.
• Under most circumstances, you should avoid writing new information in your conclusion. This is especially true if the information is vital to the argument or research presented in your paper.
• For example, in the TB paper you could summarize the information. "Tuberculosis is a widespread disease that affects millions of people worldwide. Due to the alarming rate of the spread of tuberculosis, particularly in poor countries, medical professionals are implementing new strategies for the diagnosis, treatment, and containment of this disease. In developing countries, such as those in Africa and Southeast Asia, the rate of TB infections is soaring. Crowded conditions, poor sanitation, and lack of access to medical care are all compounding factors in the spread of the disease. Medical experts, such as those from the World Health Organization are now starting campaigns to go into communities in developing countries and provide diagnostic testing and treatments. However, the treatments for TB are very harsh and have many side effects. This leads to patient non-compliance and spread of multi-drug resistant strains of the disease."

• Note that this is not needed for all research papers.
• If you already fully explained what the points in your paper mean or why they are significant, you do not need to go into them in much detail in your conclusion. Simply restating your thesis or the significance of your topic should suffice.
• It is always best practice to address important issues and fully explain your points in the body of your paper. The point of a conclusion to a research paper is to summarize your argument for the reader and, perhaps, to call the reader to action if needed.

• Note that a call for action is not essential to all conclusions. A research paper on literary criticism, for instance, is less likely to need a call for action than a paper on the effect that television has on toddlers and young children.
• A paper that is more likely to call readers to action is one that addresses a public or scientific need. Let's go back to our example of tuberculosis. This is a very serious disease that is spreading quickly and with antibiotic-resistant forms.
• A call to action in this research paper would be a follow-up statement that might be along the lines of "Despite new efforts to diagnose and contain the disease, more research is needed to develop new antibiotics that will treat the most resistant strains of tuberculosis and ease the side effects of current treatments."

• For example, if you are writing a history paper, then you might discuss how the historical topic you discussed matters today. If you are writing about a foreign country, then you might use the conclusion to discuss how the information you shared may help readers understand their own country.

Making Your Conclusion as Effective as Possible

• Since this sort of conclusion is so basic, you must aim to synthesize the information rather than merely summarizing it.
• Instead of merely repeating things you already said, rephrase your thesis and supporting points in a way that ties them all together.
• By doing so, you make your research paper seem like a "complete thought" rather than a collection of random and vaguely related ideas.

• Ask a question in your introduction. In your conclusion, restate the question and provide a direct answer.
• Write an anecdote or story in your introduction but do not share the ending. Instead, write the conclusion to the anecdote in the conclusion of your paper.
• For example, if you wanted to get more creative and put a more humanistic spin on a paper on tuberculosis, you might start your introduction with a story about a person with the disease, and refer to that story in your conclusion. For example, you could say something like this before you re-state your thesis in your conclusion: "Patient X was unable to complete the treatment for tuberculosis due to severe side effects and unfortunately succumbed to the disease."
• Use the same concepts and images introduced in your introduction in your conclusion. The images may or may not appear at other points throughout the research paper.

• Include enough information about your topic to back the statement up but do not get too carried away with excess detail.
• If your research did not provide you with a clear-cut answer to a question posed in your thesis, do not be afraid to indicate as much.
• Restate your initial hypothesis and indicate whether you still believe it or if the research you performed has begun swaying your opinion.
• Indicate that an answer may still exist and that further research could shed more light on the topic at hand.

• This may not be appropriate for all types of research papers. Most research papers, such as one on effective treatment for diseases, will have the information to make the case for a particular argument already in the paper.
• A good example of a paper that might ask a question of the reader in the ending is one about a social issue, such as poverty or government policy.
• Ask a question that will directly get at the heart or purpose of the paper. This question is often the same question, or some version of it, that you may have started with when you began your research.
• Make sure that the question can be answered by the evidence presented in your paper.
• If desired you can briefly summarize the answer after stating the question. You could also leave the question hanging for the reader to answer, though.

• Even without a call to action, you can still make a recommendation to your reader.
• For instance, if you are writing about a topic like third-world poverty, you can various ways for the reader to assist in the problem without necessarily calling for more research.
• Another example would be, in a paper about treatment for drug-resistant tuberculosis, you could suggest donating to the World Health Organization or research foundations that are developing new treatments for the disease.

Avoiding Common Pitfalls

• These sayings usually sound stiff, unnatural, or trite when used in writing.
• Moreover, using a phrase like "in conclusion" to begin your conclusion is a little too straightforward and tends to lead to a weak conclusion. A strong conclusion can stand on its own without being labeled as such.

• Always state the main argument or thesis in the introduction. A research paper is an analytical discussion of an academic topic, not a mystery novel.
• A good, effective research paper will allow your reader to follow your main argument from start to finish.
• This is why it is best practice to start your paper with an introduction that states your main argument and to end the paper with a conclusion that re-states your thesis for re-iteration.

• All significant information should be introduced in the body of the paper.
• Supporting evidence expands the topic of your paper by making it appear more detailed. A conclusion should narrow the topic to a more general point.
• A conclusion should only summarize what you have already stated in the body of your paper.
• You may suggest further research or a call to action, but you should not bring in any new evidence or facts in the conclusion.

• Most often, a shift in tone occurs when a research paper with an academic tone gives an emotional or sentimental conclusion.
• Even if the topic of the paper is of personal significance for you, you should not indicate as much in your paper.
• If you want to give your paper a more humanistic slant, you could start and end your paper with a story or anecdote that would give your topic more personal meaning to the reader.
• This tone should be consistent throughout the paper, however.

• Apologetic statements include phrases like "I may not be an expert" or "This is only my opinion."
• Statements like this can usually be avoided by refraining from writing in the first-person.
• Avoid any statements in the first-person. First-person is generally considered to be informal and does not fit with the formal tone of a research paper.

Community Q&A

You Might Also Like

• ↑ http://owl.english.purdue.edu/owl/resource/724/04/
• ↑ http://www.crlsresearchguide.org/18_Writing_Conclusion.asp
• ↑ http://writing.wisc.edu/Handbook/PlanResearchPaper.html#conclusion
• ↑ http://writingcenter.unc.edu/handouts/conclusions/
• ↑ http://writing2.richmond.edu/writing/wweb/conclude.html

About This Article

To write a conclusion for a research paper, start by restating your thesis statement to remind your readers what your main topic is and bring everything full circle. Then, briefly summarize all of the main points you made throughout your paper, which will help remind your readers of everything they learned. You might also want to include a call to action if you think more research or work needs to be done on your topic by writing something like, "Despite efforts to contain the disease, more research is needed to develop antibiotics." Finally, end your conclusion by explaining the broader context of your topic and why your readers should care about it, which will help them understand why your topic is relevant and important. For tips from our Academic co-author, like how to avoid common pitfalls when writing your conclusion, scroll down! Did this summary help you? Yes No

• Send fan mail to authors

Reader Success Stories

Did this article help you?

Ummay Aimen

Sep 30, 2016

Oct 22, 2017

Sally Larrin

Mar 17, 2018

Maya Loeven

Jun 4, 2017

Featured Articles

Trending Articles

Watch Articles

• Terms of Use
• Privacy Policy
• Do Not Sell or Share My Info
• Not Selling Info

wikiHow Tech Help Pro:

Level up your tech skills and stay ahead of the curve

Have a language expert improve your writing

Run a free plagiarism check in 10 minutes, generate accurate citations for free.

• Knowledge Base
• Dissertation

How to Write a Thesis or Dissertation Conclusion

Published on September 6, 2022 by Tegan George and Shona McCombes. Revised on November 20, 2023.

The conclusion is the very last part of your thesis or dissertation . It should be concise and engaging, leaving your reader with a clear understanding of your main findings, as well as the answer to your research question .

In it, you should:

• Clearly state the answer to your main research question
• Summarize and reflect on your research process
• Make recommendations for future work on your thesis or dissertation topic
• Show what new knowledge you have contributed to your field
• Wrap up your thesis or dissertation

Instantly correct all language mistakes in your text

Upload your document to correct all your mistakes in minutes

Table of contents

Discussion vs. conclusion, how long should your conclusion be, step 1: answer your research question, step 2: summarize and reflect on your research, step 3: make future recommendations, step 4: emphasize your contributions to your field, step 5: wrap up your thesis or dissertation, full conclusion example, conclusion checklist, other interesting articles, frequently asked questions about conclusion sections.

While your conclusion contains similar elements to your discussion section , they are not the same thing.

Your conclusion should be shorter and more general than your discussion. Instead of repeating literature from your literature review , discussing specific research results , or interpreting your data in detail, concentrate on making broad statements that sum up the most important insights of your research.

As a rule of thumb, your conclusion should not introduce new data, interpretations, or arguments.

Receive feedback on language, structure, and formatting

Professional editors proofread and edit your paper by focusing on:

• Academic style
• Vague sentences
• Style consistency

See an example

Depending on whether you are writing a thesis or dissertation, your length will vary. Generally, a conclusion should make up around 5–7% of your overall word count.

An empirical scientific study will often have a short conclusion, concisely stating the main findings and recommendations for future research. A humanities dissertation topic or systematic review , on the other hand, might require more space to conclude its analysis, tying all the previous sections together in an overall argument.

Your conclusion should begin with the main question that your thesis or dissertation aimed to address. This is your final chance to show that you’ve done what you set out to do, so make sure to formulate a clear, concise answer.

• Don’t repeat a list of all the results that you already discussed
• Do synthesize them into a final takeaway that the reader will remember.

An empirical thesis or dissertation conclusion may begin like this:

A case study –based thesis or dissertation conclusion may begin like this:

In the second example, the research aim is not directly restated, but rather added implicitly to the statement. To avoid repeating yourself, it is helpful to reformulate your aims and questions into an overall statement of what you did and how you did it.

Your conclusion is an opportunity to remind your reader why you took the approach you did, what you expected to find, and how well the results matched your expectations.

To avoid repetition , consider writing more reflectively here, rather than just writing a summary of each preceding section. Consider mentioning the effectiveness of your methodology , or perhaps any new questions or unexpected insights that arose in the process.

You can also mention any limitations of your research, but only if you haven’t already included these in the discussion. Don’t dwell on them at length, though—focus on the positives of your work.

• While x limits the generalizability of the results, this approach provides new insight into y .
• This research clearly illustrates x , but it also raises the question of y .

Prevent plagiarism. Run a free check.

You may already have made a few recommendations for future research in your discussion section, but the conclusion is a good place to elaborate and look ahead, considering the implications of your findings in both theoretical and practical terms.

• Based on these conclusions, practitioners should consider …
• To better understand the implications of these results, future studies could address …
• Further research is needed to determine the causes of/effects of/relationship between …

When making recommendations for further research, be sure not to undermine your own work. Relatedly, while future studies might confirm, build on, or enrich your conclusions, they shouldn’t be required for your argument to feel complete. Your work should stand alone on its own merits.

Just as you should avoid too much self-criticism, you should also avoid exaggerating the applicability of your research. If you’re making recommendations for policy, business, or other practical implementations, it’s generally best to frame them as “shoulds” rather than “musts.” All in all, the purpose of academic research is to inform, explain, and explore—not to demand.

Make sure your reader is left with a strong impression of what your research has contributed to the state of your field.

Some strategies to achieve this include:

• Returning to your problem statement to explain how your research helps solve the problem
• Referring back to the literature review and showing how you have addressed a gap in knowledge
• Discussing how your findings confirm or challenge an existing theory or assumption

Again, avoid simply repeating what you’ve already covered in the discussion in your conclusion. Instead, pick out the most important points and sum them up succinctly, situating your project in a broader context.

The end is near! Once you’ve finished writing your conclusion, it’s time to wrap up your thesis or dissertation with a few final steps:

• It’s a good idea to write your abstract next, while the research is still fresh in your mind.
• Next, make sure your reference list is complete and correctly formatted. To speed up the process, you can use our free APA citation generator .
• Once you’ve added any appendices , you can create a table of contents and title page .
• Finally, read through the whole document again to make sure your thesis is clearly written and free from language errors. You can proofread it yourself , ask a friend, or consider Scribbr’s proofreading and editing service .

Here is an example of how you can write your conclusion section. Notice how it includes everything mentioned above:

V. Conclusion

The current research aimed to identify acoustic speech characteristics which mark the beginning of an exacerbation in COPD patients.

The central questions for this research were as follows: 1. Which acoustic measures extracted from read speech differ between COPD speakers in stable condition and healthy speakers? 2. In what ways does the speech of COPD patients during an exacerbation differ from speech of COPD patients during stable periods?

All recordings were aligned using a script. Subsequently, they were manually annotated to indicate respiratory actions such as inhaling and exhaling. The recordings of 9 stable COPD patients reading aloud were then compared with the recordings of 5 healthy control subjects reading aloud. The results showed a significant effect of condition on the number of in- and exhalations per syllable, the number of non-linguistic in- and exhalations per syllable, and the ratio of voiced and silence intervals. The number of in- and exhalations per syllable and the number of non-linguistic in- and exhalations per syllable were higher for COPD patients than for healthy controls, which confirmed both hypotheses.

However, the higher ratio of voiced and silence intervals for COPD patients compared to healthy controls was not in line with the hypotheses. This unpredicted result might have been caused by the different reading materials or recording procedures for both groups, or by a difference in reading skills. Moreover, there was a trend regarding the effect of condition on the number of syllables per breath group. The number of syllables per breath group was higher for healthy controls than for COPD patients, which was in line with the hypothesis. There was no effect of condition on pitch, intensity, center of gravity, pitch variability, speaking rate, or articulation rate.

This research has shown that the speech of COPD patients in exacerbation differs from the speech of COPD patients in stable condition. This might have potential for the detection of exacerbations. However, sustained vowels rarely occur in spontaneous speech. Therefore, the last two outcome measures might have greater potential for the detection of beginning exacerbations, but further research on the different outcome measures and their potential for the detection of exacerbations is needed due to the limitations of the current study.

Checklist: Conclusion

I have clearly and concisely answered the main research question .

I have summarized my overall argument or key takeaways.

I have mentioned any important limitations of the research.

I have given relevant recommendations .

I have clearly explained what my research has contributed to my field.

I have  not introduced any new data or arguments.

You've written a great conclusion! Use the other checklists to further improve your dissertation.

If you want to know more about AI for academic writing, AI tools, or research bias, make sure to check out some of our other articles with explanations and examples or go directly to our tools!

Research bias

• Survivorship bias
• Self-serving bias
• Availability heuristic
• Halo effect
• Hindsight bias
• Deep learning
• Generative AI
• Machine learning
• Reinforcement learning
• Supervised vs. unsupervised learning

 (AI) Tools

• Grammar Checker
• Paraphrasing Tool
• Text Summarizer
• AI Detector
• Plagiarism Checker
• Citation Generator

In a thesis or dissertation, the discussion is an in-depth exploration of the results, going into detail about the meaning of your findings and citing relevant sources to put them in context.

The conclusion is more shorter and more general: it concisely answers your main research question and makes recommendations based on your overall findings.

While it may be tempting to present new arguments or evidence in your thesis or disseration conclusion , especially if you have a particularly striking argument you’d like to finish your analysis with, you shouldn’t. Theses and dissertations follow a more formal structure than this.

All your findings and arguments should be presented in the body of the text (more specifically in the discussion section and results section .) The conclusion is meant to summarize and reflect on the evidence and arguments you have already presented, not introduce new ones.

For a stronger dissertation conclusion , avoid including:

• Important evidence or analysis that wasn’t mentioned in the discussion section and results section
• Generic concluding phrases (e.g. “In conclusion …”)
• Weak statements that undermine your argument (e.g., “There are good points on both sides of this issue.”)

Your conclusion should leave the reader with a strong, decisive impression of your work.

The conclusion of your thesis or dissertation shouldn’t take up more than 5–7% of your overall word count.

The conclusion of your thesis or dissertation should include the following:

• A restatement of your research question
• A summary of your key arguments and/or results
• A short discussion of the implications of your research

Cite this Scribbr article

If you want to cite this source, you can copy and paste the citation or click the “Cite this Scribbr article” button to automatically add the citation to our free Citation Generator.

George, T. & McCombes, S. (2023, November 20). How to Write a Thesis or Dissertation Conclusion. Scribbr. Retrieved July 5, 2024, from https://www.scribbr.com/dissertation/write-conclusion/

Is this article helpful?

Tegan George

Other students also liked, how to write a discussion section | tips & examples, how to write an abstract | steps & examples, how to write a thesis or dissertation introduction, get unlimited documents corrected.

✔ Free APA citation check included ✔ Unlimited document corrections ✔ Specialized in correcting academic texts

• Link to facebook
• Link to linkedin
• Link to twitter
• Link to youtube
• Writing Tips

How to Write a Conclusion for a Research Paper

3-minute read

• 29th August 2023

If you’re writing a research paper, the conclusion is your opportunity to summarize your findings and leave a lasting impression on your readers. In this post, we’ll take you through how to write an effective conclusion for a research paper and how you can:

·   Reword your thesis statement

·   Highlight the significance of your research

·   Discuss limitations

·   Connect to the introduction

·   End with a thought-provoking statement

Rewording Your Thesis Statement

Begin your conclusion by restating your thesis statement in a way that is slightly different from the wording used in the introduction. Avoid presenting new information or evidence in your conclusion. Just summarize the main points and arguments of your essay and keep this part as concise as possible. Remember that you’ve already covered the in-depth analyses and investigations in the main body paragraphs of your essay, so it’s not necessary to restate these details in the conclusion.

Find this useful?

Subscribe to our newsletter and get writing tips from our editors straight to your inbox.

Highlighting the Significance of Your Research

The conclusion is a good place to emphasize the implications of your research . Avoid ambiguous or vague language such as “I think” or “maybe,” which could weaken your position. Clearly explain why your research is significant and how it contributes to the broader field of study.

Here’s an example from a (fictional) study on the impact of social media on mental health:

Discussing Limitations

Although it’s important to emphasize the significance of your study, you can also use the conclusion to briefly address any limitations you discovered while conducting your research, such as time constraints or a shortage of resources. Doing this demonstrates a balanced and honest approach to your research.

Connecting to the Introduction

In your conclusion, you can circle back to your introduction , perhaps by referring to a quote or anecdote you discussed earlier. If you end your paper on a similar note to how you began it, you will create a sense of cohesion for the reader and remind them of the meaning and significance of your research.

Ending With a Thought-Provoking Statement

Consider ending your paper with a thought-provoking and memorable statement that relates to the impact of your research questions or hypothesis. This statement can be a call to action, a philosophical question, or a prediction for the future (positive or negative). Here’s an example that uses the same topic as above (social media and mental health):

Expert Proofreading Services

Ensure that your essay ends on a high note by having our experts proofread your research paper. Our team has experience with a wide variety of academic fields and subjects and can help make your paper stand out from the crowd – get started today and see the difference it can make in your work.

Share this article:

Post A New Comment

Got content that needs a quick turnaround? Let us polish your work. Explore our editorial business services.

9-minute read

How to Use Infographics to Boost Your Presentation

Is your content getting noticed? Capturing and maintaining an audience’s attention is a challenge when...

8-minute read

Why Interactive PDFs Are Better for Engagement

Are you looking to enhance engagement and captivate your audience through your professional documents? Interactive...

7-minute read

Seven Key Strategies for Voice Search Optimization

Voice search optimization is rapidly shaping the digital landscape, requiring content professionals to adapt their...

4-minute read

Five Creative Ways to Showcase Your Digital Portfolio

Are you a creative freelancer looking to make a lasting impression on potential clients or...

How to Ace Slack Messaging for Contractors and Freelancers

Effective professional communication is an important skill for contractors and freelancers navigating remote work environments....

How to Insert a Text Box in a Google Doc

Google Docs is a powerful collaborative tool, and mastering its features can significantly enhance your...

Make sure your writing is the best it can be with our expert English proofreading and editing.

• USC Libraries
• Research Guides

Organizing Your Social Sciences Research Paper

• 9. The Conclusion
• Purpose of Guide
• Design Flaws to Avoid
• Independent and Dependent Variables
• Glossary of Research Terms
• Reading Research Effectively
• Narrowing a Topic Idea
• Broadening a Topic Idea
• Extending the Timeliness of a Topic Idea
• Academic Writing Style
• Applying Critical Thinking
• Choosing a Title
• Making an Outline
• Paragraph Development
• Research Process Video Series
• Executive Summary
• The C.A.R.S. Model
• Background Information
• The Research Problem/Question
• Theoretical Framework
• Citation Tracking
• Content Alert Services
• Evaluating Sources
• Primary Sources
• Secondary Sources
• Tiertiary Sources
• Scholarly vs. Popular Publications
• Qualitative Methods
• Quantitative Methods
• Insiderness
• Using Non-Textual Elements
• Limitations of the Study
• Common Grammar Mistakes
• Writing Concisely
• Avoiding Plagiarism
• Footnotes or Endnotes?
• Further Readings
• Generative AI and Writing
• USC Libraries Tutorials and Other Guides
• Bibliography

The conclusion is intended to help the reader understand why your research should matter to them after they have finished reading the paper. A conclusion is not merely a summary of the main topics covered or a re-statement of your research problem, but a synthesis of key points derived from the findings of your study and, if applicable based on your analysis, explain new areas for future research. For most college-level research papers, two or three well-developed paragraphs is sufficient for a conclusion, although in some cases, more paragraphs may be required in describing the key findings and highlighting their significance.

Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University.

Importance of a Good Conclusion

A well-written conclusion provides important opportunities to demonstrate to the reader your understanding of the research problem. These include:

• Presenting the last word on the issues you raised in your paper . Just as the introduction gives a first impression to your reader, the conclusion offers a chance to leave a lasting impression. Do this, for example, by highlighting key findings in your analysis that advance new understanding about the research problem, that are unusual or unexpected, or that have important implications applied to practice.
• Summarizing your thoughts and conveying the larger significance of your study . The conclusion is an opportunity to succinctly re-emphasize  your answer to the "So What?" question by placing the study within the context of how your research advances past studies about the topic.
• Identifying how a gap in the literature has been addressed . The conclusion can be where you describe how a previously identified gap in the literature [first identified in your literature review section] has been addressed by your research and why this contribution is significant.
• Demonstrating the importance of your ideas . Don't be shy. The conclusion offers an opportunity to elaborate on the impact and significance of your findings. This is particularly important if your study approached examining the research problem from an unusual or innovative perspective.
• Introducing possible new or expanded ways of thinking about the research problem . This does not refer to introducing new information [which should be avoided], but to offer new insight and creative approaches for framing or contextualizing the research problem based on the results of your study.

Bunton, David. “The Structure of PhD Conclusion Chapters.” Journal of English for Academic Purposes 4 (July 2005): 207–224; Conclusions. The Writing Center. University of North Carolina; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Conclusions. The Writing Lab and The OWL. Purdue University; Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Structure and Writing Style

I.  General Rules

The general function of your paper's conclusion is to restate the main argument . It reminds the reader of your main argument(s) strengths and reiterates the most important evidence supporting those argument(s). Do this by clearly summarizing the context, background, and the necessity of examining the research problem in relation to an issue, controversy, or a gap found in the literature. However, make sure that your conclusion is not simply a repetitive summary of the findings. This reduces the impact of the argument(s) you have developed in your paper.

When writing the conclusion to your paper, follow these general rules:

• Present your conclusions in clear, concise language. Re-state the purpose of your study, then describe how your findings differ or support those of other studies and why [i.e., describe what were the unique, new, or crucial contributions your study made to the overall research about your topic].
• Do not simply reiterate your findings or the discussion of your results. Provide a synthesis of arguments presented in the paper to show how these converge to address the research problem and the overall objectives of your study.
• Indicate opportunities for future research if you haven't already done so in the discussion section of your paper. Highlighting the need for further research provides the reader with evidence that you have an in-depth awareness of the research problem but that further analysis should take place beyond the scope of your investigation.

Consider the following points to help ensure your conclusion is presented well:

• If the argument or purpose of your paper is complex, you may need to summarize the argument for your reader.
• If, prior to your conclusion, you have not yet explained the significance of your findings or if you are proceeding inductively, use the end of your paper to describe your main points and explain their significance.
• Move from a detailed to a general level of consideration that returns the topic to the context provided by the introduction or within a new context that emerges from the data [this is opposite of the introduction, which begins with general discussion of the context and ends with a detailed description of the research problem]. 

The conclusion also provides a place for you to persuasively and succinctly restate the research problem, given that the reader has now been presented with all the information about the topic . Depending on the discipline you are writing in, the concluding paragraph may contain your reflections on the evidence presented. However, the nature of being introspective about the research you have conducted will depend on the topic and whether your professor wants you to express your observations in this way. If asked to think introspectively about the topic, do not delve into idle speculation. Being introspective means looking within yourself as an author to try and understand an issue more deeply, not to guess at possible outcomes or make up scenarios not supported by the evidence.

II.  Developing a Compelling Conclusion

Although an effective conclusion needs to be clear and succinct, it does not need to be written passively or lack a compelling narrative. Strategies to help you move beyond merely summarizing the key points of your research paper may include any of the following:

• If your paper addresses a critical, contemporary problem, warn readers of the possible consequences of not attending to the problem proactively based on the evidence presented in your study.
• Recommend a specific course or courses of action that, if adopted, could address a specific problem in practice or in the development of new knowledge leading to positive change.
• Cite a relevant quotation or expert opinion already noted in your paper in order to lend authority and support to the conclusion(s) you have reached [a good source would be from a source cited in your literature review].
• Explain the consequences of your research in a way that elicits action or demonstrates urgency in seeking change.
• Restate a key statistic, fact, or visual image to emphasize the most important finding of your paper.
• If your discipline encourages personal reflection, illustrate your concluding point by drawing from your own life experiences.
• Return to an anecdote, an example, or a quotation that you presented in your introduction, but add further insight derived from the findings of your study; use your interpretation of results from your study to recast it in new or important ways.
• Provide a "take-home" message in the form of a succinct, declarative statement that you want the reader to remember about your study.

III. Problems to Avoid

Failure to be concise Your conclusion section should be concise and to the point. Conclusions that are too lengthy often have unnecessary information in them. The conclusion is not the place for details about your methodology or results. Although you should give a summary of what was learned from your research, this summary should be relatively brief, since the emphasis in the conclusion is on the implications, evaluations, insights, and other forms of analysis that you make. Strategies for writing concisely can be found here .

Failure to comment on larger, more significant issues In the introduction, your task was to move from the general [topic studied within the field of study] to the specific [the research problem]. However, in the conclusion, your task is to move the discussion from specific [your research problem] back to a general discussion framed around the implications and significance of your findings [i.e., how your research contributes new understanding or fills an important gap in the literature]. In short, the conclusion is where you should place your research within a larger context [visualize the structure of your paper as an hourglass--start with a broad introduction and review of the literature, move to the specific method of analysis and the discussion, conclude with a broad summary of the study's implications and significance].

Failure to reveal problems and negative results Negative aspects of the research process should never be ignored. These are problems, deficiencies, or challenges encountered during your study. They should be summarized as a way of qualifying your overall conclusions. If you encountered negative or unintended results [i.e., findings that are validated outside the research context in which they were generated], you must report them in the results section and discuss their implications in the discussion section of your paper. In the conclusion, use negative or surprising results as an opportunity to explain their possible significance and/or how they may form the basis for future research.

Failure to provide a clear summary of what was learned In order to discuss how your research fits within your field of study [and possibly the world at large], you need to summarize briefly and succinctly how it contributes to new knowledge or a new understanding about the research problem. This element of your conclusion may be only a few sentences long, but it often represents the key takeaway for your reader.

Failure to match the objectives of your research Often research objectives in the social and behavioral sciences change while the research is being carried out due to unforeseen factors or unanticipated variables. This is not a problem unless you forget to go back and refine the original objectives in your introduction. As these changes emerge they must be documented so that they accurately reflect what you were trying to accomplish in your research [not what you thought you might accomplish when you began].

Resist the urge to apologize If you've immersed yourself in studying the research problem, you presumably should know a good deal about it [perhaps even more than your professor!]. Nevertheless, by the time you have finished writing, you may be having some doubts about what you have produced. Repress those doubts! Don't undermine your authority as a researcher by saying something like, "This is just one approach to examining this problem; there may be other, much better approaches that...." The overall tone of your conclusion should convey confidence to the reader concerning the validity and realiability of your research.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Concluding Paragraphs. College Writing Center at Meramec. St. Louis Community College; Conclusions. The Writing Center. University of North Carolina; Conclusions. The Writing Lab and The OWL. Purdue University; Freedman, Leora  and Jerry Plotnick. Introductions and Conclusions. The Lab Report. University College Writing Centre. University of Toronto; Leibensperger, Summer. Draft Your Conclusion. Academic Center, the University of Houston-Victoria, 2003; Make Your Last Words Count. The Writer’s Handbook. Writing Center. University of Wisconsin Madison; Miquel, Fuster-Marquez and Carmen Gregori-Signes. “Chapter Six: ‘Last but Not Least:’ Writing the Conclusion of Your Paper.” In Writing an Applied Linguistics Thesis or Dissertation: A Guide to Presenting Empirical Research . John Bitchener, editor. (Basingstoke,UK: Palgrave Macmillan, 2010), pp. 93-105; Tips for Writing a Good Conclusion. Writing@CSU. Colorado State University; Kretchmer, Paul. Twelve Steps to Writing an Effective Conclusion. San Francisco Edit, 2003-2008; Writing Conclusions. Writing Tutorial Services, Center for Innovative Teaching and Learning. Indiana University; Writing: Considering Structure and Organization. Institute for Writing Rhetoric. Dartmouth College.

Writing Tip

Don't Belabor the Obvious!

Avoid phrases like "in conclusion...," "in summary...," or "in closing...." These phrases can be useful, even welcome, in oral presentations. But readers can see by the tell-tale section heading and number of pages remaining that they are reaching the end of your paper. You'll irritate your readers if you belabor the obvious.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8.

Another Writing Tip

New Insight, Not New Information!

Don't surprise the reader with new information in your conclusion that was never referenced anywhere else in the paper. This is why the conclusion rarely has citations to sources that haven't been referenced elsewhere in your paper. If you have new information to present, add it to the discussion or other appropriate section of the paper. Note that, although no new information is introduced, the conclusion, along with the discussion section, is where you offer your most "original" contributions in the paper; the conclusion is where you describe the value of your research, demonstrate that you understand the material that you have presented, and position your findings within the larger context of scholarship on the topic, including describing how your research contributes new insights to that scholarship.

Assan, Joseph. "Writing the Conclusion Chapter: The Good, the Bad and the Missing." Liverpool: Development Studies Association (2009): 1-8; Conclusions. The Writing Center. University of North Carolina.

• << Previous: Limitations of the Study
• Next: Appendices >>
• Last Updated: Jul 3, 2024 10:07 AM
• URL: https://libguides.usc.edu/writingguide

How to write a strong conclusion for your research paper

Last updated

17 February 2024

Reviewed by

Short on time? Get an AI generated summary of this article instead

Writing a research paper is a chance to share your knowledge and hypothesis. It's an opportunity to demonstrate your many hours of research and prove your ability to write convincingly.

Ideally, by the end of your research paper, you'll have brought your readers on a journey to reach the conclusions you've pre-determined. However, if you don't stick the landing with a good conclusion, you'll risk losing your reader’s trust.

Writing a strong conclusion for your research paper involves a few important steps, including restating the thesis and summing up everything properly.

Find out what to include and what to avoid, so you can effectively demonstrate your understanding of the topic and prove your expertise.

• Why is a good conclusion important?

A good conclusion can cement your paper in the reader’s mind. Making a strong impression in your introduction can draw your readers in, but it's the conclusion that will inspire them.

• What to include in a research paper conclusion

There are a few specifics you should include in your research paper conclusion. Offer your readers some sense of urgency or consequence by pointing out why they should care about the topic you have covered. Discuss any common problems associated with your topic and provide suggestions as to how these problems can be solved or addressed.

The conclusion should include a restatement of your initial thesis. Thesis statements are strengthened after you’ve presented supporting evidence (as you will have done in the paper), so make a point to reintroduce it at the end.

Finally, recap the main points of your research paper, highlighting the key takeaways you want readers to remember. If you've made multiple points throughout the paper, refer to the ones with the strongest supporting evidence.

• Steps for writing a research paper conclusion

Many writers find the conclusion the most challenging part of any research project . By following these three steps, you'll be prepared to write a conclusion that is effective and concise.

• Step 1: Restate the problem

Always begin by restating the research problem in the conclusion of a research paper. This serves to remind the reader of your hypothesis and refresh them on the main point of the paper. 

When restating the problem, take care to avoid using exactly the same words you employed earlier in the paper.

• Step 2: Sum up the paper

After you've restated the problem, sum up the paper by revealing your overall findings. The method for this differs slightly, depending on whether you're crafting an argumentative paper or an empirical paper.

Argumentative paper: Restate your thesis and arguments

Argumentative papers involve introducing a thesis statement early on. In crafting the conclusion for an argumentative paper, always restate the thesis, outlining the way you've developed it throughout the entire paper.

It might be appropriate to mention any counterarguments in the conclusion, so you can demonstrate how your thesis is correct or how the data best supports your main points.

Empirical paper: Summarize research findings

Empirical papers break down a series of research questions. In your conclusion, discuss the findings your research revealed, including any information that surprised you.

Be clear about the conclusions you reached, and explain whether or not you expected to arrive at these particular ones.

• Step 3: Discuss the implications of your research

Argumentative papers and empirical papers also differ in this part of a research paper conclusion. Here are some tips on crafting conclusions for argumentative and empirical papers.

Argumentative paper: Powerful closing statement

In an argumentative paper, you'll have spent a great deal of time expressing the opinions you formed after doing a significant amount of research. Make a strong closing statement in your argumentative paper's conclusion to share the significance of your work.

You can outline the next steps through a bold call to action, or restate how powerful your ideas turned out to be.

Empirical paper: Directions for future research

Empirical papers are broader in scope. They usually cover a variety of aspects and can include several points of view.

To write a good conclusion for an empirical paper, suggest the type of research that could be done in the future, including methods for further investigation or outlining ways other researchers might proceed.

If you feel your research had any limitations, even if they were outside your control, you could mention these in your conclusion.

After you finish outlining your conclusion, ask someone to read it and offer feedback. In any research project you're especially close to, it can be hard to identify problem areas. Having a close friend or someone whose opinion you value read the research paper and provide honest feedback can be invaluable. Take note of any suggested edits and consider incorporating them into your paper if they make sense.

• Things to avoid in a research paper conclusion

Keep these aspects to avoid in mind as you're writing your conclusion and refer to them after you've created an outline.

Dry summary

Writing a memorable, succinct conclusion is arguably more important than a strong introduction. Take care to avoid just rephrasing your main points, and don't fall into the trap of repeating dry facts or citations.

You can provide a new perspective for your readers to think about or contextualize your research. Either way, make the conclusion vibrant and interesting, rather than a rote recitation of your research paper’s highlights.

Clichéd or generic phrasing

Your research paper conclusion should feel fresh and inspiring. Avoid generic phrases like "to sum up" or "in conclusion." These phrases tend to be overused, especially in an academic context and might turn your readers off.

The conclusion also isn't the time to introduce colloquial phrases or informal language. Retain a professional, confident tone consistent throughout your paper’s conclusion so it feels exciting and bold.

New data or evidence

While you should present strong data throughout your paper, the conclusion isn't the place to introduce new evidence. This is because readers are engaged in actively learning as they read through the body of your paper.

By the time they reach the conclusion, they will have formed an opinion one way or the other (hopefully in your favor!). Introducing new evidence in the conclusion will only serve to surprise or frustrate your reader.

Ignoring contradictory evidence

If your research reveals contradictory evidence, don't ignore it in the conclusion. This will damage your credibility as an expert and might even serve to highlight the contradictions.

Be as transparent as possible and admit to any shortcomings in your research, but don't dwell on them for too long.

Ambiguous or unclear resolutions

The point of a research paper conclusion is to provide closure and bring all your ideas together. You should wrap up any arguments you introduced in the paper and tie up any loose ends, while demonstrating why your research and data are strong.

Use direct language in your conclusion and avoid ambiguity. Even if some of the data and sources you cite are inconclusive or contradictory, note this in your conclusion to come across as confident and trustworthy.

• Examples of research paper conclusions

Your research paper should provide a compelling close to the paper as a whole, highlighting your research and hard work. While the conclusion should represent your unique style, these examples offer a starting point:

Ultimately, the data we examined all point to the same conclusion: Encouraging a good work-life balance improves employee productivity and benefits the company overall. The research suggests that when employees feel their personal lives are valued and respected by their employers, they are more likely to be productive when at work. In addition, company turnover tends to be reduced when employees have a balance between their personal and professional lives. While additional research is required to establish ways companies can support employees in creating a stronger work-life balance, it's clear the need is there.

Social media is a primary method of communication among young people. As we've seen in the data presented, most young people in high school use a variety of social media applications at least every hour, including Instagram and Facebook. While social media is an avenue for connection with peers, research increasingly suggests that social media use correlates with body image issues. Young girls with lower self-esteem tend to use social media more often than those who don't log onto social media apps every day. As new applications continue to gain popularity, and as more high school students are given smartphones, more research will be required to measure the effects of prolonged social media use.

What are the different kinds of research paper conclusions?

There are no formal types of research paper conclusions. Ultimately, the conclusion depends on the outline of your paper and the type of research you’re presenting. While some experts note that research papers can end with a new perspective or commentary, most papers should conclude with a combination of both. The most important aspect of a good research paper conclusion is that it accurately represents the body of the paper.

Can I present new arguments in my research paper conclusion?

Research paper conclusions are not the place to introduce new data or arguments. The body of your paper is where you should share research and insights, where the reader is actively absorbing the content. By the time a reader reaches the conclusion of the research paper, they should have formed their opinion. Introducing new arguments in the conclusion can take a reader by surprise, and not in a positive way. It might also serve to frustrate readers.

How long should a research paper conclusion be?

There's no set length for a research paper conclusion. However, it's a good idea not to run on too long, since conclusions are supposed to be succinct. A good rule of thumb is to keep your conclusion around 5 to 10 percent of the paper's total length. If your paper is 10 pages, try to keep your conclusion under one page.

What should I include in a research paper conclusion?

A good research paper conclusion should always include a sense of urgency, so the reader can see how and why the topic should matter to them. You can also note some recommended actions to help fix the problem and some obstacles they might encounter. A conclusion should also remind the reader of the thesis statement, along with the main points you covered in the paper. At the end of the conclusion, add a powerful closing statement that helps cement the paper in the mind of the reader.

Should you be using a customer insights hub?

Do you want to discover previous research faster?

Do you share your research findings with others?

Do you analyze research data?

Start for free today, add your research, and get to key insights faster

Editor’s picks

Last updated: 18 April 2023

Last updated: 27 February 2023

Last updated: 6 February 2023

Last updated: 6 October 2023

Last updated: 5 February 2023

Last updated: 16 April 2023

Last updated: 7 March 2023

Last updated: 9 March 2023

Last updated: 12 December 2023

Last updated: 11 March 2024

Last updated: 6 March 2024

Last updated: 5 March 2024

Last updated: 13 May 2024

Latest articles

Related topics, .css-je19u9{-webkit-align-items:flex-end;-webkit-box-align:flex-end;-ms-flex-align:flex-end;align-items:flex-end;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:row;-ms-flex-direction:row;flex-direction:row;-webkit-box-flex-wrap:wrap;-webkit-flex-wrap:wrap;-ms-flex-wrap:wrap;flex-wrap:wrap;-webkit-box-pack:center;-ms-flex-pack:center;-webkit-justify-content:center;justify-content:center;row-gap:0;text-align:center;max-width:671px;}@media (max-width: 1079px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}}@media (max-width: 799px){.css-je19u9{max-width:400px;}.css-je19u9>span{white-space:pre;}} decide what to .css-1kiodld{max-height:56px;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}@media (max-width: 1079px){.css-1kiodld{display:none;}} build next, decide what to build next.

Users report unexpectedly high data usage, especially during streaming sessions.

Users find it hard to navigate from the home page to relevant playlists in the app.

It would be great to have a sleep timer feature, especially for bedtime listening.

I need better filters to find the songs or artists I’m looking for.

Log in or sign up

Get started for free

Reference management. Clean and simple.

How to write an excellent thesis conclusion [with examples]

Restate the thesis

Review or reiterate key points of your work, explain why your work is relevant, a take-away for the reader, more resources on writing thesis conclusions, frequently asked questions about writing an excellent thesis conclusion, related articles.

At this point in your writing, you have most likely finished your introduction and the body of your thesis, dissertation, or research paper . While this is a reason to celebrate, you should not underestimate the importance of your conclusion. The conclusion is the last thing that your reader will see, so it should be memorable.

A good conclusion will review the key points of the thesis and explain to the reader why the information is relevant, applicable, or related to the world as a whole. Make sure to dedicate enough of your writing time to the conclusion and do not put it off until the very last minute.

This article provides an effective technique for writing a conclusion adapted from Erika Eby’s The College Student's Guide to Writing a Good Research Paper: 101 Easy Tips & Tricks to Make Your Work Stand Out .

While the thesis introduction starts out with broad statements about the topic, and then narrows it down to the thesis statement , a thesis conclusion does the same in the opposite order.

• Restate the thesis.
• Review or reiterate key points of your work.
• Explain why your work is relevant.
• Include a core take-away message for the reader.

Tip: Don’t just copy and paste your thesis into your conclusion. Restate it in different words.

The best way to start a conclusion is simply by restating the thesis statement. That does not mean just copying and pasting it from the introduction, but putting it into different words.

You will need to change the structure and wording of it to avoid sounding repetitive. Also, be firm in your conclusion just as you were in the introduction. Try to avoid sounding apologetic by using phrases like "This paper has tried to show..."

The conclusion should address all the same parts as the thesis while making it clear that the reader has reached the end. You are telling the reader that your research is finished and what your findings are.

I have argued throughout this work that the point of critical mass for biopolitical immunity occurred during the Romantic period because of that era's unique combination of post-revolutionary politics and innovations in smallpox prevention. In particular, I demonstrated that the French Revolution and the discovery of vaccination in the 1790s triggered a reconsideration of the relationship between bodies and the state.

Tip: Try to reiterate points from your introduction in your thesis conclusion.

The next step is to review the main points of the thesis as a whole. Look back at the body of of your project and make a note of the key ideas. You can reword these ideas the same way you reworded your thesis statement and then incorporate that into the conclusion.

You can also repeat striking quotations or statistics, but do not use more than two. As the conclusion represents your own closing thoughts on the topic , it should mainly consist of your own words.

In addition, conclusions can contain recommendations to the reader or relevant questions that further the thesis. You should ask yourself:

• What you would ideally like to see your readers do in reaction to your paper?
• Do you want them to take a certain action or investigate further?
• Is there a bigger issue that your paper wants to draw attention to?

Also, try to reference your introduction in your conclusion. You have already taken a first step by restating your thesis. Now, check whether there are other key words, phrases or ideas that are mentioned in your introduction that fit into your conclusion. Connecting the introduction to the conclusion in this way will help readers feel satisfied.

I explored how Mary Wollstonecraft, in both her fiction and political writings, envisions an ideal medico-political state, and how other writers like William Wordsworth and Mary Shelley increasingly imagined the body politic literally, as an incorporated political collective made up of bodies whose immunity to political and medical ills was essential to a healthy state.

Tip: Make sure to explain why your thesis is relevant to your field of research.

Although you can encourage readers to question their opinions and reflect on your topic, do not leave loose ends. You should provide a sense of resolution and make sure your conclusion wraps up your argument. Make sure you explain why your thesis is relevant to your field of research and how your research intervenes within, or substantially revises, existing scholarly debates.

This project challenged conventional ideas about the relationship among Romanticism, medicine, and politics by reading the unfolding of Romantic literature and biopolitical immunity as mutual, co-productive processes. In doing so, this thesis revises the ways in which biopolitics has been theorized by insisting on the inherent connections between Romantic literature and the forms of biopower that characterize early modernity.

Tip: If you began your thesis with an anecdote or historical example, you may want to return to that in your conclusion.

End your conclusion with something memorable, such as:

• a call to action
• a recommendation
• a gesture towards future research
• a brief explanation of how the problem or idea you covered remains relevant

Ultimately, you want readers to feel more informed, or ready to act, as they read your conclusion.

Yet, the Romantic period is only the beginning of modern thought on immunity and biopolitics. Victorian writers, doctors, and politicians upheld the Romantic idea that a "healthy state" was a literal condition that could be achieved by combining politics and medicine, but augmented that idea through legislation and widespread public health measures. While many nineteenth-century efforts to improve citizens' health were successful, the fight against disease ultimately changed course in the twentieth century as global immunological threats such as SARS occupied public consciousness. Indeed, as subsequent public health events make apparent, biopolitical immunity persists as a viable concept for thinking about the relationship between medicine and politics in modernity.

Need more advice? Read our 5 additional tips on how to write a good thesis conclusion.

The conclusion is the last thing that your reader will see, so it should be memorable. To write a great thesis conclusion you should:

The basic content of a conclusion is to review the main points from the paper. This part represents your own closing thoughts on the topic. It should mainly consist of the outcome of the research in your own words.

The length of the conclusion will depend on the length of the whole thesis. Usually, a conclusion should be around 5-7% of the overall word count.

End your conclusion with something memorable, such as a question, warning, or call to action. Depending on the topic, you can also end with a recommendation.

In Open Access: Theses and Dissertations you can find thousands of completed works. Take a look at any of the theses or dissertations for real-life examples of conclusions that were already approved.

How to Write a Conclusion for a Research Paper

By the time you write the conclusion, you should have pointed out in the body of your research paper why your topic is important to the reader, and you should have presented the reader with all your arguments. It is critical that you do not introduce new information or ideas in your conclusion. If you find that you have not yet made the arguments you wished to make or pointed out evidence you feel is crucial to your reader’s understanding of your subject, you are not yet ready to write the conclusion; add another body paragraph before writing the conclusion.

Academic Writing, Editing, Proofreading, And Problem Solving Services

Get 10% off with 24start discount code.

Your research paper should have a strong, succinct concluding section, where you draw together your findings. Think of it as a conclusion, not a summary. The difference is that you are reaching overall judgments about your topic, not summarizing everything you wrote about it. How to write a conclusion for a research paper? The focus should be on:

• Saying what your research has found, what the findings mean, and how well they support the argument of your thesis statement.
• Establishing the limits of your argument: How widely does it apply? What are the strengths and weaknesses of your method? How clear-cut are your findings?
• Explaining how your findings and argument fit into your field, relating them to answers others have given and to the existing literature.

You may also want to add some concise comments about possible future developments or what kind of research should come next, but don’t lay it on too thick. The place of honor goes to your own explanation. Don’t spend too much of your final section criticizing others. Don’t introduce any big new topics or ideas. You certainly don’t expect to see new characters in the last scene of a movie. For the same reasons, you shouldn’t find any big new topics being introduced in the last paragraphs of a research paper.

Your concluding statement should focus on what your findings mean. How do you interpret them? Are they just as easily explained by alternative theories or other perspectives? Here, you are returning to the questions that first animated you and answering them, based on your research. You not only want to give the answers; you also want to explain their significance. What do they mean for policy, theory, literary interpretation, moral action, or whatever? You are answering the old, hard question: “So what?”

Be wary of overreaching. You really need to do two things at the same time: explain the significance of your findings and stake out their limits. You may have a hunch that your findings apply widely but, as a social scientist, you need to assess whether you can say so confidently, based on your current research. Your reader needs to know: “Do these findings apply to all college students, to all adults, or only to white mice?” White mice don’t come up much in the humanities, but the reader still wants to know how far your approach reaches. Does your analysis apply only to this novel or this writer, or could it apply to a whole literary genre?

Make it a priority to discuss these conclusions with your professor or adviser. The main danger here is that students finally reach this final section with only a week or two left before the due date. They don’t have enough time to work through their conclusions and revise them. That leaves the research paper weakest at the end, precisely where it should be strongest, nailing down the most significant points.

Begin discussing your major findings with your adviser while you are still writing the heart of the research paper. Of course, your conclusions will be tentative at that stage, but it helps to begin talking about them. As always, a little writing helps. You could simply list your main findings or write out a few paragraphs about them. Either would serve as a launching pad for meetings with your adviser. You will find these discussions also shed light on the research that leads to these findings. That, in turn, will strengthen your middle sections. Later, when you draft the conclusion, review your notes on these talks and the short documents you wrote for them. They will serve as prewriting for the final section.

