difference between meta analysis and literature review

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Systematic reviews vs meta-analysis: what’s the difference?

Posted on 24th July 2023 by Verónica Tanco Tellechea

You may hear the terms ‘systematic review’ and ‘meta-analysis being used interchangeably’. Although they are related, they are distinctly different. Learn more in this blog for beginners.

What is a systematic review?

According to Cochrane (1), a systematic review attempts to identify, appraise and synthesize all the empirical evidence to answer a specific research question. Thus, a systematic review is where you might find the most relevant, adequate, and current information regarding a specific topic. In the levels of evidence pyramid , systematic reviews are only surpassed by meta-analyses.

To conduct a systematic review, you will need, among other things:

A specific research question, usually in the form of a PICO question.
Pre-specified eligibility criteria, to decide which articles will be included or discarded from the review.
To follow a systematic method that will minimize bias.

You can find protocols that will guide you from both Cochrane and the Equator Network , among other places, and if you are a beginner to the topic then have a read of an overview about systematic reviews.

What is a meta-analysis?

A meta-analysis is a quantitative, epidemiological study design used to systematically assess the results of previous research (2) . Usually, they are based on randomized controlled trials, though not always. This means that a meta-analysis is a mathematical tool that allows researchers to mathematically combine outcomes from multiple studies.

When can a meta-analysis be implemented?

There is always the possibility of conducting a meta-analysis, yet, for it to throw the best possible results it should be performed when the studies included in the systematic review are of good quality, similar designs, and have similar outcome measures.

Why are meta-analyses important?

Outcomes from a meta-analysis may provide more precise information regarding the estimate of the effect of what is being studied because it merges outcomes from multiple studies. In a meta-analysis, data from various trials are combined and generate an average result (1), which is portrayed in a forest plot diagram. Moreover, meta-analysis also include a funnel plot diagram to visually detect publication bias.

Conclusions

A systematic review is an article that synthesizes available evidence on a certain topic utilizing a specific research question, pre-specified eligibility criteria for including articles, and a systematic method for its production. Whereas a meta-analysis is a quantitative, epidemiological study design used to assess the results of articles included in a systematic-review.


DEFINITION	Synthesis of empirical evidence regarding a specific research question	Statistical tool used with quantitative outcomes of various studies regarding a specific topic
RESULTS	Synthesizes relevant and current information regarding a specific research question (qualitative).	Merges multiple outcomes from different researches and provides an average result (quantitative).

Remember: All meta-analyses involve a systematic review, but not all systematic reviews involve a meta-analysis.

If you would like some further reading on this topic, we suggest the following:

The systematic review – a S4BE blog article

Meta-analysis: what, why, and how – a S4BE blog article

The difference between a systematic review and a meta-analysis – a blog article via Covidence

Systematic review vs meta-analysis: what’s the difference? A 5-minute video from Research Masterminds:

About Cochrane reviews [Internet]. Cochranelibrary.com. [cited 2023 Apr 30]. Available from: https://www.cochranelibrary.com/about/about-cochrane-reviews
Haidich AB. Meta-analysis in medical research. Hippokratia. 2010;14(Suppl 1):29–37.

Verónica Tanco Tellechea

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difference between meta analysis and literature review

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The difference between a systematic review and a meta-analysis

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Covidence explains the difference between systematic review & meta-analysis.

Systematic review and meta-analysis are two terms that you might see used interchangeably. Each term refers to research about research, but there are important differences!

A systematic review is a piece of work that asks a research question and then answers it by summarising the evidence that meets a set of pre-specified criteria. Some systematic reviews present their results using meta-analysis, a statistical method that combines the results of several trials to generate an average result. Meta-analysis adds value because it can produce a more precise estimate of the effect of a treatment than considering each study individually 🎯.

Let’s take a look at a few related questions that you might have about systematic reviews and meta-analysis.

🙋🏽‍♂️ What are the stages of a systematic review?

A systematic review starts with a research question and a protocol or research plan. A review team searches for studies to answer the question using a highly sensitive search strategy. The retrieved studies are then screened for eligibility using the inclusion and exclusion criteria (this is done by at least two people working independently). Next, the reviewers extract the relevant data and assess the quality of the included studies. Finally, the review team synthesises the extracted study data (perhaps using meta-analysis) and presents the results. The process is shown in figure 1.

Covidence helps researchers complete systematic review quickly and easily! It supports reviewers with study selection, data extraction and quality assessment. Data exported from Covidence can be saved in Excel for reliable transfer to your choice of data analysis software or, if you’re writing a Cochrane Review, to RevMan 5.

🙋🏻‍♀️ What does 'systematic' actually mean?

In this context, systematic means that the methods used to search for and analyse the data are

transparent, reproducible and defined before searching begins. This is what differentiates a systematic review from a descriptive review that might be based on, for example, a subset of the literature that the author is familiar with at the time of writing. Systematic reviews strive to be as thorough and rigorous as possible to minimise the bias that would result from cherry-picking studies in a non-systematic way. Systematic reviews sit at the top of the evidence hierarchy because it is widely agreed that studies with rigorous methods are those best able to minimise the risk of bias on the results of the study. This is what makes systematic reviews the most reliable form of evidence (see figure 2).

🙋🏾‍♂️ Why don't all systematic reviews use meta-analysis?

Meta-analysis can improve the precision of an effect estimate. But it can also be misleading if it is performed with data that are not sufficiently similar, or with data whose methodological quality is poor (for example, because the study participants were not properly randomized). So it’s not always appropriate to use meta-analysis and many systematic reviews do not include them. Reviews that do not contain meta-analysis can still synthesise study data to produce something that has greater value than the sum of its parts.

🙋🏾‍♀️ What does meta-analysis do?

Meta-analysis produces a more precise estimate of treatment effect. There are several types of effect size and the most suitable type is chosen by the review team based on the type of outcomes and interventions under investigation. Typical effect sizes in systematic reviews are the odds ratio, the risk ratio, the weighted mean difference and the standardized mean difference. The results of a meta-analysis are displayed using a forest plot like the one in figure 3.

Some meta-analyses also include subgroup analysis or meta-regression. These techniques are used to explore a factor (for example, the age of the study participant) that might influence the relationship between the treatment and the intervention. Plans to analyse the data using these techniques should be described and justified before looking at the data, ideally at the research plan or protocol stage, to avoid introducing bias. Like meta-analysis, subgroup analysis and meta-regression are advisable only in certain circumstances.

Systematic reviewer pro-tip

Think carefully before you plan subgroup analysis or meta-regression and always ask a methodologist for advice

🙋🏼‍♀️ What are the other ways to synthesise evidence?

Systematic reviews combine study data in a number of ways to reach an overall understanding of the evidence. Meta-analysis is a type of statistical synthesis. Narrative synthesis combines the findings of multiple studies using words. All systematic reviews, including those that use meta-analysis, are likely to contain an element of narrative synthesis by summarising in words the evidence included in the review. But narrative synthesis doesn’t just describe the included studies: it also seeks to explain the gathered evidence, for example by looking at similarities and differences between the study findings and by exploring possible reasons for those similarities and differences in a systematic way. Narrative synthesis should not be confused with narrative review, which is a term sometimes used for a non-systematic review of the literature (for example in a textbook chapter) where there is no systematic attempt to address issues of bias.

There are many types of systematic review . What they all have in common is the use of transparent and reproducible methods that are defined before the search begins. There is no ‘best’ way to synthesise systematic review evidence, and the most suitable approach will depend on factors such as the nature of the review question, the type of intervention and the outcomes of interest.

