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• How to Write a Literature Review | Guide, Examples, & Templates

How to Write a Literature Review | Guide, Examples, & Templates

Published on January 2, 2023 by Shona McCombes . Revised on September 11, 2023.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research that you can later apply to your paper, thesis, or dissertation topic .

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates, and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarize sources—it analyzes, synthesizes , and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

What is the purpose of a literature review, examples of literature reviews, step 1 – search for relevant literature, step 2 – evaluate and select sources, step 3 – identify themes, debates, and gaps, step 4 – outline your literature review’s structure, step 5 – write your literature review, free lecture slides, other interesting articles, frequently asked questions, introduction.

• Quick Run-through
• Step 1 & 2

When you write a thesis , dissertation , or research paper , you will likely have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and its scholarly context
• Develop a theoretical framework and methodology for your research
• Position your work in relation to other researchers and theorists
• Show how your research addresses a gap or contributes to a debate
• Evaluate the current state of research and demonstrate your knowledge of the scholarly debates around your topic.

Writing literature reviews is a particularly important skill if you want to apply for graduate school or pursue a career in research. We’ve written a step-by-step guide that you can follow below.

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Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research problem and questions .

Make a list of keywords

Start by creating a list of keywords related to your research question. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list as you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some useful databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can also use boolean operators to help narrow down your search.

Make sure to read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

You likely won’t be able to read absolutely everything that has been written on your topic, so it will be necessary to evaluate which sources are most relevant to your research question.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models, and methods?
• Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible , and make sure you read any landmark studies and major theories in your field of research.

You can use our template to summarize and evaluate sources you’re thinking about using. Click on either button below to download.

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It is important to keep track of your sources with citations to avoid plagiarism . It can be helpful to make an annotated bibliography , where you compile full citation information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

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To begin organizing your literature review’s argument and structure, be sure you understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly visual platforms like Instagram and Snapchat—this is a gap that you could address in your own research.

There are various approaches to organizing the body of a literature review. Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarizing sources in order.

Try to analyze patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organize your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text , your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, you can follow these tips:

• Summarize and synthesize: give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: don’t just paraphrase other researchers — add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically evaluate: mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: use transition words and topic sentences to draw connections, comparisons and contrasts

In the conclusion, you should summarize the key findings you have taken from the literature and emphasize their significance.

When you’ve finished writing and revising your literature review, don’t forget to proofread thoroughly before submitting. Not a language expert? Check out Scribbr’s professional proofreading services !

This article has been adapted into lecture slides that you can use to teach your students about writing a literature review.

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If you want to know more about the research process , methodology , research bias , or statistics , make sure to check out some of our other articles with explanations and examples.

• Sampling methods
• Simple random sampling
• Stratified sampling
• Cluster sampling
• Likert scales
• Reproducibility

 Statistics

• Null hypothesis
• Statistical power
• Probability distribution
• Effect size
• Poisson distribution

Research bias

• Optimism bias
• Cognitive bias
• Implicit bias
• Hawthorne effect
• Anchoring bias
• Explicit bias

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a thesis, dissertation , or research paper , in order to situate your work in relation to existing knowledge.

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarize yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your thesis or dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

A literature review is a survey of credible sources on a topic, often used in dissertations , theses, and research papers . Literature reviews give an overview of knowledge on a subject, helping you identify relevant theories and methods, as well as gaps in existing research. Literature reviews are set up similarly to other  academic texts , with an introduction , a main body, and a conclusion .

An  annotated bibliography is a list of  source references that has a short description (called an annotation ) for each of the sources. It is often assigned as part of the research process for a  paper .  

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A literature review is a document or section of a document that collects key sources on a topic and discusses those sources in conversation with each other (also called synthesis ). The lit review is an important genre in many disciplines, not just literature (i.e., the study of works of literature such as novels and plays). When we say “literature review” or refer to “the literature,” we are talking about the research ( scholarship ) in a given field. You will often see the terms “the research,” “the scholarship,” and “the literature” used mostly interchangeably.

Where, when, and why would I write a lit review?

There are a number of different situations where you might write a literature review, each with slightly different expectations; different disciplines, too, have field-specific expectations for what a literature review is and does. For instance, in the humanities, authors might include more overt argumentation and interpretation of source material in their literature reviews, whereas in the sciences, authors are more likely to report study designs and results in their literature reviews; these differences reflect these disciplines’ purposes and conventions in scholarship. You should always look at examples from your own discipline and talk to professors or mentors in your field to be sure you understand your discipline’s conventions, for literature reviews as well as for any other genre.

A literature review can be a part of a research paper or scholarly article, usually falling after the introduction and before the research methods sections. In these cases, the lit review just needs to cover scholarship that is important to the issue you are writing about; sometimes it will also cover key sources that informed your research methodology.

Lit reviews can also be standalone pieces, either as assignments in a class or as publications. In a class, a lit review may be assigned to help students familiarize themselves with a topic and with scholarship in their field, get an idea of the other researchers working on the topic they’re interested in, find gaps in existing research in order to propose new projects, and/or develop a theoretical framework and methodology for later research. As a publication, a lit review usually is meant to help make other scholars’ lives easier by collecting and summarizing, synthesizing, and analyzing existing research on a topic. This can be especially helpful for students or scholars getting into a new research area, or for directing an entire community of scholars toward questions that have not yet been answered.

What are the parts of a lit review?

Most lit reviews use a basic introduction-body-conclusion structure; if your lit review is part of a larger paper, the introduction and conclusion pieces may be just a few sentences while you focus most of your attention on the body. If your lit review is a standalone piece, the introduction and conclusion take up more space and give you a place to discuss your goals, research methods, and conclusions separately from where you discuss the literature itself.

Introduction:

• An introductory paragraph that explains what your working topic and thesis is
• A forecast of key topics or texts that will appear in the review
• Potentially, a description of how you found sources and how you analyzed them for inclusion and discussion in the review (more often found in published, standalone literature reviews than in lit review sections in an article or research paper)
• Summarize and synthesize: Give an overview of the main points of each source and combine them into a coherent whole
• Analyze and interpret: Don’t just paraphrase other researchers – add your own interpretations where possible, discussing the significance of findings in relation to the literature as a whole
• Critically Evaluate: Mention the strengths and weaknesses of your sources
• Write in well-structured paragraphs: Use transition words and topic sentence to draw connections, comparisons, and contrasts.

Conclusion:

• Summarize the key findings you have taken from the literature and emphasize their significance
• Connect it back to your primary research question

How should I organize my lit review?

Lit reviews can take many different organizational patterns depending on what you are trying to accomplish with the review. Here are some examples:

• Chronological : The simplest approach is to trace the development of the topic over time, which helps familiarize the audience with the topic (for instance if you are introducing something that is not commonly known in your field). If you choose this strategy, be careful to avoid simply listing and summarizing sources in order. Try to analyze the patterns, turning points, and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred (as mentioned previously, this may not be appropriate in your discipline — check with a teacher or mentor if you’re unsure).
• Thematic : If you have found some recurring central themes that you will continue working with throughout your piece, you can organize your literature review into subsections that address different aspects of the topic. For example, if you are reviewing literature about women and religion, key themes can include the role of women in churches and the religious attitude towards women.
• Qualitative versus quantitative research
• Empirical versus theoretical scholarship
• Divide the research by sociological, historical, or cultural sources
• Theoretical : In many humanities articles, the literature review is the foundation for the theoretical framework. You can use it to discuss various theories, models, and definitions of key concepts. You can argue for the relevance of a specific theoretical approach or combine various theorical concepts to create a framework for your research.

What are some strategies or tips I can use while writing my lit review?

Any lit review is only as good as the research it discusses; make sure your sources are well-chosen and your research is thorough. Don’t be afraid to do more research if you discover a new thread as you’re writing. More info on the research process is available in our "Conducting Research" resources .

As you’re doing your research, create an annotated bibliography ( see our page on the this type of document ). Much of the information used in an annotated bibliography can be used also in a literature review, so you’ll be not only partially drafting your lit review as you research, but also developing your sense of the larger conversation going on among scholars, professionals, and any other stakeholders in your topic.

Usually you will need to synthesize research rather than just summarizing it. This means drawing connections between sources to create a picture of the scholarly conversation on a topic over time. Many student writers struggle to synthesize because they feel they don’t have anything to add to the scholars they are citing; here are some strategies to help you:

• It often helps to remember that the point of these kinds of syntheses is to show your readers how you understand your research, to help them read the rest of your paper.
• Writing teachers often say synthesis is like hosting a dinner party: imagine all your sources are together in a room, discussing your topic. What are they saying to each other?
• Look at the in-text citations in each paragraph. Are you citing just one source for each paragraph? This usually indicates summary only. When you have multiple sources cited in a paragraph, you are more likely to be synthesizing them (not always, but often
• Read more about synthesis here.

The most interesting literature reviews are often written as arguments (again, as mentioned at the beginning of the page, this is discipline-specific and doesn’t work for all situations). Often, the literature review is where you can establish your research as filling a particular gap or as relevant in a particular way. You have some chance to do this in your introduction in an article, but the literature review section gives a more extended opportunity to establish the conversation in the way you would like your readers to see it. You can choose the intellectual lineage you would like to be part of and whose definitions matter most to your thinking (mostly humanities-specific, but this goes for sciences as well). In addressing these points, you argue for your place in the conversation, which tends to make the lit review more compelling than a simple reporting of other sources.

Libraries | Research Guides

Literature reviews, what is a literature review, learning more about how to do a literature review.

• Planning the Review
• The Research Question
• Choosing Where to Search
• Organizing the Review
• Writing the Review

A literature review is a review and synthesis of existing research on a topic or research question. A literature review is meant to analyze the scholarly literature, make connections across writings and identify strengths, weaknesses, trends, and missing conversations. A literature review should address different aspects of a topic as it relates to your research question. A literature review goes beyond a description or summary of the literature you have read. 

• Sage Research Methods Core Collection This link opens in a new window SAGE Research Methods supports research at all levels by providing material to guide users through every step of the research process. SAGE Research Methods is the ultimate methods library with more than 1000 books, reference works, journal articles, and instructional videos by world-leading academics from across the social sciences, including the largest collection of qualitative methods books available online from any scholarly publisher. – Publisher

• Next: Planning the Review >>
• Last Updated: Jan 17, 2024 10:05 AM
• URL: https://libguides.northwestern.edu/literaturereviews

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• Knowledge Base
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• What is a Literature Review? | Guide, Template, & Examples

What is a Literature Review? | Guide, Template, & Examples

Published on 22 February 2022 by Shona McCombes . Revised on 7 June 2022.

What is a literature review? A literature review is a survey of scholarly sources on a specific topic. It provides an overview of current knowledge, allowing you to identify relevant theories, methods, and gaps in the existing research.

There are five key steps to writing a literature review:

• Search for relevant literature
• Evaluate sources
• Identify themes, debates and gaps
• Outline the structure
• Write your literature review

A good literature review doesn’t just summarise sources – it analyses, synthesises, and critically evaluates to give a clear picture of the state of knowledge on the subject.

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Table of contents

Why write a literature review, examples of literature reviews, step 1: search for relevant literature, step 2: evaluate and select sources, step 3: identify themes, debates and gaps, step 4: outline your literature review’s structure, step 5: write your literature review, frequently asked questions about literature reviews, introduction.

• Quick Run-through
• Step 1 & 2

When you write a dissertation or thesis, you will have to conduct a literature review to situate your research within existing knowledge. The literature review gives you a chance to:

• Demonstrate your familiarity with the topic and scholarly context
• Develop a theoretical framework and methodology for your research
• Position yourself in relation to other researchers and theorists
• Show how your dissertation addresses a gap or contributes to a debate

You might also have to write a literature review as a stand-alone assignment. In this case, the purpose is to evaluate the current state of research and demonstrate your knowledge of scholarly debates around a topic.

The content will look slightly different in each case, but the process of conducting a literature review follows the same steps. We’ve written a step-by-step guide that you can follow below.

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Writing literature reviews can be quite challenging! A good starting point could be to look at some examples, depending on what kind of literature review you’d like to write.

• Example literature review #1: “Why Do People Migrate? A Review of the Theoretical Literature” ( Theoretical literature review about the development of economic migration theory from the 1950s to today.)
• Example literature review #2: “Literature review as a research methodology: An overview and guidelines” ( Methodological literature review about interdisciplinary knowledge acquisition and production.)
• Example literature review #3: “The Use of Technology in English Language Learning: A Literature Review” ( Thematic literature review about the effects of technology on language acquisition.)
• Example literature review #4: “Learners’ Listening Comprehension Difficulties in English Language Learning: A Literature Review” ( Chronological literature review about how the concept of listening skills has changed over time.)

You can also check out our templates with literature review examples and sample outlines at the links below.

Download Word doc Download Google doc

Before you begin searching for literature, you need a clearly defined topic .

If you are writing the literature review section of a dissertation or research paper, you will search for literature related to your research objectives and questions .

If you are writing a literature review as a stand-alone assignment, you will have to choose a focus and develop a central question to direct your search. Unlike a dissertation research question, this question has to be answerable without collecting original data. You should be able to answer it based only on a review of existing publications.

Make a list of keywords

Start by creating a list of keywords related to your research topic. Include each of the key concepts or variables you’re interested in, and list any synonyms and related terms. You can add to this list if you discover new keywords in the process of your literature search.

• Social media, Facebook, Instagram, Twitter, Snapchat, TikTok
• Body image, self-perception, self-esteem, mental health
• Generation Z, teenagers, adolescents, youth

Search for relevant sources

Use your keywords to begin searching for sources. Some databases to search for journals and articles include:

• Your university’s library catalogue
• Google Scholar
• Project Muse (humanities and social sciences)
• Medline (life sciences and biomedicine)
• EconLit (economics)
• Inspec (physics, engineering and computer science)

You can use boolean operators to help narrow down your search:

Read the abstract to find out whether an article is relevant to your question. When you find a useful book or article, you can check the bibliography to find other relevant sources.

To identify the most important publications on your topic, take note of recurring citations. If the same authors, books or articles keep appearing in your reading, make sure to seek them out.

You probably won’t be able to read absolutely everything that has been written on the topic – you’ll have to evaluate which sources are most relevant to your questions.

For each publication, ask yourself:

• What question or problem is the author addressing?
• What are the key concepts and how are they defined?
• What are the key theories, models and methods? Does the research use established frameworks or take an innovative approach?
• What are the results and conclusions of the study?
• How does the publication relate to other literature in the field? Does it confirm, add to, or challenge established knowledge?
• How does the publication contribute to your understanding of the topic? What are its key insights and arguments?
• What are the strengths and weaknesses of the research?

Make sure the sources you use are credible, and make sure you read any landmark studies and major theories in your field of research.

You can find out how many times an article has been cited on Google Scholar – a high citation count means the article has been influential in the field, and should certainly be included in your literature review.

The scope of your review will depend on your topic and discipline: in the sciences you usually only review recent literature, but in the humanities you might take a long historical perspective (for example, to trace how a concept has changed in meaning over time).

Remember that you can use our template to summarise and evaluate sources you’re thinking about using!

Take notes and cite your sources

As you read, you should also begin the writing process. Take notes that you can later incorporate into the text of your literature review.

It’s important to keep track of your sources with references to avoid plagiarism . It can be helpful to make an annotated bibliography, where you compile full reference information and write a paragraph of summary and analysis for each source. This helps you remember what you read and saves time later in the process.

You can use our free APA Reference Generator for quick, correct, consistent citations.

To begin organising your literature review’s argument and structure, you need to understand the connections and relationships between the sources you’ve read. Based on your reading and notes, you can look for:

• Trends and patterns (in theory, method or results): do certain approaches become more or less popular over time?
• Themes: what questions or concepts recur across the literature?
• Debates, conflicts and contradictions: where do sources disagree?
• Pivotal publications: are there any influential theories or studies that changed the direction of the field?
• Gaps: what is missing from the literature? Are there weaknesses that need to be addressed?

This step will help you work out the structure of your literature review and (if applicable) show how your own research will contribute to existing knowledge.

• Most research has focused on young women.
• There is an increasing interest in the visual aspects of social media.
• But there is still a lack of robust research on highly-visual platforms like Instagram and Snapchat – this is a gap that you could address in your own research.

There are various approaches to organising the body of a literature review. You should have a rough idea of your strategy before you start writing.

Depending on the length of your literature review, you can combine several of these strategies (for example, your overall structure might be thematic, but each theme is discussed chronologically).

Chronological

The simplest approach is to trace the development of the topic over time. However, if you choose this strategy, be careful to avoid simply listing and summarising sources in order.

Try to analyse patterns, turning points and key debates that have shaped the direction of the field. Give your interpretation of how and why certain developments occurred.

If you have found some recurring central themes, you can organise your literature review into subsections that address different aspects of the topic.

For example, if you are reviewing literature about inequalities in migrant health outcomes, key themes might include healthcare policy, language barriers, cultural attitudes, legal status, and economic access.

Methodological

If you draw your sources from different disciplines or fields that use a variety of research methods , you might want to compare the results and conclusions that emerge from different approaches. For example:

• Look at what results have emerged in qualitative versus quantitative research
• Discuss how the topic has been approached by empirical versus theoretical scholarship
• Divide the literature into sociological, historical, and cultural sources

Theoretical

A literature review is often the foundation for a theoretical framework . You can use it to discuss various theories, models, and definitions of key concepts.

You might argue for the relevance of a specific theoretical approach, or combine various theoretical concepts to create a framework for your research.

Like any other academic text, your literature review should have an introduction , a main body, and a conclusion . What you include in each depends on the objective of your literature review.

The introduction should clearly establish the focus and purpose of the literature review.

If you are writing the literature review as part of your dissertation or thesis, reiterate your central problem or research question and give a brief summary of the scholarly context. You can emphasise the timeliness of the topic (“many recent studies have focused on the problem of x”) or highlight a gap in the literature (“while there has been much research on x, few researchers have taken y into consideration”).

Depending on the length of your literature review, you might want to divide the body into subsections. You can use a subheading for each theme, time period, or methodological approach.

As you write, make sure to follow these tips:

• Summarise and synthesise: give an overview of the main points of each source and combine them into a coherent whole.
• Analyse and interpret: don’t just paraphrase other researchers – add your own interpretations, discussing the significance of findings in relation to the literature as a whole.
• Critically evaluate: mention the strengths and weaknesses of your sources.
• Write in well-structured paragraphs: use transitions and topic sentences to draw connections, comparisons and contrasts.

In the conclusion, you should summarise the key findings you have taken from the literature and emphasise their significance.

If the literature review is part of your dissertation or thesis, reiterate how your research addresses gaps and contributes new knowledge, or discuss how you have drawn on existing theories and methods to build a framework for your research. This can lead directly into your methodology section.

A literature review is a survey of scholarly sources (such as books, journal articles, and theses) related to a specific topic or research question .

It is often written as part of a dissertation , thesis, research paper , or proposal .

There are several reasons to conduct a literature review at the beginning of a research project:

• To familiarise yourself with the current state of knowledge on your topic
• To ensure that you’re not just repeating what others have already done
• To identify gaps in knowledge and unresolved problems that your research can address
• To develop your theoretical framework and methodology
• To provide an overview of the key findings and debates on the topic

Writing the literature review shows your reader how your work relates to existing research and what new insights it will contribute.

The literature review usually comes near the beginning of your  dissertation . After the introduction , it grounds your research in a scholarly field and leads directly to your theoretical framework or methodology .

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• Literature Review: The What, Why and How-to Guide
• Introduction

Literature Review: The What, Why and How-to Guide — Introduction

• Getting Started
• How to Pick a Topic
• Strategies to Find Sources
• Evaluating Sources & Lit. Reviews
• Tips for Writing Literature Reviews
• Writing Literature Review: Useful Sites
• Citation Resources
• Other Academic Writings

What are Literature Reviews?

So, what is a literature review? "A literature review is an account of what has been published on a topic by accredited scholars and researchers. In writing the literature review, your purpose is to convey to your reader what knowledge and ideas have been established on a topic, and what their strengths and weaknesses are. As a piece of writing, the literature review must be defined by a guiding concept (e.g., your research objective, the problem or issue you are discussing, or your argumentative thesis). It is not just a descriptive list of the material available, or a set of summaries." Taylor, D.  The literature review: A few tips on conducting it . University of Toronto Health Sciences Writing Centre.

Goals of Literature Reviews

What are the goals of creating a Literature Review?  A literature could be written to accomplish different aims:

• To develop a theory or evaluate an existing theory
• To summarize the historical or existing state of a research topic
• Identify a problem in a field of research 

Baumeister, R. F., & Leary, M. R. (1997). Writing narrative literature reviews .  Review of General Psychology , 1 (3), 311-320.

What kinds of sources require a Literature Review?

• A research paper assigned in a course
• A thesis or dissertation
• A grant proposal
• An article intended for publication in a journal

All these instances require you to collect what has been written about your research topic so that you can demonstrate how your own research sheds new light on the topic.

Types of Literature Reviews

What kinds of literature reviews are written?

Narrative review: The purpose of this type of review is to describe the current state of the research on a specific topic/research and to offer a critical analysis of the literature reviewed. Studies are grouped by research/theoretical categories, and themes and trends, strengths and weakness, and gaps are identified. The review ends with a conclusion section which summarizes the findings regarding the state of the research of the specific study, the gaps identify and if applicable, explains how the author's research will address gaps identify in the review and expand the knowledge on the topic reviewed.

• Example : Predictors and Outcomes of U.S. Quality Maternity Leave: A Review and Conceptual Framework:  10.1177/08948453211037398  

Systematic review : "The authors of a systematic review use a specific procedure to search the research literature, select the studies to include in their review, and critically evaluate the studies they find." (p. 139). Nelson, L. K. (2013). Research in Communication Sciences and Disorders . Plural Publishing.

• Example : The effect of leave policies on increasing fertility: a systematic review:  10.1057/s41599-022-01270-w

Meta-analysis : "Meta-analysis is a method of reviewing research findings in a quantitative fashion by transforming the data from individual studies into what is called an effect size and then pooling and analyzing this information. The basic goal in meta-analysis is to explain why different outcomes have occurred in different studies." (p. 197). Roberts, M. C., & Ilardi, S. S. (2003). Handbook of Research Methods in Clinical Psychology . Blackwell Publishing.

• Example : Employment Instability and Fertility in Europe: A Meta-Analysis:  10.1215/00703370-9164737

Meta-synthesis : "Qualitative meta-synthesis is a type of qualitative study that uses as data the findings from other qualitative studies linked by the same or related topic." (p.312). Zimmer, L. (2006). Qualitative meta-synthesis: A question of dialoguing with texts .  Journal of Advanced Nursing , 53 (3), 311-318.

• Example : Women’s perspectives on career successes and barriers: A qualitative meta-synthesis:  10.1177/05390184221113735

Literature Reviews in the Health Sciences

• UConn Health subject guide on systematic reviews Explanation of the different review types used in health sciences literature as well as tools to help you find the right review type
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How To Write A Literature Review - A Complete Guide

Table of Contents

A literature review is much more than just another section in your research paper. It forms the very foundation of your research. It is a formal piece of writing where you analyze the existing theoretical framework, principles, and assumptions and use that as a base to shape your approach to the research question.

Curating and drafting a solid literature review section not only lends more credibility to your research paper but also makes your research tighter and better focused. But, writing literature reviews is a difficult task. It requires extensive reading, plus you have to consider market trends and technological and political changes, which tend to change in the blink of an eye.