The opening sentence of the conclusion should flow smoothly and logically from the transition sentence in the previous paragraph and lead the reader to reflect on your thesis. A good conclusion however, does not simply restate the thesis. You want to remind the reader of the thesis in your conclusion but reword it in a stronger fashion so that it is interesting and memorable to your audience.After reminding the reader of the thesis, the conclusion should then reflect on the topics in the body of the paper and summarize the key findings of your research. If you are writing a persuasive paper, it should summarize your key arguments and logically point your readers to the conclusion you wish them to reach.

Phrases for Conclusions of Research Papers

• All this requires us to (propose the next action or an alternative idea).
• Altogether, these findings indicate (point out the logical result).
• Finally, it is important to note (make your strongest point and follow with a recommendation).
• In conclusion (restate your thesis with greater emphasis).
• It is evident that (point out the logical result or obvious next action).
• In light of the evidence, (restate your thesis with greater emphasis).
• In short, (summarize your findings).
• It should be evident that we need to (propose the next action or an alternative idea).
• In summary, (summarize your findings).
• Looking ahead, it is obvious that (propose the next action or an alternative idea).
• My conclusion is (restate your thesis with greater emphasis).
• One last word must be said. (Follow with your opinion and propose a next action.)
• One concludes that (give your opinion).
• Overall, (summarize your findings).
• Reflecting on these facts,we can see that …
• The evidence presented above shows that (give your opinion).
• The reader can conclude (make the point you wish to make).
• These facts and observations support the idea that (offer a theory).
• This analysis reveals (state your findings).
• To conclude, (give an opinion based on the findings presented in the paper).
• To sum up this discussion, (summarize your findings).
• To summarize, (summarize your findings).
• We arrive at the following conclusion: (give an opinion based on the findings presented in the paper).
• We cannot ignore the fact that (state an important concern and follow with a call to action).
• We can postulate (give your opinion or offer a theory).
• We come to the conclusion that (give your opinion or offer a theory).
• We can now present the theory that (give your opinion or offer a theory).

Examples of Strong Conclusions

As an example of how to end your research paper, let’s turn again to John Dower’s splendid book on postwar Japan, Embracing Defeat: Japan in the Wake of World War II . In the final pages, Dower pulls together his findings on war-ravaged Japan and its efforts to rebuild. He then judges the legacies of that period: its continuing impact on the country’s social, political, and economic life. Some insights are unexpected, at least to me. He argues that Japan has pursued trade protection as the only acceptable avenue for its persistent nationalism. America’s overwhelming power and Japan’s self-imposed restraints—the intertwined subjects of the book—blocked any political or military expression of Japan’s nationalist sentiment. Those avenues were simply too dangerous, he says, while economic nationalism was not. Dower ends with these paragraphs:

The Japanese economists and bureaucrats who drafted the informal 1946 blueprint for a planned economy were admirably clear on these objectives [of “demilitarization and democratization”]. They sought rapid recovery and maximum economic growth, of course—but they were just as concerned with achieving economic demilitarization and economic democracy. . . . Japan became wealthy. The standard of living rose impressively at every level of society. Income distribution was far more equitable than in the United States. Job security was assured. Growth was achieved without inordinate dependence on a military-industrial complex or a thriving trade in armaments. These are hardly trivial ideas, but they are now being discarded along with all the deservedly bankrupt aspects of the postwar system. The lessons and legacies of defeat have been many and varied indeed; and their end is not yet in sight. (John W. Dower, Embracing Defeat: Japan in the Wake of World War II . New York: W. W. Norton, 1999, pp. 563–64)

Remember the anecdotal opening of Herbert’s book Impressionism: Art, Leisure, and Parisian Society , with Henry Tuckerman’s 1867 arrival in a much-changed Paris? (see research paper introduction examples) Herbert strikes a completely different tone in his conclusion. It synthesizes the art history he has presented, offers a large judgment about where Impressionism fits among art movements, and suggests why exhibitions of Monet, Manet, and Renoir are still so popular. He manages to do all that in a few well-crafted sentences:

Although we credit [Impressionism] with being the gateway to modern art, we also treat it as the last of the great Western styles based upon a perception of harmony with natural vision. That harmony, long since lost to us in this century of urbanization, industrialization, and world wars, remains a longed-for idea, so we look back to Impressionism as the painting of a golden era. We flock into exhibitions of paintings that represent cafes, boating, promenading, and peaceful landscapes precisely because of our yearning for less troubled times. The only history that we feel deeply is the kind that is useful to us. Impressionism still looms large at the end of the twentieth century because we use its leisure-time subjects and its brilliantly colored surfaces to construct a desirable history. (Herbert, Impressionism , p. 306)

Robert Dallek offers similarly accessible, powerful judgments in his conclusion to Flawed Giant: Lyndon Johnson and His Times, 1961–1973 :

[Johnson’s] presidency was a story of great achievement and terrible failure, of lasting gains and unforgettable losses. . . . In a not so distant future, when coming generations have no direct experience of the man and the passions of the sixties are muted, Johnson will probably be remembered as a President who faithfully reflected the country’s greatness and limitations—a man notable for his successes and failures, for his triumphs and tragedy. Only one thing seems certain: Lyndon Johnson will not join the many obscure—almost nameless, faceless—Presidents whose terms of office register on most Americans as blank slates. He will not be forgotten. (Robert Dallek, Flawed Giant: Lyndon Johnson and His Times, 1961–1973 . New York: Oxford University Press, 1998, p. 628)

Some writers not only synthesize their findings or compare them to others; they use the conclusion to say what their work means for appropriate methods or subject matter in their field. That is what Robert Bruegmann does in his final statement in The Architects and the City: Holabird & Roche of Chicago, 1880–1918 . His conclusion goes beyond saying that this was a great architectural firm or that it designed buildings of lasting importance. Bruegmann tells us that Holabird & Roche helped shape modern Chicago and that its work, properly studied, helps us understand “the city as the ultimate human artifact”:

Traditional architectural history has tended to see the city less as a process than as a product, a collection of high art architectural objects in a setting dominated by mundane buildings of little interest. This tended to perpetuate a destructive and divisive attitude about the built environment, suggesting that only a few buildings are worthy of careful study and preservation while all others are mere backdrop. I hope that these explorations in the work of Holabird & Roche have shed light on parts of the city rarely visited by the architectural historian and on some little explored aspects of its history. If so, perhaps it has achieved its most basic goal: providing an insight into the city as the ultimate human artifact, our most complex and prodigious social creation, and the most tangible result of the actions over time of all its citizens. (Robert Bruegmann, The Architects and the City: Holabird & Roche of Chicago, 1880–1918 . Chicago: University of Chicago Press, 1997, p. 443)

These are powerful conclusions, ending major works of scholarship on a high note. What concluding paragraphs should never do is gaze off into the sunset, offer vague homilies, or claim you have found the meaning of human existence. Be concrete. Stick to your topic. Make sure your research paper conclusions stand on solid ground. Avoid vague platitudes in your conclusion. Your goal should be reaching strong, sound judgments, firmly grounded in your readings and research. Better to claim too little than too much. Best of all, claim what you’ve earned the right to say: what your research really means.

Having finished the main parts of a research paper you can write an abstract.

Back to  How To Write A Research Paper .

ORDER HIGH QUALITY CUSTOM PAPER

• Walden University
• Faculty Portal

Writing a Paper: Conclusions

Writing a conclusion.

A conclusion is an important part of the paper; it provides closure for the reader while reminding the reader of the contents and importance of the paper. It accomplishes this by stepping back from the specifics in order to view the bigger picture of the document. In other words, it is reminding the reader of the main argument. For most course papers, it is usually one paragraph that simply and succinctly restates the main ideas and arguments, pulling everything together to help clarify the thesis of the paper. A conclusion does not introduce new ideas; instead, it should clarify the intent and importance of the paper. It can also suggest possible future research on the topic.

An Easy Checklist for Writing a Conclusion

It is important to remind the reader of the thesis of the paper so he is reminded of the argument and solutions you proposed.

Think of the main points as puzzle pieces, and the conclusion is where they all fit together to create a bigger picture. The reader should walk away with the bigger picture in mind.

Make sure that the paper places its findings in the context of real social change.

Make sure the reader has a distinct sense that the paper has come to an end. It is important to not leave the reader hanging. (You don’t want her to have flip-the-page syndrome, where the reader turns the page, expecting the paper to continue. The paper should naturally come to an end.)

No new ideas should be introduced in the conclusion. It is simply a review of the material that is already present in the paper. The only new idea would be the suggesting of a direction for future research.

Conclusion Example

As addressed in my analysis of recent research, the advantages of a later starting time for high school students significantly outweigh the disadvantages. A later starting time would allow teens more time to sleep--something that is important for their physical and mental health--and ultimately improve their academic performance and behavior. The added transportation costs that result from this change can be absorbed through energy savings. The beneficial effects on the students’ academic performance and behavior validate this decision, but its effect on student motivation is still unknown. I would encourage an in-depth look at the reactions of students to such a change. This sort of study would help determine the actual effects of a later start time on the time management and sleep habits of students.

Related Webinar

Didn't find what you need? Email us at [email protected] .

• Previous Page: Thesis Statements
• Next Page: Writer's Block
• Office of Student Disability Services

Walden Resources

Departments.

• Academic Residencies
• Academic Skills
• Career Planning and Development
• Customer Care Team
• Field Experience
• Military Services
• Student Success Advising
• Writing Skills

Centers and Offices

• Center for Social Change
• Office of Academic Support and Instructional Services
• Office of Degree Acceleration
• Office of Research and Doctoral Services
• Office of Student Affairs

Student Resources

• Doctoral Writing Assessment
• Form & Style Review
• Quick Answers
• ScholarWorks
• SKIL Courses and Workshops
• Walden Bookstore
• Walden Catalog & Student Handbook
• Student Safety/Title IX
• Legal & Consumer Information
• Website Terms and Conditions
• Cookie Policy
• Accessibility
• Accreditation
• State Authorization
• Net Price Calculator
• Contact Walden

Walden University is a member of Adtalem Global Education, Inc. www.adtalem.com Walden University is certified to operate by SCHEV © 2024 Walden University LLC. All rights reserved.

• Resources Home 🏠
• Try SciSpace Copilot
• Search research papers
• Add Copilot Extension
• Try AI Detector
• Try Paraphraser
• Try Citation Generator
• April Papers
• June Papers
• July Papers

How to Write a Conclusion for a Research Paper

Table of Contents

Writing a conclusion for a research paper is a critical step that often determines the overall impact and impression the paper leaves on the reader. While some may view the conclusion as a mere formality, it is actually an opportunity to wrap up the main points, provide closure, and leave a lasting impression. In this article, we will explore the importance of a well-crafted conclusion and discuss various tips and strategies to help you write an engaging and impactful conclusion for your research paper.

Introduction

Before delving into the specifics of writing a conclusion, it is important to understand why it is such a crucial component of a research paper. The conclusion serves to summarize the main points of the paper and reemphasize their significance. A well-written conclusion can leave the reader satisfied and inspired, while a poorly executed one may undermine the credibility of the entire paper. Therefore, it is essential to give careful thought and attention to crafting an effective conclusion.

When writing a research paper, the conclusion acts as the final destination for the reader. It is the point where all the information, arguments, and evidence presented throughout the paper converge. Just as a traveler reaches the end of a journey, the reader reaches the conclusion to find closure and a sense of fulfillment. This is why the conclusion should not be taken lightly; it is a critical opportunity to leave a lasting impact on the reader.

Moreover, the conclusion is not merely a repetition of the introduction or a summary of the main points. It goes beyond that by providing a deeper understanding of the research findings and their implications. It allows the writer to reflect on the significance of their work and its potential contributions to the field. By doing so, the conclusion elevates the research paper from a mere collection of facts to a thought-provoking piece of scholarship.

In the following sections, we will explore various strategies and techniques for crafting a compelling conclusion. By understanding the importance of the conclusion and learning how to write one effectively, you will be equipped to create impactful research papers.

Structuring the Conclusion

In order to create an effective conclusion, it is important to consider its structure. A well-structured conclusion should begin by restating the thesis statement and summarizing the main points of the paper. It should then move on to provide a concise synthesis of the key findings and arguments, highlighting their implications and relevance. Finally, the conclusion should end with a thought-provoking statement that leaves the reader with a lasting impression.

Additionally, using phrases like "this research demonstrates," "the findings show," or "it is clear that" can help to highlight the significance of your research and emphasize your main conclusions.

Tips for Writing an Engaging Conclusion

Writing an engaging conclusion requires careful consideration and attention to detail. Here are some tips to help you create an impactful conclusion for your research paper:

• Revisit the Introduction: Start your conclusion by referencing your introduction. Remind the reader of the research question or problem you initially posed and show how your research has addressed it.
• Summarize Your Main Points: Provide a concise summary of the main points and arguments presented in your paper. Be sure to restate your thesis statement and highlight the key findings.
• Offer a Fresh Perspective: Use the conclusion as an opportunity to provide a fresh perspective or offer insights that go beyond the main body of the paper. This will leave the reader with something new to consider.
• Leave a Lasting Impression: End your conclusion with a thought-provoking statement or a call to action. This will leave a lasting impression on the reader and encourage further exploration of the research topic.

Addressing Counter Arguments In Conclusion

While crafting your conclusion, you can address any potential counterarguments or limitations of your research. This will demonstrate that you have considered alternative perspectives and have taken them into account in your conclusions. By acknowledging potential counterarguments, you can strengthen the credibility and validity of your research. And by openly discussing limitations, you demonstrate transparency and honesty in your research process.

Language and Tone To Be Used In Conclusion

The language and tone of your conclusion play a crucial role in shaping the overall impression of your research paper. It is important to use clear and concise language that is appropriate for the academic context. Avoid using overly informal or colloquial language that may undermine the credibility of your research. Additionally, consider the tone of your conclusion – it should be professional, confident, and persuasive, while still maintaining a respectful and objective tone.

When it comes to the language used in your conclusion, precision is key. You want to ensure that your ideas are communicated effectively and that there is no room for misinterpretation. Using clear and concise language will not only make your conclusion easier to understand but will also demonstrate your command of the subject matter.

Furthermore, it is important to strike the right balance between formality and accessibility. While academic writing typically requires a more formal tone, you should still aim to make your conclusion accessible to a wider audience. This means avoiding jargon or technical terms that may confuse readers who are not familiar with the subject matter. Instead, opt for language that is clear and straightforward, allowing anyone to grasp the main points of your research.

Another aspect to consider is the tone of your conclusion. The tone should reflect the confidence you have in your research findings and the strength of your argument. By adopting a professional and confident tone, you are more likely to convince your readers of the validity and importance of your research. However, it is crucial to strike a balance and avoid sounding arrogant or dismissive of opposing viewpoints. Maintaining a respectful and objective tone will help you engage with your audience in a more persuasive manner.

Moreover, the tone of your conclusion should align with the overall tone of your research paper. Consistency in tone throughout your paper will create a cohesive and unified piece of writing.

Common Mistakes to Avoid While Writing a Conclusion

When writing a conclusion, there are several common mistakes that researchers often make. By being aware of these pitfalls, you can avoid them and create a more effective conclusion for your research paper. Some common mistakes include:

• Repeating the Introduction: A conclusion should not simply be a reworded version of the introduction. While it is important to revisit the main points, try to present them in a fresh and broader perspective, by foregrounding the implications/impacts of your research.
• Introducing New Information: The conclusion should not introduce any new information or arguments. Instead, it should focus on summarizing and synthesizing the main points presented in the paper.
• Being Vague or General: Avoid using vague or general statements in your conclusion. Instead, be specific and provide concrete examples or evidence to support your main points.
• Ending Abruptly: A conclusion should provide a sense of closure and completeness. Avoid ending your conclusion abruptly or leaving the reader with unanswered questions.

Editing and Revising the Conclusion

Just like the rest of your research paper, the conclusion should go through a thorough editing and revising process. This will help to ensure clarity, coherence, and impact in the conclusion. As you revise your conclusion, consider the following:

• Check for Consistency: Ensure that your conclusion aligns with the main body of the paper and does not introduce any new or contradictory information.
• Eliminate Redundancy: Remove any repetitive or redundant information in your conclusion. Instead, focus on presenting the key points in a concise and engaging manner.
• Proofread for Clarity: Read your conclusion aloud or ask someone else to read it to ensure that it is clear and understandable. Check for any grammatical or spelling errors that may distract the reader.
• Seek Feedback: Consider sharing your conclusion with peers or mentors to get their feedback and insights. This can help you strengthen your conclusion and make it more impactful.

How to Write Conclusion as a Call to Action

Finally, consider using your conclusion as a call to action. Encourage the reader to take further action, such as conducting additional research or considering the implications of your findings. By providing a clear call to action, you can inspire the reader to actively engage with your research and continue the conversation on the topic.

Adapting to Different Research Paper Types

It is important to adapt your conclusion approach based on the type of research paper you are writing. Different research paper types may require different strategies and approaches to writing the conclusion. For example, a scientific research paper may focus more on summarizing the key findings and implications, while a persuasive research paper may emphasize the call to action and the potential impact of the research. Tailor your conclusion to suit the specific goals and requirements of your research paper.

Final Thoughts

A well-crafted conclusion can leave a lasting impression on the reader and enhance the impact of your research. By following the tips and strategies outlined in this article, you can create an engaging and impactful conclusion that effectively summarizes your main points, addresses potential counterarguments, and leaves the reader with a sense of closure and inspiration. Embrace the importance of the conclusion and view it as an opportunity to showcase the significance and relevance of your research.

Important Reads

How To Humanize AI Text In Scientific Articles

Elevate Your Writing Game With AI Grammar Checker Tools

A Guide to Using AI Tools to Summarize Literature Reviews

AI for Essay Writing — Exploring Top 10 Essay Writers

Role of AI in Systematic Literature Review

You might also like

Boosting Citations: A Comparative Analysis of Graphical Abstract vs. Video Abstract

The Impact of Visual Abstracts on Boosting Citations

Introducing SciSpace’s Citation Booster To Increase Research Visibility

How to Write a Conclusion for a Research Paper

Find out which type of conclusion best suits your research, how to write it step-by-step, and common mistakes to avoid.

When writing a research paper, it can be challenging to make your point after providing an extensive amount of information. For this reason, a well-organized conclusion is essential. 

A research paper’s conclusion should be a brief summary of the paper’s substance and objectives; what you present in your research paper can gain impact by having a strong conclusion section.

In this Mind The Graph article, you will learn how to write a conclusion for a research report in a way that inspires action and helps the readers to better understand your research paper. This article will provide you the definition and some broad principles before providing step-by-step guidance.

What is a conclusion for a research paper and why is it important?

A conclusion is where you summarize the main points and, if appropriate, make new research suggestions. It is not merely a summary of the key points discussed or a rehash of your research question.

The reader is expected to comprehend from the article’s conclusion why your study should be significant to them after reading it. A conclusion of one or two well-developed paragraphs is appropriate for the majority of research papers; however, in a few unusual cases, more paragraphs may be required to highlight significant findings and their importance.

Just as the introduction is responsible for giving the reader a first impression on the subject, the conclusion is the chance to make a final impression by summarizing major information of your research paper and, most often, giving a different point of view on significant implications.

Adding a strong conclusion to your research paper is important because it’s a possibility to give the reader the comprehension of your research topic. Given that the reader is now fully informed on the subject, the conclusion also gives you a chance to restate the research problem effectively and concisely.

Examples of conclusions for a research paper

Now that you are aware of what a conclusion is and its significance for a research paper, it is time to provide you with some excellent samples of well-structured conclusions so you may get knowledge about the type of conclusion you can use for your research paper.

Argumentative Research Paper Conclusion

The most convincing arguments from your research paper should be added to the conclusion if you want to compose a strong argumentative conclusion.

Additionally, if your thesis statement expresses your perspective on the subject, you should think about restarting it as well as including any other pertinent information.

Example: As a result of the sixth extinction, which is currently affecting Earth, many species are vanishing every day. There are at least three strategies that people could employ to keep them from going extinct entirely in the ensuing fifty years. More recycling options, innovative plastic production techniques, and species preservation could save lives.

Analytical Research Paper Conclusion

The first thing you should do is reiterate your thesis and list the main elements of your arguments.

There should undoubtedly be a spotlight on a bigger context in the analytical research paper conclusion, which is the key distinction between it and other types of conclusions. It means you can add some meaning to the findings.

Example: Elon Musk has revolutionized the way we drive, pay for things, and even fly. His innovations are solely motivated by the desire to simplify things, but they inevitably alter the course of history. When Musk was a student, he had his first idea for PayPal, which is now among the most widely used methods of online payment. Likewise with Tesla automobiles.

Comparative Research Paper Conclusion

The conclusion of a comparative essay should be deeply analytical. To clearly express your conclusions, you must be very thorough when reviewing the data. Furthermore, the sources must be reliable.

A paraphrased thesis statement and a few sentences describing the significance of your study research are also required, as per normal.

Example: Gas-powered vehicles are ineffective and inefficient compared to electric vehicles. Not only do they emit fewer pollutants, but the drivers also get there more quickly. Additionally, gas cars cost more to maintain. Everything stems from the details of the far more straightforward engines used in electric cars.

How to write a conclusion for a research paper

In this section, you will learn how to write a conclusion for a research paper effectively and properly. These few easy steps will enable you to write the most convincing conclusion to your research paper.

1. Remember about the main topic

The statement must be written clearly and concisely to be effective, just one sentence. Remember that your conclusion should be concise and precise, expressing only the most important elements.

2. Reaffirm your thesis

Restate the research paper’s thesis after that. This can be done by going back to the original thesis that you presented in the research’s introduction. The thesis statement in your conclusion must be expressed differently from how it was in the introduction. This section can also be written effectively in a single sentence.

3. Sum important points in a summary

It’s time to make a list of the important arguments in your research paper. This phase can be made simpler by reading over your research and emphasizing only the main ideas and evidence.

Remember that the conclusion should not contain any new information. Focus only on the concepts you cover in your paper’s main body as a result. And also, keep in mind that this brief summary reminds your readers of the importance of the topic you are researching.

4. Emphasize the importance

At this stage, you can genuinely express a few words about how significant your arguments are. A succinct but impactful sentence can successfully achieve its aim. You could also attempt to examine this circumstance from a wider perspective.

Give an example of how your discoveries have affected a certain field. It would be beneficial if you made an effort to answer the question, “So what?” if there was any ambiguity.

5. Finish up your argument

As you wrap up your conclusion, consider posing a question or a call to action that will encourage readers to consider your point of view even further. This sentence can also answer any queries that were not addressed in the paper’s body paragraphs.

In addition, if there is an unresolved question in the main body, this is a fantastic area to comment on.

Common mistakes you should avoid

After learning the fundamentals of producing a strong research paper conclusion, it’s time to learn the common mistakes to avoid.

• Weak conclusion: If your ending is weak, readers will feel dissatisfied and disappointed. Writing ambiguous closing lines for essays also lowers the quality of the paper and the capacity of your arguments to support your main topic.
• Abrupt conclusion: Your research has to be an expression of your writing as a whole, not just a section. Therefore, make sure your thoughts are fully stated.
• Adding new information: Only your research should only be summarized in the conclusion. As the conclusion cannot contain extra information, make sure to offer all of your conclusions and supporting evidence in the body paragraphs.
• Absence of focus: A conclusion needs to be concise and well-focused. Avoid concluding the research with inane or superfluous details.
• Absurd length: Research must be of a proper length—neither too long nor too short. If you write more than is necessary, you can miss the point, which is to revisit the paper’s argument straightforwardly. Additionally, if you write too little, your readers will think you’re being negligent. It should be written in at least one or two whole paragraphs.

Communicate science visually with the power of infographics

Learn about the Mind the Graph tool, a tool to assist the scientific community in better-communicating ideas and data using amazing visual infographics and scientific figures .

Subscribe to our newsletter

Exclusive high quality content about effective visual communication in science.

About Jessica Abbadia

Jessica Abbadia is a lawyer that has been working in Digital Marketing since 2020, improving organic performance for apps and websites in various regions through ASO and SEO. Currently developing scientific and intellectual knowledge for the community's benefit. Jessica is an animal rights activist who enjoys reading and drinking strong coffee.

Content tags

How to Write Conclusion in Research Paper (With Example)

Writing a strong conclusion is a crucial part of any research paper. It provides a final opportunity to summarize your key findings, restate your thesis, and leave a lasting impression on your reader. However, many students struggle with how to effectively write a conclusion that ties everything together.

In this article, we’ll provide some tips and strategies for writing a compelling conclusion, along with an example to help illustrate the process. By following these guidelines, you can ensure that your research paper ends on a high note and leaves a lasting impact on your audience.

Why Conclusion is Important in Research Paper

The conclusion is the final chapter of your research paper journey, sealing the deal on all your hard work. After thoroughly laying out your main points and arguments in the body paragraphs, the conclusion gives you a chance to tie everything together into a neat, cohesive package.

More than just summarizing your key ideas, an effective conclusion shows readers the bigger picture of your research and why it matters. It highlights the significance of your findings , explains how your work contributes to the field, and points to potential future directions stemming from your study.

The conclusion is your last chance to leave a lasting impact and compel readers to seriously consider your perspective. With the right phrasing and tone, you can amplify the power of your work. Choose your words wisely, be persuasive yet diplomatic, and guide readers to walk away feeling satisfied by your reasoning and conclusions.

Approach the conclusion thoughtfully, reflect deeply on the larger meaning of your research, and craft impactful final sentences that linger in the reader’s mind. Wield your conclusion skillfully to make your research paper transformative and memorable. A powerful, thoughtful conclusion inspires action, sparks curiosity, and showcases the valuable insights you bring to the academic conversation.

How to Write Conclusion for a Research Paper

Crafting an effective conclusion in research paper requires thoughtful consideration and deliberate effort. After presenting your findings and analysis, the conclusion allows you to close your work with a flourish.

Begin by briefly summarizing the main points of your paper, provide a quick recap of your thesis, methodology, and key findings without repeating too much details from the body. Use this as an opportunity to reinforce your main argument and position within the field.

Next, highlight the significance and implications of your research. What new insights or perspectives does your work contribute? Discuss how your findings can inform future studies or practical applications. Convey why your research matters and how it moves the needle forward in your discipline.

Address any limitations of the current study and propose potential next steps that could be taken by you or other scholars to further the research. This shows readers you have critically considered ways to continue expanding knowledge in this area.

Finally, close with a memorable statement that captures the essence of your work and leaves a lasting impression. This could be an apt metaphor, a call to action, or a thought provoking question for readers to ponder. Choose words that will resonate with your audience and demonstrate the impact of your research.

With care and creativity, your conclusion can elevate your paper and cement your scholarly authority. Revisit often as you write to ensure your conclusion accomplishes its purpose, to convince readers of the value of your study and ignite further progress in your field.

What Not to Include in a Research Paper Conclusion

1. New Data: In a research paper conclusion, avoid presenting new data or evidence that wasn’t discussed earlier in the paper. It’s the time to summarize, analyze, or explain the significance of data already provided, not to introduce new material.

2. Irrelevant Details: The conclusion is not the spot for extraneous details not directly related to your research or its findings. Be focused and concise, tying up the paper neatly without going off-target.

3. Personal Opinions: Try not to include personal beliefs or subjective opinions unless your paper calls for it. Stick to empirical evidence, facts, and objective interpretation of your research.

4. Vague Summarization: While summarizing is the essence of a conclusion, too much of a broad or vague narrative should be avoided. Your conclusion shouldn’t be a generalization of the research but should specifically state your significant findings and their implications.

5. Overstating Results: No matter how exhilarating your research may be, don’t exaggerate its implications or general applications. Remember to acknowledge limitations or potential areas for future exploration.

6. Procrastinating: Refrain from leaving unresolved issues for future research. The conclusion is meant to tie up loose ends, not create more.

7. Repetition: While some reiteration is necessary, completely repeating the same phrases and points made previously can make your conclusion sound boring and redundant. Instead, try to look at your argument from a fresh, summarized perspective.

8. Apologies: Do not apologize or discredit your research efforts. Avoid phrases like, “This research was only” or “Although the study wasn’t able to prove”. A conclusion should confidently present your research results even if they’re unexpected or differ from your hypothesis.

9. Impractical Recommendations: While it’s often good to suggest directions for future research, don’t go overboard by proposing impractical or unachievable goals. Keep your recommendations relevant to your findings and within the realm of possibility.

10. Too Much Jargon: While it’s appropriate to use technical language throughout your research paper, remember the conclusion might be what a layman reads. Stick with a happy medium of professional lingo intermixed with understandable, plain language.

Also Check:   Conclusion for Internship Report

Conclusion in research Example

Research: Impact of Social Media Use on Adolescent Mental Health.

In conclusion, this study has demonstrated the significant impact of social media use on adolescent mental health. Our findings indicate that frequent social media use is associated with higher levels of anxiety and depression, particularly among girls. These results underscore the need for continued research in this area, as well as the development of interventions and strategies to promote healthy social media use among young people. By addressing this issue, we can help to ensure the well-being and success of the next generation.

Conclusion in Research Paper Example

Research: Impact of climate change on coral reefs in Florida.

In conclusion, the effect of climate change on Florida’s coral reefs presents a significant concern for the state’s ecosystem and economy. The data collected during this investigation reveal a direct correlation between rising ocean temperatures and coral bleaching events. This pattern has increased over the past decade, indicating that coral reefs’ health directly correlates with climate change effects.

Example Conclusion in Research

Research: The Influence of Social Media on Consumer Buying Behavior

Social media significantly shapes consumer buying behavior. Its power to influence is seen through peer opinions, online advertising, and brand communication. However, with the potential for misinformation, the reliability and quality of information are areas for further study. Despite these concerns, businesses leveraging social media can effectively boost their market reach and sales.

Research Paper Conclusion

Research: Impacts of Remote Work on Employee Productivity

Remote work has been found to notably enhance employee productivity. The elimination of commuting time, flexible scheduling, and comforting environment contribute to this increase. However, factors like home distractions and technological difficulties offer room for further research. Yet, integrating remote work can be a strategic pathway towards improved efficiency and workforce satisfaction.

These examples demonstrate techniques for crafting an effective conclusion in a research paper, providing your thesis with a powerful final statement. Now it is your turn to compose a strong concluding paragraph that summarizes your findings, reinforces your central argument, and leaves readers with a memorable takeaway.

Remember to restate your thesis without repeating it verbatim, highlight your main points without introducing new evidence, and end on a note that conveys the significance of your research. With a clear structure and purpose, proper grammar, and impactful writing, you can give your paper the persuasive conclusion it deserves.

Writing an effective conclusion takes practice, but by honing these skills you will elevate your academic writing to new heights. Use the strategies outlined here as a guide, believe in your capabilities, and soon you will be adept at concluding research papers powerfully. The final paragraph is your last chance to impress readers, so make it count!

You May Also Like

Conclusion of earthquake example, conclusion of yoga and meditation, conclusion of social media, conclusion of waste management, conclusion for assignment, conclusion of artificial intelligence | how to write | with example, leave a reply cancel reply.

Your email address will not be published. Required fields are marked *

Save my name, email, and website in this browser for the next time I comment.

How to Write a Conclusion for a Research Paper

When you're wrapping up a research paper, the conclusion is like the grand finale of a fireworks show – it's your chance to leave a lasting impression. In this article, we'll break down the steps to help you write a winning research paper conclusion that not only recaps your main points but also ties everything together. Consider it the "So what?" moment – why should people care about your research? Our professional essay writers will guide you through making your conclusion strong, clear, and something that sticks with your readers long after they've put down your paper. So, let's dive in and ensure your research ends on a high note!

What Is a Conclusion in a Research Paper

In a research paper, the conclusion serves as the final segment, where you summarize the main points and findings of your study. It's not just a repetition of what you've already said but rather a chance to tie everything together and highlight the significance of your research. As you learn how to start a research paper , a good conclusion also often discusses the implications of your findings, suggests potential areas for further research, and leaves the reader with a lasting impression of the importance and relevance of your work in the broader context of the field. Essentially, it's your last opportunity to make a strong impact and leave your readers with a clear understanding of the significance of your research. Here’s a research paper conclusion example:

In conclusion, this research paper has navigated the intricacies of sustainable urban development, shedding light on the pivotal role of community engagement and innovative planning strategies. Through applying qualitative and quantitative research methods, we've uncovered valuable insights into the challenges and opportunities inherent in fostering environmentally friendly urban spaces. The implications of these findings extend beyond the confines of this study, emphasizing the imperative for continued exploration in the realms of urban planning and environmental sustainability. By emphasizing both the practical applications and theoretical contributions, this research underscores the significance of community involvement and forward-thinking strategies in shaping the future of urban landscapes. As cities evolve, incorporating these insights into planning and development practices will create resilient and harmonious urban environments.

Conclusion Outline for Research Paper

This outline for a research paper conclusion provides a structured framework to ensure that your ending effectively summarizes the key elements of your research paper and leaves a lasting impression on your readers. Adjust the content based on the specific requirements and focus of your research.

Restate the Thesis Statement

• Briefly restate the main thesis or research question.
• Emphasize the core objective or purpose of the study.

Summarize Key Findings

• Recap the main points and key findings from each section of the paper.
• Provide a concise overview of the research journey.

Discuss Implications

• Explore the broader implications of the research findings.
• Discuss how the results contribute to the existing body of knowledge in the field.

Address Limitations

• Acknowledge any limitations or constraints encountered during the research process.
• Explain how these limitations may impact the interpretation of the findings.

Suggest Areas for Future Research

• Propose potential directions for future studies related to the topic.
• Identify gaps in the current research that warrant further exploration.

Reaffirm Significance

• Reaffirm the importance and relevance of the research in the broader context.
• Highlight the practical applications or real-world implications of the study.

Concluding Statement

• Craft a strong, memorable closing statement that leaves a lasting impression.
• Sum up the overall impact of the research and its potential contribution to the field.

Study the full guide on how to make a research paper outline here, which will also specify the conclusion writing specifics to improve your general prowess.

Tips on How to Make a Conclusion in Research

Here are key considerations regarding a conclusion for research paper to not only recap the primary ideas in your work but also delve deeper to earn a higher grade:

• Provide a concise recap of your main research outcomes.
• Remind readers of your research goals and their accomplishments.
• Stick to summarizing existing content; refrain from adding new details.
• Emphasize why your research matters and its broader implications.
• Clearly explain the practical or theoretical impact of your findings.
• Prompt readers to reflect on how your research influences their perspective.
• Briefly discuss the robustness of your research methods.
• End with a suggestion for future research or a practical application.
• Transparently address any constraints or biases in your study.
• End on a powerful note, leaving a memorable impression on your readers.

For your inspiration, we’ve also prepared this research proposal example APA , which dwells on another important aspect of research writing.

How to Write a Research Paper Conclusion

As you finish your research paper, the conclusion takes center stage. In this section, we've got five practical tips for writing a conclusion for a research paper. We'll guide you through summarizing your key findings, revisiting your research goals, discussing the bigger picture, addressing any limitations, and ending on a powerful note. Think of it as your roadmap to creating a conclusion that not only wraps up your research but also leaves a lasting impact on your readers. Let's dive in and make sure your conclusion stands out for all the right reasons!

Synthesize Core Discoveries. Initiate your conclusion by synthesizing the essential discoveries of your research. Offer a succinct recapitulation of the primary points and outcomes you have elucidated in your paper. This aids in reinforcing the gravity of your work and reiterates the pivotal information you have presented.

Revisit Research Objectives. Revisit the research objectives or questions you outlined at the beginning of your paper. Assess whether you have successfully addressed these objectives and if your findings align with the initial goals of your research. This reflection helps tie your conclusion back to the purpose of your study.

Discuss Implications and Contributions. Discuss the broader implications of your research and its potential contributions to the field. Consider how your findings might impact future research, applications, or understanding of the subject matter. This demonstrates the significance of your work and places it within a larger context.

Address Limitations and Future Research. Acknowledge any limitations in your study, such as constraints in data collection or potential biases. Briefly discuss how these limitations might have affected your results. Additionally, suggest areas for future research that could build upon your work, addressing any unanswered questions or unexplored aspects. This demonstrates a thoughtful approach to your research.

End with a Strong Conclusion Statement. Conclude your research paper with a strong and memorable statement that reinforces the key message you want readers to take away. This could be a call to action, a proposal for further investigation, or a reflection on the broader significance of your findings. Leave your readers with a lasting impression that emphasizes the importance of your research. Remember that you can buy a research paper anytime if you lack time or get stuck in writer’s block.

Want to Enjoy the Benefits of Academic Freedom?

With our top-notch writers and 24/7 support, you can relax and focus on what really matters

Stylistic Devices to Use in a Conclusion

Discover distinctive stylistic insights that you can apply when writing a conclusion for a research paper:

• Rhetorical Questions. When using rhetorical questions, strategically place them to engage readers' minds. For instance, you might pose a question that prompts reflection on the broader implications of your findings, leaving your audience with something to ponder.
• Powerful Language. Incorporate strong language to convey a sense of conviction and importance. Choose words that resonate with the overall tone of your research and amplify the significance of your conclusions. This adds weight to your key messages.
• Repetitions. Repetitions can be employed to reinforce essential ideas. Reiterate key phrases or concepts in a way that emphasizes their importance without sounding redundant. This technique serves to drive home your main points.
• Anecdotes. Integrating anecdotes into your conclusion can provide a human touch. Share a brief and relevant story that connects with your research, making the information more relatable and memorable for your audience.
• Vivid Imagery. Lastly, use vivid imagery to paint a picture in the minds of your readers. Appeal to their senses by describing scenarios or outcomes related to your research. This creates a more immersive and lasting impression.

If you have a larger paper to write, for example a thesis, use our custom dissertation writing can help you in no time.

How to Make a Conclusion Logically Appealing

Knowing how to write a conclusion for a research paper that is logically appealing is important for leaving a lasting impression on your readers. Here are some tips to achieve this:

Logical Sequencing

• Present your conclusion in a structured manner, following the natural flow of your paper. Readers should effortlessly follow your thought process, making your conclusion more accessible and persuasive.

Reinforce Main Arguments

• Emphasize the core arguments and findings from your research. By reinforcing key points, you solidify your stance and provide a logical culmination to your paper.

Address Counterarguments

• Acknowledge and address potential counterarguments or limitations in your research. Demonstrate intellectual honesty and strengthen your conclusion by preemptively addressing potential doubts.

Connect with Introduction

• Revisit themes or concepts introduced in your introduction to create a cohesive narrative, allowing readers to trace the logical progression of your research from start to finish.

Propose Actionable Insights

• Suggest practical applications or recommendations based on your findings. This will add a forward-looking dimension, making your conclusion more relevant and compelling.

Highlight Significance

• Clearly articulate the broader implications of your research to convey the importance of your work and its potential impact on the field, making your conclusion logically compelling.

Are you ready to produce an A-grade assignment? If not, opt for a custom research paper from our skilled writers across various disciplines.

Avoid These Things When Writing a Research Paper Conclusion

As you write your conclusion of research paper, there’s a list of things professional writers don’t recommend doing. Consider these issues carefully:

• Repetition of Exact Phrases
• Repetitively using the same phrases or sentences from the main body. Repetition can make your conclusion seem redundant and less engaging.
• Overly Lengthy Summaries
• Providing excessively detailed summaries of each section of your paper. Readers may lose interest if the conclusion becomes too long and detailed.
• Unclear Connection to the Introduction
• Failing to connect the conclusion back to the introduction. A lack of continuity may make the paper feel disjointed.
• Adding New Arguments or Ideas
• Introducing new arguments or ideas that were not addressed in the body. This can confuse the reader and disrupt the coherence of your paper.
• Overuse of Complex Jargon
• Using excessively complex or technical language without clarification. Clear communication is essential in the conclusion, ensuring broad understanding.
• Apologizing or Undermining Confidence
• Apologizing for limitations or expressing doubt about your work. Maintain a confident tone; if limitations exist, present them objectively without undermining your research.
• Sweeping Generalizations
• Making overly broad or unsupported generalizations. Such statements can weaken the credibility of your conclusion.
• Neglecting the Significance
• Failing to emphasize the broader significance of your research. Readers need to understand why your findings matter in a larger context.
• Abrupt Endings
• Concluding abruptly without a strong closing statement. A powerful ending leaves a lasting impression; avoid a sudden or weak conclusion.

Research Paper Conclusion Example

That covers the essential aspects of summarizing a research paper. The only remaining step is to review the conclusion examples for research paper provided by our team.

Like our examples? Order our research proposal writing service to write paper according to your instructions to avoid plagiarizing and to keep your academic integrity strong.

Final Thoughts

In conclusion, the knowledge of how to write the conclusion of a research paper is pivotal for presenting your findings and leaving a lasting impression on your readers. By summarizing the key points, reiterating the significance of your research, and offering avenues for future exploration, you can create a conclusion that not only reinforces the value of your study but also encourages further academic discourse. Remember to balance brevity and completeness, ensuring your conclusion is concise yet comprehensive. Emphasizing the practical implications of your research and connecting it to the broader academic landscape will help solidify the impact of your work. Pay someone to write a research paper if you are having a hard time finishing your coursework on time.

Tired of Stressing Over Endless Essays and Deadlines? 

Let us take the load off your shoulders! Order your custom research paper today and experience the relief of knowing that your assignment is in expert hands

How To Write A Conclusion For A Research Paper?

What should the conclusion of a research paper contain, how to start a conclusion paragraph for a research paper.

Daniel Parker

is a seasoned educational writer focusing on scholarship guidance, research papers, and various forms of academic essays including reflective and narrative essays. His expertise also extends to detailed case studies. A scholar with a background in English Literature and Education, Daniel’s work on EssayPro blog aims to support students in achieving academic excellence and securing scholarships. His hobbies include reading classic literature and participating in academic forums.

is an expert in nursing and healthcare, with a strong background in history, law, and literature. Holding advanced degrees in nursing and public health, his analytical approach and comprehensive knowledge help students navigate complex topics. On EssayPro blog, Adam provides insightful articles on everything from historical analysis to the intricacies of healthcare policies. In his downtime, he enjoys historical documentaries and volunteering at local clinics.

• Affiliate Program

• UNITED STATES
• 台灣 (TAIWAN)
• TÜRKIYE (TURKEY)
• Academic Editing Services
• - Research Paper
• - Journal Manuscript
• - Dissertation
• - College & University Assignments
• Admissions Editing Services
• - Application Essay
• - Personal Statement
• - Recommendation Letter
• - Cover Letter
• - CV/Resume
• Business Editing Services
• - Business Documents
• - Report & Brochure
• - Website & Blog
• Writer Editing Services
• - Script & Screenplay
• Our Editors
• Client Reviews
• Editing & Proofreading Prices
• Wordvice Points
• Partner Discount
• Plagiarism Checker
• APA Citation Generator
• MLA Citation Generator
• Chicago Citation Generator
• Vancouver Citation Generator
• - APA Style
• - MLA Style
• - Chicago Style
• - Vancouver Style
• Writing & Editing Guide
• Academic Resources
• Admissions Resources

How to Write a Research Paper Conclusion Section

What is a conclusion in a research paper?

The conclusion in a research paper is the final paragraph or two in a research paper. In scientific papers, the conclusion usually follows the Discussion section , summarizing the importance of the findings and reminding the reader why the work presented in the paper is relevant.

However, it can be a bit confusing to distinguish the conclusion section/paragraph from a summary or a repetition of your findings, your own opinion, or the statement of the implications of your work. In fact, the conclusion should contain a bit of all of these other parts but go beyond it—but not too far beyond! 

The structure and content of the conclusion section can also vary depending on whether you are writing a research manuscript or an essay. This article will explain how to write a good conclusion section, what exactly it should (and should not) contain, how it should be structured, and what you should avoid when writing it.  

Table of Contents:

What does a good conclusion section do, what to include in a research paper conclusion.

• Conclusion in an Essay
• Research Paper Conclusion 
• Conclusion Paragraph Outline and Example
• What Not to Do When Writing a Conclusion

The conclusion of a research paper has several key objectives. It should:

• Restate your research problem addressed in the introduction section
• Summarize your main arguments, important findings, and broader implications
• Synthesize key takeaways from your study

The specific content in the conclusion depends on whether your paper presents the results of original scientific research or constructs an argument through engagement with previously published sources.

You presented your general field of study to the reader in the introduction section, by moving from general information (the background of your work, often combined with a literature review ) to the rationale of your study and then to the specific problem or topic you addressed, formulated in the form of the statement of the problem in research or the thesis statement in an essay.

In the conclusion section, in contrast, your task is to move from your specific findings or arguments back to a more general depiction of how your research contributes to the readers’ understanding of a certain concept or helps solve a practical problem, or fills an important gap in the literature. The content of your conclusion section depends on the type of research you are doing and what type of paper you are writing. But whatever the outcome of your work is, the conclusion is where you briefly summarize it and place it within a larger context. It could be called the “take-home message” of the entire paper.

What to summarize in the conclusion

Your conclusion section needs to contain a very brief summary of your work , a very brief summary of the main findings of your work, and a mention of anything else that seems relevant when you now look at your work from a bigger perspective, even if it was not initially listed as one of your main research questions. This could be a limitation, for example, a problem with the design of your experiment that either needs to be considered when drawing any conclusions or that led you to ask a different question and therefore draw different conclusions at the end of your study (compared to when you started out).

Once you have reminded the reader of what you did and what you found, you need to go beyond that and also provide either your own opinion on why your work is relevant (and for whom, and how) or theoretical or practical implications of the study , or make a specific call for action if there is one to be made.   

How to Write an Essay Conclusion

Academic essays follow quite different structures than their counterparts in STEM and the natural sciences. Humanities papers often have conclusion sections that are much longer and contain more detail than scientific papers. There are three main types of academic essay conclusions.

Summarizing conclusion

The most typical conclusion at the end of an analytical/explanatory/argumentative essay is a summarizing conclusion . This is, as the name suggests, a clear summary of the main points of your topic and thesis. Since you might have gone through a number of different arguments or subtopics in the main part of your essay, you need to remind the reader again what those were, how they fit into each other, and how they helped you develop or corroborate your hypothesis.

For an essay that analyzes how recruiters can hire the best candidates in the shortest time or on “how starving yourself will increase your lifespan, according to science”, a summary of all the points you discussed might be all you need. Note that you should not exactly repeat what you said earlier, but rather highlight the essential details and present those to your reader in a different way. 

Externalizing conclusion

If you think that just reminding the reader of your main points is not enough, you can opt for an externalizing conclusion instead, that presents new points that were not presented in the paper so far. These new points can be additional facts and information or they can be ideas that are relevant to the topic and have not been mentioned before.

Such a conclusion can stimulate your readers to think about your topic or the implications of your analysis in a whole new way. For example, at the end of a historical analysis of a specific event or development, you could direct your reader’s attention to some current events that were not the topic of your essay but that provide a different context for your findings.

Editorial conclusion

In an editorial conclusion , another common type of conclusion that you will find at the end of papers and essays, you do not add new information but instead present your own experiences or opinions on the topic to round everything up. What makes this type of conclusion interesting is that you can choose to agree or disagree with the information you presented in your paper so far. For example, if you have collected and analyzed information on how a specific diet helps people lose weight, you can nevertheless have your doubts on the sustainability of that diet or its practicability in real life—if such arguments were not included in your original thesis and have therefore not been covered in the main part of your paper, the conclusion section is the place where you can get your opinion across.    

How to Conclude an Empirical Research Paper

An empirical research paper is usually more concise and succinct than an essay, because, if it is written well, it focuses on one specific question, describes the method that was used to answer that one question, describes and explains the results, and guides the reader in a logical way from the introduction to the discussion without going on tangents or digging into not absolutely relevant topics.

Summarize the findings

In a scientific paper, you should include a summary of the findings. Don’t go into great detail here (you will have presented your in-depth  results  and  discussion  already), but do clearly express the answers to the  research questions  you investigated.

Describe your main findings, even if they weren’t necessarily the ones anticipated, and explain the conclusion they led you to. Explain these findings in as few words as possible.

Instead of beginning with “ In conclusion, in this study, we investigated the effect of stress on the brain using fMRI …”, you should try to find a way to incorporate the repetition of the essential (and only the essential) details into the summary of the key points. “ The findings of this fMRI study on the effect of stress on the brain suggest that …” or “ While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study show that, surprisingly… ” would be better ways to start a conclusion. 

You should also not bring up new ideas or present new facts in the conclusion of a research paper, but stick to the background information you have presented earlier, to the findings you have already discussed, and the limitations and implications you have already described. The one thing you can add here is a practical recommendation that you haven’t clearly stated before—but even that one needs to follow logically from everything you have already discussed in the discussion section.

Discuss the implications

After summing up your key arguments or findings, conclude the paper by stating the broader implications of the research , whether in methods , approach, or findings. Express practical or theoretical takeaways from your paper. This often looks like a “call to action” or a final “sales pitch” that puts an exclamation point on your paper.