Covidence is a web-based tool that saves you time at the screening, selection, data extraction and quality assessment stages of your review. It provides easy collaboration across teams and a clear overview of task status, helping you to efficiently complete your review. Sign up for a free trial today! 😀

1 Effectiveness of psychosocial interventions for reducing parental substance misuse – McGovern, R – 2021 | Cochrane Library https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012823.pub2/full . Accessed 25 March 2021

Laura Mellor. Portsmouth, UK

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Systematic Reviews and Meta-Analysis: A Guide for Beginners

Affiliation.

1 Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh. Correspondence to: Prof Joseph L Mathew, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER Chandigarh. [email protected].
PMID: 34183469
PMCID: PMC9065227
DOI: 10.1007/s13312-022-2500-y

Systematic reviews involve the application of scientific methods to reduce bias in review of literature. The key components of a systematic review are a well-defined research question, comprehensive literature search to identify all studies that potentially address the question, systematic assembly of the studies that answer the question, critical appraisal of the methodological quality of the included studies, data extraction and analysis (with and without statistics), and considerations towards applicability of the evidence generated in a systematic review. These key features can be remembered as six 'A'; Ask, Access, Assimilate, Appraise, Analyze and Apply. Meta-analysis is a statistical tool that provides pooled estimates of effect from the data extracted from individual studies in the systematic review. The graphical output of meta-analysis is a forest plot which provides information on individual studies and the pooled effect. Systematic reviews of literature can be undertaken for all types of questions, and all types of study designs. This article highlights the key features of systematic reviews, and is designed to help readers understand and interpret them. It can also help to serve as a beginner's guide for both users and producers of systematic reviews and to appreciate some of the methodological issues.

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Literature Review, Systematic Review and Meta-analysis

Literature reviews can be a good way to narrow down theoretical interests; refine a research question; understand contemporary debates; and orientate a particular research project. It is very common for PhD theses to contain some element of reviewing the literature around a particular topic. It’s typical to have an entire chapter devoted to reporting the result of this task, identifying gaps in the literature and framing the collection of additional data.

Systematic review is a type of literature review that uses systematic methods to collect secondary data, critically appraise research studies, and synthesise findings. Systematic reviews are designed to provide a comprehensive, exhaustive summary of current theories and/or evidence and published research (Siddaway, Wood & Hedges, 2019) and may be qualitative or qualitative. Relevant studies and literature are identified through a research question, summarised and synthesized into a discrete set of findings or a description of the state-of-the-art. This might result in a ‘literature review’ chapter in a doctoral thesis, but can also be the basis of an entire research project.

Meta-analysis is a specialised type of systematic review which is quantitative and rigorous, often comparing data and results across multiple similar studies. This is a common approach in medical research where several papers might report the results of trials of a particular treatment, for instance. The meta-analysis then statistical techniques to synthesize these into one summary. This can have a high statistical power but care must be taken not to introduce bias in the selection and filtering of evidence.

Whichever type of review is employed, the process is similarly linear. The first step is to frame a question which can guide the review. This is used to identify relevant literature, often through searching subject-specific scientific databases. From these results the most relevant will be identified. Filtering is important here as there will be time constraints that prevent the researcher considering every possible piece of evidence or theoretical viewpoint. Once a concrete evidence base has been identified, the researcher extracts relevant data before reporting the synthesized results in an extended piece of writing.

Literature Review: GO-GN Insights

Sarah Lambert used a systematic review of literature with both qualitative and quantitative phases to investigate the question “How can open education programs be reconceptualised as acts of social justice to improve the access, participation and success of those who are traditionally excluded from higher education knowledge and skills?”

“My PhD research used systematic review, qualitative synthesis, case study and discourse analysis techniques, each was underpinned and made coherent by a consistent critical inquiry methodology and an overarching research question. “Systematic reviews are becoming increasingly popular as a way to collect evidence of what works across multiple contexts and can be said to address some of the weaknesses of case study designs which provide detail about a particular context – but which is often not replicable in other socio-cultural contexts (such as other countries or states.) Publication of systematic reviews that are done according to well defined methods are quite likely to be published in high-ranking journals – my PhD supervisors were keen on this from the outset and I was encouraged along this path. “Previously I had explored social realist authors and a social realist approach to systematic reviews (Pawson on realist reviews) but they did not sufficiently embrace social relations, issues of power, inclusion/exclusion. My supervisors had pushed me to explain what kind of realist review I intended to undertake, and I found out there was a branch of critical realism which was briefly of interest. By getting deeply into theory and trying out ways of combining theory I also feel that I have developed a deeper understanding of conceptual working and the different ways theories can be used at all stagesof research and even how to come up with novel conceptual frameworks.”

Useful references for Systematic Review & Meta-Analysis: Finfgeld-Connett (2014); Lambert (2020); Siddaway, Wood & Hedges (2019)

Research Toolkit for Librarians Copyright © by Kathy Essmiller; Jamie Holmes; and Marla Lobley is licensed under a Creative Commons Attribution 4.0 International License , except where otherwise noted.

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Expert Commentary

The literature review and meta-analysis: 2 journalism tools you should use

Reporters can get up to date on a public policy issue quickly by reading a research literature review or meta-analysis. This article from the Education Writers Association explains how to find and use them.

Republish this article

This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License .

by Denise-Marie Ordway, The Journalist's Resource June 20, 2019

This <a target="_blank" href="https://journalistsresource.org/media/meta-analysis-literature-review/">article</a> first appeared on <a target="_blank" href="https://journalistsresource.org">The Journalist's Resource</a> and is republished here under a Creative Commons license.<img src="https://journalistsresource.org/wp-content/uploads/2020/11/cropped-jr-favicon-150x150.png" style="width:1em;height:1em;margin-left:10px;">

We’re republishing this article on research literature reviews and meta-analyses with permission from the Education Writers Association , which hired Journalist’s Resource’s managing editor, Denise-Marie Ordway, late last year to write it in her free time. Ordway is a veteran education reporter who joined the EWA’s board of directors in May.

This piece was first published on the EWA’s website . It has been slightly edited to reflect Journalist’s Resource’s editorial style.

It’s important to note that while the examples used in this piece come from the education beat, the information applies to literature reviews and meta-analyses across academic fields.

———–

When journalists want to learn what’s known about a certain subject, they look for research. Scholars are continually conducting studies on education topics ranging from kindergarten readiness and teacher pay to public university funding and Ivy League admissions.

One of the best ways for a reporter to get up to date quickly, though, is to read a study of studies, which come in two forms: a literature review and a meta-analysis.

A literature review is what it sounds like — a review of all the academic literature that exists on a specific issue or research question. If your school district or state is considering a new policy or approach, there’s no better way to educate yourself on what’s already been learned. Your news coverage also benefits from literature reviews: Rather than hunting down studies on your own and then worrying whether you found the right ones, you can, instead, share the results of a literature review that already has done that legwork for you.

Literature reviews examine both quantitative research, which is based on numerical data, and qualitative research, based on observations and other information that isn’t in numerical form. When scholars conduct a literature review, they summarize and synthesize multiple research studies and their findings, highlighting gaps in knowledge and the studies that are the strongest or most pertinent.

In addition, literature reviews often point out and explain disagreements between studies — why the results of one study seem to contradict the results of another.

For instance, a literature review might explain that the results of Study A and Study B differ because the two pieces of research focus on different populations or examine slightly different interventions. By relying on literature reviews, journalists also will be able to provide the context audiences need to make sense of the cumulative body of knowledge on a topic.

A meta-analysis also can be helpful to journalists, but for different reasons. To conduct a meta-analysis, scholars focus on quantitative research studies that generally aim to answer a research question — for example, whether there is a link between student suspension rates and academic achievement or whether a certain type of program reduces binge drinking among college students.