Now streamline your literature review process with the help of SciSpace Copilot. With this AI research assistant, you can efficiently synthesize and analyze a vast amount of information, identify key themes and trends, and uncover gaps in the existing research. Get real-time explanations, summaries, and answers to your questions for the paper you're reviewing, making navigating and understanding the complex literature landscape easier.

In this comprehensive guide, we will explore everything from the definition of a literature review, its appropriate length, various types of literature reviews, and how to write one.

What is a literature review?

A literature review is a collation of survey, research, critical evaluation, and assessment of the existing literature in a preferred domain.

Eminent researcher and academic Arlene Fink, in her book Conducting Research Literature Reviews , defines it as the following:

“A literature review surveys books, scholarly articles, and any other sources relevant to a particular issue, area of research, or theory, and by so doing, provides a description, summary, and critical evaluation of these works in relation to the research problem being investigated.

Literature reviews are designed to provide an overview of sources you have explored while researching a particular topic, and to demonstrate to your readers how your research fits within a larger field of study.”

Simply put, a literature review can be defined as a critical discussion of relevant pre-existing research around your research question and carving out a definitive place for your study in the existing body of knowledge. Literature reviews can be presented in multiple ways: a section of an article, the whole research paper itself, or a chapter of your thesis.

A literature review does function as a summary of sources, but it also allows you to analyze further, interpret, and examine the stated theories, methods, viewpoints, and, of course, the gaps in the existing content.

As an author, you can discuss and interpret the research question and its various aspects and debate your adopted methods to support the claim.

What is the purpose of a literature review?

A literature review is meant to help your readers understand the relevance of your research question and where it fits within the existing body of knowledge. As a researcher, you should use it to set the context, build your argument, and establish the need for your study.

What is the importance of a literature review?

The literature review is a critical part of research papers because it helps you:

• Gain an in-depth understanding of your research question and the surrounding area
• Convey that you have a thorough understanding of your research area and are up-to-date with the latest changes and advancements
• Establish how your research is connected or builds on the existing body of knowledge and how it could contribute to further research
• Elaborate on the validity and suitability of your theoretical framework and research methodology
• Identify and highlight gaps and shortcomings in the existing body of knowledge and how things need to change
• Convey to readers how your study is different or how it contributes to the research area

How long should a literature review be?

Ideally, the literature review should take up 15%-40% of the total length of your manuscript. So, if you have a 10,000-word research paper, the minimum word count could be 1500.

Your literature review format depends heavily on the kind of manuscript you are writing — an entire chapter in case of doctoral theses, a part of the introductory section in a research article, to a full-fledged review article that examines the previously published research on a topic.

Another determining factor is the type of research you are doing. The literature review section tends to be longer for secondary research projects than primary research projects.

What are the different types of literature reviews?

All literature reviews are not the same. There are a variety of possible approaches that you can take. It all depends on the type of research you are pursuing.

Here are the different types of literature reviews:

Argumentative review

It is called an argumentative review when you carefully present literature that only supports or counters a specific argument or premise to establish a viewpoint.

Integrative review

It is a type of literature review focused on building a comprehensive understanding of a topic by combining available theoretical frameworks and empirical evidence.

Methodological review

This approach delves into the ''how'' and the ''what" of the research question —  you cannot look at the outcome in isolation; you should also review the methodology used.

Systematic review

This form consists of an overview of existing evidence pertinent to a clearly formulated research question, which uses pre-specified and standardized methods to identify and critically appraise relevant research and collect, report, and analyze data from the studies included in the review.

Meta-analysis review

Meta-analysis uses statistical methods to summarize the results of independent studies. By combining information from all relevant studies, meta-analysis can provide more precise estimates of the effects than those derived from the individual studies included within a review.

Historical review

Historical literature reviews focus on examining research throughout a period, often starting with the first time an issue, concept, theory, or phenomenon emerged in the literature, then tracing its evolution within the scholarship of a discipline. The purpose is to place research in a historical context to show familiarity with state-of-the-art developments and identify future research's likely directions.

Theoretical Review

This form aims to examine the corpus of theory accumulated regarding an issue, concept, theory, and phenomenon. The theoretical literature review helps to establish what theories exist, the relationships between them, the degree the existing approaches have been investigated, and to develop new hypotheses to be tested.

Scoping Review

The Scoping Review is often used at the beginning of an article, dissertation, or research proposal. It is conducted before the research to highlight gaps in the existing body of knowledge and explains why the project should be greenlit.

State-of-the-Art Review

The State-of-the-Art review is conducted periodically, focusing on the most recent research. It describes what is currently known, understood, or agreed upon regarding the research topic and highlights where there are still disagreements.

Can you use the first person in a literature review?

When writing literature reviews, you should avoid the usage of first-person pronouns. It means that instead of "I argue that" or "we argue that," the appropriate expression would be "this research paper argues that."

Do you need an abstract for a literature review?

Ideally, yes. It is always good to have a condensed summary that is self-contained and independent of the rest of your review. As for how to draft one, you can follow the same fundamental idea when preparing an abstract for a literature review. It should also include:

• The research topic and your motivation behind selecting it
• A one-sentence thesis statement
• An explanation of the kinds of literature featured in the review
• Summary of what you've learned
• Conclusions you drew from the literature you reviewed
• Potential implications and future scope for research

Here's an example of the abstract of a literature review

Is a literature review written in the past tense?

Yes, the literature review should ideally be written in the past tense. You should not use the present or future tense when writing one. The exceptions are when you have statements describing events that happened earlier than the literature you are reviewing or events that are currently occurring; then, you can use the past perfect or present perfect tenses.

How many sources for a literature review?

There are multiple approaches to deciding how many sources to include in a literature review section. The first approach would be to look level you are at as a researcher. For instance, a doctoral thesis might need 60+ sources. In contrast, you might only need to refer to 5-15 sources at the undergraduate level.

The second approach is based on the kind of literature review you are doing — whether it is merely a chapter of your paper or if it is a self-contained paper in itself. When it is just a chapter, sources should equal the total number of pages in your article's body. In the second scenario, you need at least three times as many sources as there are pages in your work.

Quick tips on how to write a literature review

To know how to write a literature review, you must clearly understand its impact and role in establishing your work as substantive research material.

You need to follow the below-mentioned steps, to write a literature review:

• Outline the purpose behind the literature review
• Search relevant literature
• Examine and assess the relevant resources
• Discover connections by drawing deep insights from the resources
• Structure planning to write a good literature review

1. Outline and identify the purpose of  a literature review

As a first step on how to write a literature review, you must know what the research question or topic is and what shape you want your literature review to take. Ensure you understand the research topic inside out, or else seek clarifications. You must be able to the answer below questions before you start:

• How many sources do I need to include?
• What kind of sources should I analyze?
• How much should I critically evaluate each source?
• Should I summarize, synthesize or offer a critique of the sources?
• Do I need to include any background information or definitions?

Additionally, you should know that the narrower your research topic is, the swifter it will be for you to restrict the number of sources to be analyzed.

2. Search relevant literature

Dig deeper into search engines to discover what has already been published around your chosen topic. Make sure you thoroughly go through appropriate reference sources like books, reports, journal articles, government docs, and web-based resources.

You must prepare a list of keywords and their different variations. You can start your search from any library’s catalog, provided you are an active member of that institution. The exact keywords can be extended to widen your research over other databases and academic search engines like:

• Google Scholar
• Microsoft Academic
• Science.gov

Besides, it is not advisable to go through every resource word by word. Alternatively, what you can do is you can start by reading the abstract and then decide whether that source is relevant to your research or not.

Additionally, you must spend surplus time assessing the quality and relevance of resources. It would help if you tried preparing a list of citations to ensure that there lies no repetition of authors, publications, or articles in the literature review.

3. Examine and assess the sources

It is nearly impossible for you to go through every detail in the research article. So rather than trying to fetch every detail, you have to analyze and decide which research sources resemble closest and appear relevant to your chosen domain.

While analyzing the sources, you should look to find out answers to questions like:

• What question or problem has the author been describing and debating?
• What is the definition of critical aspects?
• How well the theories, approach, and methodology have been explained?
• Whether the research theory used some conventional or new innovative approach?
• How relevant are the key findings of the work?
• In what ways does it relate to other sources on the same topic?
• What challenges does this research paper pose to the existing theory
• What are the possible contributions or benefits it adds to the subject domain?

Be always mindful that you refer only to credible and authentic resources. It would be best if you always take references from different publications to validate your theory.

Always keep track of important information or data you can present in your literature review right from the beginning. It will help steer your path from any threats of plagiarism and also make it easier to curate an annotated bibliography or reference section.

4. Discover connections

At this stage, you must start deciding on the argument and structure of your literature review. To accomplish this, you must discover and identify the relations and connections between various resources while drafting your abstract.

A few aspects that you should be aware of while writing a literature review include:

• Rise to prominence: Theories and methods that have gained reputation and supporters over time.
• Constant scrutiny: Concepts or theories that repeatedly went under examination.
• Contradictions and conflicts: Theories, both the supporting and the contradictory ones, for the research topic.
• Knowledge gaps: What exactly does it fail to address, and how to bridge them with further research?
• Influential resources: Significant research projects available that have been upheld as milestones or perhaps, something that can modify the current trends

Once you join the dots between various past research works, it will be easier for you to draw a conclusion and identify your contribution to the existing knowledge base.

5. Structure planning to write a good literature review

There exist different ways towards planning and executing the structure of a literature review. The format of a literature review varies and depends upon the length of the research.

Like any other research paper, the literature review format must contain three sections: introduction, body, and conclusion. The goals and objectives of the research question determine what goes inside these three sections.

Nevertheless, a good literature review can be structured according to the chronological, thematic, methodological, or theoretical framework approach.

Literature review samples

1. Standalone

2. As a section of a research paper

How SciSpace Discover makes literature review a breeze?

SciSpace Discover is a one-stop solution to do an effective literature search and get barrier-free access to scientific knowledge. It is an excellent repository where you can find millions of only peer-reviewed articles and full-text PDF files. Here’s more on how you can use it:

Find the right information

Find what you want quickly and easily with comprehensive search filters that let you narrow down papers according to PDF availability, year of publishing, document type, and affiliated institution. Moreover, you can sort the results based on the publishing date, citation count, and relevance.

Assess credibility of papers quickly

When doing the literature review, it is critical to establish the quality of your sources. They form the foundation of your research. SciSpace Discover helps you assess the quality of a source by providing an overview of its references, citations, and performance metrics.

Get the complete picture in no time

SciSpace Discover’s personalized suggestion engine helps you stay on course and get the complete picture of the topic from one place. Every time you visit an article page, it provides you links to related papers. Besides that, it helps you understand what’s trending, who are the top authors, and who are the leading publishers on a topic.

Make referring sources super easy

To ensure you don't lose track of your sources, you must start noting down your references when doing the literature review. SciSpace Discover makes this step effortless. Click the 'cite' button on an article page, and you will receive preloaded citation text in multiple styles — all you've to do is copy-paste it into your manuscript.

Final tips on how to write a literature review

A massive chunk of time and effort is required to write a good literature review. But, if you go about it systematically, you'll be able to save a ton of time and build a solid foundation for your research.

We hope this guide has helped you answer several key questions you have about writing literature reviews.

Would you like to explore SciSpace Discover and kick off your literature search right away? You can get started here .

Frequently Asked Questions (FAQs)

1. how to start a literature review.

• What questions do you want to answer?

• What sources do you need to answer these questions?

• What information do these sources contain?

• How can you use this information to answer your questions?

2. What to include in a literature review?

• A brief background of the problem or issue

• What has previously been done to address the problem or issue

• A description of what you will do in your project

• How this study will contribute to research on the subject

3. Why literature review is important?

The literature review is an important part of any research project because it allows the writer to look at previous studies on a topic and determine existing gaps in the literature, as well as what has already been done. It will also help them to choose the most appropriate method for their own study.

4. How to cite a literature review in APA format?

To cite a literature review in APA style, you need to provide the author's name, the title of the article, and the year of publication. For example: Patel, A. B., & Stokes, G. S. (2012). The relationship between personality and intelligence: A meta-analysis of longitudinal research. Personality and Individual Differences, 53(1), 16-21

5. What are the components of a literature review?

• A brief introduction to the topic, including its background and context. The introduction should also include a rationale for why the study is being conducted and what it will accomplish.

• A description of the methodologies used in the study. This can include information about data collection methods, sample size, and statistical analyses.

• A presentation of the findings in an organized format that helps readers follow along with the author's conclusions.

6. What are common errors in writing literature review?

• Not spending enough time to critically evaluate the relevance of resources, observations and conclusions.

• Totally relying on secondary data while ignoring primary data.

• Letting your personal bias seep into your interpretation of existing literature.

• No detailed explanation of the procedure to discover and identify an appropriate literature review.

7. What are the 5 C's of writing literature review?

• Cite - the sources you utilized and referenced in your research.

• Compare - existing arguments, hypotheses, methodologies, and conclusions found in the knowledge base.

• Contrast - the arguments, topics, methodologies, approaches, and disputes that may be found in the literature.

• Critique - the literature and describe the ideas and opinions you find more convincing and why.

• Connect - the various studies you reviewed in your research.

8. How many sources should a literature review have?

When it is just a chapter, sources should equal the total number of pages in your article's body. if it is a self-contained paper in itself, you need at least three times as many sources as there are pages in your work.

9. Can literature review have diagrams?

• To represent an abstract idea or concept

• To explain the steps of a process or procedure

• To help readers understand the relationships between different concepts

10. How old should sources be in a literature review?

Sources for a literature review should be as current as possible or not older than ten years. The only exception to this rule is if you are reviewing a historical topic and need to use older sources.

11. What are the types of literature review?

• Argumentative review

• Integrative review

• Methodological review

• Systematic review

• Meta-analysis review

• Historical review

• Theoretical review

• Scoping review

• State-of-the-Art review

12. Is a literature review mandatory?

Yes. Literature review is a mandatory part of any research project. It is a critical step in the process that allows you to establish the scope of your research, and provide a background for the rest of your work.

But before you go,

• Six Online Tools for Easy Literature Review
• Evaluating literature review: systematic vs. scoping reviews
• Systematic Approaches to a Successful Literature Review
• Writing Integrative Literature Reviews: Guidelines and Examples

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What is a literature review?

A literature review is a critical analysis of the literature related to your research topic. It evaluates and critiques the literature to establish a theoretical framework for your research topic and/or identify a gap in the existing research that your research will address.

A literature review is not a summary of the literature. You need to engage deeply and critically with the literature. Your literature review should show your understanding of the literature related to your research topic and lead to presenting a rationale for your research.

A literature review focuses on:

• the context of the topic
• key concepts, ideas, theories and methodologies
• key researchers, texts and seminal works
• major issues and debates
• identifying conflicting evidence
• the main questions that have been asked around the topic
• the organisation of knowledge on the topic
• definitions, particularly those that are contested
• showing how your research will advance scholarly knowledge (generally referred to as identifying the ‘gap’).

This module will guide you through the functions of a literature review; the typical process of conducting a literature review (including searching for literature and taking notes); structuring your literature review within your thesis and organising its internal ideas; and styling the language of your literature review.

The purposes of a literature review

A literature review serves two main purposes:

1) To show awareness of the present state of knowledge in a particular field, including:

• seminal authors
• the main empirical research
• theoretical positions
• controversies
• breakthroughs as well as links to other related areas of knowledge.

2) To provide a foundation for the author’s research. To do that, the literature review needs to:

• help the researcher define a hypothesis or a research question, and how answering the question will contribute to the body of knowledge;
• provide a rationale for investigating the problem and the selected methodology;
• provide a particular theoretical lens, support the argument, or identify gaps.

Before you engage further with this module, try the quiz below to see how much you already know about literature reviews.

Research and Writing Skills for Academic and Graduate Researchers Copyright © 2022 by RMIT University is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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Approaching literature review for academic purposes: The Literature Review Checklist

Debora f.b. leite.

I Departamento de Ginecologia e Obstetricia, Faculdade de Ciencias Medicas, Universidade Estadual de Campinas, Campinas, SP, BR

II Universidade Federal de Pernambuco, Pernambuco, PE, BR

III Hospital das Clinicas, Universidade Federal de Pernambuco, Pernambuco, PE, BR

Maria Auxiliadora Soares Padilha

Jose g. cecatti.

A sophisticated literature review (LR) can result in a robust dissertation/thesis by scrutinizing the main problem examined by the academic study; anticipating research hypotheses, methods and results; and maintaining the interest of the audience in how the dissertation/thesis will provide solutions for the current gaps in a particular field. Unfortunately, little guidance is available on elaborating LRs, and writing an LR chapter is not a linear process. An LR translates students’ abilities in information literacy, the language domain, and critical writing. Students in postgraduate programs should be systematically trained in these skills. Therefore, this paper discusses the purposes of LRs in dissertations and theses. Second, the paper considers five steps for developing a review: defining the main topic, searching the literature, analyzing the results, writing the review and reflecting on the writing. Ultimately, this study proposes a twelve-item LR checklist. By clearly stating the desired achievements, this checklist allows Masters and Ph.D. students to continuously assess their own progress in elaborating an LR. Institutions aiming to strengthen students’ necessary skills in critical academic writing should also use this tool.

INTRODUCTION

Writing the literature review (LR) is often viewed as a difficult task that can be a point of writer’s block and procrastination ( 1 ) in postgraduate life. Disagreements on the definitions or classifications of LRs ( 2 ) may confuse students about their purpose and scope, as well as how to perform an LR. Interestingly, at many universities, the LR is still an important element in any academic work, despite the more recent trend of producing scientific articles rather than classical theses.

The LR is not an isolated section of the thesis/dissertation or a copy of the background section of a research proposal. It identifies the state-of-the-art knowledge in a particular field, clarifies information that is already known, elucidates implications of the problem being analyzed, links theory and practice ( 3 - 5 ), highlights gaps in the current literature, and places the dissertation/thesis within the research agenda of that field. Additionally, by writing the LR, postgraduate students will comprehend the structure of the subject and elaborate on their cognitive connections ( 3 ) while analyzing and synthesizing data with increasing maturity.

At the same time, the LR transforms the student and hints at the contents of other chapters for the reader. First, the LR explains the research question; second, it supports the hypothesis, objectives, and methods of the research project; and finally, it facilitates a description of the student’s interpretation of the results and his/her conclusions. For scholars, the LR is an introductory chapter ( 6 ). If it is well written, it demonstrates the student’s understanding of and maturity in a particular topic. A sound and sophisticated LR can indicate a robust dissertation/thesis.

A consensus on the best method to elaborate a dissertation/thesis has not been achieved. The LR can be a distinct chapter or included in different sections; it can be part of the introduction chapter, part of each research topic, or part of each published paper ( 7 ). However, scholars view the LR as an integral part of the main body of an academic work because it is intrinsically connected to other sections ( Figure 1 ) and is frequently present. The structure of the LR depends on the conventions of a particular discipline, the rules of the department, and the student’s and supervisor’s areas of expertise, needs and interests.

Interestingly, many postgraduate students choose to submit their LR to peer-reviewed journals. As LRs are critical evaluations of current knowledge, they are indeed publishable material, even in the form of narrative or systematic reviews. However, systematic reviews have specific patterns 1 ( 8 ) that may not entirely fit with the questions posed in the dissertation/thesis. Additionally, the scope of a systematic review may be too narrow, and the strict criteria for study inclusion may omit important information from the dissertation/thesis. Therefore, this essay discusses the definition of an LR is and methods to develop an LR in the context of an academic dissertation/thesis. Finally, we suggest a checklist to evaluate an LR.

WHAT IS A LITERATURE REVIEW IN A THESIS?

Conducting research and writing a dissertation/thesis translates rational thinking and enthusiasm ( 9 ). While a strong body of literature that instructs students on research methodology, data analysis and writing scientific papers exists, little guidance on performing LRs is available. The LR is a unique opportunity to assess and contrast various arguments and theories, not just summarize them. The research results should not be discussed within the LR, but the postgraduate student tends to write a comprehensive LR while reflecting on his or her own findings ( 10 ).

Many people believe that writing an LR is a lonely and linear process. Supervisors or the institutions assume that the Ph.D. student has mastered the relevant techniques and vocabulary associated with his/her subject and conducts a self-reflection about previously published findings. Indeed, while elaborating the LR, the student should aggregate diverse skills, which mainly rely on his/her own commitment to mastering them. Thus, less supervision should be required ( 11 ). However, the parameters described above might not currently be the case for many students ( 11 , 12 ), and the lack of formal and systematic training on writing LRs is an important concern ( 11 ).

An institutional environment devoted to active learning will provide students the opportunity to continuously reflect on LRs, which will form a dialogue between the postgraduate student and the current literature in a particular field ( 13 ). Postgraduate students will be interpreting studies by other researchers, and, according to Hart (1998) ( 3 ), the outcomes of the LR in a dissertation/thesis include the following:

• To identify what research has been performed and what topics require further investigation in a particular field of knowledge;
• To determine the context of the problem;
• To recognize the main methodologies and techniques that have been used in the past;
• To place the current research project within the historical, methodological and theoretical context of a particular field;
• To identify significant aspects of the topic;
• To elucidate the implications of the topic;
• To offer an alternative perspective;
• To discern how the studied subject is structured;
• To improve the student’s subject vocabulary in a particular field; and
• To characterize the links between theory and practice.

A sound LR translates the postgraduate student’s expertise in academic and scientific writing: it expresses his/her level of comfort with synthesizing ideas ( 11 ). The LR reveals how well the postgraduate student has proceeded in three domains: an effective literature search, the language domain, and critical writing.

Effective literature search

All students should be trained in gathering appropriate data for specific purposes, and information literacy skills are a cornerstone. These skills are defined as “an individual’s ability to know when they need information, to identify information that can help them address the issue or problem at hand, and to locate, evaluate, and use that information effectively” ( 14 ). Librarian support is of vital importance in coaching the appropriate use of Boolean logic (AND, OR, NOT) and other tools for highly efficient literature searches (e.g., quotation marks and truncation), as is the appropriate management of electronic databases.

Language domain

Academic writing must be concise and precise: unnecessary words distract the reader from the essential content ( 15 ). In this context, reading about issues distant from the research topic ( 16 ) may increase students’ general vocabulary and familiarity with grammar. Ultimately, reading diverse materials facilitates and encourages the writing process itself.

Critical writing

Critical judgment includes critical reading, thinking and writing. It supposes a student’s analytical reflection about what he/she has read. The student should delineate the basic elements of the topic, characterize the most relevant claims, identify relationships, and finally contrast those relationships ( 17 ). Each scientific document highlights the perspective of the author, and students will become more confident in judging the supporting evidence and underlying premises of a study and constructing their own counterargument as they read more articles. A paucity of integration or contradictory perspectives indicates lower levels of cognitive complexity ( 12 ).

Thus, while elaborating an LR, the postgraduate student should achieve the highest category of Bloom’s cognitive skills: evaluation ( 12 ). The writer should not only summarize data and understand each topic but also be able to make judgments based on objective criteria, compare resources and findings, identify discrepancies due to methodology, and construct his/her own argument ( 12 ). As a result, the student will be sufficiently confident to show his/her own voice .