If your research topic is more theoretical in nature, your closing statement should express the significance of your argument—for example, in proposing a new understanding of a topic or laying the groundwork for future research.

Future research example

Future research into education standards should focus on establishing a more detailed picture of how novel pedagogical approaches impact young people’s ability to absorb new and difficult concepts. Moreover, observational studies are needed to gain more insight into how specific teaching models affect the retention of relationships and facts—for instance, how inquiry-based learning and its emphasis on lateral thinking can be used as a jumping-off point for more holistic classroom approaches.

Research Conclusion Example and Outline

Let’s revisit the study on the effect of stress on the brain we mentioned before and see what the common structure for a conclusion paragraph looks like, in three steps. Following these simple steps will make it easy for you to wrap everything up in one short paragraph that contains all the essential information: 

One: Short summary of what you did, but integrated into the summary of your findings:

While it has been known for a long time that stress has an effect on the brain, the findings of this fMRI study in 25 university students going through mid-term exams show that, surprisingly, one’s attitude to the experienced stress significantly modulates the brain’s response to it. 

Note that you don’t need to repeat any methodological or technical details here—the reader has been presented with all of these before, they have read your results section and the discussion of your results, and even (hopefully!) a discussion of the limitations and strengths of your paper. The only thing you need to remind them of here is the essential outcome of your work. 

Two: Add implications, and don’t forget to specify who this might be relevant for: 

Students could be considered a specific subsample of the general population, but earlier research shows that the effect that exam stress has on their physical and mental health is comparable to the effects of other types of stress on individuals of other ages and occupations. Further research into practical ways of modulating not only one’s mental stress response but potentially also one’s brain activity (e.g., via neurofeedback training) are warranted.

This is a “research implication”, and it is nicely combined with a mention of a potential limitation of the study (the student sample) that turns out not to be a limitation after all (because earlier research suggests we can generalize to other populations). If there already is a lot of research on neurofeedback for stress control, by the way, then this should have been discussed in your discussion section earlier and you wouldn’t say such studies are “warranted” here but rather specify how your findings could inspire specific future experiments or how they should be implemented in existing applications. 

Three: The most important thing is that your conclusion paragraph accurately reflects the content of your paper. Compare it to your research paper title , your research paper abstract , and to your journal submission cover letter , in case you already have one—if these do not all tell the same story, then you need to go back to your paper, start again from the introduction section, and find out where you lost the logical thread. As always, consistency is key.    

Problems to Avoid When Writing a Conclusion 

• Do not suddenly introduce new information that has never been mentioned before (unless you are writing an essay and opting for an externalizing conclusion, see above). The conclusion section is not where you want to surprise your readers, but the take-home message of what you have already presented.
• Do not simply copy your abstract, the conclusion section of your abstract, or the first sentence of your introduction, and put it at the end of the discussion section. Even if these parts of your paper cover the same points, they should not be identical.
• Do not start the conclusion with “In conclusion”. If it has its own section heading, that is redundant, and if it is the last paragraph of the discussion section, it is inelegant and also not really necessary. The reader expects you to wrap your work up in the last paragraph, so you don’t have to announce that. Just look at the above example to see how to start a conclusion in a natural way.
• Do not forget what your research objectives were and how you initially formulated the statement of the problem in your introduction section. If your story/approach/conclusions changed because of methodological issues or information you were not aware of when you started, then make sure you go back to the beginning and adapt your entire story (not just the ending). 

Consider Receiving Academic Editing Services

When you have arrived at the conclusion of your paper, you might want to head over to Wordvice AI’s AI Writing Assistant to receive a free grammar check for any academic content. 

After drafting, you can also receive English editing and proofreading services , including paper editing services for your journal manuscript. If you need advice on how to write the other parts of your research paper , or on how to make a research paper outline if you are struggling with putting everything you did together, then head over to the Wordvice academic resources pages , where we have a lot more articles and videos for you.

Free All-in-One Office Suite with PDF Editor

Edit Word, Excel, and PPT for FREE.

Read, edit, and convert PDFs with the powerful PDF toolkit.

Microsoft-like interface, easy to use.

Windows • MacOS • Linux • iOS • Android

Select areas that need to improve

• Didn't match my interface
• Too technical or incomprehensible
• Incorrect operation instructions
• Incomplete instructions on this function

Fields marked * are required please

Please leave your suggestions below

• Quick Tutorials
• Practical Skills

How to Write a Conclusion - Steps with Examples

I remember my college days when one of the most dreadful assignments was writing a research paper. It made me wonder if there was an easier way to help me through it. The worst part was writing the conclusion, which meant wrapping up the entire paper and finally drawing conclusions. It sounds pretty intimidating, doesn't it? How are you supposed to fit all that information into such a short space, and what else might you be missing? In this guide, I will show you how to write a conclusion so you can spare yourself from the distress of it all.

What to Include/ Not Include in a Conclusion?

Professors often stress a lot on writing a good conclusion that includes a wrap-up for your paper or essay. These are some factors you must consider to include in your conclusion:

Restate Your Thesis:

Begin by restating the main argument or thesis of your paper. This reinforces the central point you have been arguing throughout your work.

Summarize Key Points:

Provide a concise summary of the key points and findings from your paper. Highlight the most significant pieces of evidence that support your thesis.

Discuss the Implications:

Explain the broader implications of your findings. How do they contribute to the field of study? What practical applications or theoretical advancements arise from your research?

Address Limitations:

Acknowledge any limitations or weaknesses in your study. This demonstrates a critical and reflective approach to your research and provides a foundation for future work.

Suggest Future Research:

Propose areas for future research. What questions remain unanswered? What further investigations could build on your findings?

End with a Strong Closing Statement:

Conclude with a strong, impactful statement that leaves a lasting impression on your reader. This could be a call to action, a prediction, or a thought-provoking question related to your research topic.

There may also be certain things you would unknowingly add in your conclusion that would ultimately leave a bad impression on the reader. Keep these factors in mind so you may avoid when writing your conclusion for your paper:

New Information:

Avoid introducing new information or ideas that were not covered in the body of the paper. The conclusion is for synthesizing and reflecting on the information already presented.

Detailed Methodology:

Do not include detailed descriptions of your research methods. This information belongs in the methodology section of your paper.

Repetitive Summaries:

Refrain from simply reiterating points that were already made in the results or discussion sections. Instead, focus on synthesizing the information and highlighting its significance.

Speculative Statements:

Avoid idle speculation or guesswork about potential outcomes or implications that are not supported by your research findings.

Apologies or Undermining Your Work:

Do not undermine your work by apologizing for any perceived shortcomings. Present your conclusions confidently and assert the value of your research.

Excessive Length:

Keep the conclusion concise and to the point. Long, drawn-out conclusions can dilute the impact of your final statements.

To put things into perspective, here's what a good and bad conclusion example look like:

Good Example:

Bad Example:

Types of Conclusion

Summarizing conclusion:.

This type is the most common and involves summarizing the main points of the research, reiterating the research question, and restating the significance of the findings.

It is broadly used across different disciplines.

Example: If a study investigated the impact of social media on adolescents' mental health, a summarizing conclusion would reiterate key findings, such as the association between high social media use and increased anxiety and depression levels among adolescents, and emphasize the importance of these findings for developing effective interventions.

Editorial Conclusion:

This type is used less frequently and is suited for research papers that advocate for a particular viewpoint or policy. It presents a strong editorial opinion based on the research findings and offers recommendations or calls to action.

It is suitable for papers focusing on policy recommendations or advocating a specific viewpoint.

Example: For a study on the environmental impact of plastic waste, an editorial conclusion might call for a comprehensive ban on single-use plastics and increased recycling initiatives, urging governments, businesses, and individuals to take immediate action to protect the environment.

Externalizing Conclusion:

This type extends the research beyond the scope of the paper by suggesting future research directions or discussing broader implications of the findings. It is often used in theoretical or exploratory research papers.

It is Ideal for theoretical or exploratory studies.

Example: In a study exploring AI applications in healthcare, an externalizing conclusion might suggest future research into the ethical, legal, and social implications of AI in healthcare and emphasize the need for interdisciplinary collaboration to harness AI's potential while addressing its challenges.

How to Write a Conclusion in 4 Steps [With Examples]

Writing a conclusion may seem a bit tricky, but once you fully understand the essence of what goes into a conclusion, it will become much easier. To demonstrate how to write a conclusion, I will be using WPS Office , a tool designed to be convenient for students, thanks to its easy-to-use interface and free features. You can also utilize WPS AI, as I am in these simple 4 steps, to make the entire process smoother for yourself.

Step 1: Restate The Thesis Statement

Start your conclusion by restating the thesis statement of your research paper. This reminds the reader of the main focus and purpose of your study.

Example: If your thesis statement is "This study investigates the impact of social media on adolescents' mental health, revealing a significant association between high social media usage and increased levels of anxiety and depression.", you can use WPS AI to help improve and rewrite your thesis statement.

Here's how WPS AI can assist you with your thesis statement.

Write your thesis statement in WPS Writer and select the entire text using your mouse.

After selecting the text, a small hover menu will appear. Click on the "WPS AI" icon in this menu.

This will open a list of AI assistance options you can choose from. To ask WPS AI to improve your thesis statement, click on "Improve Writing".

WPS AI will process and return an improved thesis statement. If you don’t like the improved version, click on "Rewrite", or click on "Accept" to replace your text with the improved version.

Step 2: Review Main Supporting Points

Next, we need to summarize the key points of our research. When summarizing the key findings of your research, it’s important to highlight the most significant results and their implications.

Example: Let's say that from our research the most important findings were:

The study found that high social media usage negatively affects adolescents' self-esteem due to constant exposure to idealized images and lifestyles.

Excessive use of social media, particularly before bedtime, was linked to disrupted sleep patterns and insufficient rest, contributing to mental health issues.

Despite being a tool for connection, high social media usage can lead to feelings of loneliness and social isolation as face-to-face interactions decrease.

Here's how WPS AI can assist you summarize the key points of your research for your conclusion.

Let's switch to WPS Office again, and this time let's select the key points that we have written down from our research.

Click on the WPS AI icon from the hover menu to open the list of options you can choose from.

From the list, let's click on "Summarize" to shorten and summarize the key points from our research.

You can now choose to either accept or ask WPS AI to rewrite this summary of key points again.

Step 3: Show Why It Matters

Now that you have laid out all the findings from your paper and WPS AI has effectively summarized them, you can further prompt it to broaden the implications of your findings and follow up with real-world problems.

To get real-world insights using WPS AI, follow these steps:

Click on the WPS AI widget at the top right corner of the WPS Writer interface.

The WPS AI pane will open on the right. Here, simply type in your prompt. Here is an example of a prompt:

"Explain the significance of high social media usage leading to increased anxiety and depression in adolescents, and discuss potential real-world problems and solutions."

WPS AI will display the results, which can now be a part of your summary or can be further summarized or improved with the help of WPS AI.

Step 4: Offer Meaningful Insights

Lastly, provide some final thoughts or insights that will leave a lasting impression on your reader. This can include suggestions for future research, practical applications of your findings, or a call to action based on your conclusions.

Example: Here is an example of how Meaningful Insights can be presented:

Further research is needed to explore the long-term effects of social media usage on adolescent mental health and to identify effective interventions.

Developing and promoting apps that encourage healthy social media use and provide mental health support could mitigate the negative effects identified in the study.

Stakeholders, including policymakers, educators, and parents, should collaborate to create environments that foster healthy digital habits and support adolescents' mental health.

Now, with the help of WPS AI, these points can simply be summarized to get more concise and structured Meaningful Insights for our conclusion.

Bonus Tips: How to Polish your Conclusion with WPS AI

Writing a strong conclusion for your research paper is crucial, and WPS Office is designed to be exceptionally student-friendly. It offers accessible options and advanced features for free, making it an excellent tool for students. One of the standout features is WPS AI, which integrates AI into its writing and proofreading abilities.

Draft Generation: WPS AI can assist you in writing a conclusion by generating an initial draft. This draft serves as a solid foundation, ensuring that all essential elements are included and properly structured.

Grammar and Style Check: WPS AI can identify grammar errors, awkward phrasing, and inconsistencies in your conclusion paragraph. This ensures that your writing is polished and professional.

Sentence Structure Enhancement: The AI can suggest improvements to sentence structures, helping you to vary sentence lengths and styles for better readability and flow. This makes your conclusion more engaging and easier to read.

Vocabulary Enhancement: WPS AI offers synonyms and alternative word choices to enhance the vocabulary in your conclusion, making your writing more sophisticated and engaging.

Clarity and Conciseness: WPS AI can help you refine your conclusion to ensure it effectively summarizes your main points without unnecessary repetition or tangents. This keeps your conclusion focused and impactful.

Refinement and Customization: Once WPS AI has generated the draft, you can refine and personalize it to align with your research and style. This step allows you to inject your voice and insights into the conclusion, making it uniquely yours.

Polishing and Proofreading: After refining the draft, you can use WPS AI to polish the conclusion further. WPS AI's advanced proofreading capabilities ensure that your conclusion is not only coherent and concise but also free of grammatical errors and stylistic inconsistencies.

ByIncorporating WPS AI into your writing routine you can significantly improve your efficiency and the overall quality of your academic work. You can streamline the process of writing your research paper conclusion, saving time and effort while ensuring a high-quality result. Whether you’re summarizing key findings, making policy recommendations, or suggesting future research directions, WPS AI helps you create a compelling and impactful conclusion.

So we have seen how WPS AI can help us write more effective and accurate conclusions, but is this all the help it offers? Absolutely not! With the help of WPS AI, you can further improve your conclusion by making it more fluent and easier to read.

Furthermore, WPS AI is not just a writing tool; it also offers AI spell check features, which can help students proofread their work according to their academic style such as APA, MLA, or Chicago style.

WPS Office has a lot to offer and is a perfect tool for students who need help writing not just effective conclusions but also effective research papers. So if you are stuck with a conclusion or a research paper, consider turning to WPS AI for help.

FAQs about writing a conclusion for paper/ essay

1. how long should a conclusion be.

A well-constructed conclusion typically constitutes approximately 10% of your document's total word count. For instance, in a 1,500-word paper, aim for a conclusion of about 150 words. This provides sufficient space to summarize key points and offer a final overview of the main ideas discussed.

2. How can I make my Conclusion impactful?

Here are some effective strategies for creating an impactful conclusion:

Utilize compelling language to engage the reader effectively.

Ensure the conclusion remains clear and concise, omitting insignificant specifics.

Conclude with a stimulating statement, a call to action, or a reflection on the broader implications of your research findings to make a lasting impact.

3. How do I avoid simply repeating what I've already said in the Conclusion?

To avoid repeating yourself in your conclusion, focus on cohesively summarizing your main ideas rather than reiterating them. Additionally, consider exploring the wider impact of your arguments or suggesting directions for future research on your topic. This approach ensures your conclusion provides fresh perspectives and maintains reader interest.

Perfect Your Conclusion With WPS Office

Your research paper is not complete without a strong conclusion. The person who reads your paper should feel like they have taken away significant key insights from your work. Writing an effective conclusion can sometimes be challenging, but WPS Office, with its AI capabilities, can assist you in helping you with how to write a conclusion to perfection. Incorporate WPS AI into your writing routine to significantly improve your efficiency and the overall quality of your academic work. Try WPS Office today and experience the benefits of AI-assisted writing firsthand.

• 1. How to Write an Essay in MLA Format | For Students
• 2. How to write matrix in Word
• 3. How to write meter square in powerpoint
• 4. How to Write a Cover Letter [Tips with Examples]
• 5. How to Write an Abstract - Steps with Examples
• 6. 10 Professional Company Presentation Templates: To Write a Great Company Profile

15 years of office industry experience, tech lover and copywriter. Follow me for product reviews, comparisons, and recommendations for new apps and software.

This paper is in the following e-collection/theme issue:

Published on 4.7.2024 in Vol 8 (2024)

Capturing Home Care Information Management and Communication Processes Among Caregivers of Older Adults: Qualitative Study to Inform Technology Design

Authors of this article:

Original Paper

• Ryan Tennant 1 * , BASc, MASc   ; 
• Sana Allana 1 * , BASc   ; 
• Kate Mercer 1, 2 * , PhD   ; 
• Catherine M Burns 1 * , PEng, PhD  

1 Department of Systems Design Engineering, Faculty of Engineering, University of Waterloo, Waterloo, ON, Canada

2 Library, University of Waterloo, Waterloo, ON, Canada

*all authors contributed equally

Corresponding Author:

Ryan Tennant, BASc, MASc

Department of Systems Design Engineering

Faculty of Engineering

University of Waterloo

200 University Avenue West

Waterloo, ON, N2L 3G1

Phone: 1 5198884567

Email: [email protected]

Background: The demand for complex home care is increasing with the growing aging population and the ongoing COVID-19 pandemic. Family and hired caregivers play a critical role in providing care for individuals with complex home care needs. However, there are significant gaps in research informing the design of complex home care technologies that consider the experiences of family and hired caregivers collectively.

Objective: The objective of this study was to explore the health documentation and communication experiences of family and hired caregivers to inform the design and adoption of new technologies for complex home care.

Methods: The research involved semistructured interviews with 15 caregivers, including family and hired caregivers, each of whom was caring for an older adult with complex medical needs in their home in Ontario, Canada. Due to COVID-19–related protection measures, the interviews were conducted via Teams (Microsoft Corp). The interview guide was informed by the cognitive work analysis framework, and the interview was conducted using storytelling principles of narrative medicine to enhance knowledge. Inductive thematic analysis was used to code the data and develop themes.

Results: Three main themes were developed. The first theme described how participants were continually updating the caregiver team , which captured how health information, including their communication motivations and intentions, was shared among family and hired caregiver participants. The subthemes included binder-based health documentation , digital health documentation , and communication practices beyond the binder . The second theme described how participants were learning to improve care and decision-making , which captured how they acted on information from various sources to provide care. The subthemes included developing expertise as a family caregiver and tailoring expertise as a hired caregiver . The third theme described how participants experienced conflicts within caregiver teams , which captured the different struggles arising from, and the causes of, breakdowns in communication and coordination between family and hired caregiver participants. The subthemes included 2-way communication and trusting the caregiver team .

Conclusions: This study highlights the health information communication and coordination challenges and experiences that family and hired caregivers face in complex home care settings for older adults. Given the challenges of this work domain, there is an opportunity for appropriate digital technology design to improve complex home care. When designing complex home care technologies, it will be critical to include the overlapping and disparate perspectives of family and hired caregivers collectively providing home care for older adults with complex needs to support all caregivers in their vital roles.

Introduction

The health care landscape is undergoing a significant transformation with the advent of home care services; yet, unlike a regulated hospital or formal care setting, home care environments lack standardization in the design and implementation of technologies that support health information management and communication [ 1 , 2 ]. Effective health information sharing is essential for patient-centered care and shared decision-making to reduce the risk of adverse events [ 3 - 5 ]. Adverse events in the home are commonly associated with insufficient communication and coordination issues among family and hired caregivers [ 6 - 8 ]. In Canada and the United States, the proportion of people receiving home care who experience adverse events ranges from 4.2% to 13% [ 7 , 9 ].

With respect to home care for older adults, their health conditions and health information are often highly varied, their living environments are disparate and often involve diverse caregiver teams, and caregivers often attempt to implement nonelectronic systems to manage recordkeeping and information sharing [ 1 , 10 , 11 ]. The rapidly expanding digital world has left home care behind [ 12 ], which could be attributed to the sociotechnical complexities that make it challenging to design standardized technologies for this care environment [ 13 - 17 ]. These complexities must be addressed to ensure that all caregivers can access the benefits of digitalization and provide better care.

Prior work on the design and integration of digital technology for caregivers primarily focuses on the perspectives of family caregivers [ 12 ]. Researchers have examined family caregivers’ general needs for the design of home care technologies [ 18 ]; how family caregivers select and use assistive technologies [ 19 , 20 ]; the factors influencing family caregivers’ satisfaction with, or adoption of, technologies [ 21 , 22 ]; and design considerations to help family caregivers manage specific health care conditions [ 23 , 24 ]. Other researchers have more closely examined information management through family caregiver handoff processes in the home [ 25 , 26 ] and described how home care nurses desire a digital dashboard to support evidence-based care provision [ 17 ]; it has also been recommended to focus on quality improvement when adopting IT, along with addressing problems with information sharing, reducing excessive documentation, and providing training [ 15 ]. While recognizing the involvement of diverse care teams in complex home care, limited qualitative analyses have examined family and nonfamilial or hired caregivers [ 12 ]. There is also a need to establish a stronger contextual understanding of information management and communication experiences to inform technology design for complex home care environments [ 12 ].

Complex Home Care

People with complex home care needs include diverse individuals who typically experience any combination of chronic conditions, multimorbidity, mental health issues, polypharmacy, and social vulnerability [ 27 - 29 ]. They also face significant barriers to receiving optimized care in their homes [ 27 - 29 ].

A systematic review of home care for older adults in Canada identified that mobility issues, cognitive impairment or mental illness, and chronic conditions are typical characteristics of older adult home care recipients with greater impacts on their quality of life and need for caregiving support at home [ 2 ]; for example, older adults with mobility issues may restrict their physical activity due to a fear of falling, especially if they have fallen before, and may receive home-based rehabilitation [ 2 ]. Cognitive impairments such as Alzheimer disease and mental health illnesses such as depression or suicidal behaviors are often associated with an increased need for home care workers and family caregiver support [ 2 ]. Older adults living with disabilities and chronic illnesses such as hypertension, heart problems, diabetes, and arthritis have very high care needs [ 2 ]. Furthermore, among older Indigenous adults, the incidence of these conditions is 2 to 3 times higher than the average rate for older adults in Canada [ 2 ].

With an increasingly aging population [ 30 ], the proportion of people requiring complex home care is also growing; for example, in Ontario, Canada, it is projected that, by 2040, the number of older adults (aged ≥80 years) will more than double, with 1 in 5 having complex care needs [ 30 ]. While the ongoing COVID-19 pandemic adds new challenges with individuals already managing complex home care [ 31 , 32 ], it also contributes to new complex care needs of individuals experiencing postacute sequelae of SARS-CoV-2 infection and other long-term health impacts from reinfection [ 33 - 35 ].

The rise in the number of people needing complex care at home has increased the demand for caregivers. Caregivers of people with long-term home care needs are often unpaid family members who work 20 to 40 hours per week providing care [ 36 ]. Approximately 75% of caregivers in Ontario have expressed worries about managing their caregiving duties, and 42.1% report feeling distressed [ 36 , 37 ]. To supplement and support the work of family caregivers, approximately 20 million caregiving visits or home care support services are purchased annually from service provider organizations to help individuals remain in their homes when receiving care [ 38 ].

Study Objectives

While family caregivers are critical, it is important to remember that complex home care often requires communication across caregiver teams, including hired caregivers (in this study, hired caregivers refers to individuals such as personal support workers [PSWs] and home care nurses). Indeed, Wolff et al [ 39 ] describe the significant potential for health IT to support stronger partnerships between family caregivers and health care workers. Moreover, Lindeman et al [ 12 ] highlight key research needs in addressing the design and use of technology to support health documentation and information exchange among caregivers. There are significant gaps in existing literature informing the design of complex home care technologies that considers family and hired caregiver experiences and the integration of future technologies for health information management and communication [ 12 ].

The objectives of this study are twofold: to explore (1) the health documentation experiences of family and hired caregivers and (2) their experiences with health communication with other caregivers in the context of their respective home care environments. The results from this work provide insight into potential users’ personal, physical, and social care environments, which is a critical foundational step in informing the design and adoption of new technologies for complex home care [ 40 , 41 ].

Study Design

This research is part of a larger interview study about the perspectives of caregivers across North America regarding health IT development to support information management and communication in complex home care [ 42 , 43 ]. The first part of this research focused on caregivers’ experiences—1 study focused on family caregivers of children with special health care needs [ 42 ], while the results reported in this study focused on family and hired caregivers of older adults. The second part of this larger study explored caregivers’ expectations regarding using voice assistants to interface with health care information in the home [ 43 ].

Despite their functional differences and the unique training and education that hired caregivers have, both family and hired caregivers were included in this study because of their complementary roles and the critical need to capture unique perspectives from a holistic approach, including physical, emotional, and social dimensions of home care. We also recognize the expertise of the family caregiver. Therefore, we use the term “caregiver” in this study to encompass family and hired caregivers and have noted when hired caregiver participants were home care nurses or PSWs.

Ethical Considerations

A research ethics board at the University of Waterloo reviewed and granted ethics clearance for the study (42179). All participants were interviewed virtually from their homes due to COVID-19–related protection measures in place. Per the ethics approval, and given that this study involved minimal risk to participants, informed consent was obtained verbally. Participant data were stored electronically on a password-protected account that only the research team could access, deidentified, and referred to only by a participant code (eg, participant 1). Participants were not remunerated for their participation. Each participant received a thank-you letter after the interview.

Participants and Data Collection

Participants were eligible if they were aged at least 18 years and either a family caregiver or a hired caregiver for an older adult (aged ≥65 years) who required complex care services in their home anywhere in North America. Complex care refers to the care of individuals who need care services for any combination of chronic conditions, mental health issues, medication-related problems, and social vulnerability. In this study, a family caregiver was one who provided or coordinated care for a family member, a partner, or a friend; they assisted this person with health- or medical-related tasks in their home. A hired caregiver, who was not a family member of the care receiver, was a home care nurse, PSW, or other caregiver employed to provide home care services to an older adult.

Recruitment was supported by disseminating study materials through various nonprofit, for-profit, and public home health care agencies, as well as caregiver support agencies, including Home Care Ontario and other caregiver networks and organizations in Ontario, with which eligible participants may be associated. We also disseminated recruitment materials within groups on social media platforms, including Reddit, Facebook, and Twitter (subsequently rebranded X), that were created for family caregivers, PSWs, and nurses. We followed up with snowball sampling, where participants were asked to share the study poster with other potential participants at the end of their interviews.

One researcher (RT) developed the interview guide, guided by the cognitive work analysis framework and the storytelling principles of narrative medicine to enhance knowledge [ 44 , 45 ], which was reviewed and iterated by 2 researchers (CM and KM; Textbox 1 ). Two researchers (RT and KM) conducted semistructured interviews with each eligible participant who contacted us about participating in the study. During the interview, the participants were asked about their home care environment, their experiences of providing care, and their coordination experiences with other caregivers. Hired caregivers were asked to speak about their recent work experiences with a client or comment in general terms about their experiences. The interviews were recorded using Microsoft Teams, and only the audio recordings were used for transcription.

Home care environment

• I’d first like to talk a bit today about the in-home care you have set up or that you work in. Can you tell me about how you’ve navigated caring for them in your home, and what you’ve needed to learn to do to provide care?
• Would you mind speaking more on learning about their condition and the treatments or therapies that they need?
• What different types of technology supports do they need at home?
• Who else is on their care team? What is their role?
• Do they take any medications for their condition? How many medications do they take and how do they take them? How is this information documented?
• How long do you usually provide care for them?

Caregiving experience

• Now I’d like to talk more about your experience caring for this person. What are some of the major factors or tensions that influence the quality of care that they receive? You can comment on both before and after COVID-19 if you’ve noticed a change.
• Could you talk a little bit about your feelings of control?
• What information do you need to care for them? What information do you need from others in their caregiver team? What information do you need from other sources?
• How did the setup of their house change to care for them?
• Do you document information about their care in their home? How do you do this? Who can see the information that you record?
• What impacts your ability to document information in their home?
• Have you received formal training to care for them? Have you been trained to use their medical technology? What did the training consist of?

Coordination with other caregivers

• You mentioned that there are other caregivers providing care. Are there times when these caregivers take over primary care responsibilities for them? Can you talk a bit about what typically happens when another caregiver takes over primary care responsibilities for them?
• What information do you usually provide to this person?
• How do you communicate this information?
• What would help you communicate information more effectively?
• What tasks does this caregiver do for them?
• Do other caregivers in their health care team record information in their home? What do they record?
• Where do they record this information? Who can see this information?

Data Analysis

The interview data were stored and organized using NVivo 12 (Lumivero) and Excel 2021 (Microsoft Corp) and analyzed inductively to construct themes [ 46 ]. The analysis process involved the following steps: (1) Microsoft Stream’s closed captions feature was used to transcribe the audio recordings; (2) 2 researchers (RT and SA) reviewed and deidentified the transcripts; (3) 2 researchers (RT and SA) listened to the interview recordings and read through the transcripts to familiarize themselves with the data; (4) all interview data were thematically coded using process and open coding to identify patterns and meaning within the transcripts, and the researchers (RT and SA) regularly discussed the codes and their organization [ 47 ]; (5) the developed codes from 1 family caregiver transcript and 1 hired caregiver transcript were applied to each interview, with new codes developed as needed; and (6) the codes were grouped to construct themes that were reviewed and refined by the entire research team. Disagreements were first resolved through discussion between RT and SA; otherwise, another research member (KM) was involved. Interviews were continued until code saturation was reached within the entire data set when no new codes were identified [ 48 ].

Reflexivity Statement

The research team has prior experience providing care for older adults, which may have introduced a bias during the study. These potential effects were mitigated by using 2 researchers (RT and KM) to conduct the interviews, using 2 researchers (RT and SA) during the coding and theme-forming process to challenge any emerging preconceptions and support the reliability of the analysis, and seeking feedback on the preliminary findings from the entire research team. After each interview, the researchers (RT and KM) also conducted a debriefing session to discuss the content, reflect on the participants’ experiences, and make notes.

Participant Characteristics

The participants were aged 24 to 83 years, and they cared for various older adult clients and family members ( Table 1 ). Most of the family caregivers (6/9, 67%) provided care to a spouse, while others cared for parents (1/9, 11%), grandparents (1/9, 11%), and siblings (1/9, 11%). Of the 6 hired caregiver participants, 4 (67%) were PSWs, and 2 (33%) were home care nurses. The participants provided home care for durations ranging from 4 months to 13 years. The average time spent providing care across all participants was approximately 5 (SD 3.7) years. Participants generally described caregiving activities for individuals and loved ones with mobility issues, cognitive needs, illnesses, and wound care needs.

The codes were arranged into 3 main themes that describe the nuanced factors involving technologies, interactions, and tasks essential for health information management and communication in the complex home care environment for older adults ( Figure 1 ; Table 2 ): (1) updating the caregiver team (binder-based health documentation, digital health documentation, and communication practices beyond the binder), (2) learning to improve care and decision-making (developing expertise as a family caregiver and tailoring expertise as a hired caregiver), and (3) conflicts within caregiver teams (2-way communication and trusting the caregiver team).

a Not applicable.

Many of the codes overlapped between family and hired caregivers within the overarching themes of updating the caregiver team and learning to improve care and decision-making ( Table 2 ). There was a reliance on binder-based health documentation, which was a physical burden for some, and there was a desire for digitalizing home care information for everyone involved, while highlighting the importance of capturing holistic care information. Family and hired caregiver participants developed communication and documentation practices beyond the binder by keeping personal notes to support safer home care, managing information exchange with other caregivers via calling and texting, leaving colocated notes as reminders, and handing off information to other caregivers. They also learned from each other but had different learning needs. Their experiences diverged more prominently in their conflicts regarding information communication, coordination, and control stemming from a lack of 2-way communication, the impacts of the COVID-19 pandemic, and trust issues. The experiences relating to the similarities and differences between family and hired caregiver roles are further explained in the following subsections.

Updating the Caregiver Team

This theme captured the ways in which health information was shared between family and hired caregivers involved in the home, including their communication motivations and intentions. While all participants in this study discussed updating the caregiver team with pertinent health information about an older adult’s care, their methods and reasons for communicating information varied, depending on the context of their home care situation and their caregiving role as a family or hired caregiver.

Binder-Based Health Documentation

Overall, every participant in this study described creating written notes maintained in a central location in the home; for example, a family caregiver participant documented medications and recorded details about their spouse’s reactions:

[The hired caregivers] made written notes to all the people in their company that were coming to see [my spouse]...They would have written notes that they kept on top of the refrigerator...I would keep some notes, and there were times when I would make detailed notes about [my spouse’s] reaction to the medication...I had times when I would write things down every day. [Participant 10, family caregiver]

While hired caregivers may have more structured in-home documentation, recordkeeping by family caregiver participants varied, depending on the need for tracking information. A hired caregiver participant strongly expressed the need for caregivers of older adults to maintain paper-based records in their homes:

In the home, it’s still very basic now, as much as you can roll your eyes with that...We find it’s also helpful because if every agency has their own electronic information, that’s great for keeping their records, but remember, there’s all these different people coming into the home. Sometimes you need an old-fashioned 3-ring binder to keep everybody straight. [Participant 5, hired caregiver (home care nurse)]

Paper records were seen as important for their transparency of documentation and for providing the ability to have information stored in a single location for the family caregiver, or any other caregiver, to review. However, while documenting health information was important in our participants’ complex home care environments, there was a lack of tools to support documentation; for example, family caregiver participants sometimes designed their own detailed recordkeeping forms to organize health information that others in the caregiver team were required to use for documentation and communication during caregiver handoffs:

I just do a nice log sheet and [my hired caregivers] write down if [they] take [their] meds, did you have a bowel movement, [are they] sleeping or not? I’m pretty good at creating a form. They have to fill this in, and that’s how we communicate. One person comes, 1 person leaves, and they just look at the notes. [Participant 8, family caregiver]

A hired caregiver participant expressed that they were required to record all details, such as the ones described by participant 8, during their shifts at specific time intervals. This volume of needed paper-based documentation may be one of the most time-demanding aspects for hired caregiver participants to balance with providing physical care tasks. A hired caregiver participant commented on the compounding nature of this burden with the number of clients in their care:

If you work with 10 people, you have to care for them, and you have to document whatever happens to these 10 people. That is why the PSW job is so hard. [Participant 9, hired caregiver (PSW)]

The context for which caregivers documented information varied, depending on the severity of the patient’s conditions, such as monitoring for the effects of a new medication, and the caregiver’s recordkeeping motivations. Family caregivers expressed that they were only documenting information when they felt it was necessary to share progress updates or noticeable patterns with health care professionals. Hired caregiver participants strongly believed that updating others in the caregiver team about the health of their clients, including not only their vital signs but also a holistic picture of the patient, was a critically important factor:

But what about that person? What about how they’re feeling that day? What they’re thinking that day? I get tired of reading documents that say, “changed the sheets, toileted them twice...” But how about asking them, “How do you really feel today? I don’t want to hear ‘good.’ I want to know how you really feel. What are your thoughts?” Like, really get into it and document that. None of this “oh, every day, same document” big deal. What’s the point of even documenting? [Participant 4, hired caregiver (PSW)]

The holistic information they captured may be less structured than objective measures about a client in their home, which may be more challenging to share but essential for providing quality care.

Digital Health Documentation

In some complex home care situations, digital methods were used to share information with other caregivers. When recordkeeping was completed and transferred digitally, this information was used to update health care professionals about changes or updates regarding the patient’s care. Other caregivers in a supervisory role on the team used this information to monitor the events during another caregiver’s shift. A hired caregiver participant who was also a nurse described a web-based system that they used to communicate with PSWs in the home:

[The online system is] between the person who’s in the home as the PSW and the delegating nurse. I can go in to see that information through our system. There’s an additional link where I can log in and see how their night was. [Participant 5, hired caregiver (home care nurse)]

The family caregiver participants in this study did not have access to, or know how to use, any potential technologies to see these details other than texting or leaving a voicemail. Systems such as the one used by participant 5 may provide opportunities for family caregivers to see health information updates without physically being in the home. Despite the lack of access, family caregiver participants who controlled the home care recordkeeping were interested in developing digital documentation methods for their caregiver team but did not know how to accomplish this:

I would like to be able to make that easier for [other caregivers]. I don’t know how, but I understand that in some institutions, they do the recordkeeping on computers. [Participant 8, family caregiver]

Communication Practices Beyond the Binder

With limited access to technologies that can support communication to update caregivers, there was creativity beyond using physical notes kept in 1 area of the home. Caregivers sometimes implemented more prominent written notes and posted them around their client’s houses. The posted messages aimed to provide context-specific information in the locations where actions needed to be taken by other caregivers and as a salient reminder:

We posted notes all over the place. It was the only way! I put them on the bathroom wall for when [the PSWs] came in. There was one for the morning, one for the daytime, one for the evening, and it was simply, “This is what [the client] requires.” It was listed. They didn’t have to search through charts...I had so many thank-yous from PSWs that were coming in. [Participant 13, hired caregiver (home care nurse)]

These notes, which were participants 13’s highly effective method for ensuring that other caregivers could see information at the time and place that it was needed, obviated the need for calling or texting and captured the attention of the caregivers when they were providing specific care tasks. However, beyond physical documentation, the other process involved in updating the participant’s caregiver teams was verbal communication during client handoffs. The participants updated others in the caregiver team on new information to ensure their awareness about changes in their home care situation since the incoming caregiver’s last visit. A hired caregiver participant mentioned the details about which they needed to update other caregivers:

Whenever there’s someone’s turn to take over my shift, I would just say that “[They have] been okay. [They have] been very calm, but there are times that [they were] a bit manic.” Usually, I tell them that [they] already ate, that [they] already took [their] meds at this time, and I usually tell [them] that the only thing that’s missing is [their] meds for this hour. [Participant 2, hired caregiver (PSW)]

Information shared verbally supplemented the written record by providing a holistic picture of the situation and supported emphasizing time-sensitive details. Some family caregiver participants felt burdened by having to continually communicate with other caregivers about critical safety information that could have severe consequences if not applied correctly. A family caregiver mentioned their concerns with having to update new caregivers in their home on details about keeping their parent safe:

It’s reminding them stuff like [thickening their drinking water], which is a really, really big risk because my [parent] is prone to something called aspiration, which means if [they] eat any food that can go in [their] lungs, which has happened before, then that can develop into pneumonia...We’ve had to take [them] to the hospital multiple times for that, and that can be really scary because someone like [my parent], who is more vulnerable and prone to getting disease and infection. Especially, taking [them] to the hospital like now [during the COVID-19 pandemic] is pretty scary. [Participant 6, family caregiver]

There is a potential fear of future adverse events occurring because family caregivers understand the specific risks associated with their home environment. However, when in-person communication was not possible, but essential information needed to be shared with the caregiver team, the participants used telecommunication devices to provide updates via a telephone call or an SMS text message. A family caregiver participant mentioned that they would call their agency if an adverse event occurred in their home:

If it’s really important, then I’ll call the agency and tell them that [their] workers need to know that such and such is happening...like if there’s been a fall, for instance. [Participant 7, family caregiver]

There may be an expectation that information communicated to caregiver agencies over the telephone is subsequently shared with other caregivers involved with the client to ensure widespread awareness when visiting the home.

Telecommunication devices may also afford hired caregiver participants the means to have direct communication with caregivers. A hired caregiver participant highlighted the efficiency of this method of sharing information:

Especially with younger people, with younger family members, they will often text me on my work phone. That’s the most efficient way I find, I text. I call, but I find it even easier to text a lot with the visiting nurses who I talked to recently. [Participant 5, hired caregiver (home care nurse)]

However, the demographics of the caregivers, the urgency of the information that needs to be shared, time constraints, and the ease of use may be contributing factors to whether telephone calls or SMS text messages can be used as a reliable communication channel for complex home care.

Learning to Improve Care and Decision-Making

This theme captured how caregivers acted on information from various sources to provide care. Family and hired caregivers in this study continually learned about their patient’s conditions and the nuances of the home care situation to improve the quality of the care they provided and support their decision-making.

Developing Expertise as a Family Caregiver

The degree to which family caregivers felt the need to learn new information and develop caregiving expertise resulted from their loved one’s conditions or symptoms, as a family caregiver participant explained:

[My spouse] had delirium frequently, and [I was] trying to navigate through the delirium where you can’t deny what somebody is experiencing in a delirious state...I could never quite understand it. [Participant 10, family caregiver]

Although they did not have a medical background, there was a desire among family caregiver participants to better understand what their loved one was experiencing, despite the challenges of overcoming this knowledge gap. Navigating information often felt similar to doing their own research through reading about the condition or symptoms, learning about medical treatments, and gathering information from health care professionals:

I’ve learned that the more you can engage [individuals with Parkinson disease] intellectually and emotionally with contact, with people, and with things that they like and love, the better they are, even with their mobility. I read up on things. I learned about [my sibling’s] medications, and I know the effects of all of them, and I know the effects of that horrible [medication they were] taking that caused psychosis. I’ve got an informational sheet from some of the people who worked with us who have gone on to become RPNs [registered practical nurses] and so on. [They] gave me a whole handout on how to deal with delusional behavior, and I’ve read about it too. [Participant 8, family caregiver]

While some information that family caregivers were learning from health care professionals supported their loved ones through improved care, learning more about providing care in the home also supported their well-being, specifically for performing physical tasks. The family caregiver participant further described how they learned to help their sibling’s mobility while also supporting their own health:

I was doing things wrong for a while too. [My sibling has] mobility issues, and [they] would have difficulty getting up out of a chair. We devised a way of counting and using momentum to pull [them] up. Then I realized I’m hurting my back this way. I learned from some of the various physiotherapists and occupational therapists, and they gave us instructions. [Participant 8, family caregiver]

It is important to note that the family caregiver participants in this study were not medically trained professionals. Unlike hired caregivers, the family caregiver participants did not have a standardized knowledge base to support medical decision-making or information gathering.

Tailoring Expertise as a Hired Caregiver

The health care workers in this study highlighted the importance of their training and background in providing care; for example, a participant noted the importance of their education in recognizing a severe medical issue that could have quickly developed into sepsis, a situation in which a family caregiver might not have responded as promptly:

Well, I was doing it with the knowledge base—the preidentified wounds on [their] leg, ulcers. I knew right away, but someone that didn’t have that background wouldn’t have pushed the issue. [Participant 13, hired caregiver (home care nurse)]

A knowledge base helped participant 13 with their perception-action response to the medical issue. However, while family caregiver participants provide a significant amount of care, there may be barriers to developing perception-action responses for those without a medical background.

The health care workers in this study tailored their caregiving expertise through information acquired within the home care environment as well as information provided by family caregivers or clients. Sometimes, members of the at-home caregiver team verbally communicated this information, supporting hired caregivers who were new to the environment, to ensure that the client’s unique preferences were met, as explained by a hired caregiver participant:

I ask the ones who are already in [client 1]’s team, “What does [client 1] want to do? Whenever [client 1’s sibling] is here, I usually ask [them] what things would let [client 1] ease up [their] feelings of uneasiness or what will be their preference? [Or] you ask [the client], “You want me to do it this way or that way?” We have to be keen and diligent when it comes to [their] liking. [Participant 2, hired caregiver (PSW)]

Family caregiver participants’ importance in maintaining detailed health records was an approach to supporting all caregivers with a baseline knowledge base and enhancing their capacity to recognize potential medical issues and optimize their caregiving. Learning from physical documentation was necessary to support decision-making for hired caregiver participants who visited multiple clients daily. A hired caregiver explained how they relied on physical notes—documents that included information from the family caregiver and other hired caregivers—to learn about the most recent events that had occurred in the home and make decisions about the safest time for their client to take their medications:

I also look up their records of what happened all throughout the weekend. It’s usually placed on the table here in [my client’s] home. It’s just the first thing that you go over when you come here...You try to summarize what happened and what time [their] previous extra dose was given so that you can say, “OK, we can give [them] an extra dose at this time,” it’s safe to give [them] an extra dose. [Participant 2, hired caregiver (PSW)]

However, there remains a cognitive challenge in tailoring caregiving expertise to each home care environment to inform decisions: hired caregivers need to transform information into short summaries to support other in-home caregivers. The time required to transform the information from paper-based records may constrain busy work schedules in complex home care.

Conflicts Within Caregiver Teams

This theme captured the struggles and breakdowns in communication and coordination among caregivers, which often impacted care continuity and increased their frustration and lack of trust in each other. These conflicts stemmed from unclear roles and responsibilities as well as communication and coordination issues.

2-Way Communication

Communication challenges existed between family caregiver participants and the hired caregivers as well as between hired caregivers, their clients, and other health care professionals. Conflicts were especially evident when there was a barrier to using technologies meant to ensure that 2-way communication was occurring. This was important in situations where caregivers were required to maintain the older adult’s safety in the home. The technologies used to support communication often only provided a 1-way channel, with no feedback or confirmation of the receiving caregivers’ understanding. A hired caregiver stated as follows:

Most of the time, my frustration was with communicating with the home care and caregivers...There was no connection with me. I got to call a number and leave a voice message. I may or may not have heard back. [Participant 13, hired caregiver (home care nurse)]

Limitations in communication technologies may result in uncertainties about receiving and promptly understanding care messages. Reliable communication is critical to reduce tensions, given the number of individuals whom caregivers provide care. The challenges identified in communication among caregivers were also evident with hired and family caregivers, where conflicts emerged due to the hierarchies in caregiver teams. Perceived hierarchy issues raised frustrations for a hired caregiver, who was concerned with the effectiveness of the communication (nonstandardized information-sharing methods created stress for the caregiver team and hindered the coordination of information sharing about home care):

I was frustrated in the fact that if I identified a problem, then there needed to be only 1 person calling the doctor’s office, only 1 person calling the [agency]. They didn’t need multiple phone calls from multiple members or care providers because it was not effective. [The family caregiver] had verbally given all of these people consent for me to handle everything [but] then [they] would start calling. [Participant 13, hired caregiver (home care nurse)]

The impact of the COVID-19 pandemic meant that hired caregivers were visiting clients less frequently or performing more virtual visits, depending on the severity of health needs:

The visiting frequency really depends on their acuity now and I can see that because of COVID-19...the nursing agencies have pulled that back. Even they went to more virtual visits, which was a huge headspace change for visiting nursing agencies. [Participant 5, hired caregiver (home care nurse)]

Shifting to virtual visits would mean that physical binder-based health documents and other caregiving notes would not be readily accessible to hired caregivers. Family caregiver participants discussed the challenge of ensuring that every individual caregiver understood the nuances and preferences within their home care situation at the beginning of the COVID-19 pandemic and their responsibility to find ways to continue ensuring effective communication of their family’s needs regarding home care services:

And we’ve had some trouble with navigating that sort of thing where finding PSWs, especially at a time like now [during the COVID-19 pandemic], is pretty limited. It’s just been a little bit difficult to get them to understand our perspective and what the client needs. What my [parent] needs. [Participant 6, family caregiver]

The risk of losing a hired caregiver at the beginning of the COVID-19 pandemic, despite the communication challenges involved in having a hired caregiver care for their loved one, created more stress for family caregivers.

Trusting the Caregiver Team

As a result of conflicts over ensuring that specific care needs were being met, some family caregivers felt additional responsibility to monitor the care tasks in their homes, potentially due to a lack of trust. There was an observed need to provide feedback in real time that was specific to their home, which was not always appreciated by the hired caregiver; for example, family caregivers may have lacked trust in the ability of hired caregivers to provide safe care because they did not have expert knowledge about fall risks in their specific home environment:

If I see something not right when I’m with [them] for the last half hour [of their shift], then I will say, “This is not right. You have to stand here, or [my spouse will] fall over.” That kind of thing. Some of them like it, and some of them don’t like it. [Participant 7, family caregiver]

The conflict in this context of information sharing may stem from a lack of trust in hired caregivers performing care in their home where they are not familiar with the nuances of the physical space, but the unclear power dynamic regarding who holds primary health information or acts as the lead caregiver may also play a role.

The family caregiver participant also expressed uncertainty about whether the care needs that they had communicated were being met in their absence:

I’m there for half of the shift because [my spouse] does the last half as an exercise plan, and that’s done downstairs. I see it. If there’s a problem, they’ll tell me. But the thing is, I don’t know whether they’re [watching for fall risks] when I’m not around. That’s my biggest worry. I can’t be all there all the time. It’s just not possible. [Participant 7, family caregiver]

Ultimately, the uncertainty around hired caregivers’ vigilance with regard to specific safety risks in their homes created anxieties for family caregivers, reducing respite care’s benefits due to a potential lack of trust in others in the caregiver team.

Principal Findings

This study captured the health documentation and communication experiences of family and hired caregivers in complex home care settings. Most of the participants (13/15, 87%) in this study were women, who often experience higher caregiving burdens and stress [ 49 ], aligning with the Canadian literature and 2022 Statistics Canada data that found women to be more likely to be care providers in the home than men [ 2 , 50 ]. The results also identify the overlap in caregiving experiences among the participants regarding how they were updating the caregiver team with new information about the person receiving care and learning to improve care and decision-making through information obtained from caregivers and by other means. In addition, the results identify disparate experiences with respect to conflicts within caregiver teams when communicating health information and coordinating care responsibilities. The insights gained from this study can inform design requirements for technologies that can meet family and hired caregiver needs with respect to supporting team-based caregiving, considering the sociotechnical complexities of this work domain. Understanding caregivers’ experiences within this complex domain is essential to launch such technology development effectively [ 51 ].