After pulling together the quantitative research that exists on the topic, scholars perform a systematic analysis of the numerical data and draw their own conclusions. The findings of a meta-analysis are statistically stronger than those reached in a single study, partly because pooling data from multiple, similar studies creates a larger sample.

The results of a meta-analysis are summarized as a single number or set of numbers that represent an average outcome for all the studies included in the review. A meta-analysis might tell us, for example, how many children, on average, are bullied in middle school, or the average number of points SAT scores rise after students complete a specific type of tutoring program.

It’s important to note that a meta-analysis is vulnerable to misinterpretation because its results can be deceptively simple: Just as you can’t learn everything about students from viewing their credit ratings or graduation rates, you can miss out on important nuances when you attempt to synthesize an entire body of research with a single number or set of numbers generated by a meta-analysis.

For journalists, literature reviews and meta-analyses are important tools for investigating public policy issues and fact-checking claims made by elected leaders, campus administrators and others. But to use them, reporters first need to know how to find them. And, as with any source of information, reporters also should be aware of the potential flaws and biases of these research overviews.

Finding research

The best place to find literature reviews and meta-analyses are in peer-reviewed academic journals such as the Review of Educational Research , Social Problems and PNAS (short for Proceedings of the National Academy of Sciences of the United States of America ). While publication in a journal does not guarantee quality, the peer-review process is designed for quality control. Typically, papers appearing in top-tier journals have survived detailed critiques by scholars with expertise in the field. Thus, academic journals are an important source of reliable, evidence-based knowledge.

An easy way to find journal articles is by using Google Scholar, a free search engine that indexes published and unpublished research. Another option is to go directly to journal websites. Although many academic journals keep their research behind paywalls, some provide journalists with free subscriptions or special access codes. Other ways to get around journal paywalls are outlined in a tip sheet that Journalist’s Resource , a project of Harvard’s Shorenstein Center on Media, Politics and Public Policy, created specifically for reporters.

Another thing to keep in mind: Literature reviews and meta-analyses do not exist on every education topic. If you have trouble finding one, reach out to an education professor or research organization such as the American Educational Research Association for guidance.

Sources of bias

Because literature reviews and meta-analyses are based on an examination of multiple studies, the strength of their findings relies heavily on three factors:

the quality of each included study,
the completeness of researchers’ search for scholarship on the topic of interest, and
researchers’ decisions about which studies to include and leave out.

In fact, many of the choices researchers make during each step of designing and carrying out a meta-analysis can create biases that might influence their results.

Knowing these things can help journalists gauge the quality of a literature review or meta-analysis and ask better questions about them. This comes in handy for reporters wanting to take a critical lens to their coverage of these two forms of research, especially those claiming to have made a groundbreaking discovery.

That said, vetting a review or meta-analysis can be time-consuming. Remember that journalists are not expected to be experts in research methods. When in doubt, contact education researchers for guidance and insights. Also, be sure to interview authors about their studies’ strengths, weaknesses, limitations and real-world implications.

Study quality, appropriateness

If scholars perform a meta-analysis using biased data or data from studies that are too dissimilar, the findings might be misleading — or outright incorrect. One of the biggest potential flaws of meta-analyses is the pooling of data from studies that should not be combined. For example, even if two individual studies focus on school meals, the authors might be looking at different populations, using different definitions and collecting data differently.

Perhaps the authors of the first study consider a school meal to be a hot lunch prepared by a public school cafeteria in Oklahoma, while the research team for the second study defines a school meal as any food an adult or child eats at college preparatory schools throughout Europe. What if the first study relies on data collected from school records over a decade and the second relies on data extracted from a brief online survey of students? Researchers performing a meta-analysis would need to make a judgment call about the appropriateness of merging information from these two studies, conducted in different parts of the world.

Search completeness

Researchers should explain how hard they worked to find all the research that exists on the topic they examined. Small differences in search strategies can lead to substantial differences in search results. If, for instance, search terms are too vague or specific, scholars might miss some compelling studies. Likewise, results may vary according to the databases, websites and search engines used.

Decisions about what to include

Scholars are not supposed to cherry-pick the research they include in literature reviews and meta-analyses. But decisions researchers make about which kinds of scholarship make the cut can influence conclusions.

Should they include unpublished research, such as working papers and papers presented at academic conferences? Does it make sense to exclude studies written in foreign languages? What about doctoral dissertations? Should researchers only include studies that have been published in journals, which tend to favor research with positive findings? Some scholars argue that meta-analyses that rely solely on published research offer misleading findings.

Other factors to consider

As journalists consider how the process of conducting literature reviews and meta-analyses affects results, they also should look for indicators of quality among the individual research studies examined. For example:

Sample sizes: Bigger samples tend to provide more accurate results than smaller ones.
Study duration: Data collected over several years generally offer a more complete picture than data gathered over a few weeks.
Study age: In some cases, an older study might not be reliable anymore. If a study appears to be too old, ask yourself if there is a reason to expect that conditions have changed substantially since its publication or release.
Researcher credentials: A scholar’s education, work experience and publication history often reflect their level of expertise.

About The Author

Denise-Marie Ordway

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A systematic review collects and analyzes all evidence that answers a specific research question. In a systematic review, a question needs to be clearly defined and have inclusion and exclusion criteria. In general, specific and systematic methods selected are intended to minimize bias. This is followed by an extensive search of the literature and a critical analysis of the search results. The reason why a systematic review is conducted is to provide a current evidence-based answer to a specific question that in turn helps to inform decision making. Check out the Centers for Disease Control and Prevention and Cochrane Reviews links to learn more about Systematic Reviews.

A systematic review can be combined with a meta-analysis. A meta-analysis is the use of statistical methods to summarize the results of a systematic review. Not every systematic review contains a meta-analysis. A meta-analysis may not be appropriate if the designs of the studies are too different, if there are concerns about the quality of studies, if the outcomes measured are not sufficiently similar for the result across the studies to be meaningful.

Centers for Disease Control and Prevention. (n.d.). Systematic Reviews . Retrieved from https://www.cdc.gov/library/researchguides/sytemsaticreviews.html

Cochrane Library. (n.d.). About Cochrane Reviews . Retrieved from https://www.cochranelibrary.com/about/about-cochrane-reviews

Source: Kysh, Lynn (2013): Difference between a systematic review and a literature review. [figshare]. Available at: https://figshare.com/articles/Difference_between_a_systematic_review_and_a_literature_review/766364

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Research Process

Systematic Literature Review or Literature Review?

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As a researcher, you may be required to conduct a literature review. But what kind of review do you need to complete? Is it a systematic literature review or a standard literature review? In this article, we’ll outline the purpose of a systematic literature review, the difference between literature review and systematic review, and other important aspects of systematic literature reviews.

What is a Systematic Literature Review?

The purpose of systematic literature reviews is simple. Essentially, it is to provide a high-level of a particular research question. This question, in and of itself, is highly focused to match the review of the literature related to the topic at hand. For example, a focused question related to medical or clinical outcomes.

The components of a systematic literature review are quite different from the standard literature review research theses that most of us are used to (more on this below). And because of the specificity of the research question, typically a systematic literature review involves more than one primary author. There’s more work related to a systematic literature review, so it makes sense to divide the work among two or three (or even more) researchers.

Your systematic literature review will follow very clear and defined protocols that are decided on prior to any review. This involves extensive planning, and a deliberately designed search strategy that is in tune with the specific research question. Every aspect of a systematic literature review, including the research protocols, which databases are used, and dates of each search, must be transparent so that other researchers can be assured that the systematic literature review is comprehensive and focused.