Writing a consistent LR is an intense and complex activity that reveals the training and long-lasting academic skills of a writer. It is not a lonely or linear process. However, students are unlikely to be prepared to write an LR if they have not mastered the aforementioned domains ( 10 ). An institutional environment that supports student learning is crucial.

Different institutions employ distinct methods to promote students’ learning processes. First, many universities propose modules to develop behind the scenes activities that enhance self-reflection about general skills (e.g., the skills we have mastered and the skills we need to develop further), behaviors that should be incorporated (e.g., self-criticism about one’s own thoughts), and each student’s role in the advancement of his/her field. Lectures or workshops about LRs themselves are useful because they describe the purposes of the LR and how it fits into the whole picture of a student’s work. These activities may explain what type of discussion an LR must involve, the importance of defining the correct scope, the reasons to include a particular resource, and the main role of critical reading.

Some pedagogic services that promote a continuous improvement in study and academic skills are equally important. Examples include workshops about time management, the accomplishment of personal objectives, active learning, and foreign languages for nonnative speakers. Additionally, opportunities to converse with other students promotes an awareness of others’ experiences and difficulties. Ultimately, the supervisor’s role in providing feedback and setting deadlines is crucial in developing students’ abilities and in strengthening students’ writing quality ( 12 ).

HOW SHOULD A LITERATURE REVIEW BE DEVELOPED?

A consensus on the appropriate method for elaborating an LR is not available, but four main steps are generally accepted: defining the main topic, searching the literature, analyzing the results, and writing ( 6 ). We suggest a fifth step: reflecting on the information that has been written in previous publications ( Figure 2 ).

First step: Defining the main topic

Planning an LR is directly linked to the research main question of the thesis and occurs in parallel to students’ training in the three domains discussed above. The planning stage helps organize ideas, delimit the scope of the LR ( 11 ), and avoid the wasting of time in the process. Planning includes the following steps:

• Reflecting on the scope of the LR: postgraduate students will have assumptions about what material must be addressed and what information is not essential to an LR ( 13 , 18 ). Cooper’s Taxonomy of Literature Reviews 2 systematizes the writing process through six characteristics and nonmutually exclusive categories. The focus refers to the reviewer’s most important points of interest, while the goals concern what students want to achieve with the LR. The perspective assumes answers to the student’s own view of the LR and how he/she presents a particular issue. The coverage defines how comprehensive the student is in presenting the literature, and the organization determines the sequence of arguments. The audience is defined as the group for whom the LR is written.
• Designating sections and subsections: Headings and subheadings should be specific, explanatory and have a coherent sequence throughout the text ( 4 ). They simulate an inverted pyramid, with an increasing level of reflection and depth of argument.
• Identifying keywords: The relevant keywords for each LR section should be listed to guide the literature search. This list should mirror what Hart (1998) ( 3 ) advocates as subject vocabulary . The keywords will also be useful when the student is writing the LR since they guide the reader through the text.
• Delineating the time interval and language of documents to be retrieved in the second step. The most recently published documents should be considered, but relevant texts published before a predefined cutoff year can be included if they are classic documents in that field. Extra care should be employed when translating documents.

Second step: Searching the literature

The ability to gather adequate information from the literature must be addressed in postgraduate programs. Librarian support is important, particularly for accessing difficult texts. This step comprises the following components:

• Searching the literature itself: This process consists of defining which databases (electronic or dissertation/thesis repositories), official documents, and books will be searched and then actively conducting the search. Information literacy skills have a central role in this stage. While searching electronic databases, controlled vocabulary (e.g., Medical Subject Headings, or MeSH, for the PubMed database) or specific standardized syntax rules may need to be applied.

In addition, two other approaches are suggested. First, a review of the reference list of each document might be useful for identifying relevant publications to be included and important opinions to be assessed. This step is also relevant for referencing the original studies and leading authors in that field. Moreover, students can directly contact the experts on a particular topic to consult with them regarding their experience or use them as a source of additional unpublished documents.

Before submitting a dissertation/thesis, the electronic search strategy should be repeated. This process will ensure that the most recently published papers will be considered in the LR.

• Selecting documents for inclusion: Generally, the most recent literature will be included in the form of published peer-reviewed papers. Assess books and unpublished material, such as conference abstracts, academic texts and government reports, are also important to assess since the gray literature also offers valuable information. However, since these materials are not peer-reviewed, we recommend that they are carefully added to the LR.

This task is an important exercise in time management. First, students should read the title and abstract to understand whether that document suits their purposes, addresses the research question, and helps develop the topic of interest. Then, they should scan the full text, determine how it is structured, group it with similar documents, and verify whether other arguments might be considered ( 5 ).

Third step: Analyzing the results

Critical reading and thinking skills are important in this step. This step consists of the following components:

• Reading documents: The student may read various texts in depth according to LR sections and subsections ( defining the main topic ), which is not a passive activity ( 1 ). Some questions should be asked to practice critical analysis skills, as listed below. Is the research question evident and articulated with previous knowledge? What are the authors’ research goals and theoretical orientations, and how do they interact? Are the authors’ claims related to other scholars’ research? Do the authors consider different perspectives? Was the research project designed and conducted properly? Are the results and discussion plausible, and are they consistent with the research objectives and methodology? What are the strengths and limitations of this work? How do the authors support their findings? How does this work contribute to the current research topic? ( 1 , 19 )
• Taking notes: Students who systematically take notes on each document are more readily able to establish similarities or differences with other documents and to highlight personal observations. This approach reinforces the student’s ideas about the next step and helps develop his/her own academic voice ( 1 , 13 ). Voice recognition software ( 16 ), mind maps ( 5 ), flowcharts, tables, spreadsheets, personal comments on the referenced texts, and note-taking apps are all available tools for managing these observations, and the student him/herself should use the tool that best improves his/her learning. Additionally, when a student is considering submitting an LR to a peer-reviewed journal, notes should be taken on the activities performed in all five steps to ensure that they are able to be replicated.

Fourth step: Writing

The recognition of when a student is able and ready to write after a sufficient period of reading and thinking is likely a difficult task. Some students can produce a review in a single long work session. However, as discussed above, writing is not a linear process, and students do not need to write LRs according to a specific sequence of sections. Writing an LR is a time-consuming task, and some scholars believe that a period of at least six months is sufficient ( 6 ). An LR, and academic writing in general, expresses the writer’s proper thoughts, conclusions about others’ work ( 6 , 10 , 13 , 16 ), and decisions about methods to progress in the chosen field of knowledge. Thus, each student is expected to present a different learning and writing trajectory.

In this step, writing methods should be considered; then, editing, citing and correct referencing should complete this stage, at least temporarily. Freewriting techniques may be a good starting point for brainstorming ideas and improving the understanding of the information that has been read ( 1 ). Students should consider the following parameters when creating an agenda for writing the LR: two-hour writing blocks (at minimum), with prespecified tasks that are possible to complete in one section; short (minutes) and long breaks (days or weeks) to allow sufficient time for mental rest and reflection; and short- and long-term goals to motivate the writing itself ( 20 ). With increasing experience, this scheme can vary widely, and it is not a straightforward rule. Importantly, each discipline has a different way of writing ( 1 ), and each department has its own preferred styles for citations and references.

Fifth step: Reflecting on the writing

In this step, the postgraduate student should ask him/herself the same questions as in the analyzing the results step, which can take more time than anticipated. Ambiguities, repeated ideas, and a lack of coherence may not be noted when the student is immersed in the writing task for long periods. The whole effort will likely be a work in progress, and continuous refinements in the written material will occur once the writing process has begun.

LITERATURE REVIEW CHECKLIST

In contrast to review papers, the LR of a dissertation/thesis should not be a standalone piece or work. Instead, it should present the student as a scholar and should maintain the interest of the audience in how that dissertation/thesis will provide solutions for the current gaps in a particular field.

A checklist for evaluating an LR is convenient for students’ continuous academic development and research transparency: it clearly states the desired achievements for the LR of a dissertation/thesis. Here, we present an LR checklist developed from an LR scoring rubric ( 11 ). For a critical analysis of an LR, we maintain the five categories but offer twelve criteria that are not scaled ( Figure 3 ). The criteria all have the same importance and are not mutually exclusive.

First category: Coverage

1. justified criteria exist for the inclusion and exclusion of literature in the review.

This criterion builds on the main topic and areas covered by the LR ( 18 ). While experts may be confident in retrieving and selecting literature, postgraduate students must convince their audience about the adequacy of their search strategy and their reasons for intentionally selecting what material to cover ( 11 ). References from different fields of knowledge provide distinct perspective, but narrowing the scope of coverage may be important in areas with a large body of existing knowledge.

Second category: Synthesis

2. a critical examination of the state of the field exists.

A critical examination is an assessment of distinct aspects in the field ( 1 ) along with a constructive argument. It is not a negative critique but an expression of the student’s understanding of how other scholars have added to the topic ( 1 ), and the student should analyze and contextualize contradictory statements. A writer’s personal bias (beliefs or political involvement) have been shown to influence the structure and writing of a document; therefore, the cultural and paradigmatic background guide how the theories are revised and presented ( 13 ). However, an honest judgment is important when considering different perspectives.

3. The topic or problem is clearly placed in the context of the broader scholarly literature

The broader scholarly literature should be related to the chosen main topic for the LR ( how to develop the literature review section). The LR can cover the literature from one or more disciplines, depending on its scope, but it should always offer a new perspective. In addition, students should be careful in citing and referencing previous publications. As a rule, original studies and primary references should generally be included. Systematic and narrative reviews present summarized data, and it may be important to cite them, particularly for issues that should be understood but do not require a detailed description. Similarly, quotations highlight the exact statement from another publication. However, excessive referencing may disclose lower levels of analysis and synthesis by the student.

4. The LR is critically placed in the historical context of the field

Situating the LR in its historical context shows the level of comfort of the student in addressing a particular topic. Instead of only presenting statements and theories in a temporal approach, which occasionally follows a linear timeline, the LR should authentically characterize the student’s academic work in the state-of-art techniques in their particular field of knowledge. Thus, the LR should reinforce why the dissertation/thesis represents original work in the chosen research field.

5. Ambiguities in definitions are considered and resolved

Distinct theories on the same topic may exist in different disciplines, and one discipline may consider multiple concepts to explain one topic. These misunderstandings should be addressed and contemplated. The LR should not synthesize all theories or concepts at the same time. Although this approach might demonstrate in-depth reading on a particular topic, it can reveal a student’s inability to comprehend and synthesize his/her research problem.

6. Important variables and phenomena relevant to the topic are articulated

The LR is a unique opportunity to articulate ideas and arguments and to purpose new relationships between them ( 10 , 11 ). More importantly, a sound LR will outline to the audience how these important variables and phenomena will be addressed in the current academic work. Indeed, the LR should build a bidirectional link with the remaining sections and ground the connections between all of the sections ( Figure 1 ).

7. A synthesized new perspective on the literature has been established

The LR is a ‘creative inquiry’ ( 13 ) in which the student elaborates his/her own discourse, builds on previous knowledge in the field, and describes his/her own perspective while interpreting others’ work ( 13 , 17 ). Thus, students should articulate the current knowledge, not accept the results at face value ( 11 , 13 , 17 ), and improve their own cognitive abilities ( 12 ).

Third category: Methodology

8. the main methodologies and research techniques that have been used in the field are identified and their advantages and disadvantages are discussed.

The LR is expected to distinguish the research that has been completed from investigations that remain to be performed, address the benefits and limitations of the main methods applied to date, and consider the strategies for addressing the expected limitations described above. While placing his/her research within the methodological context of a particular topic, the LR will justify the methodology of the study and substantiate the student’s interpretations.

9. Ideas and theories in the field are related to research methodologies

The audience expects the writer to analyze and synthesize methodological approaches in the field. The findings should be explained according to the strengths and limitations of previous research methods, and students must avoid interpretations that are not supported by the analyzed literature. This criterion translates to the student’s comprehension of the applicability and types of answers provided by different research methodologies, even those using a quantitative or qualitative research approach.

Fourth category: Significance

10. the scholarly significance of the research problem is rationalized.

The LR is an introductory section of a dissertation/thesis and will present the postgraduate student as a scholar in a particular field ( 11 ). Therefore, the LR should discuss how the research problem is currently addressed in the discipline being investigated or in different disciplines, depending on the scope of the LR. The LR explains the academic paradigms in the topic of interest ( 13 ) and methods to advance the field from these starting points. However, an excess number of personal citations—whether referencing the student’s research or studies by his/her research team—may reflect a narrow literature search and a lack of comprehensive synthesis of ideas and arguments.

11. The practical significance of the research problem is rationalized

The practical significance indicates a student’s comprehensive understanding of research terminology (e.g., risk versus associated factor), methodology (e.g., efficacy versus effectiveness) and plausible interpretations in the context of the field. Notably, the academic argument about a topic may not always reflect the debate in real life terms. For example, using a quantitative approach in epidemiology, statistically significant differences between groups do not explain all of the factors involved in a particular problem ( 21 ). Therefore, excessive faith in p -values may reflect lower levels of critical evaluation of the context and implications of a research problem by the student.

Fifth category: Rhetoric

12. the lr was written with a coherent, clear structure that supported the review.

This category strictly relates to the language domain: the text should be coherent and presented in a logical sequence, regardless of which organizational ( 18 ) approach is chosen. The beginning of each section/subsection should state what themes will be addressed, paragraphs should be carefully linked to each other ( 10 ), and the first sentence of each paragraph should generally summarize the content. Additionally, the student’s statements are clear, sound, and linked to other scholars’ works, and precise and concise language that follows standardized writing conventions (e.g., in terms of active/passive voice and verb tenses) is used. Attention to grammar, such as orthography and punctuation, indicates prudence and supports a robust dissertation/thesis. Ultimately, all of these strategies provide fluency and consistency for the text.

Although the scoring rubric was initially proposed for postgraduate programs in education research, we are convinced that this checklist is a valuable tool for all academic areas. It enables the monitoring of students’ learning curves and a concentrated effort on any criteria that are not yet achieved. For institutions, the checklist is a guide to support supervisors’ feedback, improve students’ writing skills, and highlight the learning goals of each program. These criteria do not form a linear sequence, but ideally, all twelve achievements should be perceived in the LR.

CONCLUSIONS

A single correct method to classify, evaluate and guide the elaboration of an LR has not been established. In this essay, we have suggested directions for planning, structuring and critically evaluating an LR. The planning of the scope of an LR and approaches to complete it is a valuable effort, and the five steps represent a rational starting point. An institutional environment devoted to active learning will support students in continuously reflecting on LRs, which will form a dialogue between the writer and the current literature in a particular field ( 13 ).

The completion of an LR is a challenging and necessary process for understanding one’s own field of expertise. Knowledge is always transitory, but our responsibility as scholars is to provide a critical contribution to our field, allowing others to think through our work. Good researchers are grounded in sophisticated LRs, which reveal a writer’s training and long-lasting academic skills. We recommend using the LR checklist as a tool for strengthening the skills necessary for critical academic writing.

AUTHOR CONTRIBUTIONS

Leite DFB has initially conceived the idea and has written the first draft of this review. Padilha MAS and Cecatti JG have supervised data interpretation and critically reviewed the manuscript. All authors have read the draft and agreed with this submission. Authors are responsible for all aspects of this academic piece.

ACKNOWLEDGMENTS

We are grateful to all of the professors of the ‘Getting Started with Graduate Research and Generic Skills’ module at University College Cork, Cork, Ireland, for suggesting and supporting this article. Funding: DFBL has granted scholarship from Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) to take part of her Ph.D. studies in Ireland (process number 88881.134512/2016-01). There is no participation from sponsors on authors’ decision to write or to submit this manuscript.

No potential conflict of interest was reported.

1 The questions posed in systematic reviews usually follow the ‘PICOS’ acronym: Population, Intervention, Comparison, Outcomes, Study design.

2 In 1988, Cooper proposed a taxonomy that aims to facilitate students’ and institutions’ understanding of literature reviews. Six characteristics with specific categories are briefly described: Focus: research outcomes, research methodologies, theories, or practices and applications; Goals: integration (generalization, conflict resolution, and linguistic bridge-building), criticism, or identification of central issues; Perspective: neutral representation or espousal of a position; Coverage: exhaustive, exhaustive with selective citations, representative, central or pivotal; Organization: historical, conceptual, or methodological; and Audience: specialized scholars, general scholars, practitioners or policymakers, or the general public.

Literature Reviews

• Types of reviews
• Getting started

Types of reviews and examples

Choosing a review type.

• 1. Define your research question
• 2. Plan your search
• 3. Search the literature
• 4. Organize your results
• 5. Synthesize your findings
• 6. Write the review
• Artificial intelligence (AI) tools
• Thompson Writing Studio This link opens in a new window
• Need to write a systematic review? This link opens in a new window

Contact a Librarian

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• Meta-analysis
• Systematized

Definition:

"A term used to describe a conventional overview of the literature, particularly when contrasted with a systematic review (Booth et al., 2012, p. 265).

Characteristics:

• Provides examination of recent or current literature on a wide range of subjects
• Varying levels of completeness / comprehensiveness, non-standardized methodology
• May or may not include comprehensive searching, quality assessment or critical appraisal

Mitchell, L. E., & Zajchowski, C. A. (2022). The history of air quality in Utah: A narrative review.  Sustainability ,  14 (15), 9653.  doi.org/10.3390/su14159653

Booth, A., Papaioannou, D., & Sutton, A. (2012). Systematic approaches to a successful literature review. London: SAGE Publications Ltd.

"An assessment of what is already known about a policy or practice issue...using systematic review methods to search and critically appraise existing research" (Grant & Booth, 2009, p. 100).

• Assessment of what is already known about an issue
• Similar to a systematic review but within a time-constrained setting
• Typically employs methodological shortcuts, increasing risk of introducing bias, includes basic level of quality assessment
• Best suited for issues needing quick decisions and solutions (i.e., policy recommendations)

Learn more about the method:

Khangura, S., Konnyu, K., Cushman, R., Grimshaw, J., & Moher, D. (2012). Evidence summaries: the evolution of a rapid review approach.  Systematic reviews, 1 (1), 1-9.  https://doi.org/10.1186/2046-4053-1-10

Virginia Commonwealth University Libraries. (2021). Rapid Review Protocol .

Quarmby, S., Santos, G., & Mathias, M. (2019). Air quality strategies and technologies: A rapid review of the international evidence.  Sustainability, 11 (10), 2757.  https://doi.org/10.3390/su11102757

Grant, M.J. & Booth, A. (2009). A typology of reviews: an analysis of the 14 review types and associated methodologies.  Health Information & Libraries Journal , 26(2), 91-108. https://www.doi.org/10.1111/j.1471-1842.2009.00848.x

Developed and refined by the Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), this review "map[s] out and categorize[s] existing literature on a particular topic, identifying gaps in research literature from which to commission further reviews and/or primary research" (Grant & Booth, 2009, p. 97).

Although mapping reviews are sometimes called scoping reviews, the key difference is that mapping reviews focus on a review question, rather than a topic

Mapping reviews are "best used where a clear target for a more focused evidence product has not yet been identified" (Booth, 2016, p. 14)

Mapping review searches are often quick and are intended to provide a broad overview

Mapping reviews can take different approaches in what types of literature is focused on in the search

Cooper I. D. (2016). What is a "mapping study?".  Journal of the Medical Library Association: JMLA ,  104 (1), 76–78. https://doi.org/10.3163/1536-5050.104.1.013

Miake-Lye, I. M., Hempel, S., Shanman, R., & Shekelle, P. G. (2016). What is an evidence map? A systematic review of published evidence maps and their definitions, methods, and products.  Systematic reviews, 5 (1), 1-21.  https://doi.org/10.1186/s13643-016-0204-x

Tainio, M., Andersen, Z. J., Nieuwenhuijsen, M. J., Hu, L., De Nazelle, A., An, R., ... & de Sá, T. H. (2021). Air pollution, physical activity and health: A mapping review of the evidence.  Environment international ,  147 , 105954.  https://doi.org/10.1016/j.envint.2020.105954

Booth, A. (2016). EVIDENT Guidance for Reviewing the Evidence: a compendium of methodological literature and websites . ResearchGate. https://doi.org/10.13140/RG.2.1.1562.9842 . 

Grant, M.J. & Booth, A. (2009). A typology of reviews: an analysis of the 14 review types and associated methodologies.  Health Information & Libraries Journal , 26(2), 91-108.  https://www.doi.org/10.1111/j.1471-1842.2009.00848.x

"A type of review that has as its primary objective the identification of the size and quality of research in a topic area in order to inform subsequent review" (Booth et al., 2012, p. 269).

• Main purpose is to map out and categorize existing literature, identify gaps in literature—great for informing policy-making
• Search comprehensiveness determined by time/scope constraints, could take longer than a systematic review
• No formal quality assessment or critical appraisal

Learn more about the methods :

Arksey, H., & O'Malley, L. (2005) Scoping studies: towards a methodological framework.  International Journal of Social Research Methodology ,  8 (1), 19-32.  https://doi.org/10.1080/1364557032000119616

Levac, D., Colquhoun, H., & O’Brien, K. K. (2010). Scoping studies: Advancing the methodology. Implementation Science: IS, 5, 69. https://doi.org/10.1186/1748-5908-5-69

Example : 

Rahman, A., Sarkar, A., Yadav, O. P., Achari, G., & Slobodnik, J. (2021). Potential human health risks due to environmental exposure to nano-and microplastics and knowledge gaps: A scoping review.  Science of the Total Environment, 757 , 143872.  https://doi.org/10.1016/j.scitotenv.2020.143872

A review that "[compiles] evidence from multiple...reviews into one accessible and usable document" (Grant & Booth, 2009, p. 103). While originally intended to be a compilation of Cochrane reviews, it now generally refers to any kind of evidence synthesis.

• Compiles evidence from multiple reviews into one document
• Often defines a broader question than is typical of a traditional systematic review

Choi, G. J., & Kang, H. (2022). The umbrella review: a useful strategy in the rain of evidence.  The Korean Journal of Pain ,  35 (2), 127–128.  https://doi.org/10.3344/kjp.2022.35.2.127

Aromataris, E., Fernandez, R., Godfrey, C. M., Holly, C., Khalil, H., & Tungpunkom, P. (2015). Summarizing systematic reviews: Methodological development, conduct and reporting of an umbrella review approach. International Journal of Evidence-Based Healthcare , 13(3), 132–140. https://doi.org/10.1097/XEB.0000000000000055

Rojas-Rueda, D., Morales-Zamora, E., Alsufyani, W. A., Herbst, C. H., Al Balawi, S. M., Alsukait, R., & Alomran, M. (2021). Environmental risk factors and health: An umbrella review of meta-analyses.  International Journal of Environmental Research and Public Dealth ,  18 (2), 704.  https://doi.org/10.3390/ijerph18020704

A meta-analysis is a "technique that statistically combines the results of quantitative studies to provide a more precise effect of the result" (Grant & Booth, 2009, p. 98).

• Statistical technique for combining results of quantitative studies to provide more precise effect of results
• Aims for exhaustive, comprehensive searching
• Quality assessment may determine inclusion/exclusion criteria
• May be conducted independently or as part of a systematic review

Berman, N. G., & Parker, R. A. (2002). Meta-analysis: Neither quick nor easy. BMC Medical Research Methodology , 2(1), 10. https://doi.org/10.1186/1471-2288-2-10

Hites R. A. (2004). Polybrominated diphenyl ethers in the environment and in people: a meta-analysis of concentrations.  Environmental Science & Technology ,  38 (4), 945–956.  https://doi.org/10.1021/es035082g

A systematic review "seeks to systematically search for, appraise, and [synthesize] research evidence, often adhering to the guidelines on the conduct of a review" provided by discipline-specific organizations, such as the Cochrane Collaboration (Grant & Booth, 2009, p. 102).