Although the caregiving situations discussed in this study were complex, the participants described overlapping experiences within the first and second overarching themes and disparate experiences in the third. Technologies designed to keep caregiver teams updated and support learning and decision-making, while alleviating potential communication conflicts, could help both family and hired caregivers. A growing body of research describes the importance of including family caregivers as collaborators for home care and bridging their contributions to home care with hired caregivers [ 13 , 25 , 52 ]. Much of the current literature on home care technologies focuses on either family caregivers [ 18 - 26 ] or home care workers [ 15 - 17 ] when examining design and development. Our study builds on this work by highlighting the potential overlap in design needs and user requirements between these caregiver roles.

First, hired caregivers are often required to manually document their care delivery for the agencies that employ them. As we found in our study, some hired caregivers have access to electronic documentation systems that are not accessible to family caregivers, or they use paper-based systems to communicate information to other caregivers. Family caregivers may develop their own paper-based recordkeeping systems that they ask their caregivers to fill out, which can create a documentation burden for others in the caregiver team. Despite the need to involve family caregivers in digital technology design and the growing literature on family caregivers’ technology needs and experiences [ 18 , 19 , 22 , 23 , 25 ], caregiving documentation research focuses on hired caregivers [ 17 , 53 - 55 ], likely due to organizational and institutional requirements. Our study identifies that health information generated by family caregivers is important for safety in a home care environment, and future technologies should find accessible ways to include all caregivers to effectively communicate and share documented health information.

Second, given the communication challenges that caregivers described in this study, where family caregivers were concerned with ensuring that hired caregivers understood the nuances of how to safely care for their loved one in the context of their home, both desired to learn from caregivers and other health information. There is a need to combine the findings from the existing body of literature to build technologies that can address these systems-level needs and support coordinated care; for example, to support handoffs, potential technologies may provide value by efficiently gathering health information from users and intelligently transforming it into situational summaries through the use of large language models [ 56 ]. As it is vital to recognize family caregivers as important individuals in documenting the care of their loved one [ 57 ] and alleviate the high burdens that family and hired caregivers often face [ 58 , 59 ], automating this aspect of health information and communication could provide significant benefits to all caregivers.

Third, by examining the perspectives of family and hired caregivers and how their work intersects, our study identifies some of the ways in which established literature highlighting only a single caregiving perspective can be enhanced to support caregiver teams; for example, within our third theme regarding communication conflicts, we found examples of the lack of fundamental 2-way communication between caregivers, resulting in uncertainty about whether other caregivers received and understood the information shared, along with challenges related to understanding caregivers’ communication roles and responsibilities. Other research on family caregivers recommends that digital systems include secure messaging, customization, shared calendars, checklists, medication lists, and knowledge about the patient’s condition [ 25 ]. Our study highlights the importance of considering the work experience perspectives of family and hired caregivers working together. This suggests that technology design should include features that allow caregivers to confirm whether others in the caregiver team have understood shared health information across functionalities to reduce uncertainties in their caregiving tasks; in addition, the ability to share nuanced home environment details could foster trust within the caregiver team.

Other family caregiver–centered research recommends that IT should put the family caregiver in control [ 24 ]. While this is critical for situations led by a family caregiver, when multiple types of caregivers are involved, these technologies should consider all caregiving users’ needs [ 18 ], such as the needs of hired caregivers. Hired caregivers have a need for control over health documentation processes—likely due to their training, experiences, and their home care agency’s needs—and for setting appropriate communication boundaries with family caregivers because they often provide care for multiple people. Technology design could play an important role in hired caregivers’ relationships with family caregivers and perceived levels of control. Going forward, a design recommendation may include integrating caregiver profiles to support formalizing roles and care coordination responsibilities in the home.

As also indicated in prior work [ 17 , 18 , 23 ], there is agreement on the need to digitalize health information management and communication processes to support family and hired caregivers; yet, there are no standardized systems that support all caregivers. One of the challenges of building technologies for older adults’ home care environments identified across this study may be the reliance on paper-based records by home health care systems [ 24 ], where issues with the ease of use and ease of integration may prevent adoption over the status quo [ 21 ]. It is important to highlight that the participants in this study described how paper-based records supported health information documentation and provided an acceptable and effective method for sharing information with other caregivers. Unfortunately, paper-based records inherently lack functionality for real-time 2-way communication; may not support caregivers adapting to change in a fast-paced, dynamic home environment; and may be limited in supporting cognitive work demands across homes due to nonstandard designs [ 60 - 62 ].

As complex home care continues to evolve and family caregivers take on increasingly critical roles and responsibilities that require quick access to information and clearer communication, paper-based communication tools may not be a sufficient information management strategy [ 63 ] or a resilient technology during a pandemic. Existing research shows that digital personal health records for home care are perceived as useful in replacing a paper-based system because they keep relevant information in a single location, save physical space [ 24 , 25 , 64 ], and support information access on ubiquitous technologies such as smartphones and PCs [ 21 ]. The successful implementation of new technologies for caregivers of older adults, which would enable them to share information with others in the caregiver team without a physical documentation burden, review health information documented by others in the caregiver team to stay updated on the status of care, and reduce conflicts resulting from poor communication tools, hinges on maximizing the ease of use and satisfaction [ 21 , 53 , 65 , 66 ] and minimizing implementation burdens. More research is needed to identify technology designs and implementation strategies for complex home care that address these overarching needs to support the efficacy of care tasks, caregiver engagement, and system-level adoption among all caregivers.

Strengths and Limitations

To the best of our knowledge, this is one of the first studies that combines the perspectives of family and hired caregivers and their experiences regarding health information management and communication in the context of complex home care during the ongoing COVID-19 pandemic. The interview data captured rich details about the participants’ experiences and how they work with others in the caregiver team, providing insight that can guide the future development of digital technologies that support caregiving of older adults. Our findings support the need for future research to combine these work experience perspectives when developing design requirements based on user needs for complex home care.

The limitations of our study include the concentrated sample of participants from Ontario; the results may not apply to other Canadian provinces and territories or other countries. In addition, the majority of the participants (13/15, 87%) were women, and the sample size for the hired caregivers was limited. We also did not explicitly ask participants about their client’s or loved one’s specific conditions, diseases, or syndromes; however, some participants shared this information, which we have included in the Results section. One participant’s interview transcript data were unavailable for coding or presentation as anonymous quotes because they did not grant permission for their interview to be audio recorded; hence, the data were captured in detailed written notes for the analysis. While we reached code saturation in our analysis, future studies could expand on this work by recruiting caregiver team focus groups, which could contribute further insights into care coordination and communication in this complex care domain.

Conclusions

This study highlights the overlapping experiences of family and hired caregivers and the challenges they face when communicating health information and coordinating care responsibilities in complex home care settings. The results suggest the need for digitalized solutions that better support caregiver coordination and ease information sharing to consider how design requirements and user needs from 1 caregiving role overlap with those of other caregivers while addressing disparate communication challenges. Going forward, future research should involve the experiences of family and hired caregivers working together in the design and development of such technologies. By addressing these challenges and leveraging the insights from this study, we can improve the quality of care provided to those who need it most and support caregivers in their vital roles.

Acknowledgments

The authors are grateful for the participants’ willingness to share their experiences for this study. Partial financial support was received from Telus Health and a Natural Sciences and Engineering Research Council of Canada Collaborative Research and Development grant (CRDPJ-503484-2016). RT was also supported by the Ontario Graduate Scholarship and the University of Waterloo Alumni@Microsoft Graduate Scholarship.

Data Availability

The deidentified data sets generated and analyzed during this study are available from the corresponding author on reasonable request.

Conflicts of Interest

None declared.

• National Research Council, Division of Behavioral and Social Sciences and Education, Board on Human-Systems Integration, Committee on the Role of Human Factors in Home Health Care. Health Care Comes Home: The Human Factors. Washington, DC. National Academies Press; 2011.
• Johnson S, Bacsu J, Abeykoon H, McIntosh T, Jeffery B, Novik N. No Place Like Home: A Systematic Review of Home Care for Older Adults in Canada. Can J Aging. Dec 2018;37(4):400-419. [ CrossRef ] [ Medline ]
• Simpkin AL, Armstrong KA. Communicating uncertainty: a narrative review and framework for future research. J Gen Intern Med. Nov 13, 2019;34(11):2586-2591. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Fex A, Flensner G, Ek AC, Söderhamn O. Living with an adult family member using advanced medical technology at home. Nurs Inq. Dec 2011;18(4):336-347. [ CrossRef ] [ Medline ]
• Dybwik K, Nielsen EW, Brinchmann BS. Home mechanical ventilation and specialised health care in the community: between a rock and a hard place. BMC Health Serv Res. May 23, 2011;11:115. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Masotti P, McColl MA, Green M. Adverse events experienced by homecare patients: a scoping review of the literature. Int J Qual Health Care. Apr 10, 2010;22(2):115-125. [ CrossRef ] [ Medline ]
• Safety at home: a pan-Canadian home care study. Canadian Patient Safety Institute. 2013. URL: https://www.healthcareexcellence.ca/media/j0bcljjo/safety-at-home-care-final-ua.pdf [accessed 2024-06-14]
• Schildmeijer KG, Unbeck M, Ekstedt M, Lindblad M, Nilsson L. Adverse events in patients in home healthcare: a retrospective record review using trigger tool methodology. BMJ Open. Jan 03, 2018;8(1):e019267. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Sears N, Baker GR, Barnsley J, Shortt S. The incidence of adverse events among home care patients. Int J Qual Health Care. Feb 2013;25(1):16-28. [ CrossRef ] [ Medline ]
• Sezgin E, Noritz G, Elek A, Conkol K, Rust S, Bailey M, et al. Capturing at-home health and care information for children with medical complexity using voice interactive technologies: multi-stakeholder viewpoint. J Med Internet Res. Feb 13, 2020;22(2):e14202. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tennant R, Leggett A, Smith C, Tan L, Mercer K, Burns CM. Addressing human factor challenges in paediatric home care: development and evaluation of a mobile home care communication app. Proc Int Symp Hum Factors Ergon Health Care. Sep 16, 2020;9(1):37-39. [ CrossRef ]
• Lindeman DA, Kim KK, Gladstone C, Apesoa-Varano EC. Technology and caregiving: emerging interventions and directions for research. Gerontologist. Feb 14, 2020;60(Suppl 1):S41-S49. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Hassan AY. Challenges and recommendations for the deployment of information and communication technology solutions for informal caregivers: scoping review. JMIR Aging. Jul 29, 2020;3(2):e20310. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Foged S, Nørholm V, Andersen O, Petersen HV. Nurses' perspectives on how an e-message system supports cross-sectoral communication in relation to medication administration: a qualitative study. J Clin Nurs. Feb 2018;27(3-4):795-806. [ CrossRef ] [ Medline ]
• Koru G, Alhuwail D, Topaz M, Norcio AF, Mills ME. Investigating the challenges and opportunities in home care to facilitate effective information technology adoption. J Am Med Dir Assoc. Jan 2016;17(1):53-58. [ CrossRef ] [ Medline ]
• Sockolow PS, Bowles KH, Adelsberger MC, Chittams JL, Liao C. Challenges and facilitators to adoption of a point-of-care electronic health record in home care. Home Health Care Serv Q. 2014;33(1):14-35. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Dowding D, Merrill JA, Barrón Y, Onorato N, Jonas K, Russell D. Usability evaluation of a dashboard for home care nurses. Comput Inform Nurs. Jan 2019;37(1):11-19. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Xiong C, D'Souza A, El-Khechen-Richandi G, Mihailidis A, Cameron JI, Astell A, et al. Perceptions of digital technology experiences and development among family caregivers and technology researchers: qualitative study. JMIR Form Res. Jan 28, 2022;6(1):e19967. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Mortenson WB, Pysklywec A, Fuhrer MJ, Jutai JW, Plante M, Demers L. Caregivers' experiences with the selection and use of assistive technology. Disabil Rehabil Assist Technol. Aug 02, 2018;13(6):562-567. [ CrossRef ] [ Medline ]
• Qu Y, Lee OE, Park A. A qualitative study of family caregivers' technology use in Alzheimer's disease care. In: Proceedings of the IEEE 10th International Conference on Healthcare Informatics. 2022. Presented at: ICHI 2022; June 11-14, 2022; Rochester, MN. [ CrossRef ]
• Lee C, Balmuth A, D’Ambrosio L, Felts A, Coughlin JF. Technologies and services to support care: family caregivers’ experiences and perspectives. In: Proceedings of the 9th International Conference on Human Aspects of IT for the Aged Population. 2023. Presented at: ITAP 2023; July 23-28, 2023; Copenhagen, Denmark. [ CrossRef ]
• Dermody G, Fritz R, Glass C, Dunham M, Whitehead L. Family caregiver readiness to adopt smart home technology to monitor care-dependent older adults: a qualitative exploratory study. J Adv Nurs. Feb 23, 2024;80(2):628-643. [ CrossRef ] [ Medline ]
• Shin JY, Chaar D, Kedroske J, Vue R, Chappell G, Mazzoli A, et al. Harnessing mobile health technology to support long-term chronic illness management: exploring family caregiver support needs in the outpatient setting. JAMIA Open. Dec 2020;3(4):593-601. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Holden RJ, Karanam YL, Cavalcanti LH, Parmar T, Kodthala P, Fowler NR, et al. Health information management practices in informal caregiving: an artifacts analysis and implications for IT design. Int J Med Inform. Dec 2018;120:31-41. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tang C, Chen Y, Cheng K, Ngo V, Mattison JE. Awareness and handoffs in home care: coordination among informal caregivers. Behav Inf Technol. Nov 27, 2017;37(1):66-86. [ CrossRef ]
• Moen A, Brennan PF. Health@Home: the work of health information management in the household (HIMH): implications for consumer health informatics (CHI) innovations. J Am Med Inform Assoc. 2005;12(6):648-656. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Safford MM, Allison JJ, Kiefe CI. Patient complexity: more than comorbidity. the vector model of complexity. J Gen Intern Med. Dec 16, 2007;22 Suppl 3(Suppl 3):382-390. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Schaink AK, Kuluski K, Lyons RF, Fortin M, Jadad AR, Upshur R, et al. A scoping review and thematic classification of patient complexity: offering a unifying framework. J Comorb. 2012;2:1-9. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Johnson S, Bacsu J. Understanding complex care for older adults within Canadian home care: a systematic literature review. Home Health Care Serv Q. 2018;37(3):232-246. [ CrossRef ] [ Medline ]
• Population projections. Government of Ontario. URL: https://web.archive.org/web/20240319135120/https://data.ontario.ca/dataset/population-projections [accessed 2024-03-18]
• McNaughton CD, Austin PC, Sivaswamy A, Fang J, Abdel-Qadir H, Daneman N, et al. Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study. CMAJ. Oct 17, 2022;194(40):E1368-E1376. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Leite S, Monteiro KS, Santino TA, Chaves G, Barbosa JV, Santos TZ, et al. Effects of home healthcare for adults with chronic respiratory diseases and post-COVID-19 syndrome on hospital bed turnover rate: a protocol of systematic review with meta-analysis. BMJ Open. Apr 03, 2023;13(4):e069341. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Altmann DM, Whettlock EM, Liu S, Arachchillage DJ, Boyton RJ. The immunology of long COVID. Nat Rev Immunol. Oct 11, 2023;23(10):618-634. [ CrossRef ] [ Medline ]
• Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nat Med. Nov 10, 2022;28(11):2398-2405. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Al-Aly Z, Topol E. Solving the puzzle of Long Covid. Science. Feb 23, 2024;383(6685):830-832. [ CrossRef ] [ Medline ]
• Caregiver distress. Canadian Institute for Health Information. 2023. URL: https://www.cihi.ca/en/indicators/caregiver-distress [accessed 2024-06-08]
• Spotlight report: 5 year retrospective 2019-2023. The Ontario Caregiver Organization. URL: https:/​/web.​archive.org/​web/​20240319135939/​https:/​/ontariocaregiver.​ca/​wp-content/​uploads/​2023/​12/​2023SpotlightReport_ENG.​pdf [accessed 2024-03-18]
• Home care. Home Care Ontario. URL: https:/​/web.​archive.org/​web/​20220930103955/​https:/​/www.​homecareontario.ca/​home-care-services/​facts-figures/​home-care [accessed 2024-03-18]
• Wolff JL, Darer JD, Larsen KL. Family caregivers and consumer health information technology. J Gen Intern Med. Jan 2016;31(1):117-121. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Holtzblatt K, Beyer H. Contextual design: using customer work models to drive systems design. In: Proceedings of the Conference Companion on Human Factors in Computing Systems. 1996. Presented at: CHI '96; April 13-18, 1996; Vancouver, BC. [ CrossRef ]
• Holtzblatt K, Jones S. Contextual inquiry: a participatory technique for system design. In: Schuler D, Namioka A, editors. Participatory Design: Principles and Practices. Boca Raton, FL. CRC Press; 1993.
• Tennant R, Allana S, Mercer K, Burns CM. Exploring the experiences of family caregivers of children with special health care needs to inform the design of digital health systems: formative qualitative study. JMIR Form Res. Jan 05, 2022;6(1):e28895. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tennant R, Allana S, Mercer K, Burns CM. Caregiver expectations of interfacing with voice assistants to support complex home care: mixed methods study. JMIR Hum Factors. Jun 30, 2022;9(2):e37688. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Charon R. The patient-physician relationship. Narrative medicine: a model for empathy, reflection, profession, and trust. JAMA. Oct 17, 2001;286(15):1897-1902. [ CrossRef ] [ Medline ]
• Vicente KJ. Cognitive Work Analysis: Toward Safe, Productive, and Healthy Computer-Based Work. Boca Raton, FL. CRC Press; 1999.
• Seaman C. Qualitative methods in empirical studies of software engineering. IIEEE Trans Softw Eng. 1999;25(4):557-572. [ CrossRef ]
• Saldana J. The Coding Manual for Qualitative Researchers. Thousand Oaks, CA. SAGE Publications; 2015.
• Hennink MM, Kaiser BN, Marconi VC. Code saturation versus meaning saturation: how many interviews are enough? Qual Health Res. Mar 26, 2017;27(4):591-608. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Lindt N, van Berkel J, Mulder BC. Determinants of overburdening among informal carers: a systematic review. BMC Geriatr. Aug 26, 2020;20(1):304. [ FREE Full text ] [ CrossRef ] [ Medline ]
• More than half of women provide care to children and care-dependent adults in Canada, 2022. Statistics Canada. Nov 8, 2022. URL: https://www150.statcan.gc.ca/n1/daily-quotidien/221108/dq221108b-eng.htm [accessed 2024-05-05]
• Li J, Han X, Zhang X, Wang S. Spatiotemporal evolution of global population ageing from 1960 to 2017. BMC Public Health. Jan 30, 2019;19(1):127. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Hengelaar AH, van Hartingsveldt M, Wittenberg Y, van Etten-Jamaludin F, Kwekkeboom R, Satink T. Exploring the collaboration between formal and informal care from the professional perspective-a thematic synthesis. Health Soc Care Community. Jul 2018;26(4):474-485. [ CrossRef ] [ Medline ]
• Ibrahim S, Donelle L, Regan S, Sidani S. Predicting registered nurses' behavioural intention to use electronic documentation system in home care: application of an adapted unified theory of acceptance and use of technology model. Nurs Leadersh (Tor Ont). Jun 28, 2019;32(2):48-70. [ CrossRef ] [ Medline ]
• Husson NM, Trangenstein PA, Ketel C. Education to improve point of care documentation in home care nurses: a quality improvement project. Comput Inform Nurs. Aug 06, 2021;40(3):165-169. [ CrossRef ] [ Medline ]
• Gjevjon ER, Hellesø R. The quality of home care nurses' documentation in new electronic patient records. J Clin Nurs. Jan 17, 2010;19(1-2):100-108. [ CrossRef ] [ Medline ]
• Van Veen D, Van Uden C, Blankemeier L, Delbrouck JB, Aali A, Bluethgen C, et al. Adapted large language models can outperform medical experts in clinical text summarization. Nat Med. Apr 27, 2024;30(4):1134-1142. [ CrossRef ] [ Medline ]
• Cohen C, Pereira F, Kampel T, Bélanger L. Integration of family caregivers in delirium prevention care for hospitalized older adults: a case study analysis. J Adv Nurs. Jan 20, 2021;77(1):318-330. [ CrossRef ] [ Medline ]
• Slaboda JC, Nelson SH, Agha Z, Norman GJ. A national survey of caregiver's own experiences and perceptions of U.S. health care system when addressing their health and caring for an older adult. BMC Health Serv Res. Jan 29, 2021;21(1):101. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Woodgate RL, Edwards M, Ripat JD, Borton B, Rempel G. Intense parenting: a qualitative study detailing the experiences of parenting children with complex care needs. BMC Pediatr. Nov 26, 2015;15(1):197. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Shin JY, Kedroske J, Vue R, Sankaran R, Chaar D, Churay T, et al. Design considerations for family-centered health management: preliminary findings with pediatric BMT patients. In: Proceedings of the 17th ACM Conference on Interaction Design and Children. 2018. Presented at: IDC '18; June 19-22, 2018; Trondheim, Norway. [ CrossRef ]
• Bail K, Merrick E, Bridge C, Redley B. Documenting patient risk and nursing interventions: record audit. Aust J Adv Nurs. Feb 4, 2021;38(1). [ CrossRef ]
• Muinga N, Abejirinde IO, Paton C, English M, Zweekhorst M. Designing paper-based records to improve the quality of nursing documentation in hospitals: a scoping review. J Clin Nurs. Jan 07, 2021;30(1-2):56-71. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Reinhard SC, Given B, Petlick NH, Bemis A. Supporting family caregivers in providing care. In: Hughes RG, editor. Patient Safety and Quality: An Evidence-Based Handbook for Nurses. Rockville, MD. Agency for Healthcare Research and Quality (US); 2008.
• Ozok AA, Wu H, Gurses AP. Exploring patients’ use intention of personal health record systems: implications for design. Int J Hum Comput Interact. Jan 06, 2017;33(4):265-279. [ CrossRef ]
• Davis FD. Perceived usefulness, perceived ease of use, and user acceptance of information technology. MIS Q. Sep 1989;13(3):319-340. [ CrossRef ]
• Rahimi B, Nadri H, Lotfnezhad Afshar H, Timpka T. A systematic review of the technology acceptance model in health informatics. Appl Clin Inform. Jul 15, 2018;9(3):604-634. [ FREE Full text ] [ CrossRef ] [ Medline ]

Abbreviations

Edited by A Mavragani; submitted 02.10.23; peer-reviewed by A Sestino, S Oh, J Alpert; comments to author 09.03.24; revised version received 20.03.24; accepted 14.05.24; published 04.07.24.

©Ryan Tennant, Sana Allana, Kate Mercer, Catherine M Burns. Originally published in JMIR Formative Research (https://formative.jmir.org), 04.07.2024.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Formative Research, is properly cited. The complete bibliographic information, a link to the original publication on https://formative.jmir.org, as well as this copyright and license information must be included.

7 Simple Ways to Make Money from Home in 2024

In today’s digital age, the opportunity to earn money from home has become increasingly accessible. With the right strategies and tools, anyone can create a steady income without leaving their home. Here are seven simple ways to make money from home in 2024, all of which are legal and legitimate.

1. Free Cloud Mining with GDMining

What is cloud mining.

Cloud mining is a process where you can mine cryptocurrencies without owning or maintaining any hardware. Instead, you rent mining power from a company that operates mining farms with specialized hardware. This allows you to participate in cryptocurrency mining without the technical know-how or the upfront costs of purchasing mining equipment.

How Can You Profit from Cloud Mining ?

By investing in a cloud mining contract, you essentially buy a portion of the mining power provided by the mining farm. The mining profits generated from this power are then shared with you. The returns depend on factors like the cryptocurrency mined, market prices, and the efficiency of the mining operation.

Why Choose GDMining ?

GDMining is one of the world’s leading cloud mining platforms. Known for its reliability and user-friendly interface, GDMining offers a variety of mining plans to cater to different investment levels. One of the platform’s biggest advantages is offering free cloud mining contracts. Upon successful registration, each user receives a $50 bonus , which can be used to participate in free cloud mining and earn daily profits.

2. Freelancing

Freelancing is an excellent way to monetize your skills and expertise. Platforms like Upwork, Fiverr, and Freelancer connect freelancers with clients worldwide. Whether you are a writer, designer, developer, or marketer, there’s a market for your skills. The flexibility of freelancing allows you to set your rates and work hours, making it a popular choice for many.

3. Online Tutoring

If you have expertise in a particular subject, online tutoring can be a rewarding way to earn money. Websites like VIPKid, Chegg Tutors, and Tutor.com offer platforms where you can teach students of all ages. This can be particularly lucrative for subjects like math, science, and languages.

4. Selling Handmade Goods

Platforms like Etsy provide a marketplace for selling handmade goods. Whether you create jewelry, crafts, clothing, or art, you can reach a global audience. The key to success on platforms like Etsy is to offer unique, high-quality products and excellent customer service.

5. Dropshipping

Dropshipping is an e-commerce model that allows you to sell products without holding any inventory. You set up an online store, list products from suppliers, and when an order is placed, the supplier ships the product directly to the customer. This method minimizes risk and investment, making it a popular choice for entrepreneurs. Shopify and WooCommerce are excellent platforms to start your dropshipping business.

6. Content Creation

Creating content for platforms like YouTube, TikTok, and Instagram can be highly profitable. By building a substantial following, you can earn money through ad revenue, sponsorships, and merchandise sales. Consistency and creativity are key to growing your audience and monetizing your content.

7. Online Surveys and Market Research

Participating in online surveys and market research can be an easy way to make some extra cash. Websites like Swagbucks, Survey Junkie, and Vindale Research pay users for their opinions on various products and services. While this won’t make you rich, it’s a simple way to earn money in your spare time.

Earning money from home has never been easier with the array of opportunities available today. Whether through cloud mining with GDMining , freelancing, online tutoring, or any of the other methods listed, you can find a way to generate income that suits your skills and lifestyle. The key is to start with a reliable and legitimate platform, be consistent, and keep exploring new opportunities. ​

Disclaimer:  The views and opinions presented in this article do not necessarily reflect the views of CoinCheckup. The content of this article should not be considered as investment advice. Always do your own research before deciding to buy, sell or transfer any crypto assets. Past returns do not always guarantee future profits.

Previous Post Best Ethereum Mining Apps for Android – Can You Earn ETH on Your Phone?

Next post meme mania: mbappé’s euros performance sparks a surge in mpeppe (mpepe), related posts.

Earn and Stake $STREAM Tokens for Rewards on Streamable Finance

Crypto Craze: Will Bonk or Mpeppe (MPEPE) Be the Ultimate Digital Asset With 3000x Potential

Investors Choose Mpeppe (MPEPE) Over Others as Polygon (MATIC) Enthusiasm Grows

Trading and investing in digital assets is highly speculative and comes with many risks. The analysis / stats / articles on CoinCheckup.com are for informational purposes and should not be considered investment advice. Statements and financial information on CoinCheckup.com should not be construed as an endorsement or recommendation to buy, sell or hold. Please do your own research on all of your investments carefully. Scores are based on common sense Formulas that we personally use to analyse crypto coins & tokens. We’ll open source these formulas soon. Past performance is not necessarily indicative of future results.  Read the full disclaimer here . Over here you’ll find our privacy policy and cookies policy .

• Crypto Prices
• Predictions
• Best Crypto to Buy Now
• Best Crypto to Buy For Long-Term
• Next Crypto to Explode
• Best Crypto For Day Trading
• Best Crypto Hardware Wallets
• Best Metal Crypto Wallets
• Best Crypto Arbirage Scanners
• Crypto News
• Price Analysis

This paper is in the following e-collection/theme issue:

Published on 4.7.2024 in Vol 26 (2024)

Self-Management Using eHealth Technologies for Liver Transplant Recipients: Scoping Review

Authors of this article:

• Soo Hyun Kim 1 , MSN   ; 
• Kyoung-A Kim 2 , PhD   ; 
• Sang Hui Chu 3 , PhD   ; 
• Hyunji Kim 4 , MSN   ; 
• Dong Jin Joo 5 , MD   ; 
• Jae Geun Lee 5 , MD   ; 
• JiYeon Choi 6 , PhD  

1 School of Nursing, Johns Hopkins University, Baltimore, MD, United States

2 College of Nursing, Suwon Women's University, Suwon, Republic of Korea

3 College of Nursing, Mo-Im Kim Nursing Research Institute, Yonsei University, Seoul, Republic of Korea

4 School of Nursing, Yale University, Orange, CT, United States

5 Department of Surgery, College of Medicine, Yonsei University, Seoul, Republic of Korea

6 College of Nursing, Mo-Im Kim Nursing Research Institute, Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, Republic of Korea

Corresponding Author:

JiYeon Choi, PhD

College of Nursing, Mo-Im Kim Nursing Research Institute, Institute for Innovation in Digital Healthcare, Yonsei University

50-1 Yonsei-ro, Seodaemun-gu

Seoul, 03722

Republic of Korea

Phone: 82 2 2228 3301

Fax:82 2 2227 8303

Email: [email protected]

Background: Liver transplantation has become increasingly common as a last-resort treatment for end-stage liver diseases and liver cancer, with continually improving success rates and long-term survival rates. Nevertheless, liver transplant recipients face lifelong challenges in self-management, including immunosuppressant therapy, lifestyle adjustments, and navigating complex health care systems. eHealth technologies hold the potential to aid and optimize self-management outcomes, but their adoption has been slow in this population due to the complexity of post–liver transplant management.

Objective: This study aims to examine the use of eHealth technologies in supporting self-management for liver transplant recipients and identify their benefits and challenges to suggest areas for further research.

Methods: Following the Arksey and O’Malley methodology for scoping reviews, we conducted a systematic search of 5 electronic databases: PubMed, CINAHL, Embase, PsycINFO, and Web of Science. We included studies that (1) examined or implemented eHealth-based self-management, (2) included liver transplant recipients aged ≥18 years, and (3) were published in a peer-reviewed journal. We excluded studies that (1) were case reports, conference abstracts, editorials, or letters; (2) did not focus on the posttransplantation phase; (3) did not focus on self-management; and (4) did not incorporate the concept of eHealth or used technology solely for data collection. The quality of the selected eHealth interventions was evaluated using (1) the Template for Intervention Description and Replication guidelines and checklist and (2) the 5 core self-management skills identified by Lorig and Holman.

Results: Of 1461 articles, 15 (1.03%) studies were included in the final analysis. Our findings indicate that eHealth-based self-management strategies for adult liver transplant recipients primarily address lifestyle management, medication adherence, and remote monitoring, highlighting a notable gap in alcohol relapse interventions. The studies used diverse technologies, including mobile apps, videoconferencing, and telehealth platforms, but showed limited integration of decision-making or resource use skills essential for comprehensive self-management. The reviewed studies highlighted the potential of eHealth in enhancing individualized health care, but only a few included collaborative features such as 2-way communication or tailored goal setting. While adherence and feasibility were generally high in many interventions, their effectiveness varied due to diverse methodologies and outcome measures.

Conclusions: This scoping review maps the current literature on eHealth-based self-management support for liver transplant recipients, assessing its potential and challenges. Future studies should focus on developing predictive models and personalized eHealth interventions rooted in patient-generated data, incorporating digital human-to-human interactions to effectively address the complex needs of liver transplant recipients. This review emphasizes the need for future eHealth self-management research to address the digital divide, especially with the aging liver transplant recipient population, and ensure more inclusive studies across diverse ethnicities and regions.

Introduction

As the last treatment resort for individuals with end-stage liver diseases or liver cancer [ 1 ], liver transplantation (LT) has become one of the fastest-growing solid organ transplant procedures worldwide. Since its first case in 1963, LT has evolved into a more viable treatment option for those living with end-stage liver conditions. In the United States, >9000 individuals receive LTs annually [ 2 ]. In South Korea, the number of LT cases increased from 1066 in 2010 to 1515 in 2021 [ 3 ]. Over the past decades, there has been notable progress in the success of LT surgery and long-term survival rates [ 4 ]. In the United States, the 1-year survival rate reached 89%, and the 5-year survival rate is >74%, although variations exist depending on donor types, underlying diagnoses, recipient age, and region [ 5 ].

Despite the improving trend of posttransplant survival, optimizing the benefits of LT remains a complex and challenging issue for LT recipients. Research on post-LT outcomes to date has primarily focused on graft function and overall survival, corresponding to rapidly advancing surgical techniques and drug development [ 6 ]. Relatively little attention has been paid to promoting posttransplant self-management and its impact on long-term quality of life (QOL) [ 7 ]. After transplant, LT recipients must manage risks of complications, such as intestinal adhesion, bleeding, and bile leakages, and maintain a balance between graft failure risks and the side effects of immunosuppressant therapy, which often necessitate frequent dosage changes [ 8 , 9 ]. Additional lifelong challenges include management of common side effects of immunosuppressant therapy, such as hyperlipidemia, high blood pressure, chronic kidney failure, obesity, diabetes, and infection [ 10 , 11 ].

To address these challenges and maximize the benefits of LT, vigilant posttransplant self-management is crucial. Self-management has been defined in the literature as a comprehensive process that encompasses focusing on one’s illness needs (eg, acquiring knowledge and skills, monitoring symptoms, problem-solving, and decision-making), using available resources, building partnerships with health care providers (HCPs), and integrating illness management into daily life [ 12 - 14 ]. For LT recipients, major self-management issues include symptom monitoring, medication management, and engaging in healthy lifestyles after transplant [ 15 - 17 ]. Furthermore, LT recipients must navigate complex health care systems, face changes in social roles, and cope with uncertainty and mental distress associated with the ever-present risk of graft rejection [ 18 ]. During the COVID-19 pandemic, with reduced human contact support and the strained health care systems reallocating resources, self-management became more challenging for immunocompromised individuals such as LT recipients [ 19 ]. However, the increased accessibility to the internet and digital devices, coupled with the challenges posed by the pandemic, has rapidly escalated interest in interventions using the internet to promote or manage health (eHealth). These technologies hold the potential to overcome challenges related to resource allocation, geographical accessibility, and health care cost.

eHealth, defined as the use of the internet and communication technologies to deliver and improve health care services [ 20 ], has been rapidly expanding to promote self-management in acute and chronic conditions [ 21 - 23 ]. However, the application of eHealth for LT recipients has been relatively slow due to the complexity of LT management, the need for close physical examinations, and the importance of building rapport with HCPs for lifelong posttransplant care [ 24 ]. Although there have been studies investigating the application of eHealth among solid organ transplant recipients [ 25 , 26 ], to date, no review has specifically focused on eHealth for self-management support in LT recipients. Therefore, this study aimed to map the current state of the literature on self-management using eHealth technologies for LT recipients and assess their benefits and challenges to suggest areas needing further investigation in the field.

Goal of This Study

This review aimed to examine the current literature on eHealth-based self-management among adult LT recipients and its associated factors by addressing the following questions: (1) what are the characteristics and associated factors of eHealth strategies in the adult LT recipient population? (2) how effective and feasible are eHealth-based self-management interventions after LT? and (3) what are the future potential and challenges of eHealth in facilitating self-management among this population? By mapping the existing literature through this scoping review, we aimed to identify gaps and propose future directions for the development and application of eHealth-based self-management interventions for adult LT recipients.

Study Design

We conducted a scoping review based on the 6-stage scoping review framework by Arksey and O’Malley [ 27 ]. This methodology was chosen to examine the breadth and depth of knowledge in an emerging field of research. We used the population, concept, and context criteria to devise the research question for this review: adult LT recipients (population), eHealth (concept), and facilitating self-management (context) [ 28 ]. Given that previous studies on self-management among LT recipients have primarily concentrated on medication adherence, alcohol recidivism, and healthy lifestyle maintenance [ 15 ], our review specifically focused on these areas of self-management.

Databases and Search Terms

The search and screening procedure of this scoping review adhered to the guidelines provided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. We systematically searched 5 electronic databases: PubMed, CINAHL, Embase, PsycINFO, and Web of Science. The search terms comprised a combination of the following: adult LTR , e-Health , and self-management . Our concept of eHealth encompasses a range of technology, including telehealth and internet-, computer-, or mobile-based health, and strategies using video, audio, SMS text messaging, wearables, and virtual reality. To conduct the search on self-management, we included and modified terms such as alcohol , nutrition , exercise , physical activity , medication , medication adherence , self-care , self-management , and health behavior . Our search spanned inception to June 19, 2023, without any restrictions on specific study design. We validated our search strategies through consultation with a university librarian and present the detailed search strategies in Multimedia Appendix 1 .

Inclusion and Exclusion Criteria

Articles were included if they were studies that (1) examined or implemented eHealth-based self-management, (2) included LT recipients aged ≥18 years, and (3) were published in a peer-reviewed journal. We excluded studies that (1) were case reports, conference abstracts, editorials, or letters; (2) did not focus on the posttransplantation phase; (3) did not focus on self-management; and (4) did not incorporate the concept of eHealth or solely used technology for the purpose of data collection. We also considered studies that targeted various solid organ transplant recipients provided they included adult LT recipients. Our review specifically targeted adult patients in the post-LT phase as LT in children often involves dissimilar underlying conditions for transplant, such as biliary atresia [ 29 ], and post-LT self-management in pediatric patients may present additional challenges related to life stage development.

Article Selection

A total of 1460 articles were identified. After removing duplicates (51/1460, 3.49%), 1409 articles were imported to Microsoft Excel (Microsoft Corp) for screening using the inclusion and exclusion criteria. First, 2 authors (SHK and HK) independently screened the titles and excluded 95.95% (1352/1409) of the articles, which did not include LT recipients or were not about eHealth or self-management (eg, drug trials and surgery). This yielded 57 articles. In the second stage, 2 authors independently reviewed the abstracts of the 57 articles. Finally, a full-text review was conducted on 42% (24/57) of the articles. The references of the selected articles were manually examined to search for additional articles that could be eligible for this review. Consequently, 1 article was added through the manual search. A total of 15 articles were included in the final sample. The whole process was supervised by the corresponding author, and disagreements between authors were discussed in research team meetings until a consensus was reached. Figure 1 illustrates the PRISMA flow diagram.

Data Analysis

Due to the heterogeneity of the interventions and measured outcomes, a meta-analysis or meta-synthesis of the results was not feasible. Instead, we presented the organized data in tables, which include the summaries of the descriptive and intervention studies and a detailed summarization of the interventions.

The following information was extracted using data-charting forms: first author’s last name, publication year, country, study design, sample characteristics (sample size, average age, percentage of male individuals, and time since transplant), type of technology, variables with measures, and outcomes. For intervention studies, we analyzed the details of the intervention and control groups and extracted the following characteristics of the interventions: duration, providers, adherence, adverse events, and reasons for attrition.

We also evaluated the quality of the interventions reported in these studies using the Template for Intervention Description and Replication (TIDieR) checklist and guide [ 30 ]. The TIDieR checklist and guide address the items of interventions that need to be thoroughly described to enhance the replicability of trials and facilitate the appraisal of intervention reporting. To gauge the comprehensiveness of intervention content, we analyzed whether the interventions addressed the 5 core self-management skills identified by Lorig and Holman [ 14 ]. These core skills, which include problem-solving, decision-making, using resources, partnering with HCPs, and taking action, have been considered as fundamental elements of self-management in the literature that examines the definitions, components, and processes of self-management [ 12 , 13 , 31 , 32 ].

Ethical Considerations

No ethics approval was required for this scoping review as published articles rather than primary data were used in the analysis.

Study Characteristics

The general characteristics of the 5 descriptive studies and 10 intervention studies are summarized in Tables 1 - 4 . Of the 5 descriptive studies, 2 (40%) were qualitative and 3 (60%) were quantitative studies. Of the 10 intervention studies, 4 (40%) were randomized controlled trials (RCTs), 4 (40%) were prospective observational studies with cohorts, 1 (10%) was a study with a historical control group, and 1 (10%) was a single-group qualitative evaluation of a feasibility study. A total of 67% (10/15) of the studies were published in 2020 or later, with all studies (15/15, 100%) being published after 2016. Most studies were conducted in North America (7/15, 47% in the United States and 1/15, 7% in Canada) and Europe (1/15, 7% in Austria; 2/15, 13% in Belgium; and 1/15, 7% in Spain). The sample sizes of the selected studies varied, ranging from 19 to 710 participants, with the average age of the participants ranging from 46 to 63 years.

a KTR: kidney transplant recipient.

b LTR: liver transplant recipient.

c SOT: solid organ transplant.

a LT: liver transplant.

b HCP: health care provider.

c eHEALS: eHealth Literacy Scale.

d KTR: kidney transplant recipient.

e LTR: liver transplant recipient.

f PA: physical activity.

g SOT: solid organ transplant.

h IHT: interactive health technology.

i ICT: information and communications technology.

a RCT: randomized controlled trial.

b IG: intervention group.

c CG: control group.

a Not applicable.

d MEDAS: Mediterranean Diet Adherence Screener.

e QOL: quality of life.

f SF-12: 12-item Short Form Health Survey.

g MetSSS: Metabolic Syndrome Severity Score.

h MCS-12: Mental Component Summary–12 (vitality, social functioning, role limitations due to emotional health, and mental health).

i CDSS: clinical decision support system.

j THMP: telemedicine-based home management program.

k SF-36: 36-item Short Form Health Survey.

l LTR: liver transplant recipient.

m CV: intrapatient variability.

n BMQ: Beliefs About Medicines Questionnaire.

o MMAS-8: Morisky Medication Adherence Scale-8.

p IAT: immunosuppression assessment test.

Intervention Characteristics

Tables 5 and 6 summarize the details of the interventions reported in the selected studies. The most frequently addressed aspect of self-management was lifestyle education (6/10, 60%). Other topics of the interventions, allowing for overlap, included telemedicine-based remote monitoring (4/10, 40%) and medication management (3/10, 30%). The technological methods to deliver the interventions varied, including mobile apps (4/10, 40%; one of which included a wearable app), a 2-way videoconference portal (3/10, 30%), a web-based platform (1/10, 10%), Bluetooth peripherals (2/10, 20%), and a robot (1/10, 10%). The duration of the interventions ranged from short term (2 weeks after transplantation) to long term (up to 2 years after transplantation), with most (6/10, 60%) lasting 12 weeks.

Among the 6 studies that involved lifestyle interventions, 3 (50%) used synchronous video streaming to deliver exercise or diet educational sessions [ 38 , 39 , 43 ]. A total of 33% (2/6) of the studies offered mobile apps, with 17% (1/6) of the studies encompassing both lifestyle education and medication management [ 44 ]. The latter study provided information on self-management issues and allowed patients to self-document in a patient diary [ 44 ]. Another study provided a wearable accelerometer app, which was paired with financial incentives and questions regarding health engagement available on a patient portal [ 46 ]. A total of 40% (4/10) of the studies used telehealth to remotely monitor recipients’ vital signs and blood glucose levels [ 40 , 42 , 43 ] and conduct postoperative management regarding medication, gastrointestinal function, wound care, and laboratory test results [ 41 - 43 ]. For remote monitoring via telehealth, daily vital signs were collected using Bluetooth devices [ 40 , 42 ] or a robot [ 43 ].

In terms of medication management, 30% (3/10) of the studies used mobile app interventions that emphasized scheduled immunosuppressant intake [ 44 , 45 , 47 ]. These interventions used methods such as QR codes, reminder systems, and access to various resources (eg, medication and dose converter, medication lists) to facilitate medication adherence. In addition, 10% (1/10) of the studies, which delivered a telemedicine-based remote program, also monitored laboratory test results using an alarm system of predefined thresholds [ 41 ].

a IG: intervention group.

b CDSS: clinical decision support system.

a TIDieR: Template for Intervention Description and Replication.

b Not applicable.

c IG: intervention group.

d CG: control group.

Intervention Reporting and Comprehensiveness

On the basis of the TIDieR guide, the included intervention studies’ scores ranged from 6 to 10 ( Tables 5 and 6 ). Detailed scores for each criterion can be found in Multimedia Appendix 2 [ 38 - 47 ]. All studies described the content and procedure of interventions, the type of technology used, and the locations where they were implemented. Of the 10 studies, 7 (70%) reported the duration and doses of the interventions, and 6 (60%) included the providers of the interventions. Personalized interventions were delivered to participants in 30% (3/10) of the studies. A total of 30% (3/10) of the studies included strategies or assessments to improve intervention fidelity, whereas 70% (7/10) of the studies monitored the adherence and fidelity of the delivered interventions. No intervention study reported any unforeseen changes in the interventions during the study process.

Table 7 shows how the selected interventions addressed the 5 core self-management skills identified by Lorig and Holman [ 14 ]. Of the 10 interventions, 4 (40%) included training in all 5 self-management skills. The number of core skills included in other studies ranged from 1 to 3. Taking action was a component in all interventions (10/10, 100%). Partnering with health care providers was featured in 80% (8/10) of the interventions, whereas Problem-solving was included in 70% (7/10) of the interventions. Decision-making was part of 60% (6/10) of the interventions, and Using resources was the least included, addressed in 50% (5/10) of the interventions.

a Reported.

b Not reported.

Study Outcomes

The use of and preferences regarding eHealth technologies were the most commonly examined outcomes in the descriptive studies. Study results concerning the use of technologies and its correlation with educational level and age varied. In the qualitative study by Lieber et al [ 33 ], 90% of the 20-person LT recipient sample reported using smartphones. In contrast, in the study by Vanhoof et al [ 36 ], only 27.9% of 122 solid organ transplant recipients owned a smartphone despite >70% having access to a computer with internet connection.

Concerning educational characteristics, 40% (2/5) of the studies found that individuals with college-level education or higher demonstrated greater eHealth literacy and more frequent use of the web patient portal than those with a high school education or lower [ 34 , 37 ]. Conversely, the study by Vanhoof et al [ 36 ] indicated that the group with a college education and higher had lower technology acceptance than those with a high school education or lower. Regarding age, younger patients had higher eHealth literacy in one study [ 34 ]. Another study found that those with previous experience using health apps, as well as those who tried the new app, had a younger average age than that of the entire cohort [ 44 ]. However, age was not a substantial factor in the willingness to use health technologies or patient portals in another 40% (2/5) of the studies [ 36 , 37 ]. Previous or routine use of health technologies was associated with higher eHealth literacy [ 34 ] and greater technology acceptance [ 36 ].

Moreover, 40% (2/5) of the studies highlighted that patients currently used smartphones or patient portals for reminders to take medications or to view laboratory test results. However, their preferences for future eHealth technologies extended beyond these uses. They expressed interest in connecting through web-based platforms with peer recipients and HCPs and gaining access to additional supportive features that included educational resources, medication management tools, and reward systems that consider affordability [ 33 , 35 ].

The most frequently measured outcomes in the intervention studies were adherence to the intervention and feasibility. A total of 80% (8/10) of the studies reported intervention adherence using various methods, including session attendance, device use frequency, response rate, and monitoring rate [ 38 - 42 , 44 - 46 ]. In 62% (5/8) of these studies, the overall adherence rate was >70% despite variability in measures [ 32 , 40 - 42 , 46 ]. Feasibility was measured using various methods, including qualitative interviews; recruitment rates; attendance rates; initiation and continuation rates; and reported levels of adequacy, confidence, effectiveness, or satisfaction [ 38 - 41 ]. Although rates of recruitment, attendance, initiation, and continuation varied between studies, the interventions were generally well received. Participant-reported satisfactory scores were >80% in 20% (2/10) of the studies [ 40 , 41 ], and participant-reported adequacy, confidence, and effectiveness levels were >90% in 30% (3/10) of the studies [ 39 - 41 ]. In a qualitative study, participants expressed that perceived burdens of face-to-face care were reduced regarding travel, time, or pressure and that confidence level in exercise increased due to tailored and self-directed telehealth education sessions [ 38 ].

A total of 4 studies involving telemedicine-based remote monitoring included 30- or 90-day readmission rates (n=3, 75%) and QOL (n=2, 50%) as outcomes. Regarding readmission rates, all studies reported a decrease in readmission rates after the interventions, 20% (2/10) of which were RCTs that reported a significant reduction in readmission rates [ 40 , 42 , 43 ]. A total of 20% (2/10) of the studies reported improvement in varying components of QOL, such as mental and physical function and general health [ 39 , 42 ].