Most systematic literature reviews originated in the world of medicine science. Now, they also include any evidence-based research questions. In addition to the focus and transparency of these types of reviews, additional aspects of a quality systematic literature review includes:

Clear and concise review and summary
Comprehensive coverage of the topic
Accessibility and equality of the research reviewed

Systematic Review vs Literature Review

The difference between literature review and systematic review comes back to the initial research question. Whereas the systematic review is very specific and focused, the standard literature review is much more general. The components of a literature review, for example, are similar to any other research paper. That is, it includes an introduction, description of the methods used, a discussion and conclusion, as well as a reference list or bibliography.

A systematic review, however, includes entirely different components that reflect the specificity of its research question, and the requirement for transparency and inclusion. For instance, the systematic review will include:

Eligibility criteria for included research
A description of the systematic research search strategy
An assessment of the validity of reviewed research
Interpretations of the results of research included in the review

As you can see, contrary to the general overview or summary of a topic, the systematic literature review includes much more detail and work to compile than a standard literature review. Indeed, it can take years to conduct and write a systematic literature review. But the information that practitioners and other researchers can glean from a systematic literature review is, by its very nature, exceptionally valuable.

This is not to diminish the value of the standard literature review. The importance of literature reviews in research writing is discussed in this article . It’s just that the two types of research reviews answer different questions, and, therefore, have different purposes and roles in the world of research and evidence-based writing.

Systematic Literature Review vs Meta Analysis

It would be understandable to think that a systematic literature review is similar to a meta analysis. But, whereas a systematic review can include several research studies to answer a specific question, typically a meta analysis includes a comparison of different studies to suss out any inconsistencies or discrepancies. For more about this topic, check out Systematic Review VS Meta-Analysis article.

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Secondary Research is when researchers collect lots of research that has already been published on a certain subject. They conduct searches in databases, go through lots of primary research articles, and analyze the findings in those pieces of primary research. The goal of secondary research is to pull together lots of diverse primary research (like studies and trials), with the end goal of making a generalized statement. Primary research can only make statements about the specific context in which their research was conducted (for example, this specific intervention worked in this hospital with these participants), but secondary research can make broader statements because it compiled lots of primary research together. So rather than saying, "this specific intervention worked at this specific hospital with these specific participants, a piece of secondary research can say, "This intervention works at hospitals that serve this population."

Systematic Reviews are a kind of secondary research. The creators of systematic reviews are very intentional about their inclusion/exclusion criteria, or which articles they'll include in their review and the goal is to make a generalized statement so other researchers can build upon the practices or interventions they recommend. Use the chart below to understand the differences between a systematic review and a literature review.

Check out the video below to watch the Nursing and Health Sciences librarian describe the differences between primary and secondary research.

Literature Review	Systematic Review	Meta-Analysis

"Literature Reviews and Systematic Reviews: What Is the Difference?" This article explains in depth the differences between Literature Reviews and Systematic Reviews. It is from the journal RADIOLOGIC TECHNOLOGY, Nov/Dec 2013, v. 85, #2. It is one to which Bell Library subscribes and meets copyright clearance requirements through our subscription to CCC.
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InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-.

InformedHealth.org [Internet].

In brief: what are systematic reviews and meta-analyses.

Last Update: September 8, 2016 ; Next update: 2024.

Individual studies are often not big and powerful enough to provide reliable answers on their own. Or several studies on the effects of a treatment might come to different conclusions. In order to find reliable answers to research questions, you therefore have to look at all of the studies and analyze their results together.

Systematic reviews summarize the results of all the studies on a medical treatment and assess the quality of the studies. The analysis is done following a specific, methodologically sound process. In a way, it’s a “study of studies.” Good systematic reviews can provide a reliable overview of the current knowledge in a certain area.

They are normally done by teams of authors working together. The authors are usually specialists with backgrounds in medicine, epidemiology, medical statistics and research.

How are systematic reviews performed?

Systematic reviews can only provide reliable answers if the studies they are based on are searched for and selected very carefully. The individual steps needed before they can be published are usually quite complex.

Research question: First of all, the researchers have to decide exactly what question they want to find the answer to. Which treatment should be looked at in which group of people, and what should it be compared with? What should be measured? This set of key questions is also referred to as the PICO framework. PICO stands for P opulation (patient group), I ntervention (the treatment or diagnostic test under investigation), C ontrol (comparison group) and O utcome (variable to be measured). The research question also determines which criteria to use when selecting studies to include in the review – for instance, only certain types of studies .
Research : Once they know what they are looking for, the researchers have to search as thoroughly and comprehensively as possible for all the studies that might help answer the question. This can easily add up to as many as several hundred studies. Searches for studies are usually done in international databases. Most study results are published online and in English. The relevant information is filtered out using sophisticated methods. The researchers often try to find any unpublished data by contacting and asking other scientists, looking through lists of sources used in other publications, and sometimes even by looking at conference transcripts. One big problem is that some studies are never published. Compared to studies in which treatments are found to have positive outcomes, studies that don’t find any benefits are often published later or never published at all. As a result, the studies that are found and included in reviews might make a treatment seem better than it really is. This kind of systematic bias is also known as “publication bias.”
Selection: The suitability of every study that is found has to be checked using very specific pre-defined criteria. Studies that do not fulfill the criteria are not included in the review. The suitability of a study is usually assessed by at least two researchers who go through all the studies separately and then compare and discuss their conclusions. This is done in order to try to avoid including unsuitable studies in the review.
Assessment: The studies that fulfill all the inclusion criteria are carefully assessed . The analysis should provide a comprehensive overview of what is known, and what isn’t known, about the topic in question.
Peer review: The researchers provide a detailed report of the steps they took, their research methods and what they found. A draft version is critically assessed and commented on by experts. This is called "peer reviewing."
Publication: If the systematic review “passes” the peer review, it can be published in scientific journals and relevant databases. One important source of systematic reviews is the “Cochrane Library” database. It is run by the Cochrane Collaboration – an international network of researchers who have specialized in producing systematic reviews.
Keeping the information up-to-date: In order to stay up-to-date, systematic reviews must be updated regularly.
What is a meta-analysis?

Sometimes the results of all of the studies found and included in a systematic review can be summarized and expressed as an overall result. This is known as a meta-analysis. The overall outcome of the studies is often more conclusive than the results of individual studies.

But it only makes sense to do a meta-analysis if the results of the individual studies are fairly similar (homogeneous). If there are big differences between the results, there are likely to be important differences between the studies. These should be looked at more closely. It is then sometimes possible to split the participants into smaller subgroups and summarize the results separately for each subgroup.

Bucher H.C. Kritische Bewertung von Studien zu diagnostischen Tests. In: Kunz R, Ollenschläger G, Raspe H, Jonitz G, Donner-Banzhoff N (eds.): Lehrbuch evidenzbasierte Medizin in Klinik und Praxis. Cologne: Deutscher Ärzte-Verlag; 2007.
Cochrane Germany. Systematische Übersichtsarbeiten der Cochrane Library.
Greenhalgh T. Einführung in die Evidence-based Medicine: kritische Beurteilung klinischer Studien als Basis einer rationalen Medizin. Bern: Huber; 2003.
Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Glossar . [ PubMed : 23101074 ]
Ziegler, A, Lange S, Bender R. Systematische Übersichten und Meta-Analysen. Dtsch Med Wochenschr 2007; 132: e48-e52. [ PubMed : 17530598 ]

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Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.

Cite this Page InformedHealth.org [Internet]. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. In brief: What are systematic reviews and meta-analyses? [Updated 2016 Sep 8].
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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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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.

Prevent plagiarism. Run a free check.

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.

Scribbr slides are free to use, customize, and distribute for educational purposes.

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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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Open access
Published: 13 November 2023

Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis

Neng Wang 1 na1 ,
Sike He 2 na1 ,
Yu Zheng 1 &
Lichun Wang 1

BMC Gastroenterology volume 23 , Article number: 388 ( 2023 ) Cite this article

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Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear.