• Aims to compile and synthesize all known knowledge on a given topic
• Adheres to strict guidelines, protocols, and frameworks
• Time-intensive and often takes months to a year or more to complete
• The most commonly referred to type of evidence synthesis. Sometimes confused as a blanket term for other types of reviews

Gascon, M., Triguero-Mas, M., Martínez, D., Dadvand, P., Forns, J., Plasència, A., & Nieuwenhuijsen, M. J. (2015). Mental health benefits of long-term exposure to residential green and blue spaces: a systematic review.  International Journal of Environmental Research and Public Health ,  12 (4), 4354–4379.  https://doi.org/10.3390/ijerph120404354

"Systematized reviews attempt to include one or more elements of the systematic review process while stopping short of claiming that the resultant output is a systematic review" (Grant & Booth, 2009, p. 102). When a systematic review approach is adapted to produce a more manageable scope, while still retaining the rigor of a systematic review such as risk of bias assessment and the use of a protocol, this is often referred to as a  structured review  (Huelin et al., 2015).

• Typically conducted by postgraduate or graduate students
• Often assigned by instructors to students who don't have the resources to conduct a full systematic review

Salvo, G., Lashewicz, B. M., Doyle-Baker, P. K., & McCormack, G. R. (2018). Neighbourhood built environment influences on physical activity among adults: A systematized review of qualitative evidence.  International Journal of Environmental Research and Public Health ,  15 (5), 897.  https://doi.org/10.3390/ijerph15050897

Huelin, R., Iheanacho, I., Payne, K., & Sandman, K. (2015). What’s in a name? Systematic and non-systematic literature reviews, and why the distinction matters. https://www.evidera.com/resource/whats-in-a-name-systematic-and-non-systematic-literature-reviews-and-why-the-distinction-matters/

• Review Decision Tree - Cornell University For more information, check out Cornell's review methodology decision tree.
• LitR-Ex.com - Eight literature review methodologies Learn more about 8 different review types (incl. Systematic Reviews and Scoping Reviews) with practical tips about strengths and weaknesses of different methods.
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Systematic Reviews

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What Makes a Systematic Review Different from Other Types of Reviews?

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Reproduced from Grant, M. J. and Booth, A. (2009), A typology of reviews: an analysis of 14 review types and associated methodologies. Health Information & Libraries Journal, 26: 91–108. doi:10.1111/j.1471-1842.2009.00848.x

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Soc 001: introductory sociology.

• Literature Reviews: Strategies for Writing
• Fake News and Evaluating Sources

Literature Reviews

What is a Literature Review? The literature review is a critical look at the existing research that is significant to the work that you are carrying out. This overview identifies prominent research trends in addition to assessing the overall strengths and weaknesses of the existing research.

Purpose of the Literature Review

• To provide background information about a research topic.
• To establish the importance of a topic.
• To demonstrate familiarity with a topic/problem.
• To “carve out a space” for further work and allow you to position yourself in a scholarly conversation.

Characteristics of an effective literature review In addition to fulfilling the purposes outlined above, an effective literature review provides a critical overview of existing research by

• Outlining important research trends.
• Assessing strengths and weaknesses (of individual studies as well the existing research as a whole).
• Identifying potential gaps in knowledge.
• Establishing a need for current and/or future research projects.

Steps of the Literature Review Process

1) Planning: identify the focus, type, scope and discipline of the review you intend to write. 2) Reading and Research: collect and read current research on your topic. Select only those sources that are most relevant to your project. 3) Analyzing: summarize, synthesize, critique, and compare your sources in order to assess the field of research as a whole. 4) Drafting: develop a thesis or claim to make about the existing research and decide how to organize your material. 5) Revising: revise and finalize the structural, stylistic, and grammatical issues of your paper.

This process is not always a linear process; depending on the size and scope of your literature review, you may find yourself returning to some of these steps repeatedly as you continue to focus your project.

These steps adapted from the full workshop offered by the Graduate Writing Center at Penn State. 

Literature Review Format

 Introduction

• Provide an overview of the topic, theme, or issue.
• Identify your specific area of focus.
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Patient characteristics of, and remedial interventions for, complaints and medico-legal claims against doctors: a rapid review of the literature

• Timothy J. Schultz   ORCID: orcid.org/0000-0003-1419-3328 1 ,
• Michael Zhou 2 ,
• Jodi Gray 1 ,
• Jackie Roseleur 1 ,
• Richard Clark 1 , 3 ,
• Dylan A. Mordaunt 1 , 4 ,
• Peter D. Hibbert 5 , 6 ,
• Georgie Haysom 7 &
• Michael Wright 7 , 8  

Systematic Reviews volume  13 , Article number:  104 ( 2024 ) Cite this article

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It is uncertain if patient’s characteristics are associated with complaints and claims against doctors. Additionally, evidence for the effectiveness of remedial interventions on rates of complaints and claims against doctors has not been synthesised.

We conducted a rapid review of recent literature to answer: Question 1 “What are the common characteristics and circumstances of patients who are most likely to complain or bring a claim about the care they have received from a doctor?” and Question 2 “What initiatives or interventions have been shown to be effective at reducing complaints and claims about the care patients have received from a doctor?”. We used a systematic search (most recently in July 2023) of PubMed, Scopus, Web of Science and grey literature. Studies were screened against inclusion criteria and critically appraised in duplicate using standard tools. Results were summarised using narrative synthesis.

From 8079 search results, we reviewed the full text of 250 studies. We included 25 studies: seven for Question 1 (6 comparative studies with controls and one systematic review) and 18 studies for Question 2 (14 uncontrolled pre-post studies, 2 comparative studies with controls and 2 systematic reviews). Most studies were set in hospitals across a mix of medical specialties.

Other than for patients with mental health conditions (two studies), no other patient characteristics demonstrated either a strong or consistent effect on the rate of complaints or claims against their treating doctors.

Risk management programs (6 studies), and communication and resolution programs (5 studies) were the most studied of 6 intervention types. Evidence for reducing complaints and medico-legal claims, costs or premiums and more timely management was apparent for both types of programs. Only 1 to 3 studies were included for peer programs, medical remediation, shared decision-making, simulation training and continuing professional development, with few generalisable results.

Few patient characteristics can be reliably related to the likelihood of medico-legal complaints or claims. There is some evidence that interventions can reduce the number and costs of claims, the number of complaints, and the timeliness of claims. However, across both questions, the strength of the evidence is very weak and is based on only a few studies or study designs that are highly prone to bias.

Peer Review reports

Up to 10% of hospital patients experience an adverse event [ 1 ]. Medical negligence or the failure to meet the standard of care reasonably expected of an ‘average’ doctor is a contributing factor to a small proportion of adverse events [ 1 , 2 ]. Medico-legal claims seeking compensation for medical negligence may be filed against doctors by patients through civil litigation. For less serious events or to express dissatisfaction with care, patients may also make a formal complaint, either directly to their care provider or the provider’s employer or to medical and other regulators and health complaints entities [ 3 ].

Doctors’ demographic (e.g. gender, age, years spent in practice) and workplace-related factors (e.g. greater number of patient lists) are associated with the risk of complaints and malpractice claims [ 4 , 5 ]. It is less clear what, if any, patient characteristics are associated with complaints and claims, and anecdotal evidence suggests that the rate of complaints and claims is rising [ 6 ]. Though females may be more likely to complain, and complaints and claims are often raised by patients’ living or bereaved relatives [ 7 , 8 ], there are no relevant systematic reviews on this topic. This led to the following review question (Question 1) “What are the common characteristics and circumstances of patients who are most likely to complain or bring a claim about the care they have received from a doctor?”.

In addition to the impact on patient wellbeing, doctors involved in adverse events experience serious emotional and psychological impacts [ 9 ]. Additionally, the financial cost to health systems from medico-legal claims is significant, potentially jeopardising the long-term financial sustainability of some public health systems [ 10 ]. Doctors, hospitals, health services, health regulators, representative medical organisations and medical insurers are therefore all highly motivated to provide safe, high-quality care that minimises complaints and claims against them, their staff, stakeholders and members. For example, medical colleges, practitioner regulation boards and medical indemnity insurers maintain professional standards of their members and conduct activities such as continuing professional development (CPD) [ 11 ], remediation programs [ 12 ] and communication and resolution programs (CRPs) [ 13 ]. Despite a recent scoping review describing how remediation programs are delivered to regulated health professionals [ 14 ], there is no substantive review of the literature across the wide range of stakeholders and potential interventions applicable to reduce complaints and claims against doctors. We therefore posed the following additional review question (Question 2): “What initiatives or interventions have been shown to be effective at reducing complaints and claims about the care patients have received from a doctor?” [ 6 ].

Review objective and research questions

The purpose of this review was to provide an evidence-based foundation to understand which patient factors influence complaints or claims and what interventions can support a reduction in complaints or claims [ 6 ]. This information could be used by clinicians, hospital administrators, healthcare regulators and medical indemnity insurers to inform their practice and policy. For the purposes of this study, a “claim” was defined as an assertion of wrongdoing that forms the basis for a request for compensation [ 15 ]; an “unwarranted” claim occurred when the care provided had not been below the expected standard and the complaint was not otherwise warranted [ 6 ].

A protocol defining the scope of the review (PEO/PICO, inclusion and exclusion criteria, search strategy and limits) was developed according to Sax Institute guidelines [ 16 ] but was not prospectively registered. The review was conducted according to guidance provided by the Cochrane Rapid Review method [ 17 ] and the SelecTing Approaches for Rapid Reviews (STARR) approach [ 18 ]. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist was used to report review findings [ 19 ].

Scope of the review

The review focussed on health systems of high-income Commonwealth countries including Australia, New Zealand, Canada and the United Kingdom (UK). Additionally, studies from the United States of Amercia (USA), Ireland and Western Europe were included to inform the review. The review focussed on the peer-reviewed literature although grey literature of similar quality was also searched. The review was conducted over an 8-week period from September to October 2022. The search was repeated in September 2023.

Inclusion and exclusion criteria

The inclusion and exclusion criteria for Question 1 and Question 2 are included in Table  1 . The settings were hospitals (excluding the emergency department), primary care and secondary care. Regulatory complaints, complaints to practices or hospitals and claims for compensation were included, while complaints on social media were excluded. For Question 1, the review focussed on correlations between the ‘exposure’ (e.g. patient characteristics) and the number, type or nature of complaints/claims. For Question 2, the review included interventions implemented primarily to reduce the number of complaints/claims against doctors, although other secondary outcomes included the costs of claims or insurance premiums, the duration of the claims management process, doctor risk profile or performance, doctor confidence/knowledge/satisfaction, workplace culture, and patient outcomes (e.g. morbidity) or patient satisfaction.

Only English language studies using quantitative study designs included in the National Health and Medical Research Council (NHRMC) guidelines [ 20 ] were included (e.g. ranging from level I systematic review, level II randomised controlled trial, level III pseudorandomised trial/comparative study with or without concurrent controls, and level IV case series with either post-test or pre-test/post-test outcomes). Cross-sectional studies were excluded.

Search strategy and selection criteria

Given the aetiological nature of studies relevant to Question 1 in particular, we used a PEO approach (Participant, Exposure, Outcome) [ 21 ] to frame the search strategy (see Supplementary Table S 1 , S 2 , S 3 ). Terms relating to ‘participants’ included doctors and health services. Terms relating to ‘exposure’ included patient characteristics (such as demographics, socio-economic status, and health literacy) for Question 1, and patient safety interventions (such as checklists, care bundles and teamwork) or clinical risk management programs (such as medical education, risk mitigation, peer program and communication and resolution) for Question 2. Terms relating to ‘outcomes’ included malpractice, negligence, complaint, claim management and medico-legal.

We searched three bibliographic databases (PubMed, Scopus and Web of Science) and grey literature sources (Google, Proquest Theses, GreyLit.org and Mednar) for relevant studies. The reference lists and citation searching of included studies were included as other search methods. To ensure applicability to a modern healthcare system only studies published since 2011 were included. The search was conducted first in September 2022 and then repeated in July 2023.

Screening based on title and abstract was conducted independently in pairs by four members of the research team (TS, MZ, JG, JR) following training on two sets of 100 studies.

Quality appraisal

The quality of included studies was appraised independently in pairs by four members of the research team (TS, JG, JR, PH) using AMSTAR 2 for systematic reviews [ 22 ] and National Institute of Health tools for case–control studies and uncontrolled pre-post studies [ 23 ]. These tools include 16 items (systematic reviews) or 12 items (case–control studies and uncontrolled pre-post), which were scored as ‘Yes’, ‘No’, ‘Not applicable’ or ‘Cannot determine’ [ 23 ], AMSTAR 2 also uses ‘Probably yes’.

Data collection

Data was extracted from each paper into a Microsoft Excel spreadsheet that had been pilot tested by three reviewers. Extraction was conducted by a single reviewer (TS or MZ) and then checked by a second reviewer (JG, JR).

A narrative synthesis was used to describe the key findings for both review questions. For review Question 1, results are presented separately for each patient characteristic, grouped according to patient demographics (e.g. age, sex, complainant), patient risk factors (e.g. American Society of Anaesthesiologists’ (ASA) score, the existence of a mental disorder, re-operation) and the therapeutic context (e.g. aspects of treatment, diagnosis, setting and/or phase of care including length of stay (LOS) and complications). For review Question 2, results are presented for seven different types of programs implemented to reduce the number of complaints and/or claims against doctors. The consistency, clinical impact, generalisability, and applicability of study findings were appraised using the NHRMC matrix which ranks each component’s strength using a four-point scale (excellent, good, satisfactory and poor) [ 20 ].

Literature search

Nearly 8900 studies were identified across the search strategy, of which 255 full texts were reviewed (Fig.  1 ). Of these, 230 were excluded as not relevant or due to an ineligible study design. A total of seven studies were included for Question 1, and 18 studies were included for Question 2 (Supplementary Table S 4 ).

PRISMA study flow diagram [ 19 ]. * filters applied to these search results (Australia, New Zealand, Canada, UK)

The characteristics of the studies included for Question 1 are presented in Table  2 . There were six comparative studies with concurrent controls (three from the USA [ 24 , 25 , 26 ], two from the UK [ 27 , 28 ]) and one from Italy [ 29 ] and one systematic reviews of non-randomised control trials [ 3 ]. The in-patient hospital setting was most common ( n  = 5) across a range of specialties and conditions, most commonly surgery. In total, there were 27 variables reported across the seven studies, 17 of these were included in multiple studies. Sex ( n  = 6) and age ( n  = 5) were the most frequently recorded patient demographics. For patient risk factors, ASA score, mental disorders, tobacco use and body mass index (BMI) > 30 were measured in two studies. For therapeutic context, LOS, setting, complications and treatment were measured in two studies.

Quality assessment is summarised in Table  2 , Supplementary Table S 5 (comparative studies) and Supplementary Table S 6 (systematic reviews). For the 6 comparative studies, 6 to 10 (mean 8.3, SD = 1.4) of 12 criteria were met; for the systematic review, 4 of the 16 criteria were met (or probably met).

In general, there was very limited evidence for the existence of significant relationships between patient characteristics and the rate of complaints or claims (Table  3 ). For demographics, one study identified that a 10-year increase in the age of paediatric surgery patients led to a near 50% greater odds (OR = 1.47, CI 1.04–2.08) of a complaint and that male gender reduced odds of a complaint in adults by 34% (OR = 0.66, CI 0.47–0.92) [ 25 ]. However, sex and age were not significant predictors in five and four other studies, respectively. A systematic review of 36 studies (comprising 44,211 complaints) estimated that 64% of complainants were patients and 26% were family members; the remaining 10% was not specified [ 3 ]. Of patient risk factors, patients with mental, behavioural, or neurodevelopmental disorders were significantly more likely to complain following hand and upper extremity surgery [ 24 ] and spine surgery [ 26 ] (Table  3 ).

In terms of therapeutic context, there were lower odds of a complaint for two procedural features: (i) use of a general anaesthetic in both paediatric and adult populations provided odds ratios, respectively, of 0.22 (CI 0.07–0.62) and 0.67 (CI 0.47–0.95) compared to no general anaesthetic, and (ii) a 1-h delay in actual start time led to slightly higher odds of a complaint, more notably in paediatrics (OR = 1.27, CI 1.10–1.47) than in adults (OR = 1.05, CI 0.95–1.16) [ 25 ]. The odds of a complaint were seven times greater for patients undergoing surgery (CI 5.2–9.6) [ 26 ]. The overuse of non-beneficial interventions and underuse of treatment escalation plans predicted complaints from the next-of-kin of patients who died in hospital [ 28 ]. For example, treatment escalation limitation plans were used significantly less frequently in complaints (23.8% versus 47.2%, P  = 0.013) [ 28 ]. Other components of therapeutic context, including LOS, setting, and experiencing complications and harms, were not significant predictors of complaints (Table  3 ).

Uncontrolled pre-post studies ( n  = 14) were the most common study design included for Question 2, followed by comparative studies with concurrent controls ( n  = 2) and systematic reviews ( n  = 2) (Table  4 ). Studies were set in the USA ( n  = 12) [ 13 , 15 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ], Canada ( n  = 2) [ 40 , 41 ], the UK [ 12 ], Ireland [ 42 ] and New Zealand [ 43 ] ( n  = 1, each). The studies addressed malpractice claims ( n  = 9), complaints ( n  = 5), and regulatory notifications ( n  = 2) and a mix of outcomes ( n  = 1). In-patient hospital ( n  = 11) was the most common setting, followed by mixed ( n  = 4), primary care and secondary care ( n  = 1, each). There were seven types of interventions for Question 2 studies: risk management ( n  = 6), CRPs ( n  = 5) (note one study [ 31 ] assessed both), medical remediation ( n  = 3), peer program ( n  = 2) and, CPD, simulation training and shared decision-making ( n  = 1, each). Quality assessment is summarised in Table  3 , Supplementary Table S 5 (comparative studies), Table S 7 (uncontrolled pre-post studies) and Supplementary Table S 6 (systematic reviews). Eight of the 12 criteria were met for the one comparative study; 3 to 11 of the 12 criteria were met for the 14 uncontrolled pre-post studies (mean 7.6, SD = 2.6); and 8 and 11 of the 16 criteria were met for the two systematic reviews.

Findings and definitions for Question 2 across the seven types of interventions and eight included outcomes are presented in Table  5 . No studies examined doctor satisfaction or patient outcomes (such as mortality or morbidity).

The six studies of risk management programs [ 31 , 32 , 34 , 38 , 40 , 42 ], also called risk reduction programs, were heterogeneous in nature, and included enhanced evaluation of, and response to, complaints [ 42 ], active engagement of physicians in risk assessment [ 32 ], lectures followed by a mock lawsuit [ 34 ], and education [ 38 , 40 ]. Evidence from these studies of risk management programs supported reductions in claims, complaints and claims costs (Table  5 ). Other benefits included more timely complaints management, improved patient safety culture and staff confidence.

Evidence for communication and resolution programs (CRPs, five studies [ 13 , 15 , 31 , 33 , 35 ]) was consistent across four studies. There were lower rates of claims and complaints, lower claim amounts, and faster resolution of claims following the implementation of CRPs (Table  5 ) [ 15 , 31 , 33 , 35 ]. However, results were less supportive in a study using an interrupted time series (ITS) design [ 13 ]. One study demonstrated improved patient satisfaction [ 33 ].

Three studies of medical remediation showed either a reduction in claims rates [ 12 ] or an improved doctor risk profile [ 29 , 43 ].

Two studies of peer review, or the use of peer messengers, demonstrated a reduction in either complaint rates [ 36 ] or improved doctor risk profile [ 37 ] (Table  5 ).

A systematic review of five studies concluded that there was insufficient evidence to determine whether or not shared decision-making reduces claims [ 44 ]. A retrospective pre-post program evaluation of simulation training on malpractice claims among obstetrician-gynaecologists reported that the rate of claims after simulation training was halved to 5.7 claims per 100 physician years of coverage. Attending more sessions was associated with a greater reduction in claims, although there was no difference in the total costs of paid claims before and after the training [ 39 ].

In one included study of CPD, doctors who reported participation in CPD activities were significantly less likely (OR 0.60; CI 0.39 to 0.95) to receive quality of care-related complaints than those who did not report participating in CPD [ 41 ]. Participants in group-based CPD were less likely (OR 0.68; CI 0.47 to 0.98) to receive quality of care-related complaints than individual or assessment-based CPD [ 41 ].

Summary of the evidence

A summary of the included studies’ evidence base, consistency, clinical impact, generalisability and applicability is included in Table  6 . The evidence base was rated as poor for both Question 1 and 2 (Table  6 ). Consistency and clinical impact were slightly higher for Question 2 than Question 1, whereas generalisability and applicability were satisfactory for both Question 1 and Question 2.

This review has identified a clear lack of recent high-quality studies to inform an in-depth understanding of either review Question 1 or Question 2. For Question 1, seven patient characteristics were associated with patients’ likelihood to complain or make a medico-legal claim against a doctor; however, only one of these findings (presence of a mental disorder) was replicated. This may be related to the paucity of studies, for example, only half of the patient characteristics were evaluated in more than one study. While more studies were included for Question 2, the low quality of the predominant study design (case series) severely limits the strength of the review’s findings.

The main finding for Question 1 of a relationship between a patient’s mental health status and complaint behaviour may reflect non-modifiable associations between underlying mental health conditions, poorer outcomes and reduced satisfaction after surgery [ 24 , 26 ]. Alternatively, the finding may reflect the impact of stigma experienced by these patients in healthcare settings. Mental illness-related stigma is prevalent in healthcare [ 51 ]. Stigma creates barriers to accessing healthcare, such as delays in help-seeking, treatment discontinuation, suboptimal therapeutic relationships, patient safety concerns and poorer quality care [ 52 ]. The presence of these barriers may be associated with a complaint about a healthcare provider.

Findings for Question 2 offer some evidence to support most of the included interventions, particularly risk management programs and CRPs. Some of the commonly occurring attributes of risk management programs were the evaluation and analysis of complaints and claims, targeted medico-legal education, and implementation of patient safety measures. The majority of the risk management programs were developed and delivered internally, either at the level of hospital department [ 38 ], hospital-wide [ 32 , 34 ] or general practice-level [ 42 ]. Local contextualisation, incorporating the site-specific nature of malpractice claims and legislation, and delivery of risk management programs apparently enhance the acceptability of risk management programs for surgeons, in particular [ 53 , 54 , 55 ]. Nevertheless, in one study, the Society of Obstetricians and Gynaecologists of Canada partnered with a healthcare insurance representative body to support the international expansion of a risk management program [ 40 ].

Studies of CRPs were generally consistent in showing lower rates of claims and complaints, lower claim amounts, and faster resolution of claims following the implementation of CRPs. However, limited adherence to the key components of CRP, including a proliferation of partial apology laws, may detract from the effectiveness of CRP in meeting the needs of injured patients [ 56 , 57 , 58 ]. Patients involved in CRP have expressed a greater desire for information provision from hospitals about efforts to prevent recurrences of the event [ 59 ].