Due to the heterogeneity of the interventions, various clinical outcomes were measured, such as dietary or medication adherence, weight change, level of metabolic syndrome, and tacrolimus drug level. Among the studies that incorporated mobile app interventions for medication management, the study by Melilli et al [ 45 ] reported that correct dose intakes on schedule occurred 69% to 76% of the time among the regular users of the delivered mobile app, whereas the study by Zanetti-Yabur et al [ 47 ] reported no difference in medication adherence on a validated scale between the intervention and control groups. Positive results on dietary adherence and metabolic syndrome were reported on a telehealth-delivered diet and exercise education program [ 38 , 39 ], but there was no significant change in weight after a home-based exercise program using a wearable accelerometer [ 46 ]. In a study incorporating remote monitoring focused on laboratory test results, tacrolimus level determinations were higher and blood level concentrations remained lower in the intervention group [ 41 ]. Regarding the reporting of adverse events, most studies (8/10, 80%) did not provide specific descriptions. However, 20% (2/10) of the studies reported no adverse events during the intervention period [ 39 , 46 ].

Principal Findings

In this scoping review, we investigated the breadth of application and associated factors of eHealth-based self-management strategies in adult LT recipients. While previous literature on self-management among LT recipients has primarily focused on medication adherence, alcohol abstinence, and health maintenance (eg, smoking cessation, vaccination, and health screening) [ 15 ], the eHealth-based self-management studies in our review predominantly covered lifestyle management, medication adherence, and remote monitoring. Given the heterogeneity of the interventions and study measures, we assessed outcomes by describing trends, consistencies, or discrepancies among studies reporting similar outcomes. Although significant effects on reducing readmission rates or improving QOL were observed, synthesizing quantitative outcomes was not feasible due to a small number of RCTs. However, based on outcomes measured in various ways and participants’ qualitative reports, the interventions were well received, with generally high levels of feasibility, adherence, and satisfaction. The lifestyle management interventions used various modes of delivery, such as videoconferencing, web-based prerecorded videos, mobile apps, and patient portals. Remote monitoring was facilitated through a range of telehealth platforms, whereas interventions for medication adherence mainly used mobile apps. Notably, our review found that none of the eHealth-based self-management studies addressed the topic of prevention and management of alcohol relapse, a well-known concern among LT recipients [ 48 ].

Compared to intervention studies focusing on lifestyle management, the intervention studies focusing on medication adherence included relatively basic features, such as alarm reminders and logs for tracking medication intake. While these features target the action of medication taking, they fall short in promoting other essential skills such as decision-making or effective resource use to improve adherence to immunosuppressants. Given the complexity and variety of self-management behaviors required for LT recipients, eHealth technologies should be designed to support them in navigating multiple concurrent problematic situations to integrate disease management into their daily lives [ 15 ]. This objective extends beyond ensuring compliance with self-management behaviors and requires strategies to improve the self-efficacy of LT recipients and foster self-tailoring strategies [ 14 ]. This involves integrating their values, preferences, and readiness to increase motivation and confidence while also considering the various challenging scenarios that these LT recipients face, such as managing multiple medications due to comorbidities, coping with side effects, and handling varying schedules [ 9 ]. In interventions focused on lifestyle management and remote monitoring, features such as prerecorded or synchronous education sessions and platforms for asking questions and receiving answers were available. Such components could be beneficial in improving immunosuppressant adherence. In addition, incorporating elements such as role-play and quizzes that reflect challenging medication-taking scenarios along with web-based chatbots developed using frequently asked question algorithms and supplemented with emergency hotlines could enhance the decision-making and resource engagement skills of LT recipients.

While most of the reviewed studies (12/15, 80%) referred to the potential of eHealth in enhancing collaborative and individualized health care, only 33% (5/15) of them featured 2-way communication, and just 20% (3/15) incorporated personalized prescriptions or tailored goal setting. Videoconferencing emerged as the most common method for 2-way communication and building personalized strategies. Regular web-based meetings with HCPs or coaches and facilitators during these sessions can be effective, offering benefits such as reinforcing socially desirable behaviors; increasing accountability through clear, reciprocal goals and expectations; and enhancing interpersonal connectedness through support and feedback [ 49 ]. In addition, collaborative goal-setting strategies tailored to individual needs have been reported as effective in posttransplant recovery by acknowledging the variability in posttransplant health level, strength, and capacity among LT recipients [ 50 ]. The interest of LT recipients in connecting with peer recipients web-based also indicates a need for incorporating peer support groups to foster higher motivation and interpersonal connectedness [ 33 ].

In contrast, the studies that scored the lowest on the core self-management skills included minimal human collaborative elements such as communication or education sessions with HCPs [ 41 , 45 , 47 ]. These interventions primarily leveraged eHealth for its advantages in reducing labor-intensive tasks, enabling immediate evaluations, and improving accessibility while reducing exposure to infection sources [ 24 , 51 , 52 ] but overlooked the value of human support. Previous findings have suggested that digital person-to-person components can significantly improve effectiveness and adherence in eHealth interventions [ 49 , 53 ]. The selected interventions with lower levels of guidance and support included phone calls or SMS text messaging. However, assessing the relationship between the level of human support and postintervention outcomes was not feasible due to the heterogeneity of intervention strategies and the lack of clear causality between specific strategies and outcomes. Although it has been demonstrated that eHealth interventions with feedback channels are generally more effective than those without [ 49 ], further research is warranted to understand how the directiveness, interactivity, and immediacy of feedback impact the effectiveness of these interventions for sustainable behavior change in LT recipients with complex self-management needs.

In exploring untapped benefits of eHealth among the reviewed studies, we suggest that future research focus on developing predictive models and tailored interventions based on patient-generated data. The potential for creating algorithms to identify behavior patterns could be promising for personalized management or decision support systems. For instance, algorithms analyzing medication-taking logs could proactively identify individuals at risk, enabling more intensive monitoring to prevent medication errors or nonadherence [ 9 ]. The capacity of eHealth to collect extensive patient information remotely and conveniently should be maximized to create personalized management plans. By leveraging advanced data analysis and machine learning techniques, coupled with the incorporation of the preferences, needs, and circumstances of LT recipients, there is potential for a more sophisticated, patient-centered design of self-management interventions.

Another critical consideration when developing and implementing eHealth interventions is the age of the LT recipient population. Notably, in 87% (13/15) of the reviewed studies, the average age among the LT recipients was >50 years. Older age has been identified as contributing to the digital divide [ 54 , 55 ], potentially affecting the ability and access of LT recipients to self-management support using eHealth technologies [ 56 , 57 ]. While the proportion of LT recipients aged ≥65 years has increased in the past decade [ 58 ], research on older LT recipients has primarily revolved around graft function and long-term survival [ 59 , 60 ]. This indicates a need for further research addressing self-management and QOL in this demographic group [ 59 , 61 ]. The digital literacy of older adults should be assessed as a potential influential factor in eHealth self-management intervention studies [ 62 ]. The study by Andrä et al [ 44 ] examined the variability in mobile device use and usability with age as a key factor in the discrepancy between patients interested in the mobile app and those who actually used it. The study recommended a longer trial period and repeated training for the older individuals [ 44 ]. Moreover, intervention designs should accommodate older users or those with limited digital literacy. This could involve simplifying interfaces, using intuitive features, and providing clear instructions or support to aid their understanding and use of technology.

Furthermore, there is a pressing need for more studies on eHealth use and self-management outcomes among diverse ethnic groups and regions worldwide. The LT recipients in our review were primarily from North America and Europe, which does not proportionately represent the increasing number of LTs in many Asian countries. While the reviewed descriptive studies did not cover a wide array of eHealth-related characteristics, future studies examining the relationship between the digital divide and social determinants—such as ethnicity, educational level, economic status, health care access, and community resources among LT recipients—should consider the variability across different countries and regions. Such research would more accurately reflect the current global situation of LT recipients and validate the effects of eHealth in this population.

Limitations

This review has several limitations. First, as we searched for articles explicitly including terms related to self-management based on previous literature on self-management among LT recipients, it is possible that articles including nuanced aspects of self-management were excluded. Second, it should be considered that the samples of the studies in this review comprised relatively old individuals as our review specifically focused on adult LT recipients. Thus, caution should be exercised when interpreting findings as age may influence adherence and self-management outcomes. As adherence and self-management needs significantly differ across developmental stages, future reviews focusing on younger populations are warranted. Third, this review included only studies published in English. Therefore, we may have missed relevant studies published in non-English languages, which should be considered with our finding related to the disproportional geographical distribution of the studies. Finally, it was inherently challenging to stratify and compare results for a detailed synthesis because this scoping review involved a small number of studies with heterogeneous designs, aims, and contents. Consistent with the purpose of the scoping review approach [ 63 ], our focus was on providing an overall mapping of the identified literature in this topic area rather than conducting an in-depth comparison of quantitative findings. Because the topic of eHealth interventions for self-management after LT is in its infancy but rapidly evolving, analyzing the replicability of the interventions to date using the TIDieR checklist may provide better insights for researchers and clinicians interested in further advancing this topic area. We suggest that future reviews prioritize analyzing the effectiveness of eHealth-based self-management interventions on various health outcomes and examine the interactions of social determinant factors as more evidence becomes available.

Conclusions

This scoping review has highlighted the significant potential and emerging challenges of eHealth-based self-management strategies for LT recipients. The reviewed studies predominantly focused on lifestyle management, medication adherence, and remote monitoring. However, there is a noticeable gap in eHealth research concerning alcohol recidivism and the psychosocial and cognitive dimensions of progressing and evaluating self-management (eg, self-efficacy and self-regulation). Future research should aim to develop tailored eHealth interventions that encompass multifaceted elements of self-management skills. These interventions should not only leverage the benefits of technology but also incorporate digital human-to-human interactions to adequately address the complex needs of LT recipients. In addition, ensuring inclusive and equitable self-management support requires addressing the challenges of digital literacy, catering to the unique needs of older LT recipients, and considering the sociocultural contexts of LT recipients from diverse geographic regions.

Acknowledgments

This research was supported by the National Research Foundation of Korea funded by the Ministry of Education (2022R1I1A2053635; JC); the Institute for Innovation in Digital Healthcare, Yonsei University (JC); the Mo-Im Kim Nursing Research Institute (SHC and JC); and the Multidisciplinary Research Fund (6-2021-0199; SHC and JC) and Faculty Research Fund (6-2021-0177; SHC and JC) from Yonsei University College of Nursing. The authors used ChatGPT (OpenAI) [ 64 ] for grammar and language correction.

Authors' Contributions

JC and SHC conceptualized and supervised the study. JC, SHK, and SHC developed the methodology. SHK and HK screened the studies and performed the formal analysis. SHK and KK performed the validation. JC, SHK, KK, SHC, DJJ, and JGL wrote, reviewed, and edited the manuscript. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

None declared.

Summary of database search strategies.

Detailed scores according to the Template for Intervention Description and Replication checklist for the selected intervention studies.

• Maynard E. Liver transplantation: patient selection, perioperative surgical issues, and expected outcomes. Surg Clin North Am. Feb 2019;99(1):65-72. [ CrossRef ] [ Medline ]
• National data. Organ Procurement & Transplantation Network. URL: https://optn.transplant.hrsa.gov/data/view-data-reports/national-data [accessed 2024-01-06]
• 2020 Organ transplant cohort KOTRY annual report. Korean Organ Transplantation Registry. Jan 05, 2022. URL: http://www.kotryfoundation.org/rang_board/list.html?num=176&code=mem_ref [accessed 2024-01-06]
• Black CK, Termanini KM, Aguirre O, Hawksworth JS, Sosin M. Solid organ transplantation in the 21st century. Ann Transl Med. Oct 2018;6(20):409. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Kim WR, Lake JR, Smith JM, Schladt DP, Skeans MA, Harper AM, et al. OPTN/SRTR 2016 annual data report: liver. Am J Transplant. Jan 2018;18 Suppl 1:172-253. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Watt KD. Keys to long-term care of the liver transplant recipient. Nat Rev Gastroenterol Hepatol. Nov 2015;12(11):639-648. [ CrossRef ] [ Medline ]
• Yang LS, Shan LL, Saxena A, Morris DL. Liver transplantation: a systematic review of long-term quality of life. Liver Int. Oct 2014;34(9):1298-1313. [ CrossRef ] [ Medline ]
• Ho MC, Wu YM, Hu RH, Ko WJ, Ni YH, Chang MH, et al. Surgical complications and outcome of living related liver transplantation. Transplant Proc. Oct 2004;36(8):2249-2251. [ CrossRef ] [ Medline ]
• Neuberger J, Bechstein W, Kuypers D, Burra P, Citterio F, De Geest S, et al. Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the consensus on managing modifiable risk in transplantation (COMMIT) group. Transplantation. Apr 2017;101(4S Suppl 2):S1-56. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Dhanasekaran R. Management of immunosuppression in liver transplantation. Clin Liver Dis. May 2017;21(2):337-353. [ CrossRef ] [ Medline ]
• Drent G, Moons P, De Geest S, Kleibeuker JH, Haagsma EB. Symptom experience associated with immunosuppressive drugs after liver transplantation in adults: possible relationship with medication non-compliance? Clin Transplant. 2008;22(6):700-709. [ CrossRef ] [ Medline ]
• Schulman-Green D, Jaser S, Martin F, Alonzo A, Grey M, McCorkle R, et al. Processes of self-management in chronic illness. J Nurs Scholarsh. Jun 2012;44(2):136-144. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Van de Velde D, De Zutter F, Satink T, Costa U, Janquart S, Senn D, et al. Delineating the concept of self-management in chronic conditions: a concept analysis. BMJ Open. Jul 16, 2019;9(7):e027775. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Lorig KR, Holman H. Self-management education: history, definition, outcomes, and mechanisms. Ann Behav Med. Aug 2003;26(1):1-7. [ CrossRef ] [ Medline ]
• Ko D, Muehrer RJ, Bratzke LC. Self-management in liver transplant recipients: a narrative review. Prog Transplant. Jun 2018;28(2):100-115. [ CrossRef ] [ Medline ]
• Vanhoof JM, Vandenberghe B, Geerts D, Philippaerts P, De Mazière P, DeVito Dabbs A, et al. Shedding light on an unknown reality in solid organ transplant patients' self-management: a contextual inquiry study. Clin Transplant. Aug 02, 2018;32(8):e13314. [ CrossRef ] [ Medline ]
• Serper M, Patzer RE, Reese PP, Przytula K, Koval R, Ladner DP, et al. Medication misuse, nonadherence, and clinical outcomes among liver transplant recipients. Liver Transpl. Jan 2015;21(1):22-28. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Moayed MS, Ebadi A, Khodaveisi M, Nassiri Toosi M, Soltanian AR, Khatiban M. Factors influencing health self-management in adherence to care and treatment among the recipients of liver transplantation. Patient Prefer Adherence. Nov 16, 2018;12:2425-2436. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Choudhury A, Varshney M, Sahoo B, Pamecha V, Sinha P, Patil NS, et al. Impact of covid-19 pandemic on quality of life and psychosocial difficulties among liver transplant recipients. J Family Med Prim Care. Feb 2022;11(2):744-750. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Eysenbach G. What is e-health? J Med Internet Res. 2001;3(2):E20. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Badawy SM, Cronin RM, Hankins J, Crosby L, DeBaun M, Thompson AA, et al. Patient-centered eHealth interventions for children, adolescents, and adults with sickle cell disease: systematic review. J Med Internet Res. Jul 19, 2018;20(7):e10940. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Liu S, Li J, Wan DY, Li R, Qu Z, Hu Y, et al. Effectiveness of eHealth self-management interventions in patients with heart failure: systematic review and meta-analysis. J Med Internet Res. Sep 26, 2022;24(9):e38697. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tistad M, Lundell S, Wiklund M, Nyberg A, Holmner Å, Wadell K. Usefulness and relevance of an ehealth tool in supporting the self-management of chronic obstructive pulmonary disease: explorative qualitative study of a cocreative process. JMIR Hum Factors. Oct 26, 2018;5(4):e10801. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Fix OK, Serper M. Telemedicine and telehepatology during the COVID-19 pandemic. Clin Liver Dis (Hoboken). May 21, 2020;15(5):187-190. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Duettmann W, Naik MG, Zukunft B, Osmonodja B, Bachmann F, Choi M, et al. eHealth in transplantation. Transpl Int. Jan 2021;34(1):16-26. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tang J, James L, Howell M, Tong A, Wong G. eHealth interventions for solid organ transplant recipients: a systematic review and meta-analysis of randomized controlled trials. Transplantation. Aug 2020;104(8):e224-e235. [ CrossRef ] [ Medline ]
• Arksey H, O'Malley L. Scoping studies: towards a methodological framework. Int J Soc Res Methodol. Feb 23, 2007;8(1):19-32. [ CrossRef ]
• Lockwood C, Dos Santos KB, Pap R. Practical guidance for knowledge synthesis: scoping review methods. Asian Nurs Res (Korean Soc Nurs Sci). Dec 2019;13(5):287-294. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Smith SK, Miloh T. Pediatric liver transplantation. Clin Liver Dis. Aug 2022;26(3):521-535. [ CrossRef ] [ Medline ]
• Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, et al. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ. Mar 07, 2014;348(mar07 3):g1687. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Grady PA, Gough LL. Self-management: a comprehensive approach to management of chronic conditions. Am J Public Health. Aug 2014;104(8):e25-e31. [ CrossRef ] [ Medline ]
• McCorkle R, Ercolano E, Lazenby M, Schulman-Green D, Schilling LS, Lorig K, et al. Self-management: enabling and empowering patients living with cancer as a chronic illness. CA Cancer J Clin. 2011;61(1):50-62. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Lieber SR, Kim HP, Baldelli L, Evon DM, Teal R, Nash R, et al. What liver transplant recipients want in a smartphone intervention to enhance recovery: prototype for the LiveRight transplant app. Liver Transpl. Apr 2021;27(4):584-589. [ CrossRef ] [ Medline ]
• Maroney K, Curtis LM, Opsasnick L, Smith KD, Eifler MR, Moore A, et al. eHealth literacy and web-based patient portal usage among kidney and liver transplant recipients. Clin Transplant. Feb 2021;35(2):e14184. [ CrossRef ] [ Medline ]
• Mathur S, Janaudis-Ferreira T, Hemphill J, Cafazzo JA, Hart D, Holdsworth S, et al. User-centered design features for digital health applications to support physical activity behaviors in solid organ transplant recipients: a qualitative study. Clin Transplant. Dec 2021;35(12):e14472. [ CrossRef ] [ Medline ]
• Vanhoof JM, Vandenberghe B, Geerts D, Philippaerts P, De Mazière P, DeVito Dabbs A, et al. Technology experience of solid organ transplant patients and their overall willingness to use interactive health technology. J Nurs Scholarsh. Mar 2018;50(2):151-162. [ CrossRef ] [ Medline ]
• Wedd J, Basu M, Curtis LM, Smith K, Lo DJ, Serper M, et al. Racial, ethnic, and socioeconomic disparities in web-based patient portal usage among kidney and liver transplant recipients: cross-sectional study. J Med Internet Res. Apr 22, 2019;21(4):e11864. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Barnett A, Campbell KL, Mayr HL, Keating SE, Macdonald GA, Hickman IJ. Liver transplant recipients' experiences and perspectives of a telehealth-delivered lifestyle programme: a qualitative study. J Telemed Telecare. Oct 2021;27(9):590-598. [ CrossRef ] [ Medline ]
• Hickman I, Hannigan A, Johnston H, Elvin-Walsh L, Mayr HL, Staudacher HM, et al. Telehealth-delivered, cardioprotective diet and exercise program for liver transplant recipients: a randomized feasibility study. Transplant Direct. Feb 04, 2021;7(3):e667. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Ertel AE, Kaiser TE, Abbott DE, Shah SA. Use of video-based education and tele-health home monitoring after liver transplantation: results of a novel pilot study. Surgery. Oct 2016;160(4):869-876. [ CrossRef ] [ Medline ]
• Koc Ö, Pierco M, Remans K, Van den Hende T, Verbeek J, Van Malenstein H, et al. Telemedicine based remote monitoring after liver transplantation: feasible in a select group and a more stringent control of immunosuppression. Clin Transplant. Jan 2022;36(1):e14494. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Lee TC, Kaiser TE, Alloway R, Woodle ES, Edwards MJ, Shah SA. Telemedicine based remote home monitoring after liver transplantation: results of a randomized prospective trial. Ann Surg. Sep 2019;270(3):564-572. [ CrossRef ] [ Medline ]
• Tian M, Wang B, Xue Z, Dong D, Liu X, Wu R, et al. Telemedicine for follow-up management of patients after liver transplantation: cohort study. JMIR Med Inform. May 17, 2021;9(5):e27175. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Andrä M, Sibinovic M, Pfeiffer K, Kniepeiss D. Implementation of a mobile application for outpatient care after liver transplantation. Digit Health. Dec 25, 2022;8:20552076221145855. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Melilli E, Cestone G, Revuelta I, Meneghini M, Lladó L, Montero N, et al. Adoption of a novel smart mobile-health application technology to track chronic immunosuppression adherence in solid organ transplantation: results of a prospective, observational, multicentre, pilot study. Clin Transplant. May 2021;35(5):e14278. [ CrossRef ] [ Medline ]
• Serper M, Barankay I, Chadha S, Shults J, Jones LS, Olthoff KM, et al. A randomized, controlled, behavioral intervention to promote walking after abdominal organ transplantation: results from the LIFT study. Transpl Int. Jun 2020;33(6):632-643. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Zanetti-Yabur A, Rizzo A, Hayde N, Watkins AC, Rocca JP, Graham JA. Exploring the usage of a mobile phone application in transplanted patients to encourage medication compliance and education. Am J Surg. Oct 2017;214(4):743-747. [ CrossRef ] [ Medline ]
• Shenoy A, Salajegheh A, Shen NT. Multimodal multidisciplinary management of alcohol use disorder in liver transplant candidates and recipients. Transl Gastroenterol Hepatol. Jul 25, 2022;7:28. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Santarossa S, Kane D, Senn CY, Woodruff SJ. Exploring the role of in-person components for online health behavior change interventions: can a digital person-to-person component suffice? J Med Internet Res. Apr 11, 2018;20(4):e144. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Dunn MA, Rogal SS, Duarte-Rojo A, Lai JC. Physical function, physical activity, and quality of life after liver transplantation. Liver Transpl. May 2020;26(5):702-708. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Faust A, Stine JG. Leveraging the coronavirus disease 2019 pandemic: is it time to consider incorporating mobile applications into standard clinical management of the liver transplantation patient? Liver Transpl. Apr 2021;27(4):479-481. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Lee H, Shin BC, Seo JM. Effectiveness of eHealth interventions for improving medication adherence of organ transplant patients: a systematic review and meta-analysis. PLoS One. Nov 5, 2020;15(11):e0241857. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Mohr DC, Cuijpers P, Lehman K. Supportive accountability: a model for providing human support to enhance adherence to eHealth interventions. J Med Internet Res. Mar 10, 2011;13(1):e30. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Neter E, Brainin E. eHealth literacy: extending the digital divide to the realm of health information. J Med Internet Res. Jan 27, 2012;14(1):e19. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Tennant B, Stellefson M, Dodd V, Chaney B, Chaney D, Paige S, et al. eHealth literacy and Web 2.0 health information seeking behaviors among baby boomers and older adults. J Med Internet Res. Mar 17, 2015;17(3):e70. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Deshpande N, Arora VM, Vollbrecht H, Meltzer DO, Press V. eHealth literacy and patient portal use and attitudes: cross-sectional observational study. JMIR Hum Factors. Jan 27, 2023;10:e40105. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Cheng J, Arora VM, Kappel N, Vollbrecht H, Meltzer DO, Press V. Assessing disparities in video-telehealth use and ehealth literacy among hospitalized patients: cross-sectional observational study. JMIR Form Res. May 12, 2023;7:e44501. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Durand F, Levitsky J, Cauchy F, Gilgenkrantz H, Soubrane O, Francoz C. Age and liver transplantation. J Hepatol. Apr 2019;70(4):745-758. [ CrossRef ] [ Medline ]
• Dolnikov S, Adam R, Cherqui D, Allard MA. Liver transplantation in elderly patients: what do we know at the beginning of 2020? Surg Today. Jun 2020;50(6):533-539. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Wilson GC, Quillin RC3, Wima K, Sutton JM, Hoehn RS, Hanseman DJ, et al. Is liver transplantation safe and effective in elderly (≥70 years) recipients? A case-controlled analysis. HPB (Oxford). Dec 2014;16(12):1088-1094. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Werkgartner G, Wagner D, Manhal S, Fahrleitner-Pammer A, Mischinger HJ, Wagner M, et al. Long-term quality of life of liver transplant recipients beyond 60 years of age. Age (Dordr). Dec 2013;35(6):2485-2492. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Wang Y, Song Y, Zhu Y, Ji H, Wang A. Association of eHealth literacy with health promotion behaviors of community-dwelling older people: the chain mediating role of self-efficacy and self-care ability. Int J Environ Res Public Health. May 17, 2022;19(10):6092. [ FREE Full text ] [ CrossRef ] [ Medline ]
• Daudt HM, van Mossel C, Scott SJ. Enhancing the scoping study methodology: a large, inter-professional team's experience with Arksey and O'Malley's framework. BMC Med Res Methodol. Mar 23, 2013;13:48. [ FREE Full text ] [ CrossRef ] [ Medline ]
• ChatGPT | OpenAI. URL: https://openai.com/chatgpt/ [accessed 2024-06-24]

Abbreviations

Edited by G Eysenbach, S Ma; submitted 23.01.24; peer-reviewed by K Bul; comments to author 20.02.24; revised version received 24.03.24; accepted 03.06.24; published 04.07.24.

©Soo Hyun Kim, Kyoung-A Kim, Sang Hui Chu, Hyunji Kim, Dong Jin Joo, Jae Geun Lee, JiYeon Choi. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.07.2024.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research (ISSN 1438-8871), is properly cited. The complete bibliographic information, a link to the original publication on https://www.jmir.org/, as well as this copyright and license information must be included.

• Open access
• Published: 03 July 2024

The impact of evidence-based nursing leadership in healthcare settings: a mixed methods systematic review

• Maritta Välimäki 1 , 2 ,
• Shuang Hu 3 ,
• Tella Lantta 1 ,
• Kirsi Hipp 1 , 4 ,
• Jaakko Varpula 1 ,
• Jiarui Chen 3 ,
• Gaoming Liu 5 ,
• Yao Tang 3 ,
• Wenjun Chen 3 &
• Xianhong Li 3  

BMC Nursing volume  23 , Article number:  452 ( 2024 ) Cite this article

49 Accesses

Metrics details

The central component in impactful healthcare decisions is evidence. Understanding how nurse leaders use evidence in their own managerial decision making is still limited. This mixed methods systematic review aimed to examine how evidence is used to solve leadership problems and to describe the measured and perceived effects of evidence-based leadership on nurse leaders and their performance, organizational, and clinical outcomes.

We included articles using any type of research design. We referred nurses, nurse managers or other nursing staff working in a healthcare context when they attempt to influence the behavior of individuals or a group in an organization using an evidence-based approach. Seven databases were searched until 11 November 2021. JBI Critical Appraisal Checklist for Quasi-experimental studies, JBI Critical Appraisal Checklist for Case Series, Mixed Methods Appraisal Tool were used to evaluate the Risk of bias in quasi-experimental studies, case series, mixed methods studies, respectively. The JBI approach to mixed methods systematic reviews was followed, and a parallel-results convergent approach to synthesis and integration was adopted.

Thirty-one publications were eligible for the analysis: case series ( n  = 27), mixed methods studies ( n  = 3) and quasi-experimental studies ( n  = 1). All studies were included regardless of methodological quality. Leadership problems were related to the implementation of knowledge into practice, the quality of nursing care and the resource availability. Organizational data was used in 27 studies to understand leadership problems, scientific evidence from literature was sought in 26 studies, and stakeholders’ views were explored in 24 studies. Perceived and measured effects of evidence-based leadership focused on nurses’ performance, organizational outcomes, and clinical outcomes. Economic data were not available.

Conclusions

This is the first systematic review to examine how evidence is used to solve leadership problems and to describe its measured and perceived effects from different sites. Although a variety of perceptions and effects were identified on nurses’ performance as well as on organizational and clinical outcomes, available knowledge concerning evidence-based leadership is currently insufficient. Therefore, more high-quality research and clinical trial designs are still needed.

Trail registration

The study was registered (PROSPERO CRD42021259624).

Peer Review reports

Global health demands have set new roles for nurse leaders [ 1 ].Nurse leaders are referred to as nurses, nurse managers, or other nursing staff working in a healthcare context who attempt to influence the behavior of individuals or a group based on goals that are congruent with organizational goals [ 2 ]. They are seen as professionals “armed with data and evidence, and a commitment to mentorship and education”, and as a group in which “leaders innovate, transform, and achieve quality outcomes for patients, health care professionals, organizations, and communities” [ 3 ]. Effective leadership occurs when team members critically follow leaders and are motivated by a leader’s decisions based on the organization’s requests and targets [ 4 ]. On the other hand, problems caused by poor leadership may also occur, regarding staff relations, stress, sickness, or retention [ 5 ]. Therefore, leadership requires an understanding of different problems to be solved using synthesizing evidence from research, clinical expertise, and stakeholders’ preferences [ 6 , 7 ]. If based on evidence, leadership decisions, also referred as leadership decision making [ 8 ], could ensure adequate staffing [ 7 , 9 ] and to produce sufficient and cost-effective care [ 10 ]. However, nurse leaders still rely on their decision making on their personal [ 11 ] and professional experience [ 10 ] over research evidence, which can lead to deficiencies in the quality and safety of care delivery [ 12 , 13 , 14 ]. As all nurses should demonstrate leadership in their profession, their leadership competencies should be strengthened [ 15 ].

Evidence-informed decision-making, referred to as evidence appraisal and application, and evaluation of decisions [ 16 ], has been recognized as one of the core competencies for leaders [ 17 , 18 ]. The role of evidence in nurse leaders’ managerial decision making has been promoted by public authorities [ 19 , 20 , 21 ]. Evidence-based management, another concept related to evidence-based leadership, has been used as the potential to improve healthcare services [ 22 ]. It can guide nursing leaders, in developing working conditions, staff retention, implementation practices, strategic planning, patient care, and success of leadership [ 13 ]. Collins and Holton [ 23 ] in their systematic review and meta-analysis examined 83 studies regarding leadership development interventions. They found that leadership training can result in significant improvement in participants’ skills, especially in knowledge level, although the training effects varied across studies. Cummings et al. [ 24 ] reviewed 100 papers (93 studies) and concluded that participation in leadership interventions had a positive impact on the development of a variety of leadership styles. Clavijo-Chamorro et al. [ 25 ] in their review of 11 studies focused on leadership-related factors that facilitate evidence implementation: teamwork, organizational structures, and transformational leadership. The role of nurse managers was to facilitate evidence-based practices by transforming contexts to motivate the staff and move toward a shared vision of change.

As far as we are aware, however, only a few systematic reviews have focused on evidence-based leadership or related concepts in the healthcare context aiming to analyse how nurse leaders themselves uses evidence in the decision-making process. Young [ 26 ] targeted definitions and acceptance of evidence-based management (EBMgt) in healthcare while Hasanpoor et al. [ 22 ] identified facilitators and barriers, sources of evidence used, and the role of evidence in the process of decision making. Both these reviews concluded that EBMgt was of great importance but used limitedly in healthcare settings due to a lack of time, a lack of research management activities, and policy constraints. A review by Williams [ 27 ] showed that the usage of evidence to support management in decision making is marginal due to a shortage of relevant evidence. Fraser [ 28 ] in their review further indicated that the potential evidence-based knowledge is not used in decision making by leaders as effectively as it could be. Non-use of evidence occurs and leaders base their decisions mainly on single studies, real-world evidence, and experts’ opinions [ 29 ]. Systematic reviews and meta-analyses rarely provide evidence of management-related interventions [ 30 ]. Tate et al. [ 31 ] concluded based on their systematic review and meta-analysis that the ability of nurse leaders to use and critically appraise research evidence may influence the way policy is enacted and how resources and staff are used to meet certain objectives set by policy. This can further influence staff and workforce outcomes. It is therefore important that nurse leaders have the capacity and motivation to use the strongest evidence available to effect change and guide their decision making [ 27 ].

Despite of a growing body of evidence, we found only one review focusing on the impact of evidence-based knowledge. Geert et al. [ 32 ] reviewed literature from 2007 to 2016 to understand the elements of design, delivery, and evaluation of leadership development interventions that are the most reliably linked to outcomes at the level of the individual and the organization, and that are of most benefit to patients. The authors concluded that it is possible to improve individual-level outcomes among leaders, such as knowledge, motivation, skills, and behavior change using evidence-based approaches. Some of the most effective interventions included, for example, interactive workshops, coaching, action learning, and mentoring. However, these authors found limited research evidence describing how nurse leaders themselves use evidence to support their managerial decisions in nursing and what the outcomes are.

To fill the knowledge gap and compliment to existing knowledgebase, in this mixed methods review we aimed to (1) examine what leadership problems nurse leaders solve using an evidence-based approach and (2) how they use evidence to solve these problems. We also explored (3) the measured and (4) perceived effects of the evidence-based leadership approach in healthcare settings. Both qualitative and quantitative components of the effects of evidence-based leadership were examined to provide greater insights into the available literature [ 33 ]. Together with the evidence-based leadership approach, and its impact on nursing [ 34 , 35 ], this knowledge gained in this review can be used to inform clinical policy or organizational decisions [ 33 ]. The study is registered (PROSPERO CRD42021259624). The methods used in this review were specified in advance and documented in a priori in a published protocol [ 36 ]. Key terms of the review and the search terms are defined in Table  1 (population, intervention, comparison, outcomes, context, other).

In this review, we used a mixed methods approach [ 37 ]. A mixed methods systematic review was selected as this approach has the potential to produce direct relevance to policy makers and practitioners [ 38 ]. Johnson and Onwuegbuzie [ 39 ] have defined mixed methods research as “the class of research in which the researcher mixes or combines quantitative and qualitative research techniques, methods, approaches, concepts or language into a single study.” Therefore, we combined quantitative and narrative analysis to appraise and synthesize empirical evidence, and we held them as equally important in informing clinical policy or organizational decisions [ 34 ]. In this review, a comprehensive synthesis of quantitative and qualitative data was performed first and then discussed in discussion part (parallel-results convergent design) [ 40 ]. We hoped that different type of analysis approaches could complement each other and deeper picture of the topic in line with our research questions could be gained [ 34 ].

Inclusion and exclusion criteria

Inclusion and exclusion criteria of the study are described in Table  1 .

Search strategy

A three-step search strategy was utilized. First, an initial limited search with #MEDLINE was undertaken, followed by analysis of the words used in the title, abstract, and the article’s key index terms. Second, the search strategy, including identified keywords and index terms, was adapted for each included data base and a second search was undertaken on 11 November 2021. The full search strategy for each database is described in Additional file 1 . Third, the reference list of all studies included in the review were screened for additional studies. No year limits or language restrictions were used.

Information sources

The database search included the following: CINAHL (EBSCO), Cochrane Library (academic database for medicine and health science and nursing), Embase (Elsevier), PsycINFO (EBSCO), PubMed (MEDLINE), Scopus (Elsevier) and Web of Science (academic database across all scientific and technical disciplines, ranging from medicine and social sciences to arts and humanities). These databases were selected as they represent typical databases in health care context. Subject headings from each of the databases were included in the search strategies. Boolean operators ‘AND’ and ‘OR’ were used to combine the search terms. An information specialist from the University of Turku Library was consulted in the formation of the search strategies.

Study selection

All identified citations were collated and uploaded into Covidence software (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia www.covidence.org ), and duplicates were removed by the software. Titles and abstracts were screened and assessed against the inclusion criteria independently by two reviewers out of four, and any discrepancies were resolved by the third reviewer (MV, KH, TL, WC). Studies meeting the inclusion criteria were retrieved in full and archived in Covidence. Access to one full-text article was lacking: the authors for one study were contacted about the missing full text, but no full text was received. All remaining hits of the included studies were retrieved and assessed independently against the inclusion criteria by two independent reviewers of four (MV, KH, TL, WC). Studies that did not meet the inclusion criteria were excluded, and the reasons for exclusion were recorded in Covidence. Any disagreements that arose between the reviewers were resolved through discussions with XL.

Assessment of methodological quality

Eligible studies were critically appraised by two independent reviewers (YT, SH). Standardized critical appraisal instruments based on the study design were used. First, quasi-experimental studies were assessed using the JBI Critical Appraisal Checklist for Quasi-experimental studies [ 44 ]. Second, case series were assessed using the JBI Critical Appraisal Checklist for Case Series [ 45 ]. Third, mixed methods studies were appraised using the Mixed Methods Appraisal Tool [ 46 ].

To increase inter-reviewer reliability, the review agreement was calculated (SH) [ 47 ]. A kappa greater than 0.8 was considered to represent a high level of agreement (0–0.1). In our data, the agreement was 0.75. Discrepancies raised between two reviewers were resolved through discussion and modifications and confirmed by XL. As an outcome, studies that met the inclusion criteria were proceeded to critical appraisal and assessed as suitable for inclusion in the review. The scores for each item and overall critical appraisal scores were presented.

Data extraction

For data extraction, specific tables were created. First, study characteristics (author(s), year, country, design, number of participants, setting) were extracted by two authors independently (JC, MV) and reviewed by TL. Second, descriptions of the interventions were extracted by two reviewers (JV, JC) using the structure of the TIDIeR (Template for Intervention Description and Replication) checklist (brief name, the goal of the intervention, material and procedure, models of delivery and location, dose, modification, adherence and fidelity) [ 48 ]. The extractions were confirmed (MV).

Third, due to a lack of effectiveness data and a wide heterogeneity between study designs and presentation of outcomes, no attempt was made to pool the quantitative data statistically; the findings of the quantitative data were presented in narrative form only [ 44 ]. The separate data extraction tables for each research question were designed specifically for this study. For both qualitative (and a qualitative component of mixed-method studies) and quantitative studies, the data were extracted and tabulated into text format according to preplanned research questions [ 36 ]. To test the quality of the tables and the data extraction process, three authors independently extracted the data from the first five studies (in alphabetical order). After that, the authors came together to share and determine whether their approaches of the data extraction were consistent with each other’s output and whether the content of each table was in line with research question. No reason was found to modify the data extraction tables or planned process. After a consensus of the data extraction process was reached, the data were extracted in pairs by independent reviewers (WC, TY, SH, GL). Any disagreements that arose between the reviewers were resolved through discussion and with a third reviewer (MV).

Data analysis

We were not able to conduct a meta-analysis due to a lack of effectiveness data based on clinical trials. Instead, we used inductive thematic analysis with constant comparison to answer the research question [ 46 , 49 ] using tabulated primary data from qualitative and quantitative studies as reported by the original authors in narrative form only [ 47 ]. In addition, the qualitizing process was used to transform quantitative data to qualitative data; this helped us to convert the whole data into themes and categories. After that we used the thematic analysis for the narrative data as follows. First, the text was carefully read, line by line, to reveal topics answering each specific review question (MV). Second, the data coding was conducted, and the themes in the data were formed by data categorization. The process of deriving the themes was inductive based on constant comparison [ 49 ]. The results of thematic analysis and data categorization was first described in narrative format and then the total number of studies was calculated where the specific category was identified (%).

Stakeholder involvement

The method of reporting stakeholders’ involvement follows the key components by [ 50 ]: (1) people involved, (2) geographical location, (3) how people were recruited, (4) format of involvement, (5) amount of involvement, (6) ethical approval, (7) financial compensation, and (8) methods for reporting involvement.

In our review, stakeholder involvement targeted nurses and nurse leader in China. Nurse Directors of two hospitals recommended potential participants who received a personal invitation letter from researchers to participate in a discussion meeting. Stakeholders’ participation was based on their own free will. Due to COVID-19, one online meeting (1 h) was organized (25 May 2022). Eleven participants joined the meeting. Ethical approval was not applied and no financial compensation was offered. At the end of the meeting, experiences of stakeholders’ involvement were explored.

The meeting started with an introductory presentation with power points. The rationale, methods, and preliminary review results were shared with the participants [ 51 ].The meeting continued with general questions for the participants: (1) Are you aware of the concepts of evidence-based practice or evidence-based leadership?; (2) How important is it to use evidence to support decisions among nurse leaders?; (3) How is the evidence-based approach used in hospital settings?; and (4) What type of evidence is currently used to support nurse leaders’ decision making (e.g. scientific literature, organizational data, stakeholder views)?

Two people took notes on the course and content of the conversation. The notes were later transcripted in verbatim, and the key points of the discussions were summarised. Although answers offered by the stakeholders were very short, the information was useful to validate the preliminary content of the results, add the rigorousness of the review, and obtain additional perspectives. A recommendation of the stakeholders was combined in the Discussion part of this review increasing the applicability of the review in the real world [ 50 ]. At the end of the discussion, the value of stakeholders’ involvement was asked. Participants shared that the experience of participating was unique and the topic of discussion was challenging. Two authors of the review group further represented stakeholders by working together with the research team throughout the review study.

Search results

From seven different electronic databases, 6053 citations were identified as being potentially relevant to the review. Then, 3133 duplicates were removed by an automation tool (Covidence: www.covidence.org ), and one was removed manually. The titles and abstracts of 3040 of citations were reviewed, and a total of 110 full texts were included (one extra citation was found on the reference list but later excluded). Based on the eligibility criteria, 31 studies (32 hits) were critically appraised and deemed suitable for inclusion in the review. The search results and selection process are presented in the PRISMA [ 52 ] flow diagram Fig.  1 . The full list of references for included studies can be find in Additional file 2 . To avoid confusion between articles of the reference list and studies included in the analysis, the studies included in the review are referred inside the article using the reference number of each study (e.g. ref 1, ref 2).

Search results and study selection and inclusion process [ 52 ]

Characteristics of included studies

The studies had multiple purposes, aiming to develop practice, implement a new approach, improve quality, or to develop a model. The 31 studies (across 32 hits) were case series studies ( n  = 27), mixed methods studies ( n  = 3) and a quasi-experimental study ( n  = 1). All studies were published between the years 2004 and 2021. The highest number of papers was published in year 2020.

Table  2 describes the characteristics of included studies and Additional file 3 offers a narrative description of the studies.

Methodological quality assessment

Quasi-experimental studies.

We had one quasi-experimental study (ref 31). All questions in the critical appraisal tool were applicable. The total score of the study was 8 (out of a possible 9). Only one response of the tool was ‘no’ because no control group was used in the study (see Additional file 4 for the critical appraisal of included studies).

Case series studies . A case series study is typically defined as a collection of subjects with common characteristics. The studies do not include a comparison group and are often based on prevalent cases and on a sample of convenience [ 53 ]. Munn et al. [ 45 ] further claim that case series are best described as observational studies, lacking experimental and randomized characteristics, being descriptive studies, without a control or comparator group. Out of 27 case series studies included in our review, the critical appraisal scores varied from 1 to 9. Five references were conference abstracts with empirical study results, which were scored from 1 to 3. Full reports of these studies were searched in electronic databases but not found. Critical appraisal scores for the remaining 22 studies ranged from 1 to 9 out of a possible score of 10. One question (Q3) was not applicable to 13 studies: “Were valid methods used for identification of the condition for all participants included in the case series?” Only two studies had clearly reported the demographic of the participants in the study (Q6). Twenty studies met Criteria 8 (“Were the outcomes or follow-up results of cases clearly reported?”) and 18 studies met Criteria 7 (“Q7: Was there clear reporting of clinical information of the participants?”) (see Additional file 4 for the critical appraisal of included studies).

Mixed-methods studies

Mixed-methods studies involve a combination of qualitative and quantitative methods. This is a common design and includes convergent design, sequential explanatory design, and sequential exploratory design [ 46 ]. There were three mixed-methods studies. The critical appraisal scores for the three studies ranged from 60 to 100% out of a possible 100%. Two studies met all the criteria, while one study fulfilled 60% of the scored criteria due to a lack of information to understand the relevance of the sampling strategy well enough to address the research question (Q4.1) or to determine whether the risk of nonresponse bias was low (Q4.4) (see Additional file 4 for the critical appraisal of included studies).

Intervention or program components

The intervention of program components were categorized and described using the TiDier checklist: name and goal, theory or background, material, procedure, provider, models of delivery, location, dose, modification, and adherence and fidelity [ 48 ]. A description of intervention in each study is described in Additional file 5 and a narrative description in Additional file 6 .

Leadership problems

In line with the inclusion criteria, data for the leadership problems were categorized in all 31 included studies (see Additional file 7 for leadership problems). Three types of leadership problems were identified: implementation of knowledge into practice, the quality of clinical care, and resources in nursing care. A narrative summary of the results is reported below.

Implementing knowledge into practice

Eleven studies (35%) aimed to solve leadership problems related to implementation of knowledge into practice. Studies showed how to support nurses in evidence-based implementation (EBP) (ref 3, ref 5), how to engage nurses in using evidence in practice (ref 4), how to convey the importance of EBP (ref 22) or how to change practice (ref 4). Other problems were how to facilitate nurses to use guideline recommendations (ref 7) and how nurses can make evidence-informed decisions (ref 8). General concerns also included the linkage between theory and practice (ref 1) as well as how to implement the EBP model in practice (ref 6). In addition, studies were motivated by the need for revisions or updates of protocols to improve clinical practice (ref 10) as well as the need to standardize nursing activities (ref 11, ref 14).

The quality of the care

Thirteen (42%) focused on solving problems related to the quality of clinical care. In these studies, a high number of catheter infections led a lack of achievement of organizational goals (ref 2, ref 9). A need to reduce patient symptoms in stem cell transplant patients undergoing high-dose chemotherapy (ref 24) was also one of the problems to be solved. In addition, the projects focused on how to prevent pressure ulcers (ref 26, ref 29), how to enhance the quality of cancer treatment (ref 25) and how to reduce the need for invasive constipation treatment (ref 30). Concerns about patient safety (ref 15), high fall rates (ref 16, ref 19), dissatisfaction of patients (ref 16, ref 18) and nurses (ref 16, ref 30) were also problems that had initiated the projects. Studies addressed concerns about how to promote good contingency care in residential aged care homes (ref 20) and about how to increase recognition of human trafficking problems in healthcare (ref 21).

Resources in nursing care

Nurse leaders identified problems in their resources, especially in staffing problems. These problems were identified in seven studies (23%), which involved concerns about how to prevent nurses from leaving the job (ref 31), how to ensure appropriate recruitment, staffing and retaining of nurses (ref 13) and how to decrease nurses’ burden and time spent on nursing activities (ref 12). Leadership turnover was also reported as a source of dissatisfaction (ref 17); studies addressed a lack of structured transition and training programs, which led to turnover (ref 23), as well as how to improve intershift handoff among nurses (ref 28). Optimal design for new hospitals was also examined (ref 27).

Main features of evidence-based leadership

Out of 31 studies, 17 (55%) included all four domains of an evidence-based leadership approach, and four studies (13%) included evidence of critical appraisal of the results (see Additional file 8 for the main features of evidence-based Leadership) (ref 11, ref 14, ref 23, ref 27).

Organizational evidence

Twenty-seven studies (87%) reported how organizational evidence was collected and used to solve leadership problems (ref 2). Retrospective chart reviews (ref 5), a review of the extent of specific incidents (ref 19), and chart auditing (ref 7, ref 25) were conducted. A gap between guideline recommendations and actual care was identified using organizational data (ref 7) while the percentage of nurses’ working time spent on patient care was analyzed using an electronic charting system (ref 12). Internal data (ref 22), institutional data, and programming metrics were also analyzed to understand the development of the nurse workforce (ref 13).

Surveys (ref 3, ref 25), interviews (ref 3, ref 25) and group reviews (ref 18) were used to better understand the leadership problem to be solved. Employee opinion surveys on leadership (ref 17), a nurse satisfaction survey (ref 30) and a variety of reporting templates were used for the data collection (ref 28) reported. Sometimes, leadership problems were identified by evidence facilitators or a PI’s team who worked with staff members (ref 15, ref 17). Problems in clinical practice were also identified by the Nursing Professional Council (ref 14), managers (ref 26) or nurses themselves (ref 24). Current practices were reviewed (ref 29) and a gap analysis was conducted (ref 4, ref 16, ref 23) together with SWOT analysis (ref 16). In addition, hospital mission and vision statements, research culture established and the proportion of nursing alumni with formal EBP training were analyzed (ref 5). On the other hand, it was stated that no systematic hospital-specific sources of data regarding job satisfaction or organizational commitment were used (ref 31). In addition, statements of organizational analysis were used on a general level only (ref 1).