A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety.

Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90–1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88–1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58–1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81–1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29–0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period.

TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.

Peer Review reports

Introduction

Acute-on-chronic liver failure (ACLF) occurs in patients with chronic liver disease and is characterized by acute liver injury, such as jaundice and coagulopathy [ 1 ]. The global prevalence of ACLF is higher than 30%, and the highest prevalence in South Asia is approximately 65% in patients with decompensated cirrhosis [ 2 ]. The deaths of these patients within 3 months were mainly due to multisystem organ failure and severe infection [ 3 , 4 ]. In Asia, ACLF is mainly caused by hepatitis B virus (HBV) infection and has a mortality rate of 50–90% [ 1 , 5 ]. Liver transplantation is considered the ultimate treatment for ACLF. Unfortunately, liver transplantation is limited by a lack of donor organs, high cost, use of immunosuppressants, and the potential risk of serious complications [ 6 ].

HBV-ACLF exhibits different clinical features from other etiologically related ACLF. Recurrence of hepatitis B, superimposed infection with other hepatitis viruses (A or E), and mutations in resistance to antiviral therapy are common triggers of high mortality [ 7 , 8 , 9 ]. For HBV-ACLF, the guidelines recommend early use of effective antiviral nucleoside/nucleotide analogues (NAs), such as tenofovir disoproxil fumarate (TDF) and entecavir (ETV) [ 10 , 11 , 12 ]. NAs can effectively inhibit viral reverse transcriptase and reduce the HBV load in the blood, thereby reducing secondary inflammation and promoting hepatocyte regeneration and disease recovery [ 6 , 11 ]. NAs have fewer side effects, a low incidence of adverse reactions, and are safe to use. However, complications such as renal insufficiency and bone calcium and phosphorus metabolism disorders may occur due to the long-term use of NAs, especially in older adults with comorbidities [ 10 , 12 ].

Many studies have reported the efficacy of ETV on the survival of patients with HBV-ACLF. Studies have shown no difference in short-term survival after 12 weeks of ETV treatment compared to controls without antivirals [ 13 , 14 ], while other studies have reported improved survival [ 15 ]. Unlike ETV, data on the efficacy of TDF for HBV-ACLF are limited. Comparison of the efficacy of HBV-ACLF and the clinical choice of these two drugs remains controversial. To the best of our knowledge, there are no systematic reviews in the literature aimed at investigating the efficacy and safety of TDF versus ETV in the treatment of patients with HBV-ACLF.

Materials and methods

Literature search.

We performed this systematic review and meta-analysis according to the Preferred reporting items for systematic reviews and meta-analyses (The PRISMA statement) [ 16 ]. Two independent researchers (NW and SKH) searched PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, and Embase. Articles were restricted to publication until December 2022. The following combinations of keywords and Boolean operators were used in the MeSH and free-text searches: hepatitis B virus infection or HBV infection; acute-on-chronic liver failure or ACLF or HBV-ACLF; nucleoside or nucleotide analogues or Nuc or NA; tenofovir or TDF; and entecavir or ETV. The detaile d search strategy is shown in Supplementary Table 1 (Additional file 1 ). Two researchers searched independently by title and abstract. The search results were then combined to perform an initial screening of desired articles. The full text was then read to screen for articles that met the inclusion criteria. Baseline and endpoint parameters were extracted from each group.

Inclusion and exclusion criteria

Inclusion criteria: (1) meeting the Asia Pacific Association for the Study of the Liver (APASL) ACLF criteria (APASL-criteria) for serum bilirubin ≥5 mg/dL, international normalized ratio ≥ 1.5 or prothrombin activity < 40% in patients with previously diagnosed or undiagnosed chronic liver disease within 4 weeks with ascites or encephalopathy [ 17 ]; (2) age between 18 and 65 years; (3) oral treatment with TDF or ETV; (4) full-text extractable data related to the outcome metric. Exclusion criteria. (1) duplicate or unavailable publications; (2) single arm only, no comparison of TDF and ETV groups; (3) combination of antiviral therapy with other drugs during treatment, no drug control group; (4) other causes of chronic liver failure, such as drug-related liver injury, autoimmune liver disease, alcoholic liver disease and inherited metabolic diseases; malignancies and severe haematological abnormalities; (5) studies must have objective outcome indicators or they will be excluded from this analysis.

Data extraction

Two independent researchers (YZ and NW) performed all data extraction and statistics. Seven parameters were extracted: survival rate, HBV-DNA level, HBV-DNA clearance rate, serum surface antigen conversion, Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD) score, and safety. When the data was not provided directly in texts, GetData Graph Digitizer (version 2.26) would be used for extracting data from graphs. Differences in retrieval results or differences in opinion were resolved by discussion among all participants. If two investigators disagreed, a third author (LCW) was consulted.

Quality assessment

Two reviewers (SKH and NW) independently assessed the qualities of eligible studies by using the Newcastle–Ottawa Scale (NOS) [ 18 ], where scores of 1 to 3, 4 to 6, and 7 to 9 were considered low, medium, and high quality, respectively.

Outcome assessment

We focused on patient survival at 4, 12, and 48 weeks for prognostic assessment. Secondary endpoints included virologic and biochemistry response, serum surface antigen conversion, CTP score, MELD score, and safety.

Statistical analysis

Data analysis was performed using Stata (version 14.0). The results for dichotomous variables were assessed and expressed as risk ratios (RRs) and 95% confidence intervals (CIs). In addition, standardized mean differences (SMDs) and 95% CIs were selected for continuous variables due to the large differences in means between studies. Statistical heterogeneity was assessed with χ 2 and I 2 tests. Values of p < 0.10 or I 2 > 50% were considered statistically significant when combined with the results of the random-effects model. Begg’s test or Egger’s test was performed to assess the publication bias. Publication bias was considered statistically significant if the p -values were < 0.05. All statistical analyses were conducted using the Review Manager 5.4 and the Stata 14.0.

Basic characteristics of the included studies and risk of bias evaluation

The results retrieved 95 articles, and finally, a total of five studies [ 19 , 20 , 21 , 22 , 23 ] with 272 patients were included. The article screening process is shown in Fig. 1 . The five studies were divided into four prospective cohort studies [ 19 , 20 , 22 , 23 ] and one retrospective cohort study [ 21 ]. The details of the five articles are shown in Table 1 . Risk of bias analysis was performed for the included studies, and the risk of bias was acceptable for all studies based on quality analysis, as shown in Table 2 .

Identification process for eligible studies. The 95 studies initially identified from our electronic search met the inclusion criteria and were included in this meta-analysis

Survival rate

Three of the included studies [ 19 , 20 , 22 ] reported the 4-week survival rates of patients and found that TDF did not significantly improve the 4-week survival rates compared with the ETV group (RR = 1.17, 95% CI: 0.90–1.51, p = 0.24). Five studies [ 19 , 20 , 21 , 22 , 23 ] provided data on 12-week survival rates, and the combined analysis found no significant difference between the two groups (RR = 1.00, 95% CI: 0.88–1.13, p = 0.94). Two studies [ 20 , 22 ] comparing 48-week survival rates with HBV-ACLF showed that there was no significant difference between the two groups (RR = 0.96, 95% CI: 0.58–1.57, p = 0.86) (Fig. 2 ).