Interventions such as caps on compensation, attorney fees, and alternative payment systems and liabilities [ 31 ] were excluded from the review as they are not doctor-directed interventions. The impacts of these medical malpractice reforms have been recently summarised [ 60 , 61 ].

The small number of included studies (Question 1) and the low quality of included studies (Question 2) represent major gaps in the evidence. For Question 1, there were a large number of excluded studies that were uncontrolled or unadjusted cross-sectional studies of complaints or claims that simply report the underlying characteristics of a claims database. Due to the lack of a control group, these studies do not provide particularly useful insights into the relationship between patient characteristics and the rate of complaints or claims. While more studies were included for Question 2, the predominant study design (i.e. uncontrolled pre-post) is weak as it does not permit adjustments for other secular trends in claims or confounders, or include control sites. Therefore, very little strength could be offered for recommendations emanating from either Question 1 or Question 2.

For Question 1, only one study specified whether a complaint was warranted or unwarranted [ 41 ]. No study included both types of complaints to determine predictors of successful interventions targeting unwarranted claims/complaints. The finding that a substantial subset of complaints originate from non-patient sources is likely to reduce the predictive value of patient characteristics for claims and complaints in this analysis. For Question 2, no studies assessed staff satisfaction or patient outcomes, such as mortality or morbidity. Additionally, there is rarely any evidence provided about generalisability or the potential for implementation and sustainability of the intervention, and most studies are limited to a single hospital/health service. Only one included study reported on the impact on organisational culture [ 40 ] or patient satisfaction [ 33 ].

All stages of the rapid review were conducted independently in duplicate to minimise the risk of errors. However, we only included studies published since 2011. This may have excluded relevant, older literature, which may be a limitation to this rapid review. Additionally, we filtered search results from the Scopus and Web of Science databases to countries with similar health systems (Australia, New Zealand, Canada and the UK) and screened out studies with ‘emergency’ in the title.

Conclusions

Despite substantial efforts made to collect information about patient complaints and claims, research has generally failed to robustly determine patient characteristics associated with complaints and claims. There is a small amount of evidence that patients with mental health conditions are more likely to complain.

The evidence for the effectiveness of interventions to reduce the likelihood of a doctor receiving a complaint or claim is also weak, as it is dominated by low-quality, uncontrolled pre-post studies. Only one or two studies were included for five types of programs (peer programs, medical remediation, shared decision-making, simulation training and CPD). More evidence, however, offers support for the effectiveness of risk management programs and CRPs in reducing complaints and claims.

Availability of data and materials

The datasets analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the support of Eileen Goldberg and Richa Jaswal who brokered the review through the Sax Institute.

The project was funded by Avant Insurance Limited, Australia, which advised on the study protocol and approved publication. The authors alone are responsible for the views expressed in this review, and they do not necessarily represent the decisions, policies, or views of Avant Insurance Limited, Australia.

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TJS obtained funding, developed review methods, conducted the search, screened, critically appraised, extracted data, interpreted results, and wrote the manuscript. MZ screened, extracted data, interpreted results, and wrote the manuscript. JG and JR screened, critically appraised, extracted data; RC and DAM interpreted results. PDH critically appraised, interpreted results. GH and MW developed the protocol and interpreted results. All authors reviewed the manuscript and approved the submitted version. All authors are personally accountable for their own contributions.

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Additional file 1: table s1..

Pubmed search - 8 September 2022. Table S2. Scopus search - 8 September 2022. Table S3. Web of Science - 8 September 2022. Table S4. Summary of study design for included studies for Question 1 and 2 using NHMRC levels of evidence [20]. Table S5. Summary of quality appraisal for eight comparative studies with concurrent controls, six for Question 1 (Q1) and two for Question 2 (Q2). Table S6. Summary of quality appraisal for three systematic reviews (one for Question 1 (Q1) and two for Question 2 (Q2)). Table S7. Summary of quality appraisal for 14 uncontrolled pre-post studies for Question 2 (Q2).

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Schultz, T.J., Zhou, M., Gray, J. et al. Patient characteristics of, and remedial interventions for, complaints and medico-legal claims against doctors: a rapid review of the literature. Syst Rev 13 , 104 (2024). https://doi.org/10.1186/s13643-024-02501-8

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Forensic neuropathology in the past decade: a scoping literature review

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While there has been notable research activity in the field of clinical neuropathology over the recent years, forensic approaches have been less frequent. This scoping literature review explored original research on forensic neuropathology over the past decade (January 1, 2010, until February 12, 2022) using the MEDLINE database. The aims were to (1) analyze the volume of research on the topic, (2) describe meta-level attributes and sample characteristics, and (3) summarize key research themes and methods. Of 5053 initial hits, 2864 fell within the target timeframe, and 122 were included in the review. Only 3–17 articles were published per year globally. Most articles originated from the Europe (39.3%) and Asia (36.1%) and were published in forensic journals (57.4%). A median sample included 57 subjects aged between 16 and 80 years. The most common research theme was traumatic intracranial injury (24.6%), followed by anatomy (12.3%) and substance abuse (11.5%). Key methods included immunotechniques (31.1%) and macroscopic observation (21.3%). Although a number of novel findings were reported, most were of preliminary nature and will require further validation. In order to reach breakthroughs and validate novel tools for routine use, more research input is urged from researchers across the world. It would be necessary to ensure appropriate sample sizes and make use of control groups.

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Introduction

Neurological diseases [ 1 ] and trauma to the central nervous system (CNS) [ 2 ] are common causes of death globally. A comprehensive postmortem examination of the CNS often requires particular expertise and sophisticated tissue processing techniques [ 3 , 4 ]. Neuropathological expertise is therefore of high value in both clinical [ 5 ] and forensic pathology [ 3 ]. While there has been notable research activity in the field of clinical neuropathology over the recent years [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ], forensic approaches appear less frequent [ 16 , 17 , 18 , 19 , 20 ]. However, the role of CNS remains important in the medico-legal practice [ 21 , 22 , 23 , 24 ], as CNS-related findings may have pivotal significance in cause-of-death investigation [ 3 ] and legal proceedings [ 25 , 26 ].

Literature reviews aid in the efficient utilization of current knowledge. Systematic approaches are needed to summarize and disseminate research findings and identify gaps in the existing literature [ 27 ]. However, to the best of the authors’ knowledge, there are no broad-scoped overviews summarizing literature on forensic neuropathology, at least from the past decade. This scoping literature review explored literature on forensic neuropathology from January 1, 2010, until February 12, 2022. The aims were to (1) analyze the volume of research on the topic, (2) describe meta-level attributes and sample characteristics, and (3) summarize key research themes and methods.

Materials and methods

Research questions.

Scoping reviews are exploited to determine the scope and volume of literature on a given topic and to identify key concepts [ 28 , 29 ]. In contrast to systematic reviews, scoping reviews are particularly useful when the research question is broad and the body of literature has not been comprehensively reviewed before. We conducted a MEDLINE-based scoping review to explore scientific literature on forensic neuropathology published over the past decade.

The following research questions were formulated in accordance with the general aims of the study:

Volume of research

What is the volume of original research on forensic neuropathology per year?

Meta-level attributes and sample characteristics

Which journals publish studies on forensic neuropathology in terms of subspecialty and impact?

What is the geographical distribution of publications?

What kind of samples are used in terms of size and age distribution?

Research themes and methods

What are the key concepts, i.e., main research themes and methodological approaches in forensic neuropathology?

Are there knowledge gaps?

This review did not aim to summarize or classify particular findings of the studies; however, these are addressed in the supplementary material .

Search strategy, inclusion, and exclusion criteria

The search strategy was developed by the first author (P.O.) and reviewed by the last author of the paper (A.S.). Table  1 presents the specific search terms used in MEDLINE. Figure  1 is a flowchart demonstrating the article selection process with exclusions.

Flowchart demonstrating the article selection process with exclusions

We aimed to find peer-reviewed, original articles that addressed a neuropathological method or finding related to a medico-legal or forensic question in a human sample. A neuropathological method was defined as a macroscopic, microscopic, or other laboratory technique used to examine a tissue sample obtained from the CNS or intracranial structures including vasculature. We focused on English-language articles that were published and indexed in MEDLINE between January 1, 2010, and the database search date. Short communications, retrospective summaries of autopsy findings, and other similar publication types were included if they were original articles based on authentic human samples. Studies that solely focused on postmortem imaging, analysis of body fluids, human identification, or skull fractures without the use of neuropathological methods were excluded.

The search was conducted in the MEDLINE database February 12, 2022. First, P.O. screened all hits on the basis of titles, abstracts, and full texts, if necessary. Each hit was assigned with a rationale for inclusion or exclusion to be later validated by A.S.

Data extraction and synthesis

Data extraction was performed with the help of an Excel spreadsheet. Table  2 presents the variables collected in the data extraction process. The spreadsheet was a priori planned by P.O. and reviewed by A.S.; an internal pilot was carried out in the beginning of data collection (20 hits from the year 2010). Data extraction was performed on the basis of full texts and potential supplementary material of the articles. While P.O. was primarily responsible for extracting the data, the spreadsheet was reviewed and commented by A.S. A formal risk of bias assessment was not performed, as it is not customary in scoping reviews [ 28 ], and was not considered necessary in relation to the present research questions.

Data synthesis was conducted in accordance with the predefined research questions. The distributions of publication year, journal characteristics, geographical location, sample characteristics, primary research theme, and methodological approach were tabulated using frequencies with percentages or medians with interquartile ranges, as appropriate. In addition to these summary statistics, a supplementary table containing the extracted data of individual studies was constructed.

• Literature search

Of 5053 initial hits, 2864 fell within the target timeframe, and 122 were finally included in the review [ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ], corresponding to 4.3% of hits within timeframe (Fig.  1 ). Most exclusions were due to wrong context (e.g., forensic psychiatry) or article type (i.e., not original article). Individual summaries of the 122 included articles, together with aims and main findings, are presented in Supplementary Table  1 .

Meta-level attributes

Table  3 shows the annual distribution of publications over the review period; 3 to 17 articles were published per year globally. Table  4 is a bibliographic and geographic summary of the studies. Forensic journals were the most common publication channel (57.4%), followed by clinical journals (e.g., general medicine, neurology, or pediatric journals; 23.0%), and pathology journals (8.2%). Median impact factor was 2.3, while 11.5% of studies were published in journals without an Impact Factor. As for geographical distribution, Europe (39.3%) and Asia (36.1%) were the two most common study regions.

• Sample characteristics

Table  5 is a summary of sample characteristics. A median sample included 57 subjects (interquartile range 29–101; full range 4–1222), which included both cases and controls, if applicable. Control groups were utilized in less than half of the studies (43.4%). Medians of minimum and maximum ages were 16 and 80 years, respectively. A total of 30.3% of studies were based on adult-only samples, another 30.3% had both adults and minors, and 12.3% were based on minors. Subject ages were not stated in over a quarter of the studies (27.0%).

Lists of research themes and methodological approaches are presented in Table  6 . Individual summaries of the articles, together with aims and main findings, are presented in Supplementary Table  1 .

The most common research theme was traumatic intracranial injury (24.6%), which comprised focal and diffuse traumatic brain injuries [ 30 , 31 , 39 , 43 , 54 , 55 , 64 , 83 , 85 , 86 , 94 , 106 , 107 , 115 , 116 , 120 , 123 , 130 , 132 , 139 , 150 ] and traumatic intracranial hemorrhages [ 30 , 47 , 54 , 57 , 58 , 65 , 83 , 87 , 99 , 113 , 114 , 130 , 141 , 150 ]. Studies often used immunotechniques to identify traumatic changes and estimate the age of injury [ 39 , 85 , 86 , 87 , 94 , 106 , 107 , 115 , 120 , 132 , 139 ]. While some studies described macroscopic injury patterns and combinations in accident and assault scenarios [ 30 , 47 , 65 , 99 , 114 , 116 , 130 , 141 ], others used conventional histology [ 57 , 58 , 113 ] or several methods [ 31 , 43 , 54 , 55 , 64 , 83 , 150 ] to address varying research questions.

The second most common entity was anatomy (12.3%). While most studies described the anatomical variants of vasculature [ 41 , 68 , 75 , 105 , 126 , 127 , 135 ] and other intracranial structures [ 44 , 73 , 74 , 151 ], some aimed to generate reference values for brain weight in various populations [ 69 , 98 , 102 , 125 ]. The main techniques were macroscopic observation, conventional histology, and weight measurement. Moreover, one study evaluated the biomechanical properties of the dura mater [ 151 ].

Substance abuse was the primary entity in 11.5% of the studies. Both chronic and acute abuse were represented. The selection of substances included alcohols [ 38 , 52 , 82 ], opioids [ 38 , 100 , 109 , 117 , 118 , 119 ], stimulants [ 38 , 53 , 81 , 136 , 147 ], and other or multiple substances [ 48 , 50 , 117 , 118 ]. Immunotechniques [ 38 , 48 , 50 , 117 , 118 , 147 ], genetic techniques [ 81 ], or the two together [ 119 , 136 ] were often utilized to identify brain damage and distinguish substance abuse from other causes of death. Some studies primarily reported macroscopic observations [ 52 , 53 , 82 , 109 ] or brain weight [ 100 ] among substance abusers.

Laboratory methods were the main focus in 7.4% of the studies [ 45 , 67 , 70 , 72 , 97 , 111 , 133 , 138 , 148 ]. The studies showed notable heterogeneity, addressing technical aspects of, e.g., formalin pigment deposition [ 45 ], immunohistochemistry [ 133 ], DNA extraction [ 67 ], and freezing preparation of putrefied brain tissue [ 97 ].

Sudden unexpected deaths in infancy and childhood were addressed in 6.6% of the studies [ 33 , 40 , 51 , 61 , 66 , 79 , 84 , 91 ]. Immunotechniques [ 33 , 40 , 79 ], genetic techniques [ 51 ], conventional histology [ 91 ], and brain weight measurement [ 61 ] were used to uncover underlying mechanisms and identify brain tissue markers in these cases. Moreover, one study suggested an optimal neuropathologic examination protocol for these deaths in a medico-legal setting [ 66 ].

Other research themes were rarely addressed (< 5% each). Neurodegenerative diseases in medico-legal settings were approached using immunotechniques [ 128 , 143 , 144 ], image analysis [ 129 ], or a combination of several methods [ 104 , 112 ]. As for suicide, immunotechniques [ 32 , 89 ], genetic techniques [ 62 , 88 ], and brain weight measurement [ 146 ] were applied to identify factors that differentiate suicide victims from controls. Brain tissue markers of hypothermia and hyperthermia were studied by means of immunotechniques [ 78 , 140 , 145 ] and genetic techniques [ 60 ]. Studies that aimed to improve the estimation of postmortem interval were mainly based on immunotechniques [ 42 , 92 ] and genetic techniques [ 134 ]. Asphyxia and brain hypoxia [ 35 , 77 , 108 ], brain edema [ 36 , 37 , 96 ], brain tissue identification [ 95 , 121 , 122 ], drowning [ 34 , 71 ], and sudden unexpected death in epilepsy [ 63 , 149 ] were addressed in two to three individual studies each.

One article studied the markers of traumatic brain injury and mechanical asphyxiation using genetic techniques [ 49 ], while another focused on the potential markers of hypothermia, hyperthermia, and intoxication using immunotechniques and genetic techniques [ 59 ]. Finally, the following entities had one study each: sudden unexplained nocturnal death syndrome [ 46 ], pediatric subdural hemosiderin deposits [ 56 ], iron in fetal and infant leptomeninges [ 80 ], DNA identification based on brain tissue swab [ 76 ], zinc in brain tissue [ 90 ], intracranial aneurysms and dissections [ 101 ], age estimation [ 103 ], electrocution [ 124 ], insulin homicide [ 131 ], fire fatalities [ 137 ], phosphine poisoning [ 93 ], and carbon monoxide poisoning [ 142 ].

Main findings

This scoping review identified 122 original articles on forensic neuropathology from the years 2010–2022. Only 3–17 articles were published per year globally. Most articles originated from the Europe and Asia and were published in forensic journals. A median sample included 57 subjects aged between 16 and 80 years. The most common research theme was traumatic intracranial injury, followed by anatomy and substance abuse. Main methods included immunotechniques and macroscopic observation. To the best of the authors’ knowledge, this is the first scoping review to systematically explore literature on forensic neuropathology over the past decade.

Meta-level considerations

The annual volume of research output was relatively low, which may indicate rather mild research activity in the field globally. It is obvious that breakthroughs will require consistent scientific effort and active involvement of forensic pathologists in research projects. Clinical neuropathology may have outpowered the forensic branch, possibly due to stronger translational potential and active interplay with clinicians [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Neuropathology is an interdisciplinary field, touching upon neighboring fields such as neurology, neurosurgery, psychiatry, legal medicine, and general pathology. Forensic neuropathology is aligned in the midway between clinical and forensic pathology, often requiring particular expertise from a general forensic pathologist [ 22 ]. Interdisciplinary cooperation may thus be the key to increasing research activity in the field.

Articles were widely distributed between journals of various disciplines, which underlines the intersectoral nature of the field. In general, articles were published in international, field-specific journals with a median impact factor of 2.3. However, it is noteworthy that over a tenth of the articles were published in journals with no impact factor whatsoever; anatomic reports appeared to be overrepresented in this subgroup. As for geographical distribution, the vast majority of articles were from European and Asian researchers. Notably, articles from American groups were less common, and only two African articles were published over the entire review period. In order to expedite the development and implementation of forensic neuropathology globally, research input is needed from medico-legal units across the world. Unfortunately, achieving this objective may prove difficult due to resource- and policy-related barriers. It would be important to ensure sufficient personnel resources, methodological expertise, access to research funding, and comprehensible research permit policies for medico-legal data.

Sample-related considerations

Sample sizes were moderate, with a median of 57 subjects; this included both cases and potential controls. Two articles appeared to lack a clear indication of sample size. Despite the relatively small sample sizes, statistical power calculations were rarely presented. In quantitative studies, power calculations guide sample collection and corroborate the statistical approach [ 152 ]. Of note is also the fact that over a half of the studies did not have a control group, which implies that most articles were descriptive in nature. A comparative design is a prerequisite for many scientifically relevant conclusions [ 153 ].

Age ranges were generally wide, which increased the generalizability of findings across age groups. However, taking into account the moderate sample sizes, the level of heterogeneity within samples may significantly increase with widening age spans. Over a quarter of studies appeared to lack a clear statement of the minimum and maximum ages of the sample; some reported standard deviations and interquartile ranges instead.

Research themes, methods, and future directions

Traumatic intracranial injury was the most common research theme. Research activity around the topic is easy to comprehend as traumatic brain injury and intracranial hemorrhages are complex and deadly entities that often present themselves to a forensic pathologist [ 2 , 21 ]. As neuropathology may have a pivotal role in a cause-of-death investigation [ 3 ] or legal proceedings [ 25 , 26 ], novel tools are needed to identify traumatic changes and estimate the age of injury. However, significant breakthroughs are yet to come.

Alongside traumatic intracranial injury, the top-three research themes included anatomy and substance abuse. Somewhat surprisingly, macroscopic and microscopic anatomy of intracranial structures were among the most popular research themes. Many of these studies reported important findings for neurosurgeons, for example, but appeared to make a minor contribution to the field of forensic neuropathology. Substance abuse, which indeed is a central medico-legal entity [ 154 ], was approached from a variety of perspectives method- and substance-wise. However, more research input will be needed to identify substance-specific markers in brain tissue and differentiate substance abuse and intoxication from other causes of death.

Neurodegenerative diseases were addressed in a handful of studies. In spite of the vast research activity in clinical neuropathology, studies in medico-legal samples are also important, as neurodegenerative diseases appear to increase the risk of unnatural deaths [ 155 ]. Providing medico-legal units with diagnostic methods that have been validated in medico-legal samples will be of utmost importance. As for sudden unexplained deaths among infants and children, studies have kept chasing potential mechanisms and biomarkers, but again, significant breakthroughs are yet to come.

Although suicide is a major and diverse entity in forensic pathology [ 156 ], only a few studies addressed the topic. Considering the obscurity behind predisposing and underlying factors, there should be a lot to achieve mechanism- and prevention-wise. Medico-legal samples may have significant translational potential in this regard. Moreover, only a few studies addressed asphyxia, drowning, hypothermia, hyperthermia, sudden unexpected death in epilepsy, and estimation of postmortem interval. Higher research activity should be directed toward these themes in order to improve postmortem diagnostics.

Immunotechniques, i.e., immunohistochemistry and immunoblotting, were commonly applied to detect potential changes in brain tissue. Genetic techniques were exploited in various approaches such as brain tissue identification and gene expression analysis. A minority of studies used conventional histology as the main method. Although a number of novel findings were reported, most were of preliminary nature and will require further validation. Macroscopic observation of intracranial structures was a common method, but the studies often merely described injury patterns or anatomic variations. The crude measurement of brain weight was also used in some studies, but these often had null findings.

Limitations of the review

This scoping review had several limitations that should be considered. First, the scope of the literature search was notably broad, and conventional search terms were covered. However, articles that used specific or uncommon terminology may have been omitted. A large number of initial hits were obtained and manually evaluated, which may have reduced the risk of omitting in-scope articles. Second, as the review focused on original articles, emerging research themes may not have been fully covered. Moreover, there is a large body of research that may not be captured in this review even though it is relevant to forensic neuropathologists (e.g., CNS infections and emerging concepts in neurodegenerative diseases). Future reviews are expected to cover these aspects. Finally, as the aim was to explore and summarize original research in the field, there were no particular restrictions on scientific rigor, and no formal bias assessment was performed.

This scoping literature review explored original research on forensic neuropathology over the years 2010–2022. A total of 122 original articles were eventually included in the synthesis. Traumatic intracranial injury was the most common research theme, immunotechniques being the most commonly applied method. Only 3–17 articles were published per year globally. Although a number of novel findings were reported, most were of preliminary nature and will require further validation. In order to reach breakthroughs and validate novel tools for routine use, more research input is urged in forensic neuropathology from researchers across the world. Interdisciplinary cooperation may be the key to increasing research activity in the field. Researchers should ensure appropriate sample sizes and make use of comparative designs whenever possible.

Knowledge of diseases and trauma related to the central nervous system has high value in forensic pathology

This scoping review explored literature on forensic neuropathology from 2010 to 2022

A total of 122 original articles were included, corresponding to 3–17 publications per year globally

4.The most common research theme was traumatic intracranial injury (24.6%), followed by anatomy (12.3%) and substance abuse (11.5%). Key methods included immunotechniques (31.1%) and macroscopic observation (21.3%)

To reach breakthroughs and validate tools for routine practice, more research input is needed from researchers across the world

Availability of data and material

This is a review of published literature. The dataset generated and analysed during the study is presented in Supplementary Table 1 .

Code availability

Not applicable.

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Oura, P., Hakkarainen, A. & Sajantila, A. Forensic neuropathology in the past decade: a scoping literature review. Forensic Sci Med Pathol (2023). https://doi.org/10.1007/s12024-023-00672-9

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Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review

• John R. Hurst 1 ,
• MeiLan K. Han 2 ,
• Barinder Singh 3 ,
• Sakshi Sharma 4 ,
• Gagandeep Kaur 3 ,
• Enrico de Nigris 5 ,
• Ulf Holmgren 6 &
• Mohd Kashif Siddiqui 3  

Respiratory Research volume  23 , Article number:  213 ( 2022 ) Cite this article

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Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD.