Scientific evidence identified

Twenty-six studies (84%) reported the use of scientific evidence in their evidence-based leadership processes. A literature search was conducted (ref 21) and questions, PICO, and keywords were identified (ref 4) in collaboration with a librarian. Electronic databases, including PubMed (ref 14, ref 31), Cochrane, and EMBASE (ref 31) were searched. Galiano (ref 6) used Wiley Online Library, Elsevier, CINAHL, Health Source: Nursing/Academic Edition, PubMed, and the Cochrane Library while Hoke (ref 11) conducted an electronic search using CINAHL and PubMed to retrieve articles.

Identified journals were reviewed manually (ref 31). The findings were summarized using ‘elevator speech’ (ref 4). In a study by Gifford et al. (ref 9) evidence facilitators worked with participants to access, appraise, and adapt the research evidence to the organizational context. Ostaszkiewicz (ref 20) conducted a scoping review of literature and identified and reviewed frameworks and policy documents about the topic and the quality standards. Further, a team of nursing administrators, directors, staff nurses, and a patient representative reviewed the literature and made recommendations for practice changes.

Clinical practice guidelines were also used to offer scientific evidence (ref 7, ref 19). Evidence was further retrieved from a combination of nursing policies, guidelines, journal articles, and textbooks (ref 12) as well as from published guidelines and literature (ref 13). Internal evidence, professional practice knowledge, relevant theories and models were synthesized (ref 24) while other study (ref 25) reviewed individual studies, synthesized with systematic reviews or clinical practice guidelines. The team reviewed the research evidence (ref 3, ref 15) or conducted a literature review (ref 22, ref 28, ref 29), a literature search (ref 27), a systematic review (ref 23), a review of the literature (ref 30) or ‘the scholarly literature was reviewed’ (ref 18). In addition, ‘an extensive literature review of evidence-based best practices was carried out’ (ref 10). However, detailed description how the review was conducted was lacking.

Views of stakeholders

A total of 24 studies (77%) reported methods for how the views of stakeholders, i.e., professionals or experts, were considered. Support to run this study was received from nursing leadership and multidisciplinary teams (ref 29). Experts and stakeholders joined the study team in some cases (ref 25, ref 30), and in other studies, their opinions were sought to facilitate project success (ref 3). Sometimes a steering committee was formed by a Chief Nursing Officer and Clinical Practice Specialists (ref 2). More specifically, stakeholders’ views were considered using interviews, workshops and follow-up teleconferences (ref 7). The literature review was discussed with colleagues (ref 11), and feedback and support from physicians as well as the consensus of staff were sought (ref 16).

A summary of the project findings and suggestions for the studies were discussed at 90-minute weekly meetings by 11 charge nurses. Nurse executive directors were consulted over a 10-week period (ref 31). An implementation team (nurse, dietician, physiotherapist, occupational therapist) was formed to support the implementation of evidence-based prevention measures (ref 26). Stakeholders volunteered to join in the pilot implementation (ref 28) or a stakeholder team met to determine the best strategy for change management, shortcomings in evidence-based criteria were discussed, and strategies to address those areas were planned (ref 5). Nursing leaders, staff members (ref 22), ‘process owners (ref 18) and program team members (ref 18, ref 19, ref 24) met regularly to discuss the problems. Critical input was sought from clinical educators, physicians, nutritionists, pharmacists, and nurse managers (ref 24). The unit director and senior nursing staff reviewed the contents of the product, and the final version of clinical pathways were reviewed and approved by the Quality Control Commission of the Nursing Department (ref 12). In addition, two co-design workshops with 18 residential aged care stakeholders were organized to explore their perspectives about factors to include in a model prototype (ref 20). Further, an agreement of stakeholders in implementing continuous quality services within an open relationship was conducted (ref 1).

Critical appraisal

In five studies (16%), a critical appraisal targeting the literature search was carried out. The appraisals were conducted by interns and teams who critiqued the evidence (ref 4). In Hoke’s study, four areas that had emerged in the literature were critically reviewed (ref 11). Other methods were to ‘critically appraise the search results’ (ref 14). Journal club team meetings (ref 23) were organized to grade the level and quality of evidence and the team ‘critically appraised relevant evidence’ (ref 27). On the other hand, the studies lacked details of how the appraisals were done in each study.

The perceived effects of evidence-based leadership

Perceived effects of evidence-based leadership on nurses’ performance.

Eleven studies (35%) described perceived effects of evidence-based leadership on nurses’ performance (see Additional file 9 for perceived effects of evidence-based leadership), which were categorized in four groups: awareness and knowledge, competence, ability to understand patients’ needs, and engagement. First, regarding ‘awareness and knowledge’, different projects provided nurses with new learning opportunities (ref 3). Staff’s knowledge (ref 20, ref 28), skills, and education levels improved (ref 20), as did nurses’ knowledge comprehension (ref 21). Second, interventions and approaches focusing on management and leadership positively influenced participants’ competence level to improve the quality of services. Their confidence level (ref 1) and motivation to change practice increased, self-esteem improved, and they were more positive and enthusiastic in their work (ref 22). Third, some nurses were relieved that they had learned to better handle patients’ needs (ref 25). For example, a systematic work approach increased nurses’ awareness of the patients who were at risk of developing health problems (ref 26). And last, nurse leaders were more engaged with staff, encouraging them to adopt the new practices and recognizing their efforts to change (ref 8).

Perceived effects on organizational outcomes

Nine studies (29%) described the perceived effects of evidence-based leadership on organizational outcomes (see Additional file 9 for perceived effects of evidence-based leadership). These were categorized into three groups: use of resources, staff commitment, and team effort. First, more appropriate use of resources was reported (ref 15, ref 20), and working time was more efficiently used (ref 16). In generally, a structured approach made implementing change more manageable (ref 1). On the other hand, in the beginning of the change process, the feedback from nurses was unfavorable, and they experienced discomfort in the new work style (ref 29). New approaches were also perceived as time consuming (ref 3). Second, nurse leaders believed that fewer nursing staff than expected left the organization over the course of the study (ref 31). Third, the project helped staff in their efforts to make changes, and it validated the importance of working as a team (ref 7). Collaboration and support between the nurses increased (ref 26). On the other hand, new work style caused challenges in teamwork (ref 3).

Perceived effects on clinical outcomes

Five studies (16%) reported the perceived effects of evidence-based leadership on clinical outcomes (see Additional file 9 for perceived effects of evidence-based leadership), which were categorized in two groups: general patient outcomes and specific clinical outcomes. First, in general, the project assisted in connecting the guideline recommendations and patient outcomes (ref 7). The project was good for the patients in general, and especially to improve patient safety (ref 16). On the other hand, some nurses thought that the new working style did not work at all for patients (ref 28). Second, the new approach used assisted in optimizing patients’ clinical problems and person-centered care (ref 20). Bowel management, for example, received very good feedback (ref 30).

The measured effects of evidence-based leadership

The measured effects on nurses’ performance.

Data were obtained from 20 studies (65%) (see Additional file 10 for measured effects of evidence-based leadership) and categorized nurse performance outcomes for three groups: awareness and knowledge, engagement, and satisfaction. First, six studies (19%) measured the awareness and knowledge levels of participants. Internship for staff nurses was beneficial to help participants to understand the process for using evidence-based practice and to grow professionally, to stimulate for innovative thinking, to give knowledge needed to use evidence-based practice to answer clinical questions, and to make possible to complete an evidence-based practice project (ref 3). Regarding implementation program of evidence-based practice, those with formal EBP training showed an improvement in knowledge, attitude, confidence, awareness and application after intervention (ref 3, ref 11, ref 20, ref 23, ref 25). On the contrary, in other study, attitude towards EBP remained stable ( p  = 0.543). and those who applied EBP decreased although no significant differences over the years ( p  = 0.879) (ref 6).

Second, 10 studies (35%) described nurses’ engagement to new practices (ref 5, ref 6, ref 7, ref 10, ref 16, ref 17, ref 18, ref 21, ref 25, ref 27). 9 studies (29%) studies reported that there was an improvement of compliance level of participants (ref 6, ref 7, ref 10, ref 16, ref 17, ref 18, ref 21, ref 25, ref 27). On the contrary, in DeLeskey’s (ref 5) study, although improvement was found in post-operative nausea and vomiting’s (PONV) risk factors documented’ (2.5–63%), and ’risk factors communicated among anaesthesia and surgical staff’ (0–62%), the improvement did not achieve the goal. The reason was a limited improvement was analysed. It was noted that only those patients who had been seen by the pre-admission testing nurse had risk assessments completed. Appropriate treatment/prophylaxis increased from 69 to 77%, and from 30 to 49%; routine assessment for PONV/rescue treatment 97% and 100% was both at 100% following the project. The results were discussed with staff but further reasons for a lack of engagement in nursing care was not reported.

And third, six studies (19%) reported nurses’ satisfaction with project outcomes. The study results showed that using evidence in managerial decisions improved nurses’ satisfaction and attitudes toward their organization ( P  < 0.05) (ref 31). Nurses’ overall job satisfaction improved as well (ref 17). Nurses’ satisfaction with usability of the electronic charting system significantly improved after introduction of the intervention (ref 12). In handoff project in seven hospitals, improvement was reported in all satisfaction indicators used in the study although improvement level varied in different units (ref 28). In addition, positive changes were reported in nurses’ ability to autonomously perform their job (“How satisfied are you with the tools and resources available for you treat and prevent patient constipation?” (54%, n  = 17 vs. 92%, n  = 35, p  < 0.001) (ref 30).

The measured effects on organizational outcomes

Thirteen studies (42%) described the effects of a project on organizational outcomes (see Additional file 10 for measured effects of evidence-based leadership), which were categorized in two groups: staff compliance, and changes in practices. First, studies reported improved organizational outcomes due to staff better compliance in care (ref 4, ref 13, ref 17, ref 23, ref 27, ref 31). Second, changes in organization practices were also described (ref 11) like changes in patient documentation (ref 12, ref 21). Van Orne (ref 30) found a statistically significant reduction in the average rate of invasive medication administration between pre-intervention and post-intervention ( p  = 0.01). Salvador (ref 24) also reported an improvement in a proactive approach to mucositis prevention with an evidence-based oral care guide. On the contrary, concerns were also raised such as not enough time for new bedside report (ref 16) or a lack of improvement of assessment of diabetic ulcer (ref 8).

The measured effects on clinical outcomes

A variety of improvements in clinical outcomes were reported (see Additional file 10 for measured effects of evidence-based leadership): improvement in patient clinical status and satisfaction level. First, a variety of improvement in patient clinical status was reported. improvement in Incidence of CAUTI decreased 27.8% between 2015 and 2019 (ref 2) while a patient-centered quality improvement project reduced CAUTI rates to 0 (ref 10). A significant decrease in transmission rate of MRSA transmission was also reported (ref 27) and in other study incidences of CLABSIs dropped following of CHG bathing (ref 14). Further, it was possible to decrease patient nausea from 18 to 5% and vomiting to 0% (ref 5) while the percentage of patients who left the hospital without being seen was below 2% after the project (ref 17). In addition, a significant reduction in the prevalence of pressure ulcers was found (ref 26, ref 29) and a significant reduction of mucositis severity/distress was achieved (ref 24). Patient falls rate decreased (ref 15, ref 16, ref 19, ref 27).

Second, patient satisfaction level after project implementation improved (ref 28). The scale assessing healthcare providers by consumers showed improvement, but the changes were not statistically significant. Improvement in an emergency department leadership model and in methods of communication with patients improved patient satisfaction scores by 600% (ref 17). In addition, new evidence-based unit improved patient experiences about the unit although not all items improved significantly (ref 18).

Stakeholder involvement in the mixed-method review

To ensure stakeholders’ involvement in the review, the real-world relevance of our research [ 53 ], achieve a higher level of meaning in our review results, and gain new perspectives on our preliminary findings [ 50 ], a meeting with 11 stakeholders was organized. First, we asked if participants were aware of the concepts of evidence-based practice or evidence-based leadership. Responses revealed that participants were familiar with the concept of evidence-based practice, but the topic of evidence-based leadership was totally new. Examples of nurses and nurse leaders’ responses are as follows: “I have heard a concept of evidence-based practice but never a concept of evidence-based leadership.” Another participant described: “I have heard it [evidence-based leadership] but I do not understand what it means.”

Second, as stakeholder involvement is beneficial to the relevance and impact of health research [ 54 ], we asked how important evidence is to them in supporting decisions in health care services. One participant described as follows: “Using evidence in decisions is crucial to the wards and also to the entire hospital.” Third, we asked how the evidence-based approach is used in hospital settings. Participants expressed that literature is commonly used to solve clinical problems in patient care but not to solve leadership problems. “In [patient] medication and care, clinical guidelines are regularly used. However, I am aware only a few cases where evidence has been sought to solve leadership problems.”

And last, we asked what type of evidence is currently used to support nurse leaders’ decision making (e.g. scientific literature, organizational data, stakeholder views)? The participants were aware that different types of information were collected in their organization on a daily basis (e.g. patient satisfaction surveys). However, the information was seldom used to support decision making because nurse leaders did not know how to access this information. Even so, the participants agreed that the use of evidence from different sources was important in approaching any leadership or managerial problems in the organization. Participants also suggested that all nurse leaders should receive systematic training related to the topic; this could support the daily use of the evidence-based approach.

To our knowledge, this article represents the first mixed-methods systematic review to examine leadership problems, how evidence is used to solve these problems and what the perceived and measured effects of evidence-based leadership are on nurse leaders and their performance, organizational, and clinical outcomes. This review has two key findings. First, the available research data suggests that evidence-based leadership has potential in the healthcare context, not only to improve knowledge and skills among nurses, but also to improve organizational outcomes and the quality of patient care. Second, remarkably little published research was found to explore the effects of evidence-based leadership with an efficient trial design. We validated the preliminary results with nurse stakeholders, and confirmed that nursing staff, especially nurse leaders, were not familiar with the concept of evidence-based leadership, nor were they used to implementing evidence into their leadership decisions. Our data was based on many databases, and we screened a large number of studies. We also checked existing registers and databases and found no registered or ongoing similar reviews being conducted. Therefore, our results may not change in the near future.

We found that after identifying the leadership problems, 26 (84%) studies out of 31 used organizational data, 25 (81%) studies used scientific evidence from the literature, and 21 (68%) studies considered the views of stakeholders in attempting to understand specific leadership problems more deeply. However, only four studies critically appraised any of these findings. Considering previous critical statements of nurse leaders’ use of evidence in their decision making [ 14 , 30 , 31 , 34 , 55 ], our results are still quite promising.

Our results support a previous systematic review by Geert et al. [ 32 ], which concluded that it is possible to improve leaders’ individual-level outcomes, such as knowledge, motivation, skills, and behavior change using evidence-based approaches. Collins and Holton [ 23 ] particularly found that leadership training resulted in significant knowledge and skill improvements, although the effects varied widely across studies. In our study, evidence-based leadership was seen to enable changes in clinical practice, especially in patient care. On the other hand, we understand that not all efforts to changes were successful [ 56 , 57 , 58 ]. An evidence-based approach causes negative attitudes and feelings. Negative emotions in participants have also been reported due to changes, such as discomfort with a new working style [ 59 ]. Another study reported inconvenience in using a new intervention and its potential risks for patient confidentiality. Sometimes making changes is more time consuming than continuing with current practice [ 60 ]. These findings may partially explain why new interventions or program do not always fully achieve their goals. On the other hand, Dubose et al. [ 61 ] state that, if prepared with knowledge of resistance, nurse leaders could minimize the potential negative consequences and capitalize on a powerful impact of change adaptation.

We found that only six studies used a specific model or theory to understand the mechanism of change that could guide leadership practices. Participants’ reactions to new approaches may be an important factor in predicting how a new intervention will be implemented into clinical practice. Therefore, stronger effort should be put to better understanding the use of evidence, how participants’ reactions and emotions or practice changes could be predicted or supported using appropriate models or theories, and how using these models are linked with leadership outcomes. In this task, nurse leaders have an important role. At the same time, more responsibilities in developing health services have been put on the shoulders of nurse leaders who may already be suffering under pressure and increased burden at work. Working in a leadership position may also lead to role conflict. A study by Lalleman et al. [ 62 ] found that nurses were used to helping other people, often in ad hoc situations. The helping attitude of nurses combined with structured managerial role may cause dilemmas, which may lead to stress. Many nurse leaders opt to leave their positions less than 5 years [ 63 ].To better fulfill the requirements of health services in the future, the role of nurse leaders in evidence-based leadership needs to be developed further to avoid ethical and practical dilemmas in their leadership practices.

It is worth noting that the perceived and measured effects did not offer strong support to each other but rather opened a new venue to understand the evidence-based leadership. Specifically, the perceived effects did not support to measured effects (competence, ability to understand patients’ needs, use of resources, team effort, and specific clinical outcomes) while the measured effects could not support to perceived effects (nurse’s performance satisfaction, changes in practices, and clinical outcomes satisfaction). These findings may indicate that different outcomes appear if the effects of evidence-based leadership are looked at using different methodological approach. Future study is encouraged using well-designed study method including mixed-method study to examine the consistency between perceived and measured effects of evidence-based leadership in health care.

There is a potential in nursing to support change by demonstrating conceptual and operational commitment to research-based practices [ 64 ]. Nurse leaders are well positioned to influence and lead professional governance, quality improvement, service transformation, change and shared governance [ 65 ]. In this task, evidence-based leadership could be a key in solving deficiencies in the quality, safety of care [ 14 ] and inefficiencies in healthcare delivery [ 12 , 13 ]. As WHO has revealed, there are about 28 million nurses worldwide, and the demand of nurses will put nurse resources into the specific spotlight [ 1 ]. Indeed, evidence could be used to find solutions for how to solve economic deficits or other problems using leadership skills. This is important as, when nurses are able to show leadership and control in their own work, they are less likely to leave their jobs [ 66 ]. On the other hand, based on our discussions with stakeholders, nurse leaders are not used to using evidence in their own work. Further, evidence-based leadership is not possible if nurse leaders do not have access to a relevant, robust body of evidence, adequate funding, resources, and organizational support, and evidence-informed decision making may only offer short-term solutions [ 55 ]. We still believe that implementing evidence-based strategies into the work of nurse leaders may create opportunities to protect this critical workforce from burnout or leaving the field [ 67 ]. However, the role of the evidence-based approach for nurse leaders in solving these problems is still a key question.

Limitations

This study aimed to use a broad search strategy to ensure a comprehensive review but, nevertheless, limitations exist: we may have missed studies not included in the major international databases. To keep search results manageable, we did not use specific databases to systematically search grey literature although it is a rich source of evidence used in systematic reviews and meta-analysis [ 68 ]. We still included published conference abstract/proceedings, which appeared in our scientific databases. It has been stated that conference abstracts and proceedings with empirical study results make up a great part of studies cited in systematic reviews [ 69 ]. At the same time, a limited space reserved for published conference publications can lead to methodological issues reducing the validity of the review results [ 68 ]. We also found that the great number of studies were carried out in western countries, restricting the generalizability of the results outside of English language countries. The study interventions and outcomes were too different across studies to be meaningfully pooled using statistical methods. Thus, our narrative synthesis could hypothetically be biased. To increase transparency of the data and all decisions made, the data, its categorization and conclusions are based on original studies and presented in separate tables and can be found in Additional files. Regarding a methodological approach [ 34 ], we used a mixed methods systematic review, with the core intention of combining quantitative and qualitative data from primary studies. The aim was to create a breadth and depth of understanding that could confirm to or dispute evidence and ultimately answer the review question posed [ 34 , 70 ]. Although the method is gaining traction due to its usefulness and practicality, guidance in combining quantitative and qualitative data in mixed methods systematic reviews is still limited at the theoretical stage [ 40 ]. As an outcome, it could be argued that other methodologies, for example, an integrative review, could have been used in our review to combine diverse methodologies [ 71 ]. We still believe that the results of this mixed method review may have an added value when compared with previous systematic reviews concerning leadership and an evidence-based approach.

Our mixed methods review fills the gap regarding how nurse leaders themselves use evidence to guide their leadership role and what the measured and perceived impact of evidence-based leadership is in nursing. Although the scarcity of controlled studies on this topic is concerning, the available research data suggest that evidence-based leadership intervention can improve nurse performance, organizational outcomes, and patient outcomes. Leadership problems are also well recognized in healthcare settings. More knowledge and a deeper understanding of the role of nurse leaders, and how they can use evidence in their own managerial leadership decisions, is still needed. Despite the limited number of studies, we assume that this narrative synthesis can provide a good foundation for how to develop evidence-based leadership in the future.

Implications

Based on our review results, several implications can be recommended. First, the future of nursing success depends on knowledgeable, capable, and strong leaders. Therefore, nurse leaders worldwide need to be educated about the best ways to manage challenging situations in healthcare contexts using an evidence-based approach in their decisions. This recommendation was also proposed by nurses and nurse leaders during our discussion meeting with stakeholders.

Second, curriculums in educational organizations and on-the-job training for nurse leaders should be updated to support general understanding how to use evidence in leadership decisions. And third, patients and family members should be more involved in the evidence-based approach. It is therefore important that nurse leaders learn how patients’ and family members’ views as stakeholders are better considered as part of the evidence-based leadership approach.

Future studies should be prioritized as follows: establishment of clear parameters for what constitutes and measures evidence-based leadership; use of theories or models in research to inform mechanisms how to effectively change the practice; conducting robust effectiveness studies using trial designs to evaluate the impact of evidence-based leadership; studying the role of patient and family members in improving the quality of clinical care; and investigating the financial impact of the use of evidence-based leadership approach within respective healthcare systems.

Data availability

The authors obtained all data for this review from published manuscripts.

World Health Organization. State of the world’s nursing 2020: investing in education, jobs and leadership. 2020. https://www.who.int/publications/i/item/9789240003279 . Accessed 29 June 2024.

Hersey P, Campbell R. Leadership: a behavioral science approach. The Center for; 2004.

Cline D, Crenshaw JT, Woods S. Nurse leader: a definition for the 21st century. Nurse Lead. 2022;20(4):381–4. https://doi.org/10.1016/j.mnl.2021.12.017 .

Article   Google Scholar  

Chen SS. Leadership styles and organization structural configurations. J Hum Resource Adult Learn. 2006;2(2):39–46.

Google Scholar  

McKibben L. Conflict management: importance and implications. Br J Nurs. 2017;26(2):100–3.

Article   PubMed   Google Scholar  

Haghgoshayie E, Hasanpoor E. Evidence-based nursing management: basing Organizational practices on the best available evidence. Creat Nurs. 2021;27(2):94–7. https://doi.org/10.1891/CRNR-D-19-00080 .

Majers JS, Warshawsky N. Evidence-based decision-making for nurse leaders. Nurse Lead. 2020;18(5):471–5.

Tichy NM, Bennis WG. Making judgment calls. Harvard Business Rev. 2007;85(10):94.

Sousa MJ, Pesqueira AM, Lemos C, Sousa M, Rocha Á. Decision-making based on big data analytics for people management in healthcare organizations. J Med Syst. 2019;43(9):1–10.

Guo R, Berkshire SD, Fulton LV, Hermanson PM. %J L in HS. Use of evidence-based management in healthcare administration decision-making. 2017;30(3): 330–42.

Liang Z, Howard P, Rasa J. Evidence-informed managerial decision-making: what evidence counts?(part one). Asia Pac J Health Manage. 2011;6(1):23–9.

Hasanpoor E, Janati A, Arab-Zozani M, Haghgoshayie E. Using the evidence-based medicine and evidence-based management to minimise overuse and maximise quality in healthcare: a hybrid perspective. BMJ evidence-based Med. 2020;25(1):3–5.

Shingler NA, Gonzalez JZ. Ebm: a pathway to evidence-based nursing management. Nurs 2022. 2017;47(2):43–6.

Farokhzadian J, Nayeri ND, Borhani F, Zare MR. Nurse leaders’ attitudes, self-efficacy and training needs for implementing evidence-based practice: is it time for a change toward safe care? Br J Med Med Res. 2015;7(8):662.

Article   PubMed   PubMed Central   Google Scholar  

American Nurses Association. ANA leadership competency model. Silver Spring, MD; 2018.

Royal College of Nursing. Leadership skills. 2022. https://www.rcn.org.uk/professional-development/your-career/nurse/leadership-skills . Accessed 29 June 2024.

Kakemam E, Liang Z, Janati A, Arab-Zozani M, Mohaghegh B, Gholizadeh M. Leadership and management competencies for hospital managers: a systematic review and best-fit framework synthesis. J Healthc Leadersh. 2020;12:59.

Liang Z, Howard PF, Leggat S, Bartram T. Development and validation of health service management competencies. J Health Organ Manag. 2018;32(2):157–75.

World Health Organization. Global Strategic Directions for Nursing and Midwifery. 2021. https://apps.who.int/iris/bitstream/handle/10665/344562/9789240033863-eng.pdf . Accessed 29 June 2024.

NHS Leadership Academy. The nine leadership dimensions. 2022. https://www.leadershipacademy.nhs.uk/resources/healthcare-leadership-model/nine-leadership-dimensions/ . Accessed 29 June 2024.

Canadian Nurses Association. Evidence-informed decision-making and nursing practice: Position statement. 2018. https://hl-prod-ca-oc-download.s3-ca-central-1.amazonaws.com/CNA/2f975e7e-4a40-45ca-863c-5ebf0a138d5e/UploadedImages/documents/Evidence_informed_Decision_making_and_Nursing_Practice_position_statement_Dec_2018.pdf . Accessed 29 June 2024.

Hasanpoor E, Hajebrahimi S, Janati A, Abedini Z, Haghgoshayie E. Barriers, facilitators, process and sources of evidence for evidence-based management among health care managers: a qualitative systematic review. Ethiop J Health Sci. 2018;28(5):665–80.

PubMed   PubMed Central   Google Scholar  

Collins DB, Holton EF III. The effectiveness of managerial leadership development programs: a meta-analysis of studies from 1982 to 2001. Hum Res Dev Q. 2004;15(2):217–48.

Cummings GG, Lee S, Tate K, Penconek T, Micaroni SP, Paananen T, et al. The essentials of nursing leadership: a systematic review of factors and educational interventions influencing nursing leadership. Int J Nurs Stud. 2021;115:103842.

Clavijo-Chamorro MZ, Romero-Zarallo G, Gómez-Luque A, López-Espuela F, Sanz-Martos S, López-Medina IM. Leadership as a facilitator of evidence implementation by nurse managers: a metasynthesis. West J Nurs Res. 2022;44(6):567–81.

Young SK. Evidence-based management: a literature review. J Nurs Adm Manag. 2002;10(3):145–51.

Williams LL. What goes around comes around: evidence-based management. Nurs Adm Q. 2006;30(3):243–51.

Fraser I. Organizational research with impact: working backwards. Worldviews Evidence-Based Nurs. 2004;1:S52–9.

Roshanghalb A, Lettieri E, Aloini D, Cannavacciuolo L, Gitto S, Visintin F. What evidence on evidence-based management in healthcare? Manag Decis. 2018;56(10):2069–84.

Jaana M, Vartak S, Ward MM. Evidence-based health care management: what is the research evidence available for health care managers? Eval Health Prof. 2014;37(3):314–34.

Tate K, Hewko S, McLane P, Baxter P, Perry K, Armijo-Olivo S, et al. Learning to lead: a review and synthesis of literature examining health care managers’ use of knowledge. J Health Serv Res Policy. 2019;24(1):57–70.

Geerts JM, Goodall AH, Agius S, %J SS. Medicine. Evidence-based leadership development for physicians: a systematic literature review. 2020;246: 112709.

Barends E, Rousseau DM, Briner RB. Evidence-based management: The basic principles. Amsterdam; 2014. https://research.vu.nl/ws/portalfiles/portal/42141986/complete+dissertation.pdf#page=203 . Accessed 29 June 2024.

Stern C, Lizarondo L, Carrier J, Godfrey C, Rieger K, Salmond S, et al. Methodological guidance for the conduct of mixed methods systematic reviews. JBI Evid Synthesis. 2020;18(10):2108–18. https://doi.org/10.11124/JBISRIR-D-19-00169 .

Lancet T. 2020: unleashing the full potential of nursing. Lancet (London, England). 2019. p. 1879.

Välimäki MA, Lantta T, Hipp K, Varpula J, Liu G, Tang Y, et al. Measured and perceived impacts of evidence-based leadership in nursing: a mixed-methods systematic review protocol. BMJ Open. 2021;11(10):e055356. https://doi.org/10.1136/bmjopen-2021-055356 .

The Joanna Briggs Institute. Joanna Briggs Institute reviewers’ manual: 2014 edition. Joanna Briggs Inst. 2014; 88–91.

Pearson A, White H, Bath-Hextall F, Salmond S, Apostolo J, Kirkpatrick P. A mixed-methods approach to systematic reviews. JBI Evid Implement. 2015;13(3):121–31.

Johnson RB, Onwuegbuzie AJ. Mixed methods research: a research paradigm whose time has come. Educational Researcher. 2004;33(7):14–26.

Hong, Pluye P, Bujold M, Wassef M. Convergent and sequential synthesis designs: implications for conducting and reporting systematic reviews of qualitative and quantitative evidence. Syst Reviews. 2017;6(1):61. https://doi.org/10.1186/s13643-017-0454-2 .

Ramis MA, Chang A, Conway A, Lim D, Munday J, Nissen L. Theory-based strategies for teaching evidence-based practice to undergraduate health students: a systematic review. BMC Med Educ. 2019;19(1):1–13.

Sackett DL, Rosenberg WM, Gray JM, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn’t. Bmj. British Medical Journal Publishing Group; 1996. pp. 71–2.

Goodman JS, Gary MS, Wood RE. Bibliographic search training for evidence-based management education: a review of relevant literatures. Acad Manage Learn Educ. 2014;13(3):322–53.

Aromataris E, Munn Z. Chapter 3: Systematic reviews of effectiveness. JBI Manual for Evidence Synthesis. 2020; https://synthesismanual.jbi.global .

Munn Z, Barker TH, Moola S, Tufanaru C, Stern C, McArthur A et al. Methodological quality of case series studies: an introduction to the JBI critical appraisal tool. 2020;18(10): 2127–33.

Hong Q, Pluye P, Fàbregues S, Bartlett G, Boardman F, Cargo M, et al. Mixed methods Appraisal Tool (MMAT) Version 2018: user guide. Montreal: McGill University; 2018.

McKenna J, Jeske D. Ethical leadership and decision authority effects on nurses’ engagement, exhaustion, and turnover intention. J Adv Nurs. 2021;77(1):198–206.

Maxwell M, Hibberd C, Aitchison P, Calveley E, Pratt R, Dougall N, et al. The TIDieR (template for intervention description and replication) checklist. The patient Centred Assessment Method for improving nurse-led biopsychosocial assessment of patients with long-term conditions: a feasibility RCT. NIHR Journals Library; 2018.

Braun V, Clarke V. Using thematic analysis in psychology. Qualitative Res Psychol. 2006;3(2):77–101.

Pollock A, Campbell P, Struthers C, Synnot A, Nunn J, Hill S, et al. Stakeholder involvement in systematic reviews: a scoping review. Syst Reviews. 2018;7:1–26.

Braye S, Preston-Shoot M. Emerging from out of the shadows? Service user and carer involvement in systematic reviews. Evid Policy. 2005;1(2):173–93.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Syst Reviews. 2021;10(1):1–11.

Porta M. Pilot investigation, study. A dictionary of epidemiology. Oxford University Press Oxford; 2014. p. 215.

Kreis J, Puhan MA, Schünemann HJ, Dickersin K. Consumer involvement in systematic reviews of comparative effectiveness research. Health Expect. 2013;16(4):323–37.

Joseph ML, Nelson-Brantley HV, Caramanica L, Lyman B, Frank B, Hand MW, et al. Building the science to guide nursing administration and leadership decision making. JONA: J Nurs Adm. 2022;52(1):19–26.

Gifford W, Davies BL, Graham ID, Tourangeau A, Woodend AK, Lefebre N. Developing Leadership Capacity for Guideline Use: a pilot cluster Randomized Control Trial: Leadership Pilot Study. Worldviews Evidence-Based Nurs. 2013;10(1):51–65. https://doi.org/10.1111/j.1741-6787.2012.00254.x .

Hsieh HY, Henker R, Ren D, Chien WY, Chang JP, Chen L, et al. Improving effectiveness and satisfaction of an electronic charting system in Taiwan. Clin Nurse Specialist. 2016;30(6):E1–6. https://doi.org/10.1097/NUR.0000000000000250 .

McAllen E, Stephens K, Swanson-Biearman B, Kerr K, Whiteman K. Moving Shift Report to the Bedside: an evidence-based Quality Improvement Project. OJIN: Online J Issues Nurs. 2018;23(2). https://doi.org/10.3912/OJIN.Vol23No02PPT22 .

Thomas M, Autencio K, Cesario K. Positive outcomes of an evidence-based pressure injury prevention program. J Wound Ostomy Cont Nurs. 2020;47:S24.

Cullen L, Titler MG. Promoting evidence-based practice: an internship for Staff nurses. Worldviews Evidence-Based Nurs. 2004;1(4):215–23. https://doi.org/10.1111/j.1524-475X.2004.04027.x .

DuBose BM, Mayo AM. Resistance to change: a concept analysis. Nursing forum. Wiley Online Library; 2020. pp. 631–6.

Lalleman PCB, Smid GAC, Lagerwey MD, Shortridge-Baggett LM, Schuurmans MJ. Curbing the urge to care: a bourdieusian analysis of the effect of the caring disposition on nurse middle managers’ clinical leadership in patient safety practices. Int J Nurs Stud. 2016;63:179–88.

Article   CAS   PubMed   Google Scholar  

Martin E, Warshawsky N. Guiding principles for creating value and meaning for the next generation of nurse leaders. JONA: J Nurs Adm. 2017;47(9):418–20.

Griffiths P, Recio-Saucedo A, Dall’Ora C, Briggs J, Maruotti A, Meredith P, et al. The association between nurse staffing and omissions in nursing care: a systematic review. J Adv Nurs. 2018;74(7):1474–87. https://doi.org/10.1111/jan.13564 .

Lúanaigh PÓ, Hughes F. The nurse executive role in quality and high performing health services. J Nurs Adm Manag. 2016;24(1):132–6.

de Kok E, Weggelaar-Jansen AM, Schoonhoven L, Lalleman P. A scoping review of rebel nurse leadership: descriptions, competences and stimulating/hindering factors. J Clin Nurs. 2021;30(17–18):2563–83.

Warshawsky NE. Building nurse manager well-being by reducing healthcare system demands. JONA: J Nurs Adm. 2022;52(4):189–91.

Paez A. Gray literature: an important resource in systematic reviews. J Evidence-Based Med. 2017;10(3):233–40.

McAuley L, Tugwell P, Moher D. Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses? Lancet. 2000;356(9237):1228–31.

Sarah S. Introduction to mixed methods systematic reviews. https://jbi-global-wiki.refined.site/space/MANUAL/4689215/8.1+Introduction+to+mixed+methods+systematic+reviews . Accessed 29 June 2024.

Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546–53.

Download references

Acknowledgements

We want to thank the funding bodies, the Finnish National Agency of Education, Asia Programme, the Department of Nursing Science at the University of Turku, and Xiangya School of Nursing at the Central South University. We also would like to thank the nurses and nurse leaders for their valuable opinions on the topic.

The work was supported by the Finnish National Agency of Education, Asia Programme (grant number 26/270/2020) and the University of Turku (internal fund 26003424). The funders had no role in the study design and will not have any role during its execution, analysis, interpretation of the data, decision to publish, or preparation of the manuscript.

Author information

Authors and affiliations.

Department of Nursing Science, University of Turku, Turku, FI-20014, Finland

Maritta Välimäki, Tella Lantta, Kirsi Hipp & Jaakko Varpula

School of Public Health, University of Helsinki, Helsinki, FI-00014, Finland

Maritta Välimäki

Xiangya Nursing, School of Central South University, Changsha, 410013, China

Shuang Hu, Jiarui Chen, Yao Tang, Wenjun Chen & Xianhong Li

School of Health and Social Services, Häme University of Applied Sciences, Hämeenlinna, Finland

Hunan Cancer Hospital, Changsha, 410008, China

Gaoming Liu

You can also search for this author in PubMed   Google Scholar

Contributions

Study design: MV, XL. Literature search and study selection: MV, KH, TL, WC, XL. Quality assessment: YT, SH, XL. Data extraction: JC, MV, JV, WC, YT, SH, GL. Analysis and interpretation: MV, SH. Manuscript writing: MV. Critical revisions for important intellectual content: MV, XL. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xianhong Li .

Ethics declarations

Ethics approval and consent to participate.

No ethical approval was required for this study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Differences between the original protocol

We modified criteria for the included studies: we included published conference abstracts/proceedings, which form a relatively broad knowledge base in scientific knowledge. We originally planned to conduct a survey with open-ended questions followed by a face-to-face meeting to discuss the preliminary results of the review. However, to avoid extra burden in nurses due to COVID-19, we decided to limit the validation process to the online discussion only.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary material 2, supplementary material 3, supplementary material 4, supplementary material 5, supplementary material 6, supplementary material 7, supplementary material 8, supplementary material 9, supplementary material 10, rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Välimäki, M., Hu, S., Lantta, T. et al. The impact of evidence-based nursing leadership in healthcare settings: a mixed methods systematic review. BMC Nurs 23 , 452 (2024). https://doi.org/10.1186/s12912-024-02096-4

Download citation

Received : 28 April 2023

Accepted : 13 June 2024

Published : 03 July 2024

DOI : https://doi.org/10.1186/s12912-024-02096-4

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Evidence-based leadership
• Health services administration
• Organizational development
• Quality in healthcare

BMC Nursing

ISSN: 1472-6955

• General enquiries: [email protected]

• Open access
• Published: 27 June 2024

An overview of CCN4 (WISP1) role in human diseases

• Kirti Singh 1 &
• Sunday S. Oladipupo 1  

Journal of Translational Medicine volume  22 , Article number:  601 ( 2024 ) Cite this article

210 Accesses

Metrics details

CCN4 (cellular communication network factor 4), a highly conserved, secreted cysteine-rich matricellular protein is emerging as a key player in the development and progression of numerous disease pathologies, including cancer, fibrosis, metabolic and inflammatory disorders. Over the past two decades, extensive research on CCN4 and its family members uncovered their diverse cellular mechanisms and biological functions, including but not limited to cell proliferation, migration, invasion, angiogenesis, wound healing, repair, and apoptosis. Recent studies have demonstrated that aberrant CCN4 expression and/or associated downstream signaling is key to a vast array of pathophysiological etiology, suggesting that CCN4 could be utilized not only as a non-invasive diagnostic or prognostic marker, but also as a promising therapeutic target. The cognate receptor of CCN4 remains elusive till date, which limits understanding of the mechanistic insights on CCN4 driven disease pathologies. However, as therapeutic agents directed against CCN4 begin to make their way into the clinic, that may start to change. Also, the pathophysiological significance of CCN4 remains underexplored, hence further research is needed to shed more light on its disease and/or tissue specific functions to better understand its clinical translational benefit. This review highlights the compelling evidence of overlapping and/or diverse functional and mechanisms regulated by CCN4, in addition to addressing the challenges, study limitations and knowledge gaps on CCN4 biology and its therapeutic potential.

Introduction

Extracellular matrix (ECM) proteins, including but not limited to collagens, fibronectins, and elastin, provide structural stability and physical framework for cellular organization across all mammalian tissues and organs. In addition to physical scaffolding, ECM proteins play a crucial role in regulating cellular processes by interacting with cell surface receptors, cytokines, growth factors and other extracellular proteins. These regulatory functions are primarily driven by a subgroup of ECM proteins known as matricellular proteins which are non-structural in nature. Matricellular proteins, such as secreted protein acidic and rich in cysteine (SPARC)-protein family, thrombospondin, periostin, osteopontin and fibulins amongst others are multidomain proteins that are secreted in the ECM and are critical for day-to-day physiological processes, including cell proliferation, migration, and adhesion [ 1 ].

In addition to other known matricellular proteins, CCN family members are highly conserved, secreted multi-modular cysteine rich proteins, composed of six homologous proteins. The first three family members namely, (i) cysteine-rich protein 61 (Cyr61), (ii) connective tissue growth factor (CTGF) and (iii) nephroblastoma overexpressed (NOV) were discovered in early 1990’s which led to the acronym CCN based on their order of discovery. CCN is also abbreviated for “Cellular Communication Network” [ 2 ]. The other three members were discovered in the late 1990’s and were associated with Wnt-1 induced signaling pathway and hence were named, (iv) Wnt-1 induced secreted protein-1 (WISP1), (v) WISP2 and (vi) WISP3. Over the past two decades, extensive research on CCN family members uncovered their diverse cellular and biological functions, designating them with alternative names listed in Table  1 . The International CCN Society proposed a unifying nomenclature for the CCN family members to avoid confusion due to numerous synonymic names interchangeably used in scientific literature [ 3 ]. In 2018, the HUGO (Human Genome Organization) Gene Nomenclature Committee officially approved and adapted the new names CCN1-6 for the family members [ 2 , 3 ]. For this review, these proteins are named CCN1-CCN6, in accordance with the official nomenclature recommendations.

Based on PubMed (R) database, there are over 3000 publications on CCN protein family, out of which surprisingly more than 2900 studies primarily focus on CCN2 and only about 300 publications focus on CCN4, highlighting the dearth of literature and disparity towards other CCN members. Despite the overwhelming attention given to CCN protein family, relatively little is known about the role of CCN4 both in human health and diseases. Notably, the role of CCN4 has been previously studied and reviewed by researchers in a disease specific context [ 4 , 5 ]. However, here, we aim to comprehensively review the growing body of literature on the diverse functions of CCN4 and its role in a vast array of pathophysiological conditions, including cancer, fibrosis, inflammatory conditions (i.e., arthritis) and metabolic disorders, including obesity and diabetes.

CCN4 overview

CCN4 is the fourth member of the CCN family, commonly known as WISP1. The earliest study published on CCN4 dates back to the late 1990s where Pennica and colleagues first identified CCN4 in mouse mammary epithelial cells and its role in tumorigenesis [ 6 ]. WISP1 gene on chromosome 8q24.22 in humans encodes the 367 amino acid CCN4 protein with a predicted molecular mass of approximately 40 kDa. The murine and human CCN4 cDNA length is 1766 and 2830 bases, respectively, comprising of four introns and five exons [ 6 , 7 ]. Structurally, all CCN family members are characterized by four conserved cysteine rich domains, except CCN5 which lacks domain 4. The N-terminus of CCN proteins consists of a signal peptide sequence, essential for secretory proteins, which is followed by four structural domains named based on the sequence homology to (i) insulin-like growth factor binding protein like domain (IGFBP; domain 1), (ii) the von Willebrand factor C repeat (VWC; domain 2), (iii) thrombospondin-homology type 1 repeat (TSP1; domain 3) and (iv) the C-terminal Cysteine knot containing domain (CT; domain 4) as shown in Fig.  1 . The protein sequence contains 38 conserved cysteine residues, distributed across domain 1 (12 cysteine residues), domain 2 (10 cysteine residues), domain 3 (6 cysteine residues), and domain 4 (10 cysteine residues). CCN4 shares approximately 39%, 37% and 42% amino acid sequence homology to CCN2, CCN5 and CCN6, respectively [ 8 , 9 ].

Multi-modular structure of CCN family. All the CCN matricellular proteins consist of a signal peptide (SP), insulin-like growth factor binding protein like domain (IGFBP; domain 1), von Willebrand factor C repeat (VWC; domain 2), thrombospondin-homology type 1 repeat (TSP1; domain 3) and C-terminal Cysteine knot containing domain (CT; domain 4) encoded by exon 1 to exon 5 respectively. Domain 2 and domain 4 are connected by a variable hinge region which is highly susceptible to cleavage by proteolytic enzymes such as, Kallikrein-related peptidases 12 (KLK12), a disintegrin and metalloproteinase domain-containing protein 28 (ADAM28) and matrix metalloproteases (MMPs). Domain specific total cysteine residues and binding partners are also listed in the table. The image was created with BioRender.com. IGFBP: insulin-like growth factor binding protein; VWC: von Willebrand factor C repeat; TSP1: thrombospondin-homology type 1 repeat; CT: C-terminal Cysteine knot containing domain; IGF: insulin-like growth factors; BMP4: bone morphogenic protein 4; LRP1: Low density lipoprotein receptor-related protein 1; HSPGs: heparin sulphate proteoglycans; TGF-β: transforming growth factor beta

CCN family proteins have been shown to physically bind and interact with a plethora of multi-ligand receptors and proteins, ranging from ECM proteins (such as fibronectin [ 10 , 11 ], vitronectin [ 12 ], perlecan [ 13 ], integrins [ 14 , 15 , 16 ], growth factors (such as fibroblast growth factors (FGFs) [ 17 , 18 , 19 ], vascular endothelial growth factor (VEGF) [ 20 ], bone morphogenetic protein (BMP) [ 21 ] and transforming growth factor (TGF-β) [ 21 ], proteoglycans (such as heparan sulfate proteoglycans (HSPG) [ 22 , 23 , 24 ], aggrecan, decorin and biglycan [ 25 ] and low-density lipoprotein receptor-related proteins (LRP) [ 26 , 27 ], cation-independent mannose-6-phosphate [ 28 ], Neurogenic locus notch homolog protein (Notch) [ 29 ], and receptor activator of nuclear factor kappa B (NF-κB) (RANK) [ 9 , 30 , 31 ]. Despite abundance of binding partners available for CCN family of proteins, CCN4 has only been shown to interact with integrins [ 32 , 33 ] and small leucine rich proteoglycans, such as decorin and biglycan [ 25 ], and domain specific binding sites that facilitate these interactions remain unknown, owing to the bias towards other CCN members, particularly CCN1 and CCN2.

Post-translational modifications (PTMs) play a crucial role in structural and functional characteristics of a protein. With respect to the CCN family, four potential N-glycosylation sites have been identified in CCN4 [ 6 ]. Similar glycosylation patterns have also been observed in CCN2, particularly at asparagine 28 and 225 leading to either 36 kDa or 38 kDa molecular weight that appears as a double band upon immunoblotting [ 34 , 35 ]. Furthermore, researchers have also demonstrated that the glycosylated versus non-glycosylated ratio of CCN3 profoundly influences the cell proliferative, migrative and invasive properties of chondrosarcoma cell line Jeg3 [ 36 ]. Differences in the glycosylation patterns between normal and cancerous cells have also been reported, highlighting its functional significance in disease pathologies [ 37 ]. Besides glycosylation, O-fucosylation (O-linked fucose modification) has been recently identified in the TSP domain 3 of CCN2 protein [ 38 ]. Overall, these PTMs could be exploited to modulate CCN4 function; yet the PTM analysis in CCN family remains in its infancy, and more research is needed to shed more light on its clinical significance.

As previously mentioned, CCN genes contain four introns and five exons. Each of the exon codes for each domain in the structure. The N-terminus signal peptide is encoded by exon 1, whereas domain 1–4 are encoded by exon 2–5, respectively. From the evolutionary perspective, the order of CCN domains remains highly conserved and are connected through a linker. The linker connecting domain 1–2 (3aa) and domain 3–4 (9aa) in CCN4 structure are relatively short compared to domain 2–3 hinge (27aa) which makes it susceptible to proteolytic cleavage by protease enzymes, such as matrix metalloproteases (MMPs) generating truncated versions of the protein. The central variable linker has been shown to be targeted by MMP1, MMP3, MMP 7, MMP9, MMP13, MMP14 along with other peptidases, such as disintegrin and metalloproteinase domain-containing protein 28 (ADAM28), Kallikrein-related peptidases 12 (KLK12), plasmin and elastase [ 39 , 40 , 41 , 42 ]. Experimentally, the protease mediated degradome pattern has been extensively elucidated for CCN1, CCN2, CCN3 and CCN5 [ 39 , 43 , 44 , 45 ]. While the cleavage sites for CCN4 remain undiscovered, researchers have identified three truncated versions in biological samples as shown in Fig. 2 . In addition, the CCN4 mRNA is also subjected to alternative splicing, which can result in truncated variants of proteins, lacking one or more domains [ 46 ]. In 2001, Tanaka and colleagues reported a novel truncated CCN4 variant (Mol. Wt. 30 kDa), commonly known as WISP1v lacking domain 2 or VWR module as a product of alternative splicing in human scirrhous gastric carcinoma tissue [ 47 ]. Stable transfection of this variant increased gastric carcinoma cell migration up to five-fold as compared to full length CCN4 in a co-culture Boyden Chamber. Later in 2003, they also detected CCN4 truncated variant, WISP1v in human invasive cholangiocarcinoma tissues [ 48 ]. Further, in 2008, Inksonand colleagues at the National Institutes of Health (NIH) detected a similar CCN4 spliced variant lacking exon 3 in human bone marrow stromal cells (hBMSC) using RT-PCR, which they referred to as WISP1va [ 49 ]. In 2004, another truncated variant of CCN4, lacking domain 2, 3 and 4, also known as WISP1Δex3-4 was reported in 4 different human hepatocellular carcinoma cell lines (HuH-6, HuH-7, VGH and HepG2) in conjugation with full length and WISP1v. WISP1Δex3-4 variant only contains IGFBP/ domain 1 due to the alternative splicing of mRNA. The transcript contains exon 1, 2 and 5, however the conjugation of exon 2 and 5 causes a frame shift at residue 117, resulting in a premature stop of the reading frame and hence only translating to domain 1 [ 50 ]. Similarly, WISP1Δex3-4 truncated variant was also detected in chondrocytes derived from human chondrosarcoma cell line (HCS-2/8) and rabbit growth cartilage [ 51 ]. Although the functional significance of full length CCN4 has been extensively demonstrated, the domain specific activity remains unknown till date despite the detection of CCN4 truncated versions in human tissues.