Survival rates at 4, 12, and 48 weeks for TDF and ETV in all included studies

Effect of antiviral therapy on HBV-DNA

Three studies [ 19 , 20 , 21 ] compared HBV-DNA levels between the two groups at 2 weeks and found no significant difference in HBV-DNA levels between TDF and ETV (SMD = 0.07, 95% CI:-0.55–0.68, p = 0.83) (Fig. 3 A). Three studies [ 21 , 22 , 23 ] reported rates of unmonitored HBV-DNA at 12 weeks and demonstrated that TDF was not effective in improving the HBV-DNA clearance rate in patients compared to ETV (RR = 1.89, 95% CI:0.57–6.29, p = 0.30) (Fig. 3 B).

A Reduced HBV DNA levels of TDF and ETV at 2 weeks. B HBV DNA clearance rate of TDF and ETV at 12 weeks

Serum surface antigen conversion

In the study by Wan et al. [ 21 ], 2 and 4 HBeAg+ patients in the ETV group and the TDF group survived for 3 months. Of these patients, none in the ETV group (0%; 0/2) and 4 in the TDF group (100%; 4/4) had HBeAg loss ( p = 0.067). None had HBeAg serologic conversion at 3 months. Zhang et al. [ 22 ] reported no surface antigen loss in the two groups at week 48. There was 1 case of HBeAg serologic conversion in each group, and the time to conversion was 12 and 48 weeks in the TDF and ETV groups, respectively.

Biochemical response

Regarding changes in liver function, three studies [ 19 , 20 , 22 ] examined the changes in alanine aminotransferase (ALT) and total bilirubin (TBiL) at 4 weeks in the TDF and ETV groups. The results showed improvement in ALT and TBiL compared to baseline levels, but there was no remarkable difference between the two groups (ALT: SMD = 0.65, 95% CI: − 0.04 − 1.34, p = 0.06; TBiL: SMD = − 0.01, 95% CI: − 0.35 − 0.33, p = 0.93). Only one study [ 22 ] reported ALT and TBiL at 12 and 48 weeks and found that TDF did not improve ALT and TBiL levels in patients with ACLF compared to ETV ( p > 0.05). More details can be found in Fig. 4 .

A Alanine aminotransferase levels at 4 weeks after TDF and ETV therapy. B Total bilirubin levels at 4 weeks after TDF and ETV therapy

CTP score and MELD score

The CTP and MELD scores at 4 weeks were reported in one study [ 21 ] and three studies [ 20 , 21 , 22 ], respectively. Both CTP and MELD scores were in two separate groups (p > 0.05 between baselines, comparable), and after 4 weeks of treatment, ETV failed to improve CTP scores or MELD scores, whereas TDF improved CTP and MELD scores (CTP: SMD = − 0.62, 95% CI: − 1.11 − − 0.13, p = 0.01; MELD: SMD = − 0.72, 95% CI:-1.05 − − 0.39, p < 0.0001). The CTP and MELD score at 12 weeks were separately mentioned in two studies [ 21 , 23 ] and three studies [ 20 , 21 , 22 ], and TDF did not improve the two scores in patients with ACLF compared with ETV (CTP: SMD = -0.75, 95% CI:-2.81–1.30, p = 0.47; MELD: SMD = -1.10, 95% CI: − 2.29 − 0.08, p = 0.07). Forest plots are presented in Fig. 5 . Only one study [ 22 ] reported the MELD score at 24 weeks and there was no significant difference between the two groups ( p > 0.05).

A CTP score for TDF and ETV therapy. B MELD score for TDF and ETV therapy

Safety of TDF and ETV in HBV-ACLF

Two studies by Zhang et al. and Li et al. [ 20 , 22 ] provided changes in estimated glomerular filtration rate (eGFR) over 4 weeks, but no significant differences between the two groups were found in their respective reports. Li et al. [ 20 ] focused on eGFR at 4, 12 and 48 weeks and found that the eGFR decreased differently from baseline at week 4 in the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group (− 5.83 vs − 4.75 mL/min/1.73m 2 ). However, it remained unclear whether the difference in nephrotoxicity is statistically significant. The study by Zhang et al. [ 19 ] reported increased serum creatine and cystine C in both TDF and ETV groups but there was no significant difference between them. In addition, Wan et al. [ 21 ] did not find patients with severe lactic acidosis or renal impairment attributable to ETV or TDF treatment at the 3-month follow-up, while Zhang et al. and Li et al. [ 20 , 22 ] did not observe renal-related adverse events, severe renal adverse events, or proximal tubulopathy events during the 48-week follow-up, and patients tolerated antiviral therapy well.

Sensitivity analysis and publication bias

We noted large heterogeneity in the MELD score and CTP score at 12 weeks ( I 2 = 94.7% and I 2 = 91.3%). Sensitivity analysis showed that the study by Hossain et al. was the main source of heterogeneity in the two combined analyses. By removing this study and combining the analyses again, no substantial changes were found in the above results, indicating good stability of the meta-analysis results. In addition, the I 2 value of the 12-week survival forest plot decreased from 55.7 to 28.3% after removing data such as the 12-week survival rate in Wan et al.. No noteworthy publication bias was found in Begg’s test and Egger’s test, which indicates that there was no significant publication bias ( p = 0.91 in Begg’s test) (in Fig. 6 ).

Begg’s test of survival rate at 12 weeks. The horizontal line in the funnel plot indicates the fixed effects summary estimates, while the diagonal line indicates the expected 95% confidence interval given the standard errors, assuming no heterogeneity between studies. Publication bias was not observed in studies using Egger’s ( p = 0.91) test, suggesting no evidence of publication bias

ACLF was first proposed in 1995 and is now considered a life-threatening syndrome that differs from simple decompensated cirrhosis in clinical, pathophysiological, and prognostic aspects [ 24 ]. There are some differences and regional variations between the East and West regarding the underlying chronic liver disease and acute injury in ACLF. In Asia, most cases of ACLF are caused by the reactivation of hepatitis B superimposed on underlying chronic liver disease (not necessarily cirrhosis) [ 17 , 25 ]. Therefore, oral NAs therapy provides a rational method for treating HBV-ACLF, especially in Asia, by suppressing viral DNA and reducing the development of hepatic necroinflammation [ 26 ]. Our study is the first meta-analysis designed to assess the efficacy and safety of TDF versus ETV for the treatment of HBV-ACLF. The primary outcome showed that TDF was comparable to ETV in terms of the survival rates of patients with HBV-ACLF, and the secondary results demonstrated that TDF was as effective as ETV in reducing HBV DNA and hepatic biochemical responses and may be more beneficial in improving liver function in the early stage of antiviral therapy.

To date, studies on the efficacy of TDF in HBV-ACLF are limited. Wan et al. [ 21 ] showed that TDF was superior to ETV in the treatment of HBV-ACLF in terms of rapid viral suppression within 2 weeks, improvement in liver function, and 48-week survival. In contrast, Li et al. [ 20 ] reported that compared to ETV, TDF in HBV-ACLF had a treatment response and clinical outcomes similar to those of ETV. Furthermore, at week 4, there was no significant difference in renal safety between these two treatment groups. The results of our meta-analysis are consistent with those reported by Li et al. [ 20 ] for TDF and ETV in terms of short-term virologic suppression and biomarkers of liver and kidney function. Although there was no significant difference in transplantation-free survival at 48 weeks, long-term follow-up is needed to determine the virologic response to TDF in these patients. Similar results were reported in other studies focused on the efficacy of TDF and ETV in chronic hepatitis B (CHB). Some meta-analyses showed that TDF had a greater ability to inhibit HBV and ETV can better normalize the ALT levels in the early stage, but there was no significant difference in long-term therapy. Additionally, TDF and ETV presented similar HBeAg clearance and seroconversion [ 27 , 28 , 29 ].