A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD.

The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies).

Conclusions

This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide [ 1 ]. Based upon disability-adjusted life-years, COPD ranked sixth out of 369 causes of global disease burden in 2019 [ 2 ]. COPD exacerbations are associated with a worsening of lung function, and increased disease burden and mortality (of those patients hospitalized for the first time with an exacerbation, > 20% die within 1 year of being discharged) [ 3 ]. Furthermore, patients with COPD consider exacerbations or hospitalization due to exacerbations to be the most important disease outcome, having a large impact on their lives [ 4 ]. Therefore, reducing the future risk of COPD exacerbations is a key goal of COPD management [ 5 ].

Being able to predict the level of risk for each patient allows clinicians to adapt treatment and patients to adjust their lifestyle (e.g., through a smoking cessation program) to prevent exacerbations [ 3 ]. As such, identifying high-risk patients using measurable risk factors and predictors that correlate with exacerbations is critical to reduce the burden of disease and prevent a cycle of decline encompassing irreversible lung damage, worsening quality of life (QoL), increasing disease burden, high healthcare costs, and early death.

Prior history of exacerbations is generally thought to be the best predictor of future exacerbations; however, there is a growing body of evidence suggesting other demographic and clinical characteristics, including symptom burden, airflow obstruction, comorbidities, and inflammatory biomarkers, also influence risk [ 6 , 7 , 8 , 9 ]. For example, in the prospective ECLIPSE observational study, the likelihood of patients experiencing an exacerbation within 1 year of follow-up increased significantly depending upon several factors, including prior exacerbation history, forced expiratory volume in 1 s (FEV 1 ), St. George’s Respiratory Questionnaire (SGRQ) score, gastroesophageal reflux, and white blood cell count [ 9 ].

Many studies have assessed predictors of COPD exacerbations across a variety of countries and patient populations. This systematic literature review (SLR) was conducted to identify and compile the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD.

• Systematic literature review

A comprehensive search strategy was designed to identify English-language studies published in peer-reviewed journals providing data on risk factors or predictors of moderate or severe exacerbations in adults aged ≥ 40 years with a diagnosis of COPD (sample size ≥ 100). The protocol is summarized in Table 1 and the search strategy is listed in Additional file 1 : Table S1. Key biomedical electronic literature databases were searched from January 2015 until July 2019. Other sources were identified via bibliographic searching of relevant systematic reviews.

Study selection process

Implementation and reporting followed the recommendations and standards of the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement [ 10 ]. An independent reviewer conducted the first screening based on titles and abstracts, and a second reviewer performed a quality check of the excluded evidence. A single independent reviewer also conducted the second screening based on full-text articles, with a quality check of excluded evidence performed by a second reviewer. Likewise, data tables of the included studies were generated by one reviewer, and another reviewer performed a quality check of extracted data. Where more than one publication was identified describing a single study or trial, data were compiled into a single entry in the data-extraction table to avoid double counting of patients and studies. One publication was designated as the ‘primary publication’ for the purposes of the SLR, based on the following criteria: most recently published evidence and/or the article that presented the majority of data (e.g., journal articles were preferred over conference abstracts; articles that reported results for the full population were preferred over later articles providing results of subpopulations). Other publications reporting results from the same study were designated as ‘linked publications’; any additional data in the linked publications that were not included in the primary publication were captured in the SLR. Conference abstracts were excluded from the SLR unless they were a ‘linked publication.’

Included studies

A total of 5112 references (Fig.  1 ) were identified from the database searches. In total, 76 studies from 113 publications were included in the review. Primary publications and ‘linked publications’ for each study are detailed in Additional file 1 : Table S2, and study characteristics are shown in Additional file 1 : Table S3. The studies included clinical trials, registry studies, cross-sectional studies, cohort studies, database studies, and case–control studies. All 76 included studies were published in peer-reviewed journals. Regarding study design, 61 of the studies were observational (34 retrospective observational studies, 19 prospective observational studies, four cross-sectional studies, two studies with both retrospective and prospective cohort data, one case–control study, and one with cross-sectional and longitudinal data) and 15 were randomized controlled clinical trials.

PRISMA flow diagram of studies through the systematic review process. CA conference abstract, CENTRAL Cochrane Central Register of Controlled Trials, PRISMA  Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Of the 76 studies, 16 were conducted in North America (13 studies in the USA, two in Canada, and one in Mexico); 26 were conducted in Europe (seven studies in Spain, four in the UK, three in Denmark, two studies each in Bulgaria, the Netherlands, and Switzerland, and one study each in Sweden, Serbia, Portugal, Greece, Germany, and France) and 17 were conducted in Asia (six studies in South Korea, four in China, three in Taiwan, two in Japan, and one study each in Singapore and Israel). One study each was conducted in Turkey and Australia. Fifteen studies were conducted across multiple countries.

The majority of the studies (n = 54) were conducted in a multicenter setting, while 22 studies were conducted in a single-center setting. The sample size among the included studies varied from 118 to 339,389 patients.

Patient characteristics

A total of 75 studies reported patient characteristics (Additional file 1 : Table S4). The mean age was reported in 65 studies and ranged from 58.0 to 75.2 years. The proportion of male patients ranged from 39.7 to 97.6%. The majority of included studies (85.3%) had a higher proportion of males than females.

Exacerbation history (as defined per each study) was reported in 18 of 76 included studies. The proportion of patients with no prior exacerbation was reported in ten studies (range, 0.1–79.5% of patients), one or fewer prior exacerbation in ten studies (range, 46–100%), one or more prior exacerbation in eight studies (range, 18.4–100%), and two or more prior exacerbations in 12 studies (range, 6.1–55.0%).

Prognostic factors of exacerbations

A summary of the risk factors and predictors reported across the included studies is provided in Tables 2 and 3 . The overall findings of the SLR are summarized in Figs. 2 and 3 .

Risk factors for moderate-to-severe exacerbations in patients with COPD. Factors with > 30 supporting studies shown as large circles; factors with ≤ 30 supporting studies shown as small circles and should be interpreted cautiously. BDR bronchodilator reversibility, BMI body mass index, COPD chronic obstructive pulmonary disease, EOS eosinophil, QoL quality of life

Summary of risk factors for exacerbation events. a Treatment impact studies removed. BDR bronchodilator reversibility, BMI body mass index, COPD chronic obstructive pulmonary disease, EOS eosinophil, QoL quality of life

Exacerbation history within the past 12 months was the strongest predictor of future exacerbations. Across the studies assessing this predictor, 34 out of 35 studies (97.1%) reported a significant association between history of exacerbations and risk of future moderate-to-severe exacerbations (Table 3 ). Specifically, two or more exacerbations in the previous year or at least one hospitalization for COPD in the previous year were identified as reliable predictors of future moderate or severe exacerbations. Even one moderate exacerbation increased the risk of a future exacerbation, with the risk increasing further with each subsequent exacerbation (Fig.  4 ). A severe exacerbation was also found to increase the risk of subsequent exacerbation and hospitalization (Fig.  5 ). Patients experiencing one or more severe exacerbations were more likely to experience further severe exacerbations than moderate exacerbations [ 11 , 12 ]. In contrast, patients with a history of one or more moderate exacerbations were more likely to experience further moderate exacerbations than severe exacerbations [ 11 , 12 ].

Exacerbation history as a risk factor for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. CI confidence interval, ES effect size

Exacerbation history as a risk factor for severe exacerbations. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES , effect size

Overall, 35 studies assessed the association of comorbidities with the risk of exacerbation. All studies except one (97.1%) reported a positive association between comorbidities and the occurrence of moderate-to-severe exacerbations (Table 3 ). In addition to the presence of any comorbidity, specific comorbidities that were found to significantly increase the risk of moderate-to-severe exacerbations included anxiety and depression, cardiovascular comorbidities, gastroesophageal reflux disease/dyspepsia, and respiratory comorbidities (Fig.  6 ). Comorbidities that were significant risk factors for severe exacerbations included cardiovascular, musculoskeletal, and respiratory comorbidities, diabetes, and malignancy (Fig.  7 ). Overall, the strongest association between comorbidities and COPD readmissions in the emergency department was with cardiovascular disease. The degree of risk for both moderate-to-severe and severe exacerbations also increased with the number of comorbidities. A Dutch cohort study found that 88% of patients with COPD had at least one comorbidity, with hypertension (35%) and coronary heart disease (19%) being the most prevalent. In this cohort, the comorbidities with the greatest risk of frequent exacerbations were pulmonary cancer (odds ratio [OR] 1.85) and heart failure (OR 1.72) [ 7 ].

Comorbidities as risk factors for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES effect size, GERD gastroesophageal disease

Comorbidities as risk factors for severe exacerbations. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, CKD , chronic kidney disease, ES effect size

The majority of studies assessing disease severity or bronchodilator reversibility (39/41; 95.1%) indicated a significant positive relation between risk of future exacerbations and greater disease severity, as assessed by greater lung function impairment (in terms of lower FEV 1 , FEV 1 /forced vital capacity ratio, or forced expiratory flow [25–75]/forced vital capacity ratio) or more severe Global Initiative for Chronic Obstructive Lung Disease (GOLD) class A − D, and a positive relationship between risk of future exacerbations and lack of bronchodilator reversibility (Table 3 , Figs. 8 and 9 ).

Disease severity as a risk factor for moderate-to-severe exacerbations. Yun 2018 included two studies; the study from which data were extracted (COPDGene or ECLIPSE) is listed in parentheses. Where data have been extracted from a linked publication rather than the primary publication, the linked publication is listed in parentheses. CI confidence interval, ES effect size, FEV 1 f orced expiratory volume in 1 s, FVC , forced vital capacity, GOLD Global Initiative for Obstructive Lung Disease, HR hazard ratio, OR odds ratio

Disease severity and BDR as risk factors for severe exacerbations. ACCP American College of Chest Physicians, ACOS Asthma-COPD overlap syndrome, ATS  American Thoracic Society, BDR bronchodilator reversibility, CI confidence interval, ERS  European Respiratory Society, ES effect size, FEV 1 forced expiratory volume in 1 s, FVC  forced vital capacity, GINA Global Initiative for Asthma, GOLD Global Initiative for Obstructive Lung Disease

Of 21 studies assessing the relationship between blood eosinophil count and exacerbations (Table 3 ), 16 reported estimates for the risk of moderate or severe exacerbations by eosinophil count. A positive association was observed between higher eosinophil count and a higher risk of moderate or severe exacerbations, particularly in patients not treated with an inhaled corticosteroid (ICS); however, five studies reported a significant positive association irrespective of intervention effects. The risk of moderate-to-severe exacerbations was observed to be positively associated with various definitions of higher eosinophil levels (absolute counts: ≥ 200, ≥ 300, ≥ 340, ≥ 400, and ≥ 500 cells/mm 3 ; % of blood eosinophil count: ≥ 2%, ≥ 3%, ≥ 4%, and ≥ 5%). Of note, one study found reduced efficacy of ICS in lowering moderate-to-severe exacerbation rates for current smokers versus former smokers at all eosinophil levels [ 13 ].

Of 12 studies assessing QoL scales, 11 (91.7%) studies reported a significant association between the worsening of QoL scores and the risk of future exacerbations (Table 3 ). Baseline SGRQ [ 14 , 15 ], Center for Epidemiologic Studies Depression Scale (for which increased scores may indicate impaired QoL) [ 16 ], and Clinical COPD Questionnaire [ 17 , 18 ] scores were found to be associated with future risk of moderate and/or severe COPD exacerbations. For symptom scores, six out of eight studies assessing the association between moderate-to-severe or severe exacerbations with COPD Assessment Test (CAT) scores reported a significant and positive relationship. Furthermore, the risk of moderate-to-severe exacerbations was found to be significantly higher in patients with higher CAT scores (≥ 10) [ 15 , 19 , 20 , 21 ], with one study demonstrating that a CAT score of 15 increased predictive ability for exacerbations compared with a score of 10 or more [ 18 ]. Among 15 studies that assessed the association of modified Medical Research Council (mMRC) scores with the risk of moderate-to-severe or severe exacerbation, 11 found that the risk of moderate-to-severe or severe exacerbations was significantly associated with higher mMRC scores (≥ 2) versus lower scores. Furthermore, morning and night symptoms (measured by Clinical COPD Questionnaire) were associated with poor health status and predicted future exacerbations [ 17 ].

Of 36 studies reporting the relationship between smoking status and moderate-to-severe or severe exacerbations, 22 studies (61.1%) reported a significant positive association (Table 3 ). Passive smoking was also significantly associated with an increased risk of severe exacerbations (OR 1.49) [ 20 ]. Of note, three studies reported a significantly lower rate of moderate-to-severe exacerbations in current smokers compared with former smokers [ 22 , 23 , 24 ].

A total of 14 studies assessed the association of body mass index (BMI) with the occurrence of frequent moderate-to-severe exacerbations in patients with COPD. Six out of 14 studies (42.9%) reported a significant negative association between exacerbations and BMI (Table 3 ). The risk of moderate and/or severe COPD exacerbations was highest among underweight patients compared with normal and overweight patients [ 23 , 25 , 26 , 27 , 28 ].

In the 29 studies reporting an association between age and moderate or severe exacerbations, more than half found an association of older age with an increased risk of moderate-to-severe exacerbations (58.6%; Table 3 ). Four of these studies noted a significant increase in the risk of moderate-to-severe or severe exacerbations for every 10-year increase in age [ 25 , 26 , 29 , 30 ]. However, 12 studies reported no significant association between age and moderate-to-severe or severe exacerbation risk.

Sixteen out of 33 studies investigating the impact of sex on exacerbation risk found a significant association (48.5%; Table 3 ). Among these, ten studies reported that female sex was associated with an increased risk of moderate-to-severe exacerbations, while six studies showed a higher exacerbation risk in males compared with females. There was some variation in findings by geographic location and exacerbation severity (Additional file 2 : Figs. S1 and S2). Notably, when assessing the risk of severe exacerbations, more studies found an association with male sex compared with female sex (6/13 studies vs 1/13 studies, respectively).

Both studies evaluating associations between exacerbations and environmental factors reported that colder temperature and exposure to major air pollution (NO 2 , O 3 , CO, and/or particulate matter ≤ 10 μm in diameter) increased hospital admissions due to severe exacerbations and moderate-to-severe exacerbation rates [ 31 , 32 ].

Four studies assessed the association of 6-min walk distance with the occurrence of frequent moderate-to-severe exacerbations (Table 3 ). One study (25.0%) found that shorter 6-min walk distance (representing low physical activity) was significantly associated with a shortened time to severe exacerbation, but the effect size was small (hazard ratio 0.99) [ 33 ].

Five out of six studies assessing the relationship between race or ethnicity and exacerbation risk reported significant associations (Table 3 ). Additionally, one study reported an association between geographic location in the US and exacerbations, with living in the Northeast region being the strongest predictor of severe COPD exacerbations versus living in the Midwest and South regions [ 34 ].

Overall, seven studies assessed the association of biomarkers with risk of future exacerbations (Table 3 ), with the majority identifying significant associations between inflammatory biomarkers and increased exacerbation risk, including higher C-reactive protein levels [ 8 , 35 ], fibrinogen levels [ 8 , 30 ], and white blood cell count [ 8 , 15 , 16 ].

This SLR has identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Key factors associated with an increased risk of future moderate-to-severe exacerbations included a history of prior exacerbations, worse disease severity and bronchodilator reversibility, the presence of comorbidities, a higher eosinophil count, and older age (Fig.  2 ). These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the burden of COPD, including morbidity and mortality [ 36 ].

Findings from this review summarize the existing evidence, validating the previously published literature [ 6 , 9 , 23 ] and suggesting that the best predictor of future exacerbations is a history of exacerbations in the prior year [ 8 , 11 , 12 , 13 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 26 , 29 , 34 , 35 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. In addition, the effect size generally increased with the number of prior exacerbations, with a stronger effect observed with prior severe versus moderate exacerbations. This effect was observed across regions, including in Europe and North America, and in several global studies. This relationship represents a vicious circle, whereby one exacerbation predisposes a patient to experience future exacerbations and leading to an ever-increasing disease burden, and emphasizes the importance of preventing the first exacerbation event through early, proactive exacerbation prevention. The finding that prior exacerbations tended to be associated with future exacerbations of the same severity suggests that the severity of the underlying disease may influence exacerbation severity. However, the validity of the traditional classification of exacerbation severity has recently been challenged [ 61 ], and further work is required to understand relationships with objective assessments of exacerbation severity.

In addition to exacerbation history, disease severity and bronchodilator reversibility were also strong predictors for future exacerbations [ 8 , 14 , 16 , 18 , 19 , 20 , 22 , 23 , 24 , 26 , 28 , 29 , 33 , 37 , 40 , 43 , 44 , 45 , 46 , 48 , 50 , 51 , 52 , 56 , 59 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 ]. The association with disease severity was noted in studies that used GOLD disease stages 1–4 and those that used FEV 1 percent predicted and other lung function assessments as continuous variables. Again, this risk factor is self-perpetuating, as evidence shows that even a single moderate or severe exacerbation may almost double the rate of lung function decline [ 79 ]. Accordingly, disease severity and exacerbation history may be correlated. Margüello et al. concluded that the severity of COPD could be associated with a higher risk of exacerbations, but this effect was partly determined by the exacerbations suffered in the previous year [ 23 ]. It should be noted that FEV 1 is not recommended by GOLD for use as a predictor of exacerbation risk or mortality alone due to insufficient precision when used at the individual patient level [ 5 ].

Another factor that should be considered when assessing individual exacerbation risk is the presence of comorbidities [ 7 , 14 , 16 , 18 , 19 , 20 , 21 , 22 , 24 , 25 , 26 , 27 , 28 , 30 , 33 , 34 , 35 , 40 , 41 , 44 , 45 , 46 , 47 , 48 , 51 , 52 , 53 , 54 , 56 , 58 , 59 , 63 , 64 , 73 , 74 , 76 , 77 , 80 , 81 , 82 , 83 , 84 , 85 ]. Comorbidities are common in COPD, in part due to common risk factors (e.g., age, smoking, lifestyle factors) that also increase the risk of other chronic diseases [ 7 ]. Significant associations were observed between exacerbation risk and comorbidities, such as anxiety and depression, cardiovascular disease, diabetes, and respiratory comorbidities. As with prior exacerbations, the strength of the association increased with the number of comorbidities. Some comorbidities that were found to be associated with COPD exacerbations share a common biological mechanism of systemic inflammation, such as cardiovascular disease, diabetes, and depression [ 86 ]. Furthermore, other respiratory comorbidities, including asthma and bronchiectasis, involve inflammation of the airways [ 87 ]. In these patients, optimal management of comorbidities may reduce the risk of future COPD exacerbations (and improve QoL), although further research is needed to confirm the efficacy of this approach to exacerbation prevention. As cardiovascular conditions, including hypertension and coronary heart disease, are the most common comorbidities in people with COPD [ 7 ], reducing cardiovascular risk may be a key goal in reducing the occurrence of exacerbations. For other comorbidities, the mechanism for the association with exacerbation risk may be related to non-biological factors. For example, in depression, it has been suggested that the mechanism may relate to greater sensitivity to symptom changes or more frequent physician visits [ 88 ].

There is now a growing body of evidence reporting the relationship between blood eosinophil count and exacerbation risk [ 8 , 13 , 14 , 20 , 37 , 48 , 52 , 56 , 59 , 60 , 62 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ]. Data from many large clinical trials (SUNSET [ 89 ], FLAME [ 96 ], WISDOM [ 98 ], IMPACT [ 13 ], TRISTAN [ 99 ], INSPIRE [ 99 ], KRONOS [ 91 ], TRIBUTE [ 48 ], TRILOGY [ 52 ], TRINITY [ 56 ]) have also shown relationships between treatment, eosinophil count, and exacerbation rates. Evidence shows that eosinophil count, along with other effect modifiers (e.g., exacerbation history), can be used to predict reductions in exacerbations with ICS treatment. Identifying patients most likely to respond to ICS should contribute to personalized medicine approaches to treat COPD. One challenge in drawing a strong conclusion from eosinophil counts is the choice of a cut-off value, with a variety of absolute and percentage values observed to be positively associated with the risk of moderate-to-severe exacerbations. The use of absolute counts may be more practical, as these are not affected by variations in other immune cell numbers; however, there is a lack of consensus on this point [ 100 ].

Across the studies examined, associations between sex and the risk of moderate and/or severe exacerbations were variable [ 14 , 16 , 18 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 37 , 40 , 42 , 44 , 45 , 46 , 47 , 48 , 51 , 52 , 56 , 58 , 59 , 63 , 73 , 74 , 77 , 80 , 83 , 84 , 85 ]. A greater number of studies showed an increased risk of exacerbations in females compared with males. In contrast, some studies failed to detect a relationship, suggesting that country-specific or cultural factors may play a role. A majority of the included studies evaluated more male patients than female patients; to further elucidate the relationship between sex and exacerbations, more studies in female patients are warranted. Over half of the studies that assessed the relationship between age and exacerbation risk found an association between increasing age and increasing risk of moderate-to-severe COPD exacerbations [ 14 , 16 , 18 , 20 , 21 , 22 , 23 , 24 , 26 , 27 , 28 , 29 , 33 , 40 , 42 , 44 , 45 , 47 , 51 , 52 , 54 , 56 , 63 , 73 , 74 , 77 , 80 , 83 , 85 ].

Our findings also suggested that patients with low BMI have greater risk of moderate and/or severe exacerbations. The mechanism underlying this increased risk in underweight patients is poorly understood; however, loss of lean body mass in patients with COPD may be related to ongoing systemic inflammation that impacts skeletal muscle mass [ 101 , 102 , 103 ].

A limitation of this SLR, that may have resulted in some studies with valid results being missed, was the exclusion of non-English-language studies and the limitation by date; however, the search strategy was otherwise broad, resulting in the review of a large number of studies. The majority of studies captured in this SLR were from Europe, North America, and Asia. The findings may therefore be less generalizable to patients in other regions, such as Africa or South America. Given that one study reported an association between geographic location within different regions of the US and exacerbations [ 34 ], it is plausible that risk of exacerbations may be impacted by global location. As no formal meta-analysis was planned, the assessments are based on a qualitative synthesis of studies. A majority of the included studies looked at exposures of certain factors (e.g., history of exacerbations) at baseline; however, some of these factors change over time, calling into question whether a more sophisticated statistical analysis should have been conducted in some cases to consider time-varying covariates. Our results can only inform on associations, not causation, and there are likely bidirectional relationships between many factors and exacerbation risk (e.g., health status). Finally, while our review of the literature captured a large number of prognostic factors, other variables such as genetic factors, lung microbiome composition, and changes in therapy over time have not been widely studied to date, but might also influence exacerbation frequency [ 104 ]. Further research is needed to assess the contribution of these factors to exacerbation risk.

This SLR captured publications up to July 2019. However, further studies have since been published that further support the prognostic factors identified here. For example, recent studies have reported an increased risk of exacerbations in patients with a history of exacerbations [ 105 ], comorbidities [ 106 ], poorer lung function (GOLD stage) [ 105 ], higher symptomatic burden [ 107 ], female sex [ 105 ], and lower BMI [ 106 , 108 ].