Functional effects of CCN4 Truncated variants. The image was created with BioRender.com

Meanwhile, emerging evidence in the literature suggests that CCN4 can in turn modulate MMP expression. CCN4 treatment for 24 h in human chondrosarcoma cell line, JJ012 increased MMP2 expression in cell lysate and supernatant, detected at both protein and transcript level utilizing western blot and qPCR [ 33 ]. Further, CCN4 has also been shown to promote cell motility by upregulating MMP2 and MMP9 expression in human osteosarcoma cell line, U2OS as pretreatment with selective MMP2 and MMP9 inhibitors abrogated CCN4 induced wound healing and migration [ 32 ]. In addition, stimulation of murine macrophages (RAW 264.7), primary human chondrocytes and synovial cells with CCN4 (1.0 µg/ml) for 24 h upregulates MMP3 and MMP9 expression [ 52 ]. Also, CCN4 drives MMP2 and MMP9 expression in murine primary renal tubular epithelial cells as shRNA mediated CCN4 knockdown decreased MMP2 and MMP9 [ 53 ]. Finally, CCN4 has also been shown to upregulate the expression of MMP1, MMP2, MMP3, MMP9 and MMP14 in vein smooth muscle cells via β-catenin mediated pathways. CCN4 mediated MMP9 induction is partly due to activator protein-1 (AP-1) [ 54 ].

The control exercised by CCN4 on the MMPs can drive cell motility via two distinct, though parallel mechanisms. The observations derived from literature unveil that CCNs can indirectly influence cell motility by upregulating MMPs, which drives ECM degradation, facilitating cell migration and invasion [ 55 ]. Another direct mechanism by which CCN4 can influence cellular processes could be through MMP-dependent self-regulation, where CCN4-induced MMP can in turn act on CCN4 itself to generate different truncated versions of the protein. Depending on the tissue expression profile of MMP subtypes and their corresponding CCN4 cleavage sites, these truncated variants can possess similar and/or unique functional signature as compared to the full length CCN4 protein. Further, alterations in CCN4 expression profile have been observed in a plethora of diseases, ranging from cancer [ 56 ], liver fibrosis [ 57 ], idiopathic pulmonary fibrosis (IPF) [ 58 , 59 , 60 ], obesity and type 2 diabetes mellitus [ 61 , 62 ], amongst others. The CCN-MMP interplay can continue to regulate one another, leading to a vicious positive-feedback cycle which can potentially aggravate the underlying condition by generating truncated CCN4 which could be responsible for diverse cellular functions. Taken together, CCN4 mediated regulation of MMPs is a highly complex, expression dependent, cell type and tissue-specific mechanism which yet remains underexamined and warrants further investigation.

In humans, CCN4 expression has been confirmed in various organs, such as lung, heart, kidney, pancreas, placenta, brain, small intestine, ovaries, and skeletal muscle, amongst others [ 6 ]. Within the organs, the expression is cell type specific. For example, CCN4 is mainly expressed in fibroblasts (lung [ 63 ], liver [ 57 ], heart [ 64 ]), epithelial cells (lung) [ 60 ], cardiomyocytes (heart) [ 65 ], neurons [ 66 ], microglia (brains) [ 67 ], chondrocytes [ 33 ], osteoblast (bone) [ 32 ] and many more. The diverse expression profile endows CCN4 protein with pleotropic functions in a tissue and cell specific manner. CCN4 plays a crucial role in cell proliferation, migration, adhesion, wound healing and repair in embryogenesis, fibrosis, tumorigenesis, osteoarthritis, etc. [ 68 ]. In addition, differential expression of CCN4 has been attributed to numerous diseases, which can be utilized as a prognostic biomarker.

CCN4 in cancer

Cancer represents a global health issue with increasing cases every year [ 69 ]. According to the national cancer society, cancer is the second leading cause of death, with approximately 1 in 3 people suffering in the US. Recent technological advances in cellular and molecular biology have opened endless avenues for the development of targeted anti-cancer treatment, ranging from stem-cell therapy, gene therapy to targeted precision therapy [ 70 ]. Differential gene expression and novel biomarker discovery efforts help identify promising druggable targets with potential therapeutic benefits in the clinic. CCN4 is one such recently identified protein which plays a crucial role in inflammation and tumorigenesis [ 71 ].

Over two decades, numerous studies have investigated the role of CCN4 in tumor microenvironment, however the ambiguous expression profile and paradoxical functional outcomes of CCN4 in various cancers makes it a challenging yet controversial target. Generally, CCN4 dysregulation and atypical expression profile have been linked in a range of pathophysiological conditions, such as fibrosis, diabetes, obesity etc. [ 57 , 72 ]. Similar aberrant expression profile has been observed in various cancer types as well. For instance, CCN4 is upregulated in a vast array of cancer tissue specimens compared to healthy controls, such as lung cancer [ 73 ], ovarian cancer [ 74 ], colon cancer [ 75 ], gastric cancer [ 76 ], breast cancer [ 77 ] and esophageal squamous cell carcinoma [ 78 ], among others. CCN4 is also characterized as an oncogene, that promotes tumor progression by positively regulating pro-oncogenic cellular functions, like cell proliferation, migration, and invasion. In addition, higher CCN4 protein levels were associated with low survival rate in cancer patients [ 79 , 80 , 81 ]. In contrast, others have reported tumor suppressive nature of CCN4, promoting cellular apoptosis whilst inhibiting cell growth, migration, invasion, and metastasis. Many researchers have also reported CCN4 downregulation in breast cancer [ 82 , 83 ], liver cancer [ 84 ] and skin cancer [ 85 ]. The discrepancies could also be attributed to other confounding variables, such as patient family-history, age, gender, co-morbidities, treatment regimen, cancer-type, cancer-stage, tumor size etc., however in-depth analysis is required before establishing any correlation. Rather than simply distinguishing all diseased patients as either high or low expressers, some studies also segregate the diseased cohort into two groups, CCN4 low and high expressing patients based on the expression profile [ 79 , 80 , 81 ]. The spatial and temporal tumor heterogeneity leads to a complex dynamic cellular state which can also govern the distinct CCN4 expression patterns. A summary of the functional and mechanistic effects of CCN4 on diverse tumor types, along with the expression patterns is provided in Table  2 .

Tumor microenvironment is composed of cancer cells, stromal cells, such as immune cells, fibroblasts, endothelial cells in conjunction with ECM, all of which are constantly communicating and influencing each other via cytokines, chemokines and inflammatory signaling molecules [ 86 ]. Although numerous cell-based and animal experimental models have been utilized to study the effect of CCN4 in cancer, majority of the studies are conducted in an isolated single cancer cell line model, which fails to capture the intricate crosstalk amongst different cell types within the tumor microenvironment. Given that CCN4 is a secreted protein, better understanding of both autocrine and paracrine effects is crucial to decipher the functional disparity and clinical significance of CCN4 to develop novel pharmacological interventions targeting CCN4 in cancer [ 87 ]. Furthermore, mechanistic data is derived from either loss-of function approach, including shRNA, siRNA or CRISPR mediated transcriptional repression or protein overexpression approach using viral vector. Every experimental approach has its own caveats, here both approaches may fail to capture the true function of endogenous CCN4 due to the off-target effects and lack of specificity leading to partial loss-of function or by attaining supraphysiological protein levels [ 88 , 89 ]. Some studies also utilize recombinant CCN4 protein to understand its biology, which has its own drawbacks. Besides the time-consuming and costly process, the multi-modular structure of CCN4 is susceptible to proteolytic cleavage generating functionally active or in-active truncated variants. Additionally, species to species variations in post-translational modification patterns could also influence the biological activity of the protein [ 90 ]. Hence, caution must be exercised while interpreting the functional consequences of full-length CCN4 protein.

Molecular pathways governing CCN4 mediated cellular oncogenic responses remains undiscovered, due to the lack of one CCN-specific cognate receptor. However, within the limited available literature, integrins have been identified as the major contributors in driving CCN4-dependent biological responses. Researchers have shown that CCN4 binds and interacts with integrins, such as, αVβ1, αVβ3, αVβ5, α4β1, α5β1 and α6β1 in myriad cancerous conditions to drive cell proliferation, migration, invasion etc. making them one of the most extensively documented functionally significant receptors for CCN4 till date [ 32 , 33 , 37 , 74 , 87 , 91 , 92 , 93 , 94 , 95 ]. In addition, CCN4 polymorphism directly influences the risk of developing tumor [ 96 , 97 ], disease progression [ 98 ], response to chemotherapy toxicity [ 99 ] and CCN4 expression via epigenetic modulation such as DNA methylation [ 100 ].

CCN4 in fibrosis

Fibroblasts are highly plastic cells with mesenchymal origin found throughout the body to provide structural integrity and basic framework for cells and tissues. Fibroblasts are elongated stellate shaped cells that are most commonly present in the stroma. They are responsible for maintaining, synthesizing, and organizing ECM proteins, such as collagen, fibronectin (FN1), laminins etc. and therefore, play a key role in wound healing and tissue repair [ 128 ]. Mechanical or chemical stimuli from the site of injury can activate the otherwise quiescent tissue resident fibroblasts and initiate their transformation into myofibroblasts. Under physiological homeostasis, once the wound healing and repair has been completed, myofibroblasts undergo apoptosis to prevent excessive ECM deposition. However, chronic persistent injury and insult, can dysregulate and disrupt the body’s natural restorative process, leading to excessive ECM deposition, tissue scarring and architectural remodeling, loss of tissue elasticity and function, resulting in fibrosis [ 129 ]. Fibrosis is the most common pathological outcome in chronic inflammatory conditions related to lungs (Idiopathic pulmonary fibrosis; IPF), skin (scleroderma), kidney diseases, liver, and heart (cardiac fibrosis) [ 130 ].

Fibrosis is a chronic, highly progressive, and irreversible condition that is the leading cause of organ dysfunction and death. Although, two FDA (Food and Drug Administration) approved drugs, Nintedanib and Pirfenidone provide symptomatic relief in IPF, there are currently no drugs that address the underlying cause to cure fibrosis [ 131 ]. Emerging evidence indicates that CCN4 protein is pro-fibrotic in nature and modulates fibroblast proliferation. CCN4 is highly upregulated in both pre-clinical bleomycin model of pulmonary fibrosis, paraquat induced model [ 132 , 133 ] and in clinical IPF patients compared to non-diseased control. Furthermore, Klee and colleagues demonstrated that CCN4 is downstream of TGF-β and TNF-α, which are the master regulators of fibrosis and inflammation. CCN4 promotes the proliferation of human lung fibroblast in an IL-6 dependent manner as siRNA mediated knockdown or antibody-mediated neutralization of CCN4 abrogates the effect [ 63 ]. The CCN4 upregulation could be partly due to the downstream effects of TGF-β in conjunction with the downregulation of microRNAs (miRNAs), particularly miR-92a, which has been shown to modulate CCN4 expression. miR-92a expression is inversely corelated with CCN4 expression in IPF patient lung specimens [ 134 ]. In addition, miR-101 and miR-181a-5p regulate CCN4 expression in cystic fibrosis [ 135 ]. Airway epithelial cells not only act as the first line of defense against environmental threats but also serve as a dynamic junction to relay the extracellular signal to other immune cells that underlay smooth muscle cells, fibroblasts and myofibroblasts. Chronic epithelial insult and dysfunction have been attributed to the pathogenesis of asthma and IPF [ 136 , 137 , 138 ]. Heise and colleagues demonstrated that mechanical stress and stretch can induce CCN4 expression in primary mouse type II alveolar epithelial cells (AT-II cells) and drive epithelial to mesenchymal transition (EMT). Further, CCN4 neutralizing antibody significantly abrogated stretch induced EMT, emphasizing the critical role of CCN4 in EMT [ 139 ]. Similar findings were validated by another group, where treatment with recombinant CCN4 (1 µg/ml) promoted cell proliferation and EMT in primary mouse AT-II cells. In addition, stimulation with CCN4 (1 µg/ml) for 6 to 12 h upregulates fibrotic genes, such as Col1A1, Col1A2 and FN1 in mouse and human fibroblasts and the effects were attenuated in the presence of a CCN4 neutralizing antibody in the bleomycin model [ 60 ]. CCN4 mediated cell adhesion in airway epithelial cells (A549) is partly mediated by integrins, as αVβ5, αVβ3 or αVβ1 neutralizing antibodies partially blocked the effect [ 140 ]. Irradiation has been shown to upregulate CCN4 expression in human lung fibroblasts with implications in radiation-induced lung injury in cancer patients [ 141 ]. Nintedanib, a small molecule receptor tyrosine kinase inhibitor, approved for IPF has also been shown to regulate Wnt/β-catenin pathway and prevent myofibroblast activation by inhibiting CCN4 in mouse lung myofibroblast cell line, Mlg [ 142 ]. Furthermore, secreted CCN4 was significantly decreased upon treatment with Nintedanib (1 µM) in ex-vivo 3D-human lung tissue. While CCN4 levels remained unaffected upon treatment with Pirfenidone (500 µM) detected by ELISA (Enzyme-linked immunosorbent assay) [ 143 ]. However, in another study, both Nintedanib (0.3 µM) and Pirfenidone (1 mM) reduced in precision cut rat-lung slices [ 144 ]. CCN4 can also facilitate inflammatory response in fibrosis. In addition to IL6 and CCL2 production [ 63 , 145 ]. CCN4 also mediates the release of the proinflammatory cytokine TNF-α from macrophages (RAW264.7) in an integrin αVβ3 dependent manner and regulates TLR4 signaling in an acute lung injury pre-clinical model [ 146 ].

Apart from pulmonary fibrosis, CCN4 has also been involved in liver fibrosis and inhibition of CCN4 can reverse liver fibrosis [ 147 , 148 , 149 ]. Stimulation with pro-fibrotic/ pleotropic cytokines, such as TGF-β and TNF-α increased CCN4 induction in-vitro in hepatic stellate cell lines (LX-2 and HSC-T6/ HSC). In addition, recombinant CCN4 drives LX-2 cell proliferation in a dose-dependent manner. CCN4 protein expression was also significantly upregulated in-vivo in carbon tetrachloride (CCl 4 )-induced liver fibrosis model [ 148 ] and CCN4 antibody significantly decreased pro-fibrotic protein expression (collagen, α-smooth muscle actin (αSMA), TGF-β1), reduced liver necrosis, NF-κB activation and pro-inflammatory cytokine production, such as IL-6, CCL-2 and TNF-α [ 149 ]. Huang and colleagues utilized RNA sequencing analysis to identify a set of differentially expressed genes in ex-vivo precision-cut lung tissue slice to design a robust biomarker panel to assess antifibrotic effects of various interventions. CCN4 was amongst other genes and secretory proteins in the panel and was used as a reliable end point parameter to evaluate the efficacy and anti-fibrotic activity of the compounds [ 144 ]. Interestingly, as the molecular mechanisms driving the initiation and progression of fibrosis remain poorly understood, recent study identified a novel pathway dissecting the role of CCN4 in the progression of liver fibrosis and not initiation of the disease as CCN4 knockout animals were protected against liver-fibrosis progression in pre-clinical CCl 4 -liver fibrosis and choline-deficient, L-amino-acid-defined, along with the high-fat diet (CDA-HFD)-induced NASH models. Furthermore, functional analysis confirmed that CCN4 mediated fibrogenesis and myofibroblast motility is partly driven by integrin (αV, α11) dependent myocardin-related transcription factor (MRTF) activation, that drives MRTF-downstream cytoskeletal gene targets, such as αSMA, myosin light chain 9, filamin A, etc., in primary HSCs. Although the precise mechanism of fibrosis remains elusive, evidence from current literature indicate that CCN4 could serve as a potential therapeutic target for the treatment of liver fibrosis and small or large molecule therapeutic modalities that inhibit CCN4 can elicit protective effects in liver injury and fibrosis.

CCN4 has a crucial role in skin biology, wound healing, and repair. CCN4 protein expression was upregulated 4–7 days post cutaneous wounding and facilitated wound healing as the extent of wound closure was significantly delayed in CCN4-knockout mice due to the downregulation of ECM proteins, such as Col1A1 and FN1 [ 150 ]. Immunohistochemistry analysis of the incision reveals that CCN4 is also abundantly expressed in inflammatory cells, such as neutrophils. CCN4 is crucial for wound healing as it drives proliferation and migration of both human and mouse dermal fibroblasts through integrin α5β1 as selective siRNA mediated CCN4-knockdown resulted in the loss of function. Furthermore, stimulation with 100 ng/ml CCN4 induced activation and phosphorylation of ERK and c-Jun N-terminal kinase (JNK), crucial for cell proliferation, an effect which was blocked in the presence of selective small molecule MAPK inhibitor, PD98059 and αVβ1-antibody [ 150 ]. CCN4 not only binds with integrins but can also interact with cell surface small-leucine rich proteoglycans such as, decorin and biglycan on human dermal fibroblasts [ 25 ], although the downstream mechanistic pathway engagement from the latter remains unknown.

Besides the role of CCN4 in lung, liver, and skin fibrosis, CCN4 has also been shown to be implicated in cardiac remodeling and fibrosis associated with cardiomyopathies. Similar to what others have shown in diverse pathological conditions, CCN4 is substantially upregulated post-myocardial infarction (MI) and ischemic injury [ 64 , 65 , 151 , 152 ]. CCN4 modulates cardiac remodeling by positively influencing cardiomyocyte hypertrophy in an Akt-dependent manner and stimulation with recombinant CCN4 induces cardiac fibroblast proliferation and enhances ECM protein deposition, particularly collagen [ 65 ]. As previously mentioned, pro-inflammatory cytokines and chemokines are closely intertwined with CCN4 biology, and both have been shown to positively regulate each other. Along the same lines, stimulation with either TNF-α and/or IL-1β significantly induced CCN4 protein expression both in left-ventricular myocardium post-MI in-vivo and in rat cardiac myocytes in-vitro [ 65 ]. These findings were further strengthened in another study, where TNF- α induced CCN4 upregulation was shown to be dependent on ERK1/2 mediated CREB phosphorylation at Ser133 as pretreatment with small molecule inhibitors such as PD98059 (ERK1/2) and U0126 (MEK) failed to induce CREB-phosphorylation [ 64 ]. As TNF-α is known to activate a vast array of downstream signaling molecules, the authors also ruled out the involvement of JNK- and NF-κB activation for CCN4 upregulation and concluded that TNF-α mediated responses were strictly dependent on MEK1-ERK1/2-CREB signaling in cardiac fibroblasts [ 64 ]. In addition to CCN4, biglycan, the potential binding partner of CCN4 is also upregulated in cardiac fibroblasts up to threefold post-MI in-vivo suggesting intracellular CCN4 signal amplification [ 65 ].

Renal fibrosis is one of the most common pathological hallmarks in chronic kidney diseases (CKD). A recent study found that CCN4 levels were highly upregulated in preclinical unilateral ureteral obstruction (UUO) renal fibrosis model in animals and clinically in serum and kidney tissue biopsy samples from CKD patients [ 153 , 154 , 155 ]. Mechanistically, antibody mediated neutralization or siRNA mediation knockdown of CCN4 provides protection against renal fibrosis by attenuating fibrotic markers, such as Collagen, FN1 and αSMA deposition both in tubular epithelial cells (NRK52E cell line) and in-vivo in mouse models. Interestingly, the role of autophagy in fibrosis remains controversial as there are opposing results on whether it promotes or inhibits fibrogenesis. However, previous investigations have reported enhanced autophagic markers in proximal tubular cells, pharmacological inhibition of which reversed renal fibrosis. Similarly, CCN4 inhibition significantly reduced autophagy in UUO renal fibrosis model, suggesting that CCN4 also exercise control over pathways governing programmed cell death, modulating the development of renal fibrosis [ 156 ]. Serum CCN4 levels were also found to be elevated in vast array of CKDs (chronic kidney disease), such as diabetic nephropathy, IgA nephropathy and primary focal segmental glomerular sclerosis [ 153 , 157 ]. CCN4 has also been implicated to drive migration, invasion and EMT in primary renal tubular epithelial cells in uremia associated with end-stage renal failure [ 53 ]. In addition, the growing body of literature on non-coding RNAs, particularly miRNA and circular RNA (circRNA) and its prominent role in the pathophysiology of a wide array of disease highlights them as potent gene regulators. Regarding CCN4 gene regulators, miR-92a, miR-101 and miR-181a-5p have been identified to inversely modulate CCN4 expression in lungs. A recent study discovered two novel non-coding RNAs that target CCN4 to modulate renal fibrosis. The results demonstrate that circRNA-33702 is overexpressed in UUU-renal fibrosis models and possess profibrotic role by aggravating collagen and FN1 expression [ 158 ]. Conversely, miR-29b-3p negatively modulates CCN4 expression, in conjunction with other ECM proteins in mouse proximal tubule cell line (BUMPT cells). Since circRNA-33702 and miR-29b-3p have opposing effects on CCN4 expression and colocalization, luciferase analysis revealed that circRNA-33702 directly binds miR-29b-3p to upregulate CCN4 expression and consequently promote renal fibrosis [ 158 ]. The anti-fibrotic effects of miR-29b-3p on cardiac and liver fibrosis have also been demonstrated by others [ 159 , 160 , 161 , 162 ]. Apart from miR-29b, long non-coding RNA, Gm12840 and miR-677-5p also target CCN4/Akt signaling pathway to modulate fibroblast activation in ischemia–reperfusion induced renal fibrosis [ 163 ]. Overall, non-coding RNAs possess exciting potential as novel therapeutic targets for the treatment of fibrosis, however more investigation in this area is required to comprehensively understand the crosstalk amongst non-coding RNAs in a tissue-specific context to target CCN4.

In addition, all the CCN family members are functionally interconnected with a high degree of crosstalk by compensatory or opposing mechanisms. Emerging evidence points towards the anti-fibrotic effects of CCN3 protein and one of the possible anti-fibrotic mechanisms involves downregulation of profibrotic CCN4 protein. Overexpression of CCN3 in the skin fibroblast cell line NIH3T3 significantly downregulated CCN4 expression and hence conferred protection against fibrosis, although the exact mechanisms by which CCN3 modulates CCN4 remains unknown. It is speculated that due to its presence in the nucleus, CCN3 may behave as a transcription factor and can directly inhibit CCN4 gene transcription. Another mechanistic explanation could be due to direct sequestration of CCN4 by protein–protein interaction, preventing the initiation of CCN4 mediated pro-fibrotic pathway [ 164 ]. Similar findings were also reported by others where CCN3 was identified as an endogenous inhibitor of pro-fibrotic CCN family members. A deeper understanding of the interactome of CCN family members is required for utilizing the antagonistic approach to develop anti-fibrotic therapeutics [ 165 , 166 ]. Taken together, these results show that CCN4 is highly upregulated in fibrotic tissues, such as lungs, heart, liver and skin and can directly influence fibrogenesis, partly by integrin dependent mechanisms to promote fibroblast proliferation and migration, suggesting that CCN4 can not only serve as a diagnostic biomarker but also be exploited as a novel therapeutic target for the treatment of fibrosis. In addition, targeting CCN4 may eliminate the need for multiple tissue specific therapies in multi-organ fibrosis, given its role in the fibrogenesis of major organs, such as lung, liver, heart, kidney, and skin which encompasses a majority of all the fibrosis cases.

CCN4 in obesity and diabetes

Obesity is defined as excessive accumulation of fat in the adipose tissue throughout the body due to imbalance in the energy intake and expenditure, leading to various cardiovascular and metabolic disorders. Numerous environmental, genetic and lifestyle related factors also contribute to the increased body mass index (BMI) and weight gain [ 167 ]. Previously considered to be inactive, adipose tissue is a highly dynamic metabolically active endocrine organ, that produces a wide variety of cell-signaling molecules, namely adipocytokines or adipokines such as leptin, adiponectin, resistin, TNF-α, and IL-6, amongst others [ 168 ]. These adipokines are crucial for biochemical and metabolic homeostasis, however increased adiposity mediated adipokine dysregulation is the major culprit involved in the pathogenesis of metabolic syndrome, such as insulin resistance, diabetes mellitus, atherosclerosis, etc. [ 169 ]. CCN4 has recently been identified as a novel adipokine in humans, adding a unique functional aspect to its diverse biological repertoire [ 170 ]. Interestingly, recent studies have shown that CCN4 is also expressed and secreted by human adipocytes endowing it with the title of novel adipokine. Amongst other CCN protein members, CCN3 is also a fairly recently discovered adipokine linked to obesity [ 171 ]. Discovery of CCN4 and CCN3 as novel metabolic regulators opens new avenues for the treatment and management of obesity and associated co-morbidities.

Over the last decade, emerging evidence directly correlates systemic CCN4 levels with obesity, inflammation, and insulin-resistance. Large human cohort studies with obese and/or glucose tolerant patients revealed that circulating CCN4 is positively correlated with percent fat mass, leptin, triglyceride levels, adiposity, and BMI [ 172 , 173 ]. Another study shows that serum CCN4 levels and CCN4 mRNA expression in visceral adipose tissue were significantly higher in obese men compared to non-obese men, independent of their glycemic status [ 174 ]. CCN4 also leads to insulin resistance by impairing insulin signaling in hepatocytes and primary human skeletal muscle cells. In a dose-dependent manner, CCN4 significantly abrogated insulin-mediated phosphorylation of insulin receptor (IRβ)-Tyr1150/1151, along with decreased Akt-Ser473/Thr308, GSK3β-Ser9 phosphorylation at the lowest dose of 0.1 µg/l in both human skeletal muscle cells and murine hepatocyte cell line AML12. Insulin receptor substrate 1 (IRS1) is a key cytoplasmic adaptor protein crucial for signal transmission downstream of the receptor and treatment with 0.1 µg/l and 1 µg/l CCN4 decreased IRS1 protein expression by 50%, suggesting the direct inhibitory effect of CCN4 on insulin cascade in human skeletal muscle cells [ 174 ]. Preincubation with 0.1 µg/l and 1 µg/l of CCN4 for 24 h significantly abrogated insulin-dependent glycogen synthesis in human primary myotubes [ 174 ]. To further validate the mechanism, Woo et al. demonstrated the effect of CCN4 knockdown on insulin resistance and glucose in skeletal muscle cells of HFD-mice [ 175 ]. CCN4 knockdown significantly abrogated the inhibitory effects on insulin signaling by restoring Akt and IRS1 phosphorylation. Mechanistically, the authors also showed that CCN4 mediated insulin resistance and inflammation in murine skeletal muscle cells (C2C12 cells) and hepatocytes respectively is driven via Toll-like receptor-4 (TLR4) as TLR4 knockdown significantly abrogated CCN4-mediated JNK phosphorylation, NF-κB translocation, insulin resistance and triglyceride accumulation in hepatocytes and C2C12 cells [ 175 ]. siRNA mediated knockdown of NF-κB and JNK prevents CCN4-mediated insulin resistance, highlighting a novel mechanism for CCN4-driven impaired insulin sensitivity. In addition, siRNA-mediated CCN4 knockdown significantly ameliorates hepatic steatosis, lipogenesis and insulin resistance in HFD-fed mice suggesting that CCN4 requires TLR4 activation to drive inflammation and insulin resistance [ 175 ].

Contrary to the previously described inhibitory effect of CCN4 on insulin signaling, another study reports that it drives insulin-producing pancreatic beta (β)-cell proliferation via Akt modulation in both mouse and human cells [ 176 ]. Cell proliferation markers such as antigen kiel 67 (Ki67) and phospho-histone H3 (pHH3) were significantly reduced in CCN4 knockout mice (CCN −/− ) as compared to wild-type (CCN +/+ ). Further, CCN −/− mice treated with recombinant CCN4 exhibited twofold higher β-cell proliferation as compared to saline. Adenovirus-mediated systemic overexpression of CCN4 in streptozotocin-induced diabetes model, significantly increased plasma insulin levels by augmenting total β-cell mass and insulin positive area, however failed to reverse hyperglycemia [ 176 ]. CCN4 has also been implicated in the development and regeneration of pancreas [ 177 , 178 ]. More recently, researchers have also identified that CCN4 is highly expressed upon treatment with high concentration of glucose (30 mM) in human kidney proximal tubular cells and in renal tissue of streptozotocin-induced diabetic nephropathy (DN) mouse model [ 179 ]. Functionally, CCN4 overexpression drives cell proliferation, migration, EMT and fibrosis and these effects were partially rescued via silencing N6-adenosine methyltransferase (METTL3), which decreases DN development by decreasing CCN4 expression in-vitro [ 179 ]. Given the current body of conflicting literature on the effect of CCN4 on glucose homeostasis and rising rate of metabolic disorders, it is extremely important to decipher the functional and mechanistic consequences of CCN4 due to its profound physiological relevance.

Two independent studies have also shown that CCN4 serum level in pregnant women with gestational diabetes mellitus (GDM) is significantly higher as compared to healthy non-GDM pregnant women [ 180 , 181 ]. In addition, circulating CCN4 level in obese pregnant women with GDM is positively correlated with numerous clinical metabolic parameters such as systolic blood pressure, fasting blood glucose and aspartate aminotransferase (AST), highlighting the crucial role of CCN4 in the pathophysiology of GDM [ 180 ]. Overall, CCN4 can serve as a strong independent risk predictor and diagnostic marker and possess immense therapeutic potential in maternal-neonatal health and obstetric research. However, maternal, and neonatal safety drug assessment becomes crucial to assess the impact of possible CCN4 interventions on the fetal growth and development as CCN4 is expressed in osteoblasts and their progenitor cells during skeletogenic processes in embryonic development [ 182 ].

Obesity is also characterized as a chronic low-grade systemic inflammation due to the proinflammatory cytokine release from adipocytes and macrophages [ 183 ]. Studies show that macrophage infiltration and accumulation in adipose tissue was significantly higher in obese HFD mice as compared to normal mice [ 184 ]. Furthermore, phenotypical polarization of the infiltrated macrophages was observed in obese individuals with predominant pro-inflammatory M1 macrophages as compared to lean individuals with more anti-inflammatory M2 macrophages. The increased M1 population in obese adipose tissue overexpresses pro-inflammatory genes such as IL-6 and TNFα and lower anti-inflammatory cytokines such as IL-10, contributing to the persistent low-grade systemic inflammation and insulin resistance [ 184 , 185 ]. In addition, CCN4 protein expression is upregulated in visceral and subcutaneous adipose tissue in glucose-tolerant patients and is positively correlated with the markers of obesity, inflammation, and insulin resistance [ 170 , 172 , 174 ]. Serum CCN4 levels were also significantly elevated in obese children and adolescents with direct positive correlation to IL-18, adiponectin, and leptin [ 61 ]. Interestingly, these effects were completely reversed upon weight loss as adipose tissue CCN4 expression was significantly decreased after weight reduction, suggesting that adipocytes are the major source of circulating CCN4 [ 170 ]. These findings were further validated in another single-center randomized trial with breast cancer survivor females, where a 12-week exercise regime significantly decreased waist circumference and body fat composition accompanied by reduced serum β-catenin and CCN4 levels [ 186 ]. Furthermore, studies have shown that stimulation of macrophages with CCN4 can significantly increase pro-inflammatory cytokines such as IL-6, TNF-α and IL1B at both mRNA and protein level [ 170 , 187 ]. However, CCN4 stimulation had no significant pro-inflammatory effect on adipocytes suggesting that adipocyte-derived CCN4 does not elicit autocrine-response but rather have paracrine inflammatory effects on nearby macrophages. Additionally, stimulation of macrophages with CCN4 significantly increased the expression of pro-inflammatory M1 specific markers, such as CCR7 and COX2, whereas the expression of anti-inflammatory M2 specific markers such as CD36, CD163, MRC1 and COX1 were either markedly decreased or remained unchanged. This suggests that ‘M2 to M1’ phonotypical switch is driven at least in part due to adipocyte derived CCN4, along with other unknown mechanisms [ 170 ]. CCN4 alone does not initiate the release of inflammatory cytokines from adipocytes, however CCN4 imparts protective effects on LPS-treated adipocytes (3T3-L1) by preventing cell apoptosis and injury [ 188 ].

Murahovschi and colleagues have reported increased CCN4 expression and release during adipocyte differentiation, however no effect of CCN4 on adipocyte differentiation [ 170 ]. Yet another conflicting report suggests that CCN4 expression significantly decreases during adipocyte differentiation from preadipocytes to mature adipocytes and negatively regulates adipogenesis by physically interacting and redirecting transcriptional factor peroxisome proliferator-activated receptor gamma (PPARγ) to proteasomal degradation, which serves as a master regulator of adipocyte differentiation [ 189 ]. Potentially CCN4 does not promote new adipocyte formation, however, it can maintain and protect the pre-existing adipocytes that contribute heavily to the circulating CCN4 levels. CCN4 positively self-regulates itself by protecting the source, i.e., adipocytes, which can further aggravate systemic CCN4 levels, worsening the condition.

Increased adiposity and overexpressed CCN4 in adipocytes of obese individuals significantly contribute to the pro-inflammatory cytokine release by stimulating adipose tissue resident macrophages in a paracrine fashion and drives macrophage polarization with can further worsen the condition. Similarly, supraphysiological serum CCN4 levels also lead to insulin resistance by impairing insulin signaling. Taken together, all the evidence indicates that CCN4 is a central player and key contributor towards aggravation and perpetuation of the inflammatory response and insulin desensitization in obesity. Targeting CCN4 could have great therapeutic potential for metabolic disorders that would benefit numerous patients across the globe.

CCN4 in musculoskeletal system-osteoarthritis (OA) and rheumatoid arthritis (RA)

As per CDC, Arthritis is the leading cause of disability affecting nearly 1 out of 4 adults in the US. Arthritis means ‘disease of the joints’ and is usually characterized by chronic inflammation, pain, stiffness, loss of mobility and function due to progressive damage to the joint, bone and cartilage [ 190 ]. OA and RA are the most prevalent joint decaying diseases, with diverse etiologies but overlapping clinical hallmarks [ 191 ]. While there is no cure for debilitating OA and RA, treatment paradigms focus on symptomatic relief using a combination of pain management and physical therapy. A better functional and mechanistic understanding of the disease will assist in the discovery of novel diagnostic and therapeutic biomarkers for developing novel treatment strategies [ 190 ]. Given the diverse pharmacological effects of CCN4 in the human body, emerging evidence indicates the involvement of the Wnt-pathway in joint diseases.

The significance of CCN4 in the pathophysiology of OA and RA has been abundantly demonstrated by numerous researchers over the last decades. Substantial evidence implicates deleterious effects of CCN4 in the development of musculoskeletal disorders. Differential gene expression and transcriptomics analysis revealed significantly higher CCN4 expression in the cartilage of OA patients as compared to healthy controls [ 52 , 100 , 192 , 193 , 194 , 195 , 196 ]. Spatial expression profile of CCN4 reveals moderate to weak expression in the superficial layer, matrix and synovial perivascular cells of the knee and hip of RA and OA patients [ 192 ]. Another study revealed notable CCN4 upregulation in both synovium and cartilage specimens from OA-human patients and collagenase-induced OA mouse model [ 52 , 195 ]. CCN4 augmentation has been shown to stimulate chondrocytes, synovial cells, and macrophages, to induce the expression of matrix-degrading proteolytic enzymes such as MMPs that impart deleterious effects on the joint tissue of OA and RA patients. Adenovirus-mediated CCN4 overexpression in knee joints of naïve mice significantly damaged cartilage by inducing MMP13, MMP9, ADAMTS-4 and ADAMTS-5 in synovium and cartilage, exacerbating the condition [ 52 ]. In addition, treatment with recombinant human CCN4 increases MMP1, MMP2, MMP3, MMP9 and MMP13 mRNA expression in human OA synovial specimens [ 197 ]. Interestingly, CCN4 expression is directly corelated with OA severity and was densely expressed in the most damaged and degraded areas of the joint, confirming its detrimental effects, and highlighting the key role of CCN4 in OA and RA progression [ 198 ]. These findings were also confirmed in another study that demonstrated a direct role of CCN4 in the pathogenesis of OA utilizing CCN4-knockdown approach in three different experimental models of OA, that is, intra-articular collagenase induced (CIOA), anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) model. Cartilage degradation was significantly decreased in CCN4 − / − mice in all three OA-models compared to WT (wild type). These effects were attributed to decreased expression of protease, MMP3, MMP9, ADAMTS-4 and ADAMTS-5 in the synovium of CCN4 − / − mice, suggesting CCN4 is one of the key culprits in OA-pathogenesis, [ 197 ]. Interestingly, miR-128-3p expression is notably decreased in human OA tissue, and overexpression of miR-128-3p significantly decreased CCN4 expression. Furthermore, CCN4 mediates chondrocyte apoptosis, inflammation, and ECM degradation via PI3K/Akt/ NF-κB pathway, an effect that was inhibited by miR-128-3p providing protection against the harmful effects of CCN4, emerging as a novel therapeutic target for OA [ 196 ]. Besides low miR-128-3p expression, elevated levels of TGF-β in OA drive CCN4 expression in chondrocytes [ 199 ]. CCN4 can also contribute to OA pathology by skewing TGF-β signaling in chondrocytes from protective/ non-hypertrophic ALK-5/Smad 2/3 pathway towards damaging/ hypertrophic ALK-1/ Smad 1/5/8 pathway [ 200 ].

As previously described CCN4 binds to certain integrins, predominantly αVβ5, αVβ3 and αVβ1 to mediate its functional effects in fibrosis and cancer. Similarly, researchers have also shown that CCN4 engages integrins expressed on chondrocytes and synovial fibroblasts in OA. Contrary to the previously reported degenerative effects of CCN4 on chondrocyte matrix, another study shows that CCN4 displays a protective effect on primary human OA articular chondrocytes by inhibiting senescence and apoptosis. This effect was blocked in the presence of either αVβ3 antibody or a potent small molecule PI3K inhibitor (LY294002), suggesting that CCN4 mediated protective effects are αVβ3/PI3K/Akt dependent [ 198 ]. In another study, pretreatment with αVβ5 integrin blocking antibody, but not αVβ3 or α5β1 significantly reduces CCN4 induced concentration and time dependent increase in IL-6 production in OA synovial fibroblasts. Furthermore, CCN4-dependent IL-6 production was also obliterated in the presence of PI3K (Wortmannin and LY294002), Akt (Akti) and NF-κB (TPCK and PCTC) inhibitors suggesting that CCN4 drives pro-inflammatory cytokine IL-6 release via αVβ5/PI3K/Akt/NF-κB pathway in OA [ 201 ]. Together with CCN4, the expression of integrin αV and α5 subunit was significantly higher in human OA cartilage as compared to controls and assists CCN4-dependent chondrocyte differentiation [ 199 ]. Chondrocytes are terminally differentiated cells, possessing poor self-restoring capacity leading to longer recovery time after the avascular cartilage injury. Chondrocyte dedifferentiation causes multiple phenotypical changes, that accelerates hypertrophy, matrix calcification, degradation, and fibrosis. Dedifferentiated chondrocyte markers were notably upregulated in OA cartilage, suggesting that in conjunction with other mediators, CCN4 also promotes the destructive dedifferentiation process, aggravating disease progression [ 202 ]. Contrary to the general consensus, CCN4 also promotes chondrocyte proliferation, independent of integrins [ 199 ]. Treatment with CCN4 have been shown to also drive primary human OA chondrocyte migration, however the migratory chondrocytes were not phenotypically characterized to conclude whether they are non-differentiated which could facilitate repair or dedifferentiated which can cause damage [ 203 ].

Stimulation of human-osteoblast-like cells with recombinant human CCN4 dose-dependently increases mitogenic activity assessed by BrdU incorporation and osteoblastic differentiation measured by alkaline phosphatase activity [ 49 ]. Another study reported positive influence of CCN4 on bone formation. CCN4 overexpression both in-vivo and in-vitro in osteogenic hBMSC drives osteogenesis, increased bone volume and thickness by increasing bone morphogenic protein 2 (BMP-2) expression and activity in an α5β1 integrin dependent manner [ 204 ]. Furthermore, stimulation of mesenchymal stem cells (MSC) with recombinant CCN4 stimulates proliferation in a dose-dependent manner via BMP-3 induction, as CCN4-siRNA mediated knockdown significantly reduced the mitogenic effects of BMP-3 [ 205 ]. CCN4 also promotes recruitment, adhesion, and migration of monocytes by dose-dependently increasing VCAM-1 expression in osteoarthritic synovial lining, an effect that was abolished in the presence of an α6β1 or αVβ5 integrin neutralizing antibody. CCN4 also increases activation of protein kinase C (PKCδ), JNK, AP-1 and Syk (Spleen tyrosine kinase) proteins, all of which are necessary for CCN4-mediated VCAM-1 upregulation [ 206 ]. Based on literature evidence, CCN4 elicits diverse and sometimes opposite functional effects depending on the cell-type and the spatial expression pattern within the musculoskeletal system. Another study conducted in 304 postmenopausal Japanese women indicates that genetic variations such as single nucleotide polymorphism in CCN4 gene locus has been linked with spinal osteoarthritis determined by radiographical observations such as disc space narrowing, endplate sclerosis and osteophyte formation, again highlighting its therapeutic utility as a novel diagnostic biomarker [ 207 ].

Conclusion and future directions

From the literature summarized herein, aberrant CCN4 expression is highly correlated with adverse clinical outcomes and demonstrates the significant role of CCN4 in diverse pathophysiological conditions, such as cancer, fibrosis, metabolic disorders, and arthritis. Altered CCN4 expression may not be the only factor controlling vast array of cellular functions, such as cell proliferation, migration, invasion, and wound healing, but it could be modulating and working in conjunction with other mitogenic signaling molecules, growth factors and inflammatory mediators in driving pathogenesis, as shown in Fig. 3 .

Functional effects of CCN4 in different diseases. CCN4 drives many cellular processes such as cell-proliferation, migration, invasion, epithelial to mesenchymal transition (EMT), apoptosis, wound healing, repair, and angiogenesis. Some of these functional effects are overlapping amongst a diverse array of pathological conditions like cancer, fibrosis, obesity, and inflammatory diseases. The image was created with BioRender.com

As more translational studies unearth the CCN4-dependent molecular mechanisms, it is highly likely that CCN4 could be involved in the progression of many more undiscovered co-morbid pathologies. However, the slow growing research on CCN family is largely due to some major challenges in the field that remains to be addressed in future research. Besides the full-length CCN4 protein, identifying the domain specific function is crucial to understand the contribution of the variable linker in CCN biology. Development of domain specific detection tools for human and murine biological tissues or fluids is crucial to understand the tissue specific degradome/cleavage pattern of CCN4 in clinical models. In conjugation with protein–protein interaction studies, researchers could possibly identify functionally active domain(s) for monoclonal antibody mediated targeted therapy. Furthermore, an indirect approach could also be utilized by targeting the key proteolytic enzyme to prevent CCN4 cleavage and subsequently the formation of functionally active single or multi-domain structures. The proportion and expression kinetics of these multi-modular truncated CCN4 variants could reveal the functional redundancy and/or diverse effects in various diseases. Novel tools and reagents are also required to carefully assess the tightly regulated spaciotemporal expression and half-life of these individual or multi-domain structures which yet remains imperative to uncover its holistic biological significance. In addition, CCN4 signaling in diverse cell/tissue specific context still remains understudied. Multi-omics-based approaches at both transcript (RNA seq) and protein level (Proteomics) could be utilized to unravel other CCN4-dependent downstream targets and/or pathways. Also, immunoassays for multi-analyte profiling could further shed light on CCN4-dependend inflammatory secretome-signature. Furthermore, homo- or hetero-multimerization within CCN family members adds to the preexisting complexities. In addition, identifying the cognate receptor/s for CCN family members is important.

Another major challenge is to study crosstalk between CCN family of proteins. One of the major gaps in the current research is how other CCN members interact and modulate CCN4 in a synergistic or antagonistic manner in a pathological context. Some CCN family members have opposing effects with respect to CCN4. A bispecific targeting approach could also be utilized to target antithetical or synergistic CCN members to attain better therapeutic outcomes. However, given the high degree of structural and sequential homology, it is of paramount importance to first understand why some CCN members have opposite functional effects in a disease specific context. Minor changes in the amino acid sequence can bring about huge variations in the overall protein folding and 3-dimensional structure, affecting the surface charge and substrate binding potency, which could be utilized for targeted strategies. Given that CCN4 drives diverse cellular processes in a tissue-specific context, a comprehensive analysis encompassing the molecular network between all the CCN family members remains indispensable. Taken together, the results from the literature reviewed here suggest that CCN4 plays a critical role in the development and progression of diverse pathologies and is emerging as a promising candidate with therapeutic potential yet untapped.

Availability of data and materials

Not applicable.

Abbreviations

Disintegrin and metalloproteinase domain-containing protein 28

Protein kinase B

Activator protein-1

Type II alveolar epithelial cells

Body mass index

Bone morphogenetic protein

Chemokine C–C motif ligand

Cellular communication network factor 4

Cluster of differentiation

Chronic kidney diseases

C-terminal cysteine knot

Connective tissue growth factor

Chemokine C-X-C motif ligand

Cysteine-rich protein 61

Diabetic nephropathy

• Extracellular matrix

Epidermal growth factor receptor

Epithelial to mesenchymal transition

Extracellular signal-regulated kinase

Focal adhesion kinase

Fibroblast growth factor

Fibronectin

Glucose transporter 1

Hypoxia inducible factor 1 alpha

Intracellular adhesion kinase 1

Interferon gamma

Insulin-like growth factor binding protein like domain

Interlukin-6

Idiopathic pulmonary fibrosis

Insulin receptor substrate 1

C-Jun N-terminal kinase

Low-density lipoprotein receptor-related proteins

Mitogen-activated protein kinase kinase

Matrix metalloproteases

Myocardin-related transcription factor

Mechanistic target of rapamycin

Nuclear factor kappa B

Nephroblastoma overexpressed

Osteoarthritis

Phosphoinositol 3-kinase

Protein kinase C

Peroxisome proliferator-activated receptor gamma

Post-translational modification

Rheumatoid arthritis

Transforming growth factor: β

Toll-like receptor

Thrombospondin-homology type 1 repeat

Vascular cell adhesion protein 1

Vascular endothelial growth factor

von Willebrand factor C repeat

Wnt-1 induced secreted protein-1

α-Smooth muscle actin

Bornstein P. Matricellular proteins: an overview. J Cell Commun Signal. 2009;3(3–4):163–5.

Article   PubMed   PubMed Central   Google Scholar  

Perbal B, Tweedie S, Bruford E. The official unified nomenclature adopted by the HGNC calls for the use of the acronyms, CCN1–6, and discontinuation in the use of CYR61, CTGF, NOV and WISP 1–3 respectively. J Cell Commun Signal. 2018;12(4):625–9.

Brigstock DR, Goldschmeding R, Katsube KI, Lam SCT, Lau LF, Lyons K, et al. Proposal for a unified CCN nomenclature. J Clin Pathol Mol Pathol. 2003;56(2):127–8.

Article   CAS   Google Scholar  

Gurbuz I, Chiquet-Ehrismann R. CCN4/WISP1 (WNT1 inducible signaling pathway protein 1): A focus on its role in cancer. Int J Biochem Cell Biol. 2015;62:142–6. https://doi.org/10.1016/j.biocel.2015.03.007 .