Since renal dysfunction is the most frequent complication in ACLF, the nephrotoxicity of therapeutic drugs is an important reference for clinical drug selection [ 3 ]. The nephrotoxicity of TDF initially raised concerns because of its structural similarity to adefovir, which is known to be nephrotoxic [ 30 ]. Both TDF and ETV are NAs that induce nephrotoxicity by mechanisms including renal tubular damage and mitochondrial toxicity [ 31 ]. Notably, in our study, TDF showed an unfavorable renal safety trend even in short-term treatment, although there was no significant difference between the two groups in terms of 4-week renal function changes. A recent real-world study in Korea indicated that TDF treatment reduced overall renal function in patients with CHB during the first 2 years [ 32 ]. Another systematic review based on 21 studies indicated that patients treated with TDF were not more likely to show renal function alteration than those treated with ETV. However, the eGFRs of patients receiving TDF tended to be more significantly decreased than those of patients receiving ETV [ 33 ]. Summarily, TDF and ETV are not contraindications in patients with underlying renal disease, but patients should be monitored closely due to the high risk of associated adverse effects. The dose of drugs should be adjusted according to the eGFR [ 34 ]. In our meta-analysis, TDF was reported to be more nephrotoxic than ETV. However, the significance of toxicity differences requires further investigation. Therefore, long-term follow-up may be useful to understand renal impairment in patients with ACLF receiving different antiviral therapies.

The limitations of this meta-analysis are as follows. First, only five studies were eligible, and four of them were prospective cohort studies without relevant randomized controlled trials (RCTs). All five studies were based on the Asian population, which may cause bias. Considering the high prevalence of HBV in other areas (e.g., sub-Saharan Africa), data from these regions are essential. Second, in our analysis, only two studies compared 48-week survival rates in both groups, and only one study consecutively reported changes in patients’ renal function over 48 weeks, so there was insufficient evidence to comprehensively and systematically assess the efficacy and safety of TDF and ETV. In addition, some data were extracted from the graphs provided in the text and may not be precise enough, as some studies did not provide raw data. Finally, our analysis mainly covered a period of up to 48 weeks, and a longer comparison of the efficacy of the two approaches is needed.

In summary, our results suggest that TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response ETV, while the difference in nephrotoxicity needs further investigation. In the future, more studies are necessary, especially RCTs.

Abbreviations

Acute-on-chronic liver failure

Child-Turcotte-Pugh

Model for end-stage liver disease

Nucleotide analogues

estimated Glomerular filtration rate

Alanine aminotransferase

Total bilirubin

Confidence interval

Standardized mean difference

Randomized controlled trials

Hepatitis B virus

Chronic hepatitis B

Acute-on-chronic liver failure associated with hepatitis B virus

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Acknowledgements

We are grateful for the useful comments and suggestions from anonymous referees.

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Neng Wang and Sike He contributed equally to this work.

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Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China

Neng Wang, Yu Zheng & Lichun Wang

West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China

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NW and YZ performed the statistical analysis. NW and SH participated in the analysis, interpretation and drafting of the data in the manuscript. LW revised the manuscript for important intellectual content. SH and NW prepared all the figures and table. All authors reviewed the manuscript.

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Wang, N., He, S., Zheng, Y. et al. Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis. BMC Gastroenterol 23 , 388 (2023). https://doi.org/10.1186/s12876-023-03024-7

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Comparison of autologous platelet concentrates and topical steroids on oral lichen planus: a systematic review and meta-analysis

Bita Azizi ORCID: orcid.org/0000-0002-1918-5303 1 ,
Katayoun Katebi ORCID: orcid.org/0000-0002-6595-6359 1 ,
Hosein Azizi ORCID: orcid.org/0000-0002-4163-6158 2 &
Maryam Hosseinpour Sarmadi ORCID: orcid.org/0000-0002-2599-4553 1

BMC Oral Health volume 24 , Article number: 674 ( 2024 ) Cite this article

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Metrics details

Oral lichen planus is a chronic and potentially malignant disorder of oral mucosa. Corticosteroids are used as first-line therapy for oral lichen planus patients; however, they have many side effects. Platelet concentrates (platelet-rich plasma and platelet-rich fibrin) are autologous bioactive materials. This systematic review investigated the effects of autologous platelet concentrates compared to topical steroids in treating symptomatic oral lichen planus patients.

Materials and methods

A systematic literature search was performed in PubMed, Web of Science, Scopus, Embase, and Cochrane for randomized controlled trials. Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines were observed for article selection. For the pooling of studies, meta-analysis using Standardized Mean Differences by random effects model was carried out to estimate summary effect sizes for the treatment of oral lichen planus.

A total of six studies, incorporating 109 oral lichen planus patients, were involved. Both treatment modalities showed a statistically significant improvement in the outcome parameters (lesion size, pain score, Thongprasom score) from the baseline to the end of treatment and further to the follow-up visits. There was no significant difference in the pooled estimate SMD of pain decline in patients of the two groups (SMD = 0.17 (95% CI: -0.47 to 0.81); I 2 = 63.6%). The SMD of Thongprasom score in patients receiving autologous platelet concentrates was lower than the corticosteroid groups, with no significant effect size (SMD= -2.88 (95% CI: -5.51 to -0.25); I 2 = 91.7%). Therefore, there was no statistically significant difference between the autologous platelet concentrates and topical steroids regarding pain and clinical score.

Autologous platelet concentrates, and topical steroids decreased the size of lesions, Thongprasom scale, and pain in oral lichen planus patients, but the difference between the two treatments was not statistically significant. Thus, autologous platelet concentrates could be considered as an alternative treatment to topical steroids.

Peer Review reports

Introduction

Lichen planus is a chronic autoimmune mucocutaneous condition [ 1 ] that involves oral and genital mucous membranes, skin, nails, and scalp [ 2 ]. Its prevalence is about 5% in the general adult population and has a female predilection of 2 to 1 [ 3 ]. Approximately 77% of patients with lichen planus show oral manifestations [ 4 ]. Oral lichen planus (OLP) is a chronic disorder with a global prevalence of 0.1 to 3.2% [ 5 ]. It usually appears in 50 to 70-year-old women [ 6 ].

The etiology of OLP is unknown, but it is considered a multifactorial process; psychological problems, infections, malnutrition, allergy, endocrine disorders, and genetic susceptibility have been reported as possible triggering factors [ 7 ]. The development of a chronic, dysregulated immune response to OLP-mediating antigens leads to increased cytokine, chemokine, and expression of adhesion molecules, which results in keratinocyte cell death, mucosal basement membrane destruction, and long-term chronicity of the disease [ 8 ]. This immune response is presumed to be mediated by CD4 + and CD8 + T-lymphocytes [ 9 ]. Oral lichen planus is characterized by white striae, known as Wickham’s striae, which highly indicate OLP. It can be reticular, popular, plaque-like, erosive (ulcerated), atrophic, and bullous. Atrophic, erosive, and bullous forms are associated with symptoms such as burning sensations and pain [ 9 ].

For many patients, OLP considerably limits their essential daily activities, such as eating, drinking, talking, or interacting with others [ 10 ]. Despite being a benign disorder,1.4% of oral lesions transform into malignancy, and the World Health Organization has categorized OLP as an oral potentially malignant disorder (OPMD) [ 11 ]. Ulceration, location on the tongue, and female sex are reported as possible risk factors for malignant transformation [ 12 ]. A recent systematic review on this subject concluded that OLP behaves as an OPMD, whose malignancy ratio is probably underestimated due to inadequate diagnostic criteria and the low methodological quality of the studies [ 13 ].

Currently, the treatment of OLP focuses on reducing ulcerations and symptoms and possibly increasing the disease-free period. Corticosteroids (CSs), calcineurin inhibitors, retinoids, photodynamic therapy, and natural alternatives are current treatment options; however, their efficacy degrees vary [ 14 , 15 ]. Corticosteroids can be administered as first-line therapy by topical, intralesional, or systemic routes. Topical use of CSs poses a risk of oral candidiasis and tachyphylaxis. During long-term treatment courses with systemic CS, the patient becomes susceptible to Cushing’s syndrome, hypertension, diabetes, gastric ulcers, and immune suppression. Thus, an effective treatment method with fewer or no side effects is needed.