In summary, the literature assessing risk factors for moderate-to-severe COPD exacerbations shows that there are associations between several demographic and disease characteristics with COPD exacerbations, potentially allowing clinicians to identify patients most at risk of future exacerbations. Exacerbation history, comorbidities, and disease severity or bronchodilator reversibility were the factors most strongly associated with exacerbation risk, and should be considered in future research efforts to develop prognostic tools to estimate the likelihood of exacerbation occurrence. Importantly, many prognostic factors for exacerbations, such as symptom burden, QoL, and comorbidities, are modifiable with optimal pharmacologic and non-pharmacologic treatments or lifestyle modifications. Overall, the evidence suggests that, taken together, predicting and reducing exacerbation risk is an achievable goal in COPD.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Body mass index

COPD Assessment Test

Chronic obstructive pulmonary disease

Forced expiratory volume in 1 s

Global Initiative for Chronic Obstructive Lung Disease

Inhaled corticosteroid

Modified Medical Research Council

Quality of life

St. George’s Respiratory Questionnaire

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Acknowledgements

Medical writing support, under the direction of the authors, was provided by Julia King, PhD, and Sarah Piggott, MChem, CMC Connect, McCann Health Medical Communications, funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines [ 109 ].

This study was supported by AstraZeneca.

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UCL Respiratory, University College London, London, WC1E 6BT, UK

John R. Hurst

Division of Pulmonary and Critical Care, University of Michigan, Ann Arbor, MI, USA

MeiLan K. Han

Formerly of Parexel International, Mohali, India

Barinder Singh, Gagandeep Kaur & Mohd Kashif Siddiqui

Parexel International, Mohali, India

Sakshi Sharma

Formerly of AstraZeneca, Cambridge, UK

Enrico de Nigris

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The authors have made the following declaration about their contributions. JRH and MKH made substantial contributions to the interpretation of data; BS, SS, GK, and MKS made substantial contributions to the acquisition, analysis, and interpretation of data; EdN and UH made substantial contributions to the conception and design of the work and the interpretation of data. All authors contributed to drafting or critically revising the article, have approved the submitted version, and agree to be personally accountable for their own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. All authors read and approved the final manuscript.

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JRH reports consulting fees from AstraZeneca; speaker fees from AstraZeneca, Chiesi, Pfizer, and Takeda; and travel support from GlaxoSmithKline and AstraZeneca. MKH reports assistance with conduction of this research and publication from AstraZeneca; personal fees from Aerogen, Altesa Biopharma, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, DevPro, GlaxoSmithKline, Integrity, Medscape, Merck, Mylan, NACE, Novartis, Polarean, Pulmonx, Regeneron, Sanofi, Teva, Verona, United Therapeutics, and UpToDate; either in kind research support or funds paid to the institution from the American Lung Association, AstraZeneca, Biodesix, Boehringer Ingelheim, the COPD Foundation, Gala Therapeutics, the NIH, Novartis, Nuvaira, Sanofi, and Sunovion; participation in Data Safety Monitoring Boards for Novartis and Medtronic with funds paid to the institution; and stock options from Altesa Biopharma and Meissa Vaccines. BS, GK, and MKS are former employees of Parexel International. SS is an employee of Parexel International, which was funded by AstraZeneca to conduct this analysis. EdN is a former employee of AstraZeneca and previously held stock and/or stock options in the company. UH is an employee of AstraZeneca and holds stock and/or stock options in the company.

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Additional file1: table s1..

Search strategies. Table S2. List of included studies with linked publications. Table S3. Study characteristics across the 76 included studies. Table S4. Clinical characteristics of the patients assessed across the included studies.

Additional file 2: Fig. S1.

Sex (male vs female) as a risk factor for moderate-to-severe exacerbations. Fig. S2. Sex (male vs female) as a risk factor for severe exacerbations.

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Hurst, J.R., Han, M.K., Singh, B. et al. Prognostic risk factors for moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease: a systematic literature review. Respir Res 23 , 213 (2022). https://doi.org/10.1186/s12931-022-02123-5

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Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades

• Antonio Messina 1 , 2 ,
• Lorenzo Calabrò 1 ,
• Luca Pugliese 1 ,
• Aulona Lulja 1 ,
• Alexandra Sopuch 1 ,
• Daniela Rosalba 3 ,
• Emanuela Morenghi 1 , 2 ,
• Glenn Hernandez 4 ,
• Xavier Monnet 5 , 6 , 7 &
• Maurizio Cecconi 1 , 2  

Critical Care volume  26 , Article number:  186 ( 2022 ) Cite this article

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Introduction

Fluid challenges are widely adopted in critically ill patients to reverse haemodynamic instability. We reviewed the literature to appraise fluid challenge characteristics in intensive care unit (ICU) patients receiving haemodynamic monitoring and considered two decades: 2000–2010 and 2011–2021.

We assessed research studies and collected data regarding study setting, patient population, fluid challenge characteristics, and monitoring. MEDLINE, Embase, and Cochrane search engines were used. A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in predefined haemodynamic variables above a predetermined threshold.

We included 124 studies, 32 (25.8%) published in 2000–2010 and 92 (74.2%) in 2011–2021, overall enrolling 6,086 patients, who presented sepsis/septic shock in 50.6% of cases. The fluid challenge usually consisted of 500 mL (76.6%) of crystalloids (56.6%) infused with a rate of 25 mL/min. Fluid responsiveness was usually defined by a cardiac output/index (CO/CI) increase ≥ 15% (70.9%). The infusion time was quicker (15 min vs 30 min), and crystalloids were more frequent in the 2011–2021 compared to the 2000–2010 period.

Conclusions

In the literature, fluid challenges are usually performed by infusing 500 mL of crystalloids bolus in less than 20 min. A positive fluid challenge response, reported in 52% of ICU patients, is generally defined by a CO/CI increase ≥ 15%. Compared to the 2000–2010 decade, in 2011–2021 the infusion time of the fluid challenge was shorter, and crystalloids were more frequently used.

Fluid administration in the intensive care unit (ICU) is one of the most common and disputed interventions triggered at the bedside by several clinical variables [ 1 , 2 ].

Fluid therapy aims to increase stroke volume (SV) and cardiac output (CO) to optimise systemic blood flow and tissue perfusion. As with any therapeutic intervention, the final clinical effect elicited may vary because of a complex interplay between the patient's intrinsic conditions and the therapy itself.

Fluid responsiveness can occur only if both ventricles work on the ascending, steep part of the Frank–Starling curve, i.e. in cases where CO is preload dependent [ 3 , 4 ]. Preload dependency is assessed using a diagnostic test performed by infusing a fixed aliquot of fluid, the fluid challenge [ 5 , 6 , 7 ]. From a clinical perspective, this approach also allows titration of fluid administration (when the patient becomes no longer responsive to the fluid challenge) and reduces the risk of fluid overload, which worsens the outcome of ICU patients [ 8 , 9 ].

Several variables defining the characteristics of the fluid challenge have been further investigated in studies adopting continuous haemodynamic monitoring, showing that the amount of fluids given, the rate of administration, and the threshold adopted to define fluid responsiveness impact the outcome of a fluid challenge [ 10 , 11 , 12 ]. Moreover, despite conflicting results on shock reversal efficacy between crystalloids and colloids, crystalloids are now recommended as the first-line fluid type in patients with septic shock, being inexpensive and widely available. Also, the administration of colloids compared to crystalloids has not demonstrated any clear benefit in the literature [ 13 , 14 ].

However, neither the nature, mode of administration, and method to assess the effectiveness of the fluid challenge are standardised in current clinical practice, and the definition of fluid challenge responsiveness is also variable among studies [ 15 , 16 , 17 , 18 ].

Whether or not these findings have modified the modalities of fluid challenge and the definition of fluid responsiveness in published studies is uncertain. To address this issue, we systematically reviewed existing literature from the year 2000. We appraised the characteristics of fluid challenges in critically ill patients (i.e., amount and kind of fluid administration, time of infusion, hemodynamic variables, and thresholds for fluid responsiveness) enrolled in research studies receiving continuous haemodynamic monitoring and assessed the relationship between the reported fluid responsiveness and predefined independent variables. Secondarily, we compared data from studies published in 2011–2021 versus those published in 2000–2010.

Material and methods

We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocols (PRISMA-P) guidelines (Additional file 1 : Table S1). The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in November 2021 (CRD42021284761).

Search strategy

A systematic literature search was performed, including the following databases: PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials register. The following keywords and their related MeSh terms were used: “fluid challenge”, “fluid responsiveness”, “stroke volume variation”, “pulse pressure variation”, “dynamic indices OR indexes”, “passive leg raising”, OR “passive leg raising test”, “functional haemodynamic test OR tests”. Included papers were also examined to identify other studies of interest missed during the primary search.

Study selection and inclusion criteria

Articles enrolling at least 20 adult critically ill patients, written in English and published from 1st January 2000 to 31st December 2021 in indexed scientific journals, were considered. Editorials, commentaries, letters to the editor, opinion articles, reviews, and meeting abstracts were excluded. Studies enrolling paediatric or obstetric populations were excluded. References of selected papers, review articles, commentaries, and editorials on this topic were also reviewed to identify other studies of interest missed during the primary search. When multiple publications of the same research group/centre described potentially overlapping cohorts, the most recent publications were selected.

A fluid challenge was defined as an infusion of a definite quantity of fluid (expressed as a volume in mL or ml/kg) in a fixed time (expressed in minutes), whose outcome was defined as a change in one of the following haemodynamic variables above a predetermined threshold: CO, cardiac index (CI), SV, SV index (SVI), or surrogate of SV, i.e., velocity–time integral (VTI) in the left ventricular outflow tract and aortic blood flow (ABF), as assessed by transthoracic, transoesophageal echocardiography or oesophageal Doppler. We included studies adopting both a specific (i.e., Ringer lactate, saline, etc.) and a broad definition (i.e., crystalloids, colloids, etc.) of the fluid used for the fluid challenge. Studies adopting changes in systemic arterial pressure to define fluid responsiveness were excluded. Finally, we considered the predefined clinical reasons and triggers to start fluid challenge infusion.

Data extraction

Three couples of examiners independently evaluated titles and abstracts. The articles were then subdivided into three subgroups: “included” and “excluded” (if the two examiners agreed with the selection) or “uncertain” (in case of disagreement). In the case of “uncertain” classification, discrepancies were resolved by further examination performed by one of the three expert authors (A.M., X.M., or M.C.). We used a standardised electronic spreadsheet (Microsoft Excel, V 14.4.1; Microsoft, Redmond, WA) to extract data from all included studies, recording: the study setting (type of study, geographical area and time, where and when the study was carried out, and sample size), patient characteristics (gender, age, reason for admission, underlying diseases, ICU scores of severity, mode of ventilation, and inotropic/vasopressor support), criteria for haemodynamic instability, fluid challenge characteristics, pre- and post-fluid challenge haemodynamic variables. When necessary, the corresponding authors of the included studies were contacted to obtain missing data related to trial demographics, methods, and outcomes (Additional file 1 : Table S2).

Statistical analysis

Statistical analysis was conducted on the summary statistics described in the selected articles (e.g., means, medians, proportions) and, therefore, the statistical unit of observation for all the selected variables was the single study and not the patient. Due to the discrepancy between the overall patients enrolled in the trials over the two considered decaders, the comparisons were not weighted for study size.

Fluid challenge was the exposure variable, and clinical and haemodynamic characteristics were considered outcome variables. Descriptive statistics of individual studies used different statistical indicators for central tendency and variability, such as means and standard deviations (i.e., age, tidal volume, fluid responders, severity scores), whereas absolute and relative frequencies were adopted for qualitative variables. To show one indicator for the quantitative variables, we collected means with standard deviations (SD) or medians and inter-quartile ranges (IQR).

Student's t test or Mann–Whitney test in case of parametric or nonparametric distributions, respectively, were used to assess the difference in mean values between responders and non-responders.

Statistical analyses were conducted using GraphPad PRISM® 8 (GraphPad Software Inc., San Diego, CA, USA) and STATA®15 (StataCorp, College Station, TX, USA). For all comparisons, we considered p values < 0.05 significant.

The electronic search identified 3,963 potentially relevant studies. Figure  1 and Additional file 1 : Table S3 provide a detailed description of the selection process flow. After evaluating 160 full-text manuscripts, the inclusion criteria were met by 124 studies, 32 (25.8%) published in the period 2000–2010 and 92 (74.2%) in the period 2011–2021. Ten studies (8.1%) required revision by senior examiners because of disagreement regarding inclusion criteria between the initial examiners. We did not find any further relevant publications by reviewing the bibliography of the selected studies.

Flow of the studies; *Reasons for studies' exclusion are reported in the Supplementary materials

The general characteristics of the patients are reported in Table 1 . We included 6,086 patients, with a median (IQR) of 38 (30–59) patients enrolled in each study. Six studies (4.8%) [ 20 , 21 , 22 , 23 , 24 , 25 ] were retrospective, while the others were prospective. The median (IQR) period of enrolment [reported in 66 (52.8%) studies] was 12 (6–18) months. At baseline, 2,985 (49.0%) patients received norepinephrine, 179 (2.9%) dopamine, 416 (6.8%) dobutamine, and 177 (2.8%) epinephrine.

The reliability of a functional haemodynamic test in predicting fluid responsiveness was assessed in 46 (37.1%) studies. Comparing the two considered decades, no difference was found in the rate of FC administration [17 min (17–33) vs. 33 min (17–50); p  = 0.39), in the percentage of fluid responders [52% (43–67) vs. 53% (45–60); p  = 0.91], in the percentage of studies adopting crystalloids over colloids [63.6% vs. 67.9%; p  = 1.00), or in the threshold of increase in CO or surrogates adopted to define fluid responsiveness (10% over 15%) [18.2% vs. 24.1%; p  = 1.00).

Forty-four studies (35.4%) investigated the reliability of a dynamic index in predicting fluid responsiveness. Comparing the two considered decades, no differences were found in the rate of FC administration [17 min (17–25) vs. 29 min (13–33) p  = 0.42), or in the rate of fluid responders [53% (41–62) vs. 50% (44–56) p  = 0.81), or in the threshold of increase in CO or surrogates adopted to define fluid responsiveness (10% over 15%) (78.5% vs. 66.67 p  = 0.42), as compared to studies in the decade 2000–2010. On the contrary, in the decade 2010-2021 we adopted more frequently crystalloids (21.4% vs. 60.0% p  = 0.024).

Fluid challenge characteristics and haemodynamic monitoring

Overall, the included studies infused 6,333 fluid challenges. The median (IQR) proportion of fluid responders was 52 (44–62)% (Table 2 ).

In 19 studies (15.3%), the volume of the fluid challenge was reported in mL/kg, with a median (IQR) of 7 (6–8) mL/kg (Table 2 ). A fixed volume of 500 mL was administered in 95 (76.6)% of the included studies. The median (IQR) of the dispensed volume of fluid was 500 (500–500) mL, infused in a median (IQR) of 18 (11–30) min. Then, the median (IQR) infusion rate was 25 (17–33) mL/min.

CO/CI was used as target variables in 78 (62.9%) studies, while SV/SVI was used in 40 (32.2%) studies. The other six studies (4.8%) adopted SV surrogates (ABF in 4 studies and VTI in two studies). In 88 (70.9%) studies, the threshold adopted to define the fluid responsiveness was an increase of the considered variable ≥ 15% from baseline (Table 2 ).

Three studies (2.4%) [ 25 , 26 , 27 ] did not report the type of fluid used for the fluid challenge. Among the others, crystalloids were used in 68 (56.6)% studies, colloids in 52 (43.3) %, and blood in one (0.8)% (Table 2 ).

The majority of the studies [49 (39.5%)] used transpulmonary thermodilution/dye dilution calibrated haemodynamic monitoring; 22 (17.7%) studies adopted the pulmonary artery catheter monitoring. Echocardiography (either transthoracic or transoesophageal) was used in 31 (25.0)% of studies, and 5 (4.0%) used oesophageal doppler monitoring. Uncalibrated pulse wave analysis monitoring was used in the other 14 (11.2)% studies (Table 2 ). Finally, bioreactance was adopted in three studies (2.4%). Haemodynamic pre–post-fluid challenge variables in responders and non-responders populations are reported in Table 3 .

Trigger of fluid challenge administration.

Hypotension (i.e., systolic or mean arterial pressure below a fixed value or reduced by a fixed percentage from baseline) was used in 68 (62.4)% of studies. Oliguria (i.e. a drop in urine output below 0.5 mL/h for 2 or 3 consecutive hours) was used in 54 (49.5)% studies, skin mottling or peripheral hypoperfusion in 47 (43.1)% studies, tachycardia (i.e. an increase in heart rate above 100–110 beats/min) in 43 (39.4)%, the need for initiating the infusion or reducing the dose of vasoactive drugs in 41 (37.6)% studies, an increase in blood lactate in 34 (31.2)% studies, a diagnosis of sepsis/septic shock in 12 (11.0)% studies, and renal or hepatic dysfunction in seven (6.4)% studies. Fifteen studies (12.1%) did not report any trigger to start fluid challenge administration.

Comparison of publication periods 2011–2021 versus 2000–2010

The comparison between the 2000–2010 and 2011–2021 decades is reported in Table 4 . The percentage of fluid responders (52% for both the decades) and the volume infused (500 mL) were comparable. On the contrary, the infusion time was lower in the last decade (a median of 15 (10–30) min vs 30 (15–30) min, p  = 0.03). Crystalloids were used in 61.9% of studies published between 2011–2021 and 34.3% in the 2000–2010 decade ( p  = 0.007) (Figs.  2 and S1 in the Additional file 1 ).

Percentage of studies in the two decades adopting different infusion timings. Fluid challenge, fluid challenge

CO/CI was used in 67% of the studies published in 2011–2021 and in 60% of those published in 2000–2010 ( p  = 0.51). The threshold adopted was an increase in CO or surrogates ≥ 15% in 67.4% of the studies of the 2011–2021 decade and in 81.2% of the studies published in 2000–2010 ( p  = 0.17) (Additional file 1 : Figure S1).

The results of this review, including research studies investigating the fluid challenge effect in critically ill adult patients receiving haemodynamic monitoring, may be summarised as follows: 1) fluid challenge is usually performed infusing a bolus of 500 mL of fluid, most often a crystalloid, in less than 20 min; 2) the response to fluid challenge is usually defined as a CI or CO increase ≥ 15% as compared to baseline; 3) positive response to fluid challenge is reported in about 50% of ICU patients; 4) the most common trigger for fluid challenge administration is usually the occurrence of hypotension, followed by oliguria and clinical signs of hypoperfusion; 5) the comparison between the 2000–2010 and 2011–2021 decades of publication showed no difference in the percentage of fluid responders (52% on average for both the decades), the volume infused (500 ml), and the criteria defining fluid responsiveness. On the contrary, compared to the 2000–2010 decade, in the period 2011–2021, the fluid challenge infusion time was lower, and crystalloids were more frequently used.

Fluid challenge characteristics

Among the included studies, the fluid challenge usually consisted of a median volume of 500 mL administered over a 20-min period and defined as a positive response by an increase ≥ 15% of CO or surrogate. These characteristics and responsiveness definition are to be considered good practice, for the response of CO to a fluid bolus is poorly followed by the simultaneous changes in arterial pressure [ 28 , 29 ] or heart rate [ 30 ]. However, this is not the case in clinical practice, where the fluid challenge effect is often assessed by a rise in arterial blood pressure [ 16 ].

Interestingly, 500 mL was also the median volume fluid challenge used in the FENICE study (an observational study including 311 centres across 46 countries) [ 16 ], whereas a fluid challenge of 250 mL is usually adopted in high-risk surgical patients undergoing goal-directed therapy optimisation [ 31 ]. The use of large volumes for fluid challenge optimisation should be balanced to the detrimental risk of fluid overload [ 9 ], primarily if safety limits (i.e. , increase in CVP) dynamically indicate fluid non-responsiveness are rarely used [ 19 ]. Since fluid challenge volume should be at least 4 mL/kg [ 32 ], smaller fluid challenge volumes may be considered for repetitive tests.

Moreover, the FENICE study reported a median of 24 min of infusion time and a rate of 17 mL/min [ 16 ]. Hence, the volume and rate of administration seem comparable between clinical and research settings. On the contrary, the infusion time was lower in the last decade (a median of 15 min vs 30 min, p  = 0.03), indicating a trend towards the increase in the infusion rate in more recent studies. This global inception cohort study evaluated the clinical use of the fluid challenge in daily practice, whereas our review considered only research papers adopting the fluid challenge as a part of a protocol, limiting the comparison with the results of the FENICE. Moreover, in contrast with a previous metanalysis, including ICU studies up to 2014 [ 19 ], crystalloids are used in most studies. Crystalloids have been used in two-thirds of the studies from 2011 to 2021, compared to one-third from 2000 to 2010. These data indicate an alignment between research studies, recent guidelines, and metanalyses [ 13 , 14 ].

Limitations

Limitations of our review have to be considered when extrapolating the results to clinical practice. First, the present study does not report any outcome endpoints. A recent large randomised-controlled trial showed no difference in mortality rate among ICU patients receiving different fluid bolus infusion rates [ 33 ]. However, the faster rate adopted in this study (5.5 mL/min) is below the median rate found in the studies included in the present review (25 mL/min) [ 33 ]. The administration of aliquots of fluids at a slow rate should not probably be indicated as a fluid challenge. Moreover, all the included studies are research papers whose aim was to evaluate the haemodynamic changes after the fluid challenge infusion or assess the reliability of indexes or functional haemodynamic tests in predicting the response to a fluid challenge. We did not include studies on the fluid challenge clinical use in ICU patients.

Another potential source of bias is related to the different haemodynamic monitorings used to assess fluid challenge responsiveness. When considering the median cut-off value identifying responders from non-responders, the accuracy of measurement of the changes in CO, or its surrogates, is undoubtedly relevant. Additionally, the reliability of different monitorings in tracking the dynamic trends of CO may not be consistent and may be below the boundaries of accuracy and precision of the Critchley–Critchley criteria [ 34 ]. Hence, the reproducibility of CO measurements obtained by the different monitoring systems may be limited. Moreover, cut-off values and measurement techniques potentially induce heterogeneity in response to the fluid challenge administration. As confirmed, responders ranged from 23 to 100% across the included studies (Table 2 ). The use of echocardiography is associated with high proportions of fluid responders compared to other haemodynamic monitoring devices. The operator-dependent bias may affect the evaluation of SV changes after fluid challenge.

We excluded studies in which the fluid challenge response has been assessed without haemodynamic monitoring and, hence assessing changes in systemic arterial pressures, potentially limiting the whole comparability of the technique in the two considered decades. Finally, the overall number of patients enrolled in the trials of the two considered decades was considerably different. This could bias the comparisons between the two groups if weighted for study size.

This systematic review, including research studies on fluid challenge use in critically ill adult patients receiving haemodynamic monitoring, showed a positive response in 52% of the patients. This test was usually performed infusing a bolus of 500 mL fluid, more often a crystalloid, in less than 20 min, and fluid responsiveness was generally indicated as a CI or CO increase ≥ 15% compared to baseline. Fluid challenge administration is usually triggered by hypotension. In the 2011–2021, the infusion time was shorter, and crystalloids were more frequently used than in the 2000–2010 decade.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

Cardiac index

Stroke volume index

Cardiac output

Stroke volume

Intensive care unit

Central venous pressure

Velocity–time integral in the left ventricular outflow tract

Aortic blood flow

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Acknowledgements

We are thankful to Dr. Katerina Negri for the linguistic revision of this manuscript.