Article   CAS   PubMed   Google Scholar  

Sun C, Zhang H, Liu X. Emerging role of CCN family proteins in fibrosis. J Cell Physiol. 2021;236(6):4195–206.

Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, et al. WISP genes are members of the connective tissue growth factor family that are up-regulated in Wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci U S A. 1998;95(25):14717–22.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Berschneider B, Königshoff M. WNT1 inducible signaling pathway protein 1 (WISP1): A novel mediator linking development and disease. Int J Biochem Cell Biol. 2011;43(3):306–9. https://doi.org/10.1016/j.biocel.2010.11.013 .

Walker JM. CCN proteins. In: Takigawa M, editor. Springer protocols, vol. XIV. 2nd ed. Berlin: Springer; 2017. p. 430. https://doi.org/10.1007/978-1-0716-2744-0 .

Chapter   Google Scholar  

Jun J-I, Lau LF. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov. 2011;10(12):945–63. https://doi.org/10.1038/nrd3599 .

Yoshida K, Munakata H. Connective tissue growth factor binds to fibronectin through the type I repeat modules and enhances the affinity of fibronectin to fibrin. Biochim Biophys Acta Gen Subj. 2007;1770(4):672–80.

Hoshijima M, Hattori T, Inoue M, Araki D, Hanagata H, Miyauchi A, et al. CT domain of CCN2/CTGF directly interacts with fibronectin and enhances cell adhesion of chondrocytes through integrin α5β1. FEBS Lett. 2006;580(5):1376–82.

Francischetti IMB, Kotsyfakis M, Andersen JF, Lukszo J. Cyr61/CCN1 displays high-affinity binding to the somatomedin B 1-44 domain of vitronectin. PLoS ONE. 2010;5(2):1–12.

Article   Google Scholar  

Nishida T, Kubota S, Fukunaga T, Kondo S, Yosimichi G, Nakanishi T, et al. CTGF/Hcs24, hypertrophic chondrocyte-specific gene product, interacts with perlecan in regulating the proliferation and differentiation of chondrocytes. J Cell Physiol. 2003;196(2):265–75.

Chen N, Leu SJ, Todorović V, Lam SCT, Lau LF. Identification of a novel integrin αvβ3 binding site in CCN1 (CYR61) critical for pro-angiogenic activities in vascular endothelial cells. J Biol Chem. 2004;279(42):44166–76.

Kireeva ML, Lam SC, Lau LF, Biol LFMC. Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin αvβ3. J Biol Chem. 1998;273(5):3090–6. https://doi.org/10.1074/jbc.273.5.3090 .

Lin CG, Leu S-J, Chen N, Tebeau CM, Lin S-X, Yeung C-Y, et al. CCN3 ( NOV ) is a novel angiogenic regulator of the CCN protein family. J Biol Chem. 2003;278(26):24200–8. https://doi.org/10.1074/jbc.M302028200 .

Abd El Kader T, Kubota S, Anno K, Tanaka S, Nishida T, Furumatsu T, et al. Direct interaction between CCN family protein 2 and fibroblast growth factor 1. J Cell Commun Signal. 2014;8(2):157–63.

Aoyama E, Kubota S, Takigawa M. CCN2/CTGF binds to fibroblast growth factor receptor 2 and modulates its signaling. FEBS Lett. 2012;586(24):4270–5. https://doi.org/10.1016/j.febslet.2012.10.038 .

Nishida T, Kubota S, Aoyama E, Janune D, Maeda A, Takigawa M. Effect of CCN2 on FGF2-induced proliferation and MMP9 and MMP13 productions by chondrocytes. Endocrinology. 2011;152(11):4232–41.

Inoki I, Shiomi T, Hashimoto G, Enomoto H, Nakamura H, Makino K-I, et al. Connective tissue growth factor binds vascular endothelial growth factor (VEGF) and inhibits VEGF-induced angiogenesis. FASEB J. 2002;16(2):219–21.

Abreu JG, Ketpura NI, Reversade B, De Robertis EM. Connective-tissue growth factor (CTGF) modulates cell signalling by bmp and TGF-β. Nat Cell Biol. 2002;4(8):599–604.

Bai T, Chen CC, Lau LF. The matricellular protein CCN1 activates a pro-inflammatory genetic program in murine macrophages. J Immunol. 2010;184(6):1–7.

Chen N, Chen CC, Lau LF. Adhesion of human skin fibroblasts to Cyr61 is mediated through integrin α6β1 and cell surface heparan sulfate proteoglycans. J Biol Chem. 2000;275(32):24953–61. https://doi.org/10.1074/jbc.M003040200 .

Kireeva ML, Latinkić BV, Kolesnikova TV, Chen CC, Yang GP, Abler AS, et al. Cyr61 and Fisp12 are both ECM-associated signaling molecules: activities, metabolism, and localization during development. Exp Cell Res. 1997;233(1):63–77.

Desnoyers L, Arnott D, Pennica D. WISP-1 binds to decorin and biglycan. J Biol Chem. 2001;276(50):47599–607. https://doi.org/10.1074/jbc.M108339200 .

Juric V, Chen CC, Lau LF. TNFα-induced apoptosis enabled by CCN1/CYR61: pathways of reactive oxygen species generation and cytochrome C release. PLoS ONE. 2012;7(2):1–10.

Mercurio S, Latinkic B, Itasaki N, Krumlauf R, Smith JC. Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex. Development. 2004;131(9):2137–47.

Blalock TD, Gibson DJ, Duncan MR, Tuli SS, Grotendorst GR, Schultz GS. A connective tissue growth factor signaling receptor in corneal fibroblasts. Investig Ophthalmol Vis Sci. 2012;53(7):3387–94.

Sakamoto K, Yamaguchi S, Ando R, Miyawaki A, Kabasawa Y, Takagi M, et al. The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1 extracellular domain and inhibits myoblast differentiation via Notch signaling pathway. J Biol Chem. 2002;277(33):29399–405. https://doi.org/10.1074/jbc.M203727200 .

Lau LF. Cell surface receptors for CCN proteins. J Cell Commun Signal. 2016;10:121–7. https://doi.org/10.1007/s12079-016-0324-z .

Aoyama E, Kubota S, Khattab HM, Nishida T, Takigawa M. CCN2 enhances RANKL-induced osteoclast differentiation via direct binding to RANK and OPG. Bone. 2015;73:242–8. https://doi.org/10.1016/j.bone.2014.12.058 .

Wu CL, Tsai HC, Chen ZW, Wu CM, Li TM, Fong YC, et al. Ras activation mediates WISP-1-induced increases in cell motility and matrix metalloproteinase expression in human osteosarcoma. Cell Signal. 2013;25(12):2812–22. https://doi.org/10.1016/j.cellsig.2013.09.005 .

Hou CH, Chiang YC, Fong YC, Tang CH. WISP-1 increases MMP-2 expression and cell motility in human chondrosarcoma cells. Biochem Pharmacol. 2011;81(11):1286–95. https://doi.org/10.1016/j.bcp.2011.03.016 .

Bradham DM, Igarashi A, Potter RL, Grotendorst GR. Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol. 1991;114(6):1285–94.

Phanish MK, Winn SK, Dockrell MEC. Connective tissue growth factor-(CTGF, CCN2)—a marker, mediator and therapeutic target for renal fibrosis. Nephron Exp Nephrol. 2010;114(3):83–92.

Yang W, Wagener J, Wolf N, Schmidt M, Kimmig R, Winterhager E, et al. Impact of CCN3 (NOV) glycosylation on migration/invasion properties and cell growth of the choriocarcinoma cell line Jeg3. Hum Reprod. 2011;26(10):2850–60.

Soon LL, Yie TA, Shvarts A, Levine AJ, Su F, Tchou-Wong KM. Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation. J Biol Chem. 2003;278(13):11465–70. https://doi.org/10.1074/jbc.M210945200 .

Neupane S, Berardinelli SJ, Cameron DC, Grady RC, Komatsu DE, Percival CJ, et al. O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development. Matrix Biol. 2022;107:77–96.

Pendurthi UR, Tran TT, Post M, Rao LVM. Proteolysis of CCN1 by plasmin: functional implications. Cancer Res. 2005;65(21):9705–11.

Choi J, Lin A, Shrier E, Lau LF, Grant MB, Chaqour B. Degradome products of the matricellular protein CCN1 as modulators of pathological angiogenesis in the retina. J Biol Chem. 2013;288(32):23075–89. https://doi.org/10.1074/jbc.M113.475418 .

Hashimoto G, Inoki I, Fujii Y, Aoki T, Ikeda E, Okada Y. Matrix metalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor 165. J Biol Chem. 2002;277(39):36288–95. https://doi.org/10.1074/jbc.M201674200 .

Guillon-munos A, Oikonomopoulou K, Smith CR, Canepa S, Reverdiau P, Heuze N, et al. Kallikrein-related peptidase 12 hydrolyzes matricellular proteins of the CCN family and modifies interactions of CCN1 and CCN5 with growth factors. J Biol Chem. 2011;286(29):25505–18.

Mochizuki S, Tanaka R, Shimoda M, Onuma J, Fujii Y, Jinno H, et al. Connective tissue growth factor is a substrate of ADAM28. Biochem Biophys Res Commun. 2010;402(4):651–7.

Kaasbøll OJ, Gadicherla AK, Wang JH, Monsen VT, Hagelin EMV, Dong MQ, et al. Connective tissue growth factor (CCN2) is a matricellular preproprotein controlled by proteolytic activation. J Biol Chem. 2018;293(46):17953–70.

Butler GS, Connor AR, Sounni NE, Eckhard U, Morrison CJ, Noël A, et al. Degradomic and yeast 2-hybrid inactive catalytic domain substrate trapping identifies new membrane-type 1 matrix metalloproteinase (MMP14) substrates: CCN3 (Nov) and CCN5 (WISP2). Matrix Biol. 2017;59:23–38. https://doi.org/10.1016/j.matbio.2016.07.006 .

Perbal B. Alternative splicing of CCN mRNAs… It has been upon us. J Cell Commun Signal. 2009;3(2):153–7.

Tanaka S, Sugimachi K, Saeki H, Kinoshita J, Ohga T, Shimada M, et al. A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma. Oncogene. 2001;20(39):5525–32.

Tanaka S, Sugimachi K, Kameyama T, Maehara SI, Shirabe K, Shimada M, et al. Human WISP1v, a member of the CCN family, is associated with invasive cholangiocarcinoma. Hepatology. 2003;37(5):1122–9.

Inkson CA, Ono M, Kuznetsov SA, Fisher LW, Gehron P, Young MF. TGF-β1 and WISP-1/CCN-4 can regulate each other’s activity to cooperatively control osteoblast function. J Cell Biochem. 2009;104(5):1865–78.

Cervello M, Giannitrapani L, Labbozzetta M, Notarbartolo M, D’Alessandro N, Lampiasi N, et al. Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells. Ann N Y Acad Sci. 2004;1028:432–9.

Yanagita T, Kubota S, Kawaki H, Kawata K, Kondo S, Takano-Yamamoto T, et al. Expression and physiological role of CCN4/Wnt-induced secreted protein 1 mRNA splicing variants in chondrocytes. FEBS J. 2007;274(7):1655–65.

Blom AB, Brockbank SM, Van Lent PL, Van Beuningen HM, Geurts J, Takahashi N, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthr Rheum. 2009;60(2):501–12.

Chen YZ, Sun DQ, Zheng Y, Zheng GK, Chen RQ, Lin M, et al. WISP1 silencing confers protection against epithelial–mesenchymal transition of renal tubular epithelial cells in rats via inactivation of the wnt/β-catenin signaling pathway in uremia. J Cell Physiol. 2019;234(6):9673–86.

Madrigano J. Interleukin-18/WNT1-inducible signaling pathway protein-1 signaling mediates human saphenous vein smooth muscle cell proliferation. Occup Env Med. 2008;23(1):1–7.

Google Scholar  

Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun. 2020. https://doi.org/10.1038/s41467-020-18794-x .

Liu Y, Song Y, Ye M, Hu X, Wang ZP, Zhu X. The emerging role of WISP proteins in tumorigenesis and cancer therapy. J Transl Med. 2019. https://doi.org/10.1186/s12967-019-1769-7 .

Xi Y, LaCanna R, Ma HY, N’Diaye EN, Gierke S, Caplazi P, et al. A WISP1 antibody inhibits MRTF signaling to prevent the progression of established liver fibrosis. Cell Metab. 2022;34(9):1377-1393.e8. https://doi.org/10.1016/j.cmet.2022.07.009 .

Kadam AH, Schnitzer JE. Characterization of acute lung injury in the bleomycin rat model. Physiol Rep. 2023;11(5):1–13.

Kim MS, Kim SH, Jeon D, Kim HY, Lee K. Changes in expression of cytokines in polyhexamethylene guanidine-induced lung fibrosis in mice: comparison of bleomycin-induced lung fibrosis. Toxicology. 2017;2018(393):185–92.

Königshoff M, Kramer M, Balsara N, Wilhelm J, Amarie OV, Jahn A, Rose F, Fink L, Seeger W, Schaefer L, Günther A, Eickelberg O. WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. J Clin Invest. 2009;119(4):772–87.

PubMed   PubMed Central   Google Scholar  

Wang A-R, Yan X-Q, Zhang C, Du C-Q, Long W-J, Zhan D, et al. Characterization of Wnt1-inducible signaling pathway protein-1 in obese children and adolescents. Curr Med Sci. 2018;38(5):868–74.

Maiese K. Prospects and perspectives for WISP1 (CCN4) in diabetes mellitus. Curr Neurovasc Res. 2020;17(3):327–31.

Klee S, Lehmann M, Wagner DE, Baarsma HA, Konigshoff M. WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts. Sci Rep. 2016;6:1–11. https://doi.org/10.1038/srep20547 .

Venkatachalam K, Venkatesan B, Valente AJ, Melby PC, Nandish S, Reusch JEB, et al. WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-α (TNF-α)-stimulated cardiac fibroblast proliferation but inhibits TNF-α-induced cardiomyocyte death. J Biol Chem. 2009;284(21):14414–27.

Colston JT, De Rosa SD, Koehler M, Gonzales K, Mestril R, Freeman GL, et al. Wnt-induced secreted protein-1 is a prohypertrophic and profibrotic growth factor. Am J Physiol Circ Physiol. 2007;293:78229.

Wang S, Chong ZZ, Shang YC, Maiese K. WISP1 (CCN4) autoregulates its expression and nuclear trafficking of β-catenin during oxidant stress with limited effects upon neuronal autophagy. Curr Neurovasc Res. 2012;9(2):91–101.

Shang YC, Chong ZZ, Wang S, Maiese K. Wnt1 inducible signaling pathway protein 1 (WISP1) targets PRAS40 to govern β-amyloid apoptotic injury of microglia. Curr Neurovasc Res. 2012;9(4):239–49.

Maiese K. WISP1: clinical insights for a proliferative and restorative member of the CCN family. Curr Neurovasc Res. 2014;11:378.

Brown JS, Amend SR, Austin RH, Gatenby RA, Hammarlund EU, Pienta KJ. Updating the definition of cancer. Mol Cancer Res. 2023;21(11):1142–7.

Shuel SL. Targeted cancer therapies. Can Fam Phys. 2022;68(7):515–8.

Jia Q, Xu B, Zhang Y, Ali A, Liao X. CCN family proteins in cancer: insight into their structures and coordination role in tumor microenvironment. Front Genet. 2021;12:1–13.

Yaribeygi H, Atkin SL, Sahebkar A. Wingless-type inducible signaling pathway protein-1 (WISP1) adipokine and glucose homeostasis. J Cell Physiol. 2019;234(10):16966–70.

Chen PP, Li WJ, Wang Y, Zhao S, Li DY, Feng LY, et al. Expression of Cyr61, CTGF, and WISP-1 correlates with clinical features of lung cancer. PLoS ONE. 2007;2(6):1–9.

Li Y, Wang F, Liu T, Lv N, Yuan X, Li P. WISP1 induces ovarian cancer via the IGF1/αvβ3/Wnt axis. J Ovarian Res. 2022. https://doi.org/10.1186/s13048-022-01016-x .

Wu J, Long Z, Cai H, Du C, Liu X, Yu S, et al. High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis. Oncotarget. 2016;7(31):49834–47.

Zhu Y, Li W, Yang Y, Li Y, Zhao Y. WISP1 indicates poor prognosis and regulates cell proliferation and apoptosis in gastric cancer via targeting AKT/mTOR signaling pathway. Am J Transl Res. 2020;12(11):7297–311.

CAS   PubMed   PubMed Central   Google Scholar  

Chiang KC, Yeh CN, Chung LC, Feng TH, Sun CC, Chen MF, et al. WNT-1 inducible signaling pathway protein-1 enhances growth and tumorigenesis in human breast cancer. Sci Rep. 2015;5:1–12.

Zhang H, Luo H, Hu Z, Peng J, Jiang Z, Song T, et al. Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation. Oncotarget. 2015. https://doi.org/10.18632/oncotarget.3358 .

Jung EK, Kim S, Yoon TM, Lee KH, Kim HK, Lee DH, et al. WNT1-inducible signaling pathway protein-1 contributes to tumor progression and treatment failure in oral squamous cell carcinoma. Oncol Lett. 2017;14:1719–24.

Wang QY, Feng YJ, Ji R. High expression of WISP1 promotes metastasis and predicts poor prognosis in hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 2020;24(20):10445–51.

PubMed   Google Scholar  

Fernandez A, Deng W, McLaughlin SL, Pirkey AC, Rellick SL, Razazan A, et al. Cell communication network factor 4 promotes tumor-induced immunosuppression in melanoma. EMBO Rep. 2022;23(4):1–16.

Davies SR, Watkins G, Mansel RE, Jiang WG. Differential expression and prognostic implications of the CCN family members WISP-1, WISP-2, and WISP-3 in human breast cancer. Ann Surg Oncol. 2007;14(6):1909–18.

Article   PubMed   Google Scholar  

Taghavi A, Akbari ME, Bahremani MH. Gene expression profiling of the 8q22-24 position in human breast cancer: TSPYL5, MTDH, ATAD2 and CCNE2 genes are implicated in oncogenesis, while WISP1 and EXT1 genes may predict a risk of metastasis. Oncol Lett. 2016;12:3845–55.

Zhang H, Li W, Huang P, Lin L, Ye H, Lin D, et al. Expression of CCN family members correlates with the clinical features of hepatocellular carcinoma. Oncol Rep. 2015;33(3):1481–92.

Shao H, Cai L, Grichnik JM, Livingstone AS, Velazquez OC, Liu ZJ. Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1. Oncogene. 2011;30(42):4316–26.

Anderson NM, Simon MC. The tumor microenvironment. Curr Biol. 2020;30(16):R921-5. https://doi.org/10.1016/j.cub.2020.06.081 .

Tao W, Chu C, Zhou W, Huang Z, Zhai K, Fang X, et al. Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma. Nat Commun. 2020. https://doi.org/10.1038/s41467-020-16827-z .

Zimmer AM, Pan YK, Chandrapalan T, Kwong RWM, Perry SF. Loss-of-function approaches in comparative physiology: is there a future for knockdown experiments in the era of genome editing ? J Exp Biol. 2019;222(7): jeb175737.

Prelich G. Gene overexpression: uses, mechanisms, and interpretation. Genetics. 2012;190:841–54.

Beltrao P, Bork P, Krogan NJ, Van NV. Evolution and functional cross-talk of protein post-translational modifications. Mol Syst Biol. 2013;9(714):1–13.

Tai H-C, Chang A-C, Yu H-J, Huang C-Y, Lai Y-W, Sun H-L, et al. Osteoblast-derived WISP-1 increases VCAM-1 expression and enhances prostate cancer metastasis by down-regulating miR-126. Oncotarget. 2014;5(17):7589.

Chang A-C, Lien M-Y, Tsai M-H, Hua C-H. WISP-1 promotes epithelial-mesenchymal transition in oral squamous cell carcinoma cells via the miR-153–3p/Snail axis. Cancers. 2019;11(1903):1–16.

Chuang JY, Chang AC, Chiang IP, Tsai MH, Tang CH. Apoptosis signal-regulating kinase 1 is involved in WISP-1-promoted cell motility in human oral squamous cell carcinoma cells. PLoS ONE. 2013;8(10): e78022.

Chuang JY, Chen PC, Tsao CW, Chang AC, Lein MY, Lin CC, et al. WISP-1, a novel angiogenic regulator of the CCN family, promotes oral squamous cell carcinoma angiogenesis through VEGF-A expression. Oncotarget. 2015;6(6):4239–52.

Lin CC, Chen PC, Lein MY, Tsao CW, Huang CC, Wang SW, et al. WISP-1 promotes VEGF-C-dependent lymphangiogenesis by inhibiting miR-300 in human oral squamous cell carcinoma cells. Oncotarget. 2016;7(9):9993–10005.

Lee H-L, Chiou H-L, Wang S-S, Hung S-C, Chou M-C, Yang S-F, et al. WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma. Urol Oncol Semin Orig Investig. 2018;36(4):160.e15-160.e21. https://doi.org/10.1016/j.urolonc.2017.11.023 .

Chen CT, Lee HL, Chiou HL, Chou CH, Wang PH, Yang SF, et al. Impacts of wnt1-inducible signaling pathway protein 1 polymorphism on hepatocellular carcinoma development. PLoS ONE. 2018;13(6):1–15.

He J, Wang Z, Wang Y, Zou T, Li XP, Cao L, et al. The effects of WISP1 polymorphisms on the prognosis of lung cancer patients with platinum-based chemotherapy. Pharmgenomics Pers Med. 2021;14:1193–203.

Chen J, Yin J, Li X, Wang Y, Zheng Y, Qian C, et al. WISP1 polymorphisms contribute to platinum-based chemotherapy toxicity in lung cancer patients. Int J Mol Sci. 2014;15:21011–27.

Van Den Bosch MHJ, Ramos YFM, Den Hollander W, Bomer N, Nelissen RGHH, Bovée JVMG, et al. Increased WISP1 expression in human osteoarthritic articular cartilage is epigenetically regulated and decreases cartilage matrix production. Rheumatology. 2019;58(6):1065–74.

Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP. Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features 1. Cancer Res. 2001;61:8917–23.

CAS   PubMed   Google Scholar  

Fang F, Xu W, Zhang J, Gu J, Yang G. Ultrasound microbubble-mediated RNA interference targeting WNT1 inducible signaling pathway protein 1 (WISP1) suppresses the proliferation and metastasis of breast cancer cells. Bioengineered. 2022;13(4):11050–60. https://doi.org/10.1080/21655979.2022.2068738 .

Ii DJK. Induction of Wnt-inducible signaling protein-1 correlates with invasive breast cancer oncogenesis and reduced type 1 cell-mediated cytotoxic immunity : a retrospective study. PLoS Comput Biol. 2014;10(1): e1003409.

Mirza Z, Ansari S, Iqbal S, Ahmad N, Alganmi N, Banjar H, et al. Identification of novel diagnostic and prognostic gene signature biomarkers for breast cancer using artificial intelligence and machine learning assisted transcriptomics analysis. Cancers. 2023. https://doi.org/10.3390/cancers15123237 .

Jia H, Janjanam J, Wu SC, Wang R, Pano G, Celestine M, et al. The tumor cell - secreted matricellular protein WISP 1 drives pro-metastatic collagen linearization. FASEB J. 2019. https://doi.org/10.1096/fj.202000713RR .

Liu S, Wu D, Sun X, Fan Y, Zha R, Jalali A, et al. Mechanical stimulations can inhibit local and remote tumor progression by downregulating WISP1. FASEB J. 2020;34(9):12847–59.

Li Y, Zhu Z, Hou X, Sun Y. LncRNA AFAP1-AS1 promotes the progression of colorectal cancer through miR-195–5p and WISP1. J Oncol. 2021;2021:1–10.

Nagai Y, Watanabe M, Ishikawa S, Karashima R, Kurashige J, Iwagami S, et al. Clinical significance of Wnt-induced secreted protein-1 ( WISP-1/CCN4) in esophageal squamous cell carcinoma. Anticancer Res. 2011;998:991–7.

Yang C, Li F, Zhou W, Huang J. Knockdown of long non-coding RNA CCAT2 suppresses growth and metastasis of esophageal squamous cell carcinoma by inhibiting the β-catenin/WISP1 signaling pathway. J Int Med Res. 2021;49(5):030006052110199.

Jing D, Zhang Q, Yu H, Zhao Y, Shen L. Identification of WISP1 as a novel oncogene in glioblastoma. Int J Oncol. 2017;51:1261–70.

Wang L, Sun J, Gao P, Su K, Wu H, Junli L, et al. Wnt1-inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway. J Cell Physiol. 2019. https://doi.org/10.1002/jcp.28253 .

Wang L, Sun J, Cao H. MicroRNA-384 regulates cell proliferation and apoptosis through directly targeting WISP1 in laryngeal cancer. J Cell Biochem. 2018;2019:3018–26.

Yan J, Lei J, Chen L, Deng H, Dong D, Jin T, et al. Human leukocyte antigen F locus adjacent transcript 10 overexpression disturbs WISP1 protein and mRNA expression to promote hepatocellular carcinoma progression. Hepatology. 2018;68(6):2268–84.

Margalit O, Eisenbach L, Amariglio N, Kaminski N, Harmelin A, Pfeffer R, et al. Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines. Br J Cancer. 2003;89(2):314–9.

Clausen MJAM, Melchers LJ, Mastik MF, Slagter-menkema L. Identification and validation of WISP1 as an epigenetic regulator of metastasis in oral squamous cell carcinoma. Genes Chromosom Cancer. 2016;59:45–59.

Tsai H-C, Tzeng H-E, Huang C-Y, Huang Y-L, Tsai C-H, Wang S-W, et al. WISP-1 positively regulates angiogenesis by controlling VEGF-A expression in human osteosarcoma. Cell Death Dis. 2017;8(4):e2750-11. https://doi.org/10.1038/cddis.2016.421 .

Graumann J, Finkernagel F, Reinartz S, Stief T, Brödje D, Renz H, et al. Multi-platform affinity proteomics identify proteins linked to metastasis and immune suppression in ovarian cancer plasma. Front Oncol. 2019;9:1–12.

Ono M, Inkson CA, Sonn R, Kilts TM, de Castro LF, Maeda A, et al. WISP1/CCN4: a potential target for inhibiting prostate cancer growth and spread to bone. PLoS ONE. 2013;8(8): e71709.

Mao A, Tang J, Tang D, Wang F, Liao S, Yuan H, et al. MicroRNA-29b-3p enhances radiosensitivity through modulating WISP1-mediated mitochondrial apoptosis in prostate cancer cells. J Cancer. 2020;11:6356.

Gaudreau PO, Clairefond S, Class CA, Boulay PL, Chrobak P, Allard B, et al. WISP1 is associated to advanced disease, EMT and an inflamed tumor microenvironment in multiple solid tumors. Oncoimmunology. 2019;8(5):1–18. https://doi.org/10.1080/2162402X.2019.1581545 .

Chang AC, Chen PC, Lin YF, Su CM, Liu JF, Lin TH, et al. Osteoblast-secreted WISP-1 promotes adherence of prostate cancer cells to bone via the VCAM-1/integrin α4β1 system. Cancer Lett. 2018;426:47–56. https://doi.org/10.1016/j.canlet.2018.03.050 .

Chang KS, Chen ST, Sung HC, Hsu SY, Lin WY, Hou CP, et al. WNT1 inducible signaling pathway protein 1 is a stroma-specific secreting protein inducing a fibroblast contraction and carcinoma cell growth in the human prostate. Int J Mol Sci. 2022;23(19):1–18.

Chang AC, Lin LW, Chen YC, Chen PC, Liu SC, Tai HC, et al. The ADAM9/WISP-1 axis cooperates with osteoblasts to stimulate primary prostate tumor growth and metastasis. Int J Biol Sci. 2023;19(3):760–71.

Zheng Y, Chen CJ, Lin ZY, Li JX, Liu J, Lin FJ, et al. Circ_KATNAL1 regulates prostate cancer cell growth and invasiveness through the mir-145-3p/WISP1 pathway. Biochem Cell Biol. 2020;98(3):396–404.

Deng W, Fernandez A, McLaughlin SL, Klinke DJ. WNT1-inducible signaling pathway protein 1 (WISP1/CCN4) stimulates melanoma invasion and metastasis by promoting the epithelial mesenchymal transition. J Biol Chem. 2019;294(14):5261–80.

Deng W, Fernandez A, McLaughlin SL, Klinke DJ. Cell communication network factor 4 (CCN4/WISP1) shifts melanoma cells from a fragile proliferative state to a resilient metastatic state. Cell Mol Bioeng. 2020;13(1):45–60.

Pirkey AC, Deng W, Norman D, Razazan A, Klinke DJ. Head-to-head comparison of CCN4, DNMT3A, PTPN11, and SPARC as suppressors of anti-tumor immunity. Cell Mol Bioeng. 2023;16(5–6):431–42. https://doi.org/10.1007/s12195-023-00787-7 .

Plikus MV, Wang X, Sinha S, Forte E, Thompson SM. Fibroblasts: origins, definitions, and functions in health and disease. Cell. 2021;184(15):3852–72. https://doi.org/10.1016/j.cell.2021.06.024 .

Kendall RT, Feghali-bostwick CA, Rauch BH. Fibroblasts in fibrosis: novel roles and mediators. Front Pharmacol. 2014;5:1–13.

Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210.

Abuserewa ST, Duff R, Becker G. Treatment of idiopathic pulmonary fibrosis. Cureus. 2021;13(5):1–10.

Liu J, Lv S, Ma W, Yang D, Zhang X. Effect of WISP1 on paraquat-induced EMT. Toxicol Vitro. 2023;93:105693. https://doi.org/10.1016/j.tiv.2023.105693 .

Sun Z, Yang Z, Wang M, Huang C, Ren Y, Zhang W, et al. Paraquat induces pulmonary fibrosis through Wnt/β-catenin signaling pathway and myofibroblast differentiation. Toxicol Lett. 2020;333(June):170–83. https://doi.org/10.1016/j.toxlet.2020.08.004 .

Berschneider B, Ellwanger DC, Baarsma HA, Thiel C, Shimbori C, White ES, et al. MiR-92a regulates TGF-β1-induced WISP1 expression in pulmonary fibrosis. Int J Biochem Cell Biol. 2014;53:432–41. https://doi.org/10.1016/j.biocel.2014.06.011 .

Pommier A, Varilh J, Bleuse S, Delétang K, Bonini J, Bergougnoux A, et al. miRNA repertoires of cystic fibrosis ex vivo models highlight miR-181a and miR-101 that regulate WISP1 expression. J Pathol. 2021;253(2):186–97.

Injury E, Fibrosis IP. Epithelial injury and dysfunction in the pathogenesis of idiopathic pulmonary fibrosis. Am J Med Sci. 2020;357(5):374–8.

Singh K, Teyani RL, Moniri NH. Agonists and hydrogen peroxide mediate hyperoxidation of β 2-adrenergic receptor in airway epithelial cells : implications for tachyphylaxis to β 2-agonists in constrictive airway disorders. Biomed Pharmacother. 2023;168:115763. https://doi.org/10.1016/j.biopha.2023.115763 .

Heijink IH, Kuchibhotla VNS, Roffel MP, Maes T, Knight DA, Sayers I, et al. Epithelial cell dysfunction, a major driver of asthma development. Allergy. 2020;75:1902–17.

Heise RL, Stober V, Cheluvaraju C, Hollingsworth JW, Garantziotis S. Mechanical stretch induces epithelial-mesenchymal transition in alveolar epithelia via hyaluronan activation of innate immunity. J Biol Chem. 2011;286(20):17435–44.

Stephens S, Palmer J, Konstantinova I, Pearce A, Jarai G, Day E. A functional analysis of Wnt inducible signalling pathway protein−1 (WISP-1/CCN4). J Cell Commun Signal. 2015;9(1):63–72.

Zhang C, Zhu Y, Zhang Y, Gao L, Zhang N, Feng H. Therapeutic potential of umbilical cord mesenchymal stem cells for inhibiting myofibroblastic differentiation of irradiated human lung fibroblasts. Tohoku J Exp Med. 2015;236(3):209–17.

Li X, Liu X, Deng R, Gao S, Yu H, Huang K, et al. Nintedanib inhibits Wnt3a-induced myofibroblast activation by suppressing the Src/b-catenin pathway. Front Pharmacol. 2020;11:1–11.

Lehmann M, Buhl L, Alsafadi HN, Klee S, Hermann S, Mutze K, et al. Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis. Respir Res. 2018;19(1):1–12.

Huang X, Cai H, Ammar R, Zhang Y, Wang Y, Ravi K, et al. Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds. Am J Physiol Gastrointest Liver Physiol. 2019;316(1):G15-24.

Pivovarova-Ramich O, Loske J, Hornemann S, Markova M, Seebeck N, Rosenthal A, et al. Hepatic wnt1 inducible signaling pathway protein 1 (WISP-1/CCN4) associates with markers of liver fibrosis in severe obesity. Cells. 2021;10(5):1048.

Chen Z, Ding X, Jin S, Pitt B, Zhang L, Billiar T, et al. WISP1-αvβ3 integrin signaling positively regulates TLR-triggered inflammation response in sepsis induced lung injury. Sci Rep. 2016;6:1–11. https://doi.org/10.1038/srep28841 .

Rong X, Liu J, Yao X, Jiang T, Wang Y, Xie F. Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/β-catenin pathway. Stem Cell Res Ther. 2019;10(1):1–11.

Jian YC, Wang JJ, Dong S, Hu JW, Hu LJ, Yang GM, et al. Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo. Clin Lab. 2014;60(1):29–35.

Li X, Chen Y, Ye W, Tao X, Zhu J, Wu S, et al. Blockade of CCN4 attenuates CCl4-induced liver fibrosis. Arch Med Sci. 2015;11(3):647–53.

Ono M, Masaki A, Maeda A, Kilts TM. CCN4 / WISP1 controls cutaneous wound healing by modulating proliferation, migration and ECM expression in dermal fibroblasts via α 5 β 1 and TNF α. Matrix Biol. 2018;68–69:533–46. https://doi.org/10.1016/j.matbio.2018.01.004 .

Tank J, Lindner D, Wang X, Stroux A, Gilke L, Gast M, et al. Single-target RNA interference for the blockade of multiple interacting proinflammatory and profibrotic pathways in cardiac fibroblasts. J Mol Cell Cardiol. 2014;66:141–56.

Green LC, Slone S, Anthony SR, Guarnieri AR, Parkins S, Shearer SM, et al. HuR-dependent expression of Wisp1 is necessary for TGFβ-induced cardiac myofibroblast activity. J Mol Cell Cardiol. 2022;2023(174):38–46.

Zhong X, Tu YJ, Li Y, Zhang P, Wang W, Chen SS, et al. Serum levels of WNT1-inducible signaling pathway protein-1 (WISP-1): a noninvasive biomarker of renal fibrosis in subjects with chronic kidney disease. Am J Transl Res. 2017;9(6):2920–32.

Zhou Y, Chai P, Wang J, Li L, Chen MH. Wingless/int-1induced secreted protein-1: a new biomarker for renal fibrosis. J Biol Regul Homeost Agents. 2021;35(1):33480221.

Hennemeier I, Humpf HU, Gekle M, Schwerdt G. The food contaminant and nephrotoxin ochratoxin A enhances Wnt1 inducible signaling protein 1 and tumor necrosis factor-α expression in human primary proximal tubule cells. Mol Nutr Food Res. 2012;56(9):1375–84.

Yang X, Wang H, Tu Y, Li Y, Zou Y, Li G, et al. WNT1-inducible signaling protein-1 mediates TGF-β1-induced renal fibrosis in tubular epithelial cells and unilateral ureteral obstruction mouse models via autophagy. J Cell Physiol. 2020;235(3):2009–22.

Wang B, Ding C, Ding X, Tesch G, Zheng J, Tian PY, et al. WNT1-inducible signaling pathway protein 1 regulates kidney inflammation through the NF-κB pathway. Clin Sci. 2022;136(1):29–44.

Ai K, Yi L, Wang Y, Li Y. CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WNT1-inducible signaling pathway protein 1 pathway. J Pharmacol Exp Ther. 2023;384(1):225–6.

Liang J-N, Zou X, Fang X-H, Xu J-D, Xiao Z, Zhu J-N, et al. The Smad3-miR-29b/miR-29c axis mediates the protective effect of macrophage migration inhibitory factor against cardiac fibrosis. Biochim Biophys Acta Mol Basis Dis. 2019;1865(9):2441–50. https://doi.org/10.1016/j.bbadis.2019.06.004 .

Gong X, Wang X, Zhou F. Liver microRNA-29b-3p positively correlates with relative enhancement values of magnetic resonance imaging and represses liver fibrosis. J Biochem. 2020;168(6):603–9.

Xue Y, Fan X, Yang R, Jiao Y, Li Y. miR-29b-3p inhibits post-infarct cardiac fibrosis by targeting FOS. Biosci Rep. 2020;40(9):1–11.

Fan X, Gao Y, Zhang X, Lughmani HY, Kennedy DJ, Haller ST, et al. A strategic expression method of miR-29b and its anti-fibrotic effect based on RNA-sequencing analysis. PLoS ONE. 2020;15:1–16. https://doi.org/10.1371/journal.pone.0244065 .

Chen H, Fan Y, Jing H, Tang S, Huang Z, Liao M, et al. LncRNA Gm12840 mediates WISP1 to regulate ischemia-reperfusion-induced renal fibrosis by sponging miR-677-5p. Epigenomics. 2020;12(24):2205–18.

Abd El-Kader T, Kubota S, Janune D. Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family. J Cell Commun Signal. 2013;7:11–8.

Leask A. Yin and Yang revisited: CCN3 as an anti-fibrotic therapeutic? J Cell Commun Signal. 2015;9(1):97–8.

Leask A. CCN3: a novel anti-fibrotic treatment in end-stage renal disease? J Cell Commun Signal. 2012;6(2):115–6.

Lin X, Li H. Obesity: epidemiology, pathophysiology, and therapeutics. Front Endocrinol. 2021;12(September):1–9.

Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9(2):191–200.

Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol. 2011;11:85–97.

Murahovschi V, Pivovarova O, Ilkavets I, Dmitrieva RM, Döcke S, Keyhani-Nejad F, et al. WISP1 Is a novel adipokine linked to inflammation in obesity. Diabetes. 2015;64(3):856–66.

Martinerie C, Garcia M, Do TTH, Antoine B, Moldes M, Dorothee G, et al. NOV/CCN3: A new adipocytokine involved in obesity-associated insulin resistance. Diabetes. 2016;65(9):2502–15.

Tacke C, Aleksandrova K, Rehfeldt M, Murahovschi V, Markova M, Kemper M, et al. Assessment of circulating Wnt1 inducible signalling pathway protein 1 (WISP-1)/CCN4 as a novel biomarker of obesity. J Cell Commun Signal. 2018;12(3):539–48.

Barchetta I, Cimini FA, Capoccia D, De Gioannis R, Porzia A, Mainiero F, et al. WISP1 is a marker of systemic and adipose tissue inflammation in dysmetabolic subjects with or without type 2 diabetes. J Endocr Soc. 2017;1:660–70.

Hörbelt T, Tacke C, Markova M, de Wiza DH, Van de Velde F, Bekaert M, et al. The novel adipokine WISP1 associates with insulin resistance and impairs insulin action in human myotubes and mouse hepatocytes. Diabetologia. 2018;61(9):2054–65.

Jung TW, Kang C, Goh J, Chae SI, Kim HC, Lee TJ, et al. WISP1 promotes non-alcoholic fatty liver disease and skeletal muscle insulin resistance via TLR4/JNK signaling. J Cell Physiol. 2018;233(8):6077–87.

Fernandez-ruiz R, García-alamán A, Esteban Y, Mir-coll J, Serra-navarro B, Fontcuberta-pisunyer M, et al. Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells. Nat Commun. 2020. https://doi.org/10.1038/s41467-020-19657-1 .

Seong JK, Park J. Identification of differentially expressed mRNA during pancreas regeneration of rat by mRNA differential display. Biochem Biophys Res Commun. 2002;299:806–12.

Kapasa M, Sera I, Gavalas A, Kossida S. Genomics identification of phylogenetically conserved enhancer elements implicated in pancreas development in the WISP1 and CTGF orthologs. Genomics. 2008;92:301–8.

Chen Y, Li P, Lin M, Jiang Y, Tan G, Huang L, et al. Silencing of METTL3 prevents the proliferation, migration, epithelial-mesenchymal transition, and renal fibrosis of high glucose-induced HK2 cells by mediating WISP1 in m6A-dependent manner. Aging. 2024;16(2):1237–48.

Liu L, Hu J, Yang L, Wang N, Liu Y, Wei X, et al. Association of WISP1/CCN4 with risk of overweight and gestational diabetes mellitus in Chinese pregnant women. Dis Markers. 2020;2020:1–10.

CAS   Google Scholar  

Sahin Ersoy G, Altun Ensari T, Subas S, Giray B, Simsek EE, Cevik O. WISP1 is a novel adipokine linked to metabolic parameters in gestational diabetes mellitus. J Matern Neonatal Med. 2017;30(8):942–6.

French DM, Kaul RJ, Souza ALD, Crowley CW, Bao M, Frantz GD, et al. WISP-1 is an osteoblastic regulator expressed during skeletal development and fracture repair. Am J Pathol. 2004;165(3):855–67.

Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: a chronic low-grade inflammation and its markers. Cureus. 2022;14(2): e2271.

Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Investig. 2007;117(1):175–84.

Lacy P, Murray RZ, Moraes-vieira PM. The macrophage switch in obesity. Development. 2016;6(Jan):1–11.

Chang JS, Kim TH, Kong ID. Exercise intervention lowers aberrant serum WISP-1 levels with insulin resistance in breast cancer survivors : a randomized controlled trial. Sci Rep. 2020;10(2):1–9. https://doi.org/10.1038/s41598-020-67794-w .

Yu Z, Wang T, Zhang L, Yang X, Li Q, Ding X. WISP1 and TLR4 on macrophages contribute to ventilator-induced lung injury. Inflammation. 2020;43(2):425–32.

Liu L, Xu S, Li P, Li L. A novel adipokine WISP1 attenuates lipopolysaccharide-induced cell injury in 3T3-L1 adipocytes by regulating the PI3K/Akt pathway. Obes Res Clin Pract. 2022;16(2):122–9. https://doi.org/10.1016/j.orcp.2022.03.001 .

Ferrand N, Béreziat V, Moldes M, Zaoui M, Larsen AK, Sabbah M. WISP1/CCN4 inhibits adipocyte differentiation through repression of PPAR γ activity. Sci Rep. 2017;7:1–12.

Senthelal S, Li J, Ardeshirzadeh S, Thomas MA. Arthritis. StatPearls: Treasure Island; 2023.

Eakin GS, Amodeo KL, Kahlon RS. Arthritis and its public health burden. Del J Public Heal. 2017;3(1):36–44.

Komatsu M, Nakamura Y, Maruyama M, Abe K, Watanapokasin R, Kato H. Expression profiles of human CCN genes in patients with osteoarthritis or rheumatoid arthritis. J Orthop Sci. 2015;20(4):708–16.

Macsai CE, Georgiou KR, Foster BK, Zannettino ACW, Xian CJ. Microarray expression analysis of genes and pathways involved in growth plate cartilage injury responses and bony repair. Bone. 2012;50(5):1081–91. https://doi.org/10.1016/j.bone.2012.02.013 .

Geyer M, Grässel S, Straub RH, Schett G, Dinser R, Grifka J, et al. Differential transcriptome analysis of intraarticular lesional vs intact cartilage reveals new candidate genes in osteoarthritis pathophysiology. Osteoarthr Cartil. 2009;17(3):328–35.

Chou CH, Wu CC, Song IW, Chuang HP, Lu LS, Chang JH, et al. Genome-wide expression profiles of subchondral bone in osteoarthritis. Arthr Res Ther. 2013;15(6):R190.

Chen S, Li B. MiR-128-3p post-transcriptionally inhibits WISP1 to suppress apoptosis and inflammation in human articular chondrocytes via the PI3K/AKT/NF-κB signaling pathway. Cell Transpl. 2020;29(8):1–13.

van den Bosch MH, Blom AB, Kram V, Maeda A, Sikka S, Gabet Y, et al. WISP1/CCN4 aggravates cartilage degeneration in experimental osteoarthritis. Osteoarthr Cartil. 2017;25(11):1900–11. https://doi.org/10.1016/j.joca.2017.07.012 .

Cheng C, Tian J, Zhang F, Deng Z, Tu M, Li L, et al. WISP1 protects against chondrocyte senescence and apoptosis by regulating αvβ3 and PI3K/Akt pathway in osteoarthritis. DNA Cell Biol. 2021;40(4):629–37.

Zhang M, Meng QC, Yang XF, Mu WD. TGF-β1/WISP1/Integrin-α interaction mediates human chondrocytes dedifferentiation. Eur Rev Med Pharmacol Sci. 2020;24(17):8675–84.

Van den Bosch MH, Blom AB, van Lent PL, van Beuningen HM, Blaney Davidson EN, van der Kraan PM, et al. Canonical Wnt signaling skews TGF-β signaling in chondrocytes towards signaling via ALK1 and smad 1/5/8. Cell Signal. 2014;26(5):951–8. https://doi.org/10.1016/j.cellsig.2014.01.021 .

Hou CH, Tang CH, Hsu CJ, Hou SM, Liu JF. CCN4 induces IL-6 production through αvβ5 receptor, PI3K, Akt, and NF-κB singling pathway in human synovial fibroblasts. Arthr Res Ther. 2013;15(1):R19.

Charlier E, Deroyer C, Ciregia F, Malaise O, Neuville S, Plener Z, et al. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem Pharmacol. 2019;165(Feb):49–65. https://doi.org/10.1016/j.bcp.2019.02.036 .

Timmermans RGM, Blom AB, Bloks NGC, Nelissen RGHH, van der Linden EHMJ, van der Kraan PM, et al. CCN4/WISP1 promotes migration of human primary osteoarthritic chondrocytes. Cartilage. 2023;14(1):67–75.

Ono M, Inkson CA, Kilts TM, Young MF. WISP-1/CCN4 regulates osteogenesis by enhancing BMP-2 activity. J Bone Miner Res. 2011;26(1):193–208.

Cernea M, Tang W, Guan H, Yang K. Wisp1 mediates Bmp-3 stimulated mesenchymal stem cell proliferation. J Mol Endocrinol. 2016;56(1):39–46.

Liu JF, Hou SM, Tsai CH, Huang CY, Hsu CJ, Tang CH. CCN4 induces vascular cell adhesion molecule-1 expression in human synovial fibroblasts and promotes monocyte adhesion. Biochim Biophys Acta Mol Cell Res. 2013;1833(5):966–75. https://doi.org/10.1016/j.bbamcr.2012.12.023 .

Urano T, Narusawa K, Shiraki M, Usui T, Sasaki N, Hosoi T, et al. Association of a single nucleotide polymorphism in the WISP1 gene with spinal osteoarthritis in postmenopausal Japanese women. J Bone Miner Metab. 2007;25(4):253–8.

Download references

Acknowledgements

The authors wish to acknowledge Dr. Kannan Thirunavukkarasu and Dr. Marta A. Witek for providing critical feedback on the manuscript. The authors would also like to thank the Department of Biotherapeutic Enabling Biology for all the help and support.

The work was supported and funded by Eli Lilly and Company.

Author information

Authors and affiliations.

Biotherapeutic Enabling Biology, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46225, USA

Kirti Singh & Sunday S. Oladipupo

You can also search for this author in PubMed   Google Scholar

Contributions

KS conceptualized, compiled, reviewed literature, edited, designed figures, tables and wrote the manuscript. SSO supervised, reviewed, edited, and provided critical feedback on the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Sunday S. Oladipupo .

Ethics declarations

Ethics approval and consent to participate.

Not Applicable.

Consent for publication

Competing interests.

The authors have no competing interests related to this work.

Additional information

Publisher's note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Singh, K., Oladipupo, S.S. An overview of CCN4 (WISP1) role in human diseases. J Transl Med 22 , 601 (2024). https://doi.org/10.1186/s12967-024-05364-8

Download citation

Received : 02 April 2024

Accepted : 01 June 2024

Published : 27 June 2024

DOI : https://doi.org/10.1186/s12967-024-05364-8

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Matricellular proteins
• Inflammation

Journal of Translational Medicine

ISSN: 1479-5876

• Submission enquiries: Access here and click Contact Us
• General enquiries: [email protected]