This work has not been funded by an external source.

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Department of Anesthesia and Intensive Care Medicine, Humanitas Clinical and Research Center—IRCCS, Via Alessandro Manzoni, 56, 20089, Rozzano, Milano, Italy

Antonio Messina, Lorenzo Calabrò, Luca Pugliese, Aulona Lulja, Alexandra Sopuch, Emanuela Morenghi & Maurizio Cecconi

Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milano, Italy

Antonio Messina, Emanuela Morenghi & Maurizio Cecconi

Università del Piemonte Orientale, Vercelli, Italy

Daniela Rosalba

Departamento de Medicina Intensiva, Facultad de Medicina, Pontificia Universidad Católica de Chile, Diagonal Paraguay 362, Santiago, Chile

Glenn Hernandez

Hôpitaux Universitaires Paris-Sud, Hôpital de Bicêtre, Medical Intensive Care Unit, Le Kremlin-Bicêtre, F-94270, Paris, France

Xavier Monnet

Université Paris-Saclay, AP-HP, Service de médecine intensive-réanimation, Hôpital de Bicêtre, Paris, France

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Contributions

AM designed the study, performed data analysis, and drafted the manuscript; EM: helped in data analysis and manuscript preparation; LC, LP, AL, AS, and DR substantially contributed to data collection and interpretation; MC, XM, and GE substantially contributed to data interpretation and manuscript draft. All the authors approved the final version of the paper and agreed to be accountable for all aspects of the work, thereby ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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Competing interests.

Dr. Messina received travel expenses and registration for meetings, congresses, and courses and lecture fees from Vygon, Edwards, Philips, and Getinge. Xavier Monnet is a member of the medical advisory board of Pulsion Medical Systems (Getinge), and has given lectures for Baxter. Prof. Cecconi is a consultant of Edwards Lifesciences (Directed Systems Consultancy).

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Supplementary Information

Additional file 1.

. Table S1. PRISMA-DTA checklist. Table S2. Extracted data in each study assessed for eligibility. Table S3. Full-text articles excluded, not fitting eligibility criteria. Table S4. Studies on functional haemodynamic tests or dynamic indexes of fluid responsiveness. Figure S1.  Characteristics of fluid challenge administration and monitoring along the considered years.

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Messina, A., Calabrò, L., Pugliese, L. et al. Fluid challenge in critically ill patients receiving haemodynamic monitoring: a systematic review and comparison of two decades. Crit Care 26 , 186 (2022). https://doi.org/10.1186/s13054-022-04056-3

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Case report article, graded exercise with motion style acupuncture therapy for a patient with failed back surgery syndrome and major depressive disorder: a case report and literature review.

• 1 Department of Acupuncture and Moxibustion, Jaseng Korean Medicine Hospital, Seoul, Republic of Korea
• 2 Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, Republic of Korea

Effective treatment of failed back surgery syndrome (FBSS) remains challenging despite urgent medical attention requirements. Depression is a contributing factor to the development and poor prognosis of FBSS, and vice versa. We report the case of a patient with FBSS and major depressive disorder (MDD) treated with graded exercise combined with motion-style acupuncture therapy (MSAT). A 53-year-old male veteran who had undergone lumbar discectomy and laminectomy with instrumented fusion was admitted to the hospital with re-current back pain and radiative pain in the left leg. The effects of failed surgery triggered MDD as a comorbidity. After a six-week routine treatment without remarkable improvement, a three-week program of graded exercise with MSAT was applied. The numeric rating scale (NRS) and short form-36 (SF-36) were used to assess low back pain with radiating leg pain, and daily functioning levels, respectively. The voluntary walking distance of the patients was measured. To analyze the therapeutic effects and other applications of the intervention, we surveyed clinical trials using MSAT or graded exercise therapy (GET). Three weeks of graded exercise with MSAT reduced physical and mental functional disabilities (SF-36, physical component: 15.0 to 37.2, mental component: 21.9 to 30.1) as well as the intensity of low back pain and/or radiative leg pain (NRS: 50 to 30). Furthermore, as the therapeutic intensity gradually increased, there was a significant corresponding increase in daily walking distance (mean daily walking distance, the first week vs. baseline, second, and third week, 3.05 ± 0.56: 2.07 ± 0.79, 4.27 ± 0.96, and 4.72 ± 1.04 km, p  = 0.04, p  = 0.02, and p  = 0.003, respectively). Three randomized controlled trials of GET were included, all showing statistically significant antidepressant effects in the diseased population. Graded exercise with MSAT may be an effective rehabilitative therapy for patients with FBSS and MDD who have impaired daily routines.

1 Introduction

Failed back surgery syndrome (FBSS) is a post-spinal surgery condition characterized by persistent or recurrent spinal pain and/or radiating pain in the lower extremities ( 1 ). The incidence of FBSS is estimated to range from 10 to 40% after lumbar laminectomy, with or without instrumented fusion ( 2 ). Recently, owing to the increased demand for lumbar surgeries to treat degenerative spinal diseases, that is, an approximately 140% increase from 2004 to 2015 in the United States and 2-fold increase from 1997 to 2018 in Finland, FBSS requires medical attention ( 3 , 4 ). Patients with FBSS exhibit debilitated mental and physical functions and experience a lower health-related quality of life (QoL) than patients with cancer or stroke ( 5 ). The estimated annual cost of medical and productivity losses ranges from US $22,403 to US $26,170 per patient in Washington State ( 6 ).

Factors contributing to the development of FBSS include recurrent spinal disease, postoperative infection, nerve injury, and psychological disorders such as depression ( 1 ). Psychiatric problems are frequently encountered in cases of medically unexplainable pain with a challenging pathophysiology. Patients with FBSS have a significantly higher risk of developing mental disorders ( 7 ). According to the National Inpatient Sample database, the incidence of comorbid depression in hospitalized patients with FBSS was estimated to be 23% in 2015, and this was dominant in the working-age population ( 8 ). Moreover, chronic pain and mood disorders mutually contribute to a poor prognosis ( 9 ). Given the absence of an established treatment for FBSS accompanied by the unexplainable pain, not even with depression, the development of valid therapeutic approaches for FBSS with depressive disorder is imperatively required.

Acupuncture and exercise therapy are commonly recommended as effective non-pharmacological treatments for chronic low back pain (LBP) ( 10 ). The mechanism of pain relief provided by acupuncture involves neuronal modulation within the central nervous system (CNS) through peripheral stimuli ( 11 ). A modification of acupuncture, motion-style acupuncture therapy (MSAT), wherein acupuncture is combined with coordinated motion, demonstrated a decent analgesic effect on chronic LBP in spinal degenerative disorders such as herniated intervertebral disc (HIVD) ( 12 , 13 ). MSAT reinforces the stimuli to invade tissues using the targeted muscles. In contrast, graded exercise therapy (GET) is a type of physical training in which the intensity of exercise is gradually increased ( 14 ). GET strengthens physical capacity and provides psychological encouragement by demonstrating objective improvements in patient performance ( 15 ). GET has been shown to be effective in ameliorating the conditions of patients with cancer with comorbid mental disabilities such as depression, anxious mood, and catastrophizing ( 16 ). The respective therapeutic effects of MSAT and exercise for LBP or depressive mood are widely recognized; however, the clinical application and synergies of combining these treatments are novel for pain or mental disorders. Considering the pain-relief effect and neuronal activity improvement provided by acupuncture, we hypothesized that MSAT with simultaneous GET would improve both physical and mental health in chronic pain with depressive disorder.

Herein, we evaluated the effect of GET with MSAT in a patient with FBSS and major depressive disorder (MDD). We also undertook a literature review of clinical trials that used MSAT or GET for depressive mood therapy in a diseased population to corroborate the findings of the case study and further clinical applicability.

2 Case presentation

2.1 patient characteristics and medical history.

A 53-year-old Asian male veteran was admitted to Jaseng Hospital of Korean Medicine on October 7, 2022, presenting complaints of LBP and numbness in the left shin and hallux, which initially manifested 3 years prior. His anthropometric measurements include a height of 168.3 cm, weight of 65.2 kg, and a body mass index (BMI) of 23.0, positioning him on the border between normal and overweight classifications. Over the past 3 years since the onset of pain, he has maintained a sedentary lifestyle, engaging in less than 30 min of walking per day. He adheres to non-smoking and non-drinking habits and reports no comorbidities or significant familial history of underlying diseases. The range of motion (ROM) of the lumbar spine was limited only in flexion/extension, measuring 70/10 degrees respectively, and a negative straight leg raise test was observed. The blood and urine analyses conducted upon admission, which encompassed a complete blood count, glucose/lipid metabolic panel, liver and kidney function tests, and inflammatory markers, did not reveal any remarkable findings.

In his medical history, the patient had been diagnosed with L4–5 HIVD and had undergone discectomy and laminectomy with instrumented fusion in September 2021. Before diagnosis and surgery, he received no treatment other than arbitrary analgesic administration when the pain was severe. Although the surgery was successful with no abnormal findings on magnetic resonance imaging (MRI) or computed tomography (CT), the patient had no symptomatic changes in the lower back or lower extremities ( Figure 1B ). Subsequently, he had to be discharged from the army because of disturbance in his activities of daily living, which had become strikingly worse than before becoming diseased. Moreover, following two ineffective functional intramuscular stimulation (FIMS) treatments, the patient developed helplessness and hopelessness. This triggered depression, manifesting as sleep disturbance, reduced appetite, pessimism regarding his symptoms, and a subsequent attempted suicide. Later that year, he was diagnosed with MDD. Four admissions for integrative medicine treatment, before and after the diagnosis of MDD, did not indicate any pain management strategies ( Figure 1A ).

Figure 1 . Timeline of the patient’s medical history. (A) Timeline of the medical events between the onset of the pain and the current treatment period. Narrative demonstrations of the timeline are in the boxes. (B) Radiological images of the lumbar spine (a: lateral view of X-ray image, b: Sagittal section of T2-weighted magnetic resonance image). Adm, admission; Dx, diagnosis; FIMS, functional intramuscular stimulation; HIVD, herniated intervertebral disc; IMT, integrative medicine treatment; MDD, major depressive disorder; MRI, magnetic resonance imaging; MSAT, motions style acupuncture therapy; Tx, treatment.

2.2 Diagnosis and treatment

The diagnosis of FBSS was determined based on the persistent LBP with left radiative pain and numbness that existed despite surgery being performed in 2021. Furthermore, MDD was diagnosed in accordance with the Diagnostic and Statistical Manual of mental disorders-5 ( 17 ).

Routine treatments, as standardized by practice guideline ( 18 ), included acupuncture with electronic stimulus, pharmacopuncture, herbal medicine, analgesics, and psychopharmacotherapy which were prescribed and administered, since his admission in October 2022, by the psychiatric clinics that had confirmed the diagnosis of MDD ( Supplementary Table 1 ). Since the 6-week routine treatment did not provide remarkable improvement, graded exercise with MSAT was additionally performed after excluding analgesics from the routine treatment. It was prospectively employed with the expectation of curative effects on debilitating pain and depressive mood by referring to its successful application in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) ( 19 ).

MSAT is a physical restoration technique performing the specific movements with needles inserted into the muscles associated with restricted motion ( 12 ). The treatment method used in this case combines the characteristics of MSAT, usually employed as a one-off treatment, with GET, which gradually increases the distance and weight. The acupoints utilized were both sides of LR3, ST36, and BL25. These points were chosen to stimulate muscles associated with walking pain (BL25: erector spinae, ST36: tibialis anterior) as well as brain activities related to pain perception and emotional processing (LR3) ( 20 ). Needles measuring 0.25 × 30 (DongBang Co., Seoul, Korea) were used. With the needles retained at the acupoints, the patient was instructed to walk at a pace of one step per second, while carrying 0–2 sandbags, each weighing 800 g. ( 21 ). Exercise was performed on weekdays for 3 weeks. The number of exercise sets (50 m per set) and sandbags were gradually increased based on the patient’s exercise performance under the physician’s judgment. The rest intervals between sets are 30 s.

2.3 Course of symptom and physical performance

The numeric rating scale (NRS) for LBP and radiating leg pain was recorded at baseline and every end of weekly treatments. Also, daily functioning levels was assessed with short form-36 (SF-36) at baseline and the end of the intervention ( 22 ). In addition, spontaneous daily walking distances, except for intervention-associated steps, were measured using a Samsung Health Pedometer (Samsung Electronics Co., Suwon, Korea).

As shown in Figure 2A , 3 weeks of graded exercise with MSAT reduced the intensity of LBP and radiative leg pain (NRS: 50 to 30), as well as improved both physical and mental health (SF-36, physical component: 15.0 to 37.2; mental component: 21.9 to 30.1). Furthermore, the physical function of the SF-36, which includes general activities of daily living including walking, climbing stairs, and carrying objects, showed improvement. However, his emotional state, particularly in feeling blue, nervous, and worn out, still persisted, as evidenced by the SF-36 mental component scores.

Figure 2 . Course of symptoms. (A) Changes in low back pain (LBP), leg pain, physical and mental health scores, measured using the numeric rating scale (NRS) and Short Form-36 (SF-36), respectively. (B) Mean daily walking distances were calculated at baseline (Week 0, before the intervention) and the first to third week during which the intervention was applied, with gradually increased exercise intensity. # p  < 0.05, compared with baseline. * p  < 0.05; ** p  < 0.01 compared with the first week. Mann–Whitney U test was used to analyze statistical significance.

The intensity of the intervention was gradually escalated. During the initial week of treatment, the patient executed two sets (100 m) daily without the use of sandbags. Subsequently, in the second week, the regimen progressed to three sets with the addition of one sandbag (800 g), and by the third week, the patient advanced to four sets while incorporating two sandbags.

Similarly, the vitality and physical function of the patient improved as daily walking distance increased. An immediate increase in the distance was shown in the first week (3.05 ± 0.56 km compared to that of the previous week at 2.07 ± 0.79 km, p  = 0.04). This improving pattern was maintained in the following 2 weeks as well (4.27 ± 0.96 and 4.72 ± 1.04 km compared to the distance in the first week, p  = 0.02 and p  = 0.003, respectively) in accordance with gradually intensified exercise ( Figure 2B ). No adverse events were observed during the treatment.

2.4 Literature review

A literature survey was conducted using a single database: PubMed, up to December 2024, to identify clinical trials that employed MSAT or GET to treat depressive mood as a symptom in diseased populations. The inclusion criteria were as follows: (1) studies following a randomized controlled trial (RCT) design and assessed the effects of MSAT or GET, (2) studies being conducted on participants who were diseased adults, and (3) studies that evaluated changes in depressive mood using a relevant measuring tool. The search term used was “(motion style acupuncture or graded exercise therapy) and (depression) and (randomized controlled trial),” and references were screened by examining their titles, abstracts, and full texts.

Out of the total of 123 surveyed initial articles, none included RCTs assessing the MSAT for its antidepressant effect. Consequently, three RCTs with GET were reviewed, and the characteristics of the trials are summarized in Table 1 . Two RCTs were conducted on patients with ME/CFS and presented statistically significant improvements in depressive mood and fatigue following therapy ( 23 , 25 ). The antidepressant effect of GET was also demonstrated in another RCT that included patients with chronic neck pain ( 24 ).

Table 1 . Characteristics of the studies in the literature review.

3 Discussion

Pain commonly accompanies depressive symptoms ( 26 ). Greater pain severity and refractory treatment outcomes are associated with more depressive symptoms and worse depression outcomes ( 27 ). In our case, the patient had a negative and hopeless mood, exacerbated by impairments on his daily living, such as restricted mobility, driven by ineffective therapeutic interventions. This involved the conservative and symptomatic management for medically unexplainable pain he had been undergoing without abnormal findings on MRI or CT. Accumulating evidence suggests that spinal cord stimulation can reduce pain and improve physical function in patients with FBSS but would not affect mental health ( 28 ). Despite 1.5 months of routine care, including paravertebral electroacupuncture, depressive symptoms and pain persisted in our patient ( Supplementary Table S1 ). However, we demonstrated how we used GET and MSAT to improve pain outcomes as well as physical and mental function in a patient with FBSS and MDD.

Acupuncture is recommended as an effective nonpharmacological intervention for the treatment of chronic LBP ( 10 ). Needling of abnormally strained muscles, known as trigger points, can ameliorate spasticity and pain in patients with LBP ( 29 ). MSAT reinforces the stimulus quantity of acupuncture by moving the needled muscles. It promotes the pain-relief effect of therapy such that the patient gradually expands their limited ROM, leading to restored physical function ( 13 ). The analgesic effect of MSAT in this case, which is not achieved through conventional acupuncture, may arise from the release of instrumented surgery-derived hyper-strained tissues by activating muscles involved in gait cycles. The selected acupoints, BL25 and ST36, were strategically chosen due to their proximity to primary pain regions and their involvement in locomotion. Additionally, the pain regulation effect of acupuncture includes the modulation of neuronal activity in the CNS ( 11 ). The peripheral stimulus-derived opioids 5-hydroxytryptamine (5-HT) and norepinephrine in the CNS are believed to regulate inflammatory and neuropathic pain ( 30 , 31 ). A study using electroencephalography suggested that pain improvement following electrocutaneous treatment in patients with FBSS was associated with increased cerebral activity, primarily in the anterior cingulate gyrus, which participates in pain and emotion processing ( 32 , 33 ). Likewise, the acupoint LR3 employed in this case is recognized for its modulatory effects on pain perception and emotional functions ( 20 ). By increasing the peripheral stimulus, MSAT may provide a greater analgesic effect with neuronal modulation in the CNS than conventional acupuncture therapy ( Figure 2A ).

Exercise has been used in musculoskeletal reinforcement and psychological therapy ( 15 ). Regarding chronic pain, exercise therapy is a nonpharmacological and noninvasive approach recommended by the Centers for Disease Control and Prevention ( 34 ). Activation of the deep trunk muscles by exercise and performing of complex functional tasks is recommended as an effective noninvasive treatment for chronic LBP ( 35 ). In our patient, exercise with MSAT focused on the trunk muscles via acupuncture and slow walking while maintaining the body’s balance. Gradually increasing the intensity and repeating the processes provided cardiovascular training and muscle strengthening. In addition, aerobic exercise has been shown to have a positive mood regulation effect in patients with depression ( 36 ). Cardiovascular exercise is believed to promote 5-HT metabolism in the CNS and reconfigure the brain structure in patients with depression, thereby improving neuroprocessing and delaying cognitive degradation ( 37 ). Therefore, the graded exercise technique used may have contributed to mood regulation and pain control in our case ( Figure 2A ).

During the exercise, the physician closely guided and corrected the posture of the patient in a step-by-step manner and encouraged him to perform more tasks by demonstrating the results of what had been achieved objectively. Thus, the physician provided not only exercise feedback but also mental support. Cognitive behavior therapy, a type of mental support intervention, has been applied to chronic pain, including LBP, in which aberrant pain perception caused by heightened interoceptive awareness is a common clinical feature ( 38 , 39 ). Likewise, the GET also has psychological benefits as it provides patients with confidence through a gradual increase in physical performance. In this context, cognitive behavior therapy and GET are recommended interventions for debilitating mental symptoms such as those of in ME/CFS ( 19 ). Therefore, it can be suggested that the mental-supportive features of graded exercise with MSAT might have motivated our patient to increase spontaneous activities ( Figure 2B ).

We prospectively adopted MSAT combined with GET as a therapeutic approach for a patient with FBSS and MDD, expecting amelioration of the low mood and pain. As a positive outcome was observed in this case, we analyzed its clinical utility by surveying RCTs to evaluate the antidepressant effects of MSAT or GET in diseased participants. All three RCTs we reviewed employed GET; the results demonstrated statistically significant improvements in the patients’ depression scores on the Beck Depression Inventory (BDI) or Hospital Anxiety and Depression Scale (HADS), compared with the scores of those in the control group ( Table 1 ). Regarding the two RCTs for ME/CFS, unlike the overall positive outcomes of mental function scores in both trials, the results for physical fatigue were not aligned in the same positive direction ( 23 , 25 ). Similarly, psychological impairment was significantly improved by GET in another RCT among patients with chronic neck pain, whereas the physical function in the neck measured by the Neck Disability Index was not ( 24 ). This might be due to the immoderate application on the patient vulnerable for excision, and one adverse event of increasing pain was reported. In fact, one survey on patients with ME/CFS reported that approximately 79% of respondents experienced their health worsening due to the GET ( 40 ). This implies that the clinical adoption of the GET requires the intensity of tasks to be adjusted considering the patient’s physical capacity and the possibility of increased pain. Regarding FBSS, moderate exercise enhances daily living, strength, and fearlessness in patients ( 41 ). Therefore, we hypothesized that MSAT assisted in providing adequate exercise intensity and pain control in our patient. The results of the case study and literature review indicate that graded exercise with MSAT may offer effective rehabilitation for individuals suffering from depression induced by pain disorders, and vice versa, facilitating a resumption of their daily activities.

This case study has several limitations. First, follow-up data were not available after the patient was discharged from the hospital, which can induce uncertainty regarding therapeutic effects and its generalizability, such as the Hawthorne effect. Second, routine integrative Korean medicine treatments were used previously and simultaneously with the intervention, which could have induced synergistic therapeutic effects. Third, depression-specific scales such as the BDI or the HADS were not used for evaluating the depressive status of the patient. While our primary focus lay in functional rehabilitation utilizing the SF-36, employing measurements specialized for MDD could provide more explicit assessments of mental status. The SF-36 survey is originally intended for measuring the QoL of patients, and we employed it considering the etiological history of this case, where restrictions in daily living, closely related to QoL, resulting from failed surgery caused depression. Nonetheless, to our knowledge, this is the first report of successful treatment of FBSS and MDD, unresponsive to usual medications, by employing graded exercise with MSAT. Further, there were no adverse events noted in the patient. However, to facilitate the clinical use of this intervention, further well-designed clinical trials on its efficacy and safety are warranted.

Data availability statement

The original data presented in the study are included in the article/ Supplementary material , further inquiries can be directed to the corresponding author.

Ethics statement

The ethical review and approval of this study were waived by the Institutional Review Board of Jaseng Hospital of Korean Medicine, Seoul, Korea (IRB file No. JASENG 2023–12-002) for the study design: a single case study with literature review. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Written informed consent was obtained from the minor(s)’ legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

Author contributions

D-YK: Conceptualization, Investigation, Methodology, Visualization, Writing – original draft, Writing – review & editing. I-HH: Conceptualization, Writing – review & editing. J-YK: Supervision, Visualization, Writing – review & editing.

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Supplementary material

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmed.2024.1376680/full#supplementary-material

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Keywords: failed back surgery syndrome, major depressive disorder, rehabilitation therapy, motion-style acupuncture therapy, graded exercise therapy

Citation: Kim D-Y, Ha I-H and Kim J-Y (2024) Graded exercise with motion style acupuncture therapy for a patient with failed back surgery syndrome and major depressive disorder: a case report and literature review. Front. Med . 11:1376680. doi: 10.3389/fmed.2024.1376680

Received: 26 January 2024; Accepted: 19 March 2024; Published: 08 April 2024.

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Copyright © 2024 Kim, Ha and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Ju-Yeon Kim, [email protected]

This article is part of the Research Topic

Rehabilitation and Alternative Medicine in the Healthcare for Chronic Rheumatic Pain Disorders