Autologous platelet concentrates (APCs, including platelet-rich plasma and platelet-rich fibrin) are autologous bioactive materials with various applications in the medical and dental fields. The foundation of these preparations is to extract specific elements from the patient’s blood and use them for indorsing tissue regeneration. First-generation platelet concentrate, called platelet-rich plasma (PRP), contains high concentrations of platelets but negligible natural fibrinogen. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate that accelerates soft and hard tissue healing. Its ease of preparation and application, lower cost, and lack of need for biochemical modification give it an advantage over PRP [ 16 ].

These products have higher growth factors than the usual amounts necessary for regeneration and tissue repair [ 17 ]. Platelet-derived growth factors (PGFs) are important in inflammation, proliferation, and remodeling, the three phases of wound healing and repair cascade. Activated platelets release several growth factors leading to cell proliferation, differentiation, neo-angiogenesis, toxins removal, and cell regeneration. No side effects have been reported with autologous platelet concentrates [ 18 ].

Considering that several studies have investigated the effects of APCs on oral lichen planus compared to topical steroids, we have done this systematic review and meta-analysis to compare the summary effects of APCs on treating oral lichen planus with topical steroids.

This systematic review study is done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [ 19 ]. The study protocol has been registered in PROSPERO (Registration ID: CRD42022329977). The principal question of this study was formulated based on the “PICO” (population, intervention, comparison, and outcome) approach, where “P” indicates patients diagnosed with oral lichen planus who need treatment, “I” indicates Autologous Platelet Concentrates, including platelet-rich fibrin and platelet-rich plasma, “C” indicates topical steroids and “O” indicates changes in the pain based on visual analog scale (VAS) or numerical rating scale (NRS), changes in the clinical presentations based on Thongprasom scale, and changes in the lesion size. Therefore, the research question was,” Are there any differences regarding pain and clinical presentations between Autologous Platelet Concentrates and topical steroids in the treatment of oral lichen planus?”.

Search strategy

Electronic research without restriction on publication start date was carried out until 30 December 2023 using five primary electronic databases: PubMed, the Cochrane Central Register for Controlled Trials, Web of Science, Scopus, and Embase.

Every possible combination of free and MESH (Medical Subject Heading) terms with “OR” and “AND” operators was used for searching. The reference lists of the included articles were also searched to identify more research studies. The search keywords were “oral lichen planus”, “oral lichenoid reactions”, “oral lichenoid lesions”, “platelet-rich-plasma”, “platelet-rich-fibrin”, “platelet-rich fibrin”, “platelet-rich plasma”, “thrombocyte rich fibrin”, “thrombocyte rich plasma”.

The EndNote Basic software was used to manage the references, and duplicate references were identified and removed. The exact search keywords are provided in Appendix 1 .

Eligibility criteria

Studies were included if they were randomized, controlled clinical trials, and published in English. Studies were excluded if they were semi-experimental studies, In-vitro or animal studies, Reprinted articles that use information from the same sample, Letters to the editor and correspondence, Review articles, and Studies with limited information that do not provide the absolute frequency of outcomes and independent variables.

Screening and selection

Two independent reviewers (K.K. and B.A.) screened the titles. In the next stage, the abstracts were analyzed to ensure their compliance with the eligibility criteria. The full texts of the remaining articles were reviewed to select the final articles that met the inclusion criteria. The authors discussed with the third reviewer (M.H.S.) whenever there was any disagreement. Cohen’s Kappa score was used to assess the level of agreement between the reviewers.

Data extraction

After the final selection of studies, the required information was extracted and summarized using a table designed in the Microsoft Excel software environment. First author, year, country, study duration in months, follow-up in months, mean age, gender of participants, total sample size, size of lesions, VAS score, and Thongprasom score were extracted from the included studies by two independent reviewers (K.K. and B.A.).

Risk of bias assessment

The revised Cochrane risk-of-bias tool for randomized trials (RoB2) [ 20 ] was used by two independent reviewers (M.H.S and B.A) to assess the risk of bias. Disagreements were discussed with a third reviewer (K.K.). RoB2 is structured in five domains and a judgment of the overall risk of bias.

Outcome parameters

The outcomes of this article based on PICO were changes in the size of the lesions in mm 2 , changes in the pain and burning sensation evaluated by visual analogue scale (VAS) or numeric rating scale (NRS), and changes in the clinical score.

The visual analogue scale (VAS) and numeric rating scale (NRS) are validated measurements for acute and chronic pain [ 21 ]. NRS and VAS are not identical scales; however, they have similarities [ 22 ], so they can be compared to each other in a meta-analysis using the standard method.

VAS scores are recorded by making a handwritten mark on a 10-cm line representing a continuum between “no pain = 0” and “worst pain = 10”. The patient rates the current pain level by placing a mark on the line [ 21 ].

NRS is an 11-point scale, on which 0 represents ‘‘no pain’’ and 10 represents either ‘‘the worst possible pain’’ or ‘‘the most intense pain imaginable’’ [ 23 ].

Thongprasom score is used for clinical evaluation of the size and shape of oral lichen planus lesions, which varies from 0 to 5: score 0, normal mucosa; score 1, a lesion having only white striae; score 2, a lesion with white striae and atrophic areas less than 1 cm 2 ; score 3, a lesion with white striae and atrophic areas larger than 1 cm 2 ; score 4, a lesion with white striae and erosive areas less than 1 cm 2 ; and score 5, a lesion with white striae with erosive regions larger than 1 cm 2 [ 24 ].

Statistical analysis

The Standardized Mean Differences (SMD), endpoint scores, or change scores were used as effect sizes since the studies had different measuring scales (NRS and VAS). The values were compared between intervention and control groups. SMD has calculated the difference of values between intervention and control groups divided into pooled Standard Deviation (SD). Pooled SMDs and 95% CIs were calculated using the Der Simonian and Laird method via the random effects model. Cochran’s Q test and I 2 were measured to assess the heterogeneity between studies [ 25 ]. All statistical analyses were performed by STATA 14.0 (StataCorp, College Station, TX, US).

The electronic search in the mentioned databases yielded 210 articles. After removing the duplicates, 169 articles were screened; out of the 169 articles, 10 were related to the subject, from which two were case reports, and one was a review. Seven articles entered the full-text stage, but one did not have a control group; at last, six articles fulfilled the inclusion criteria. The details of the search results are presented in the PRISMA 2020 flow diagram (Fig. 1 ). The k value for inter-reviewer agreement for article selection for both abstract and full-text article steps was 0.87, indicating an “almost perfect” agreement.

PRISMA flowchart of the articles’ selection process

Characteristics of the studies

The descriptive characteristics of the included studies are presented in Table 1 . The total number of participants in these six studies was 109. The publication date of the studies ranged from 2020 to 2023. All of the six studies were randomized controlled trials (RCT). Three studies were split-mouth designed. The majority of the patients included in the studies were females (79 out of 109 patients; 72.5%). The mean age of the patients ranged from 42.6 to 59.5.

Five studies used VAS as a pain assessment scale before and after the interventions, and one used NRS as a pain assessment tool. Four out of six studies used the Thongprasom scale as a clinical score before and after treatment for both the intervention and control groups. Two studies compared the lesion size in mm 2 before and after interventions.

Three studies used PRP, and three studies used PRF as platelet concentrate. The applied corticosteroid in the studies was triamcinolone acetonide (TA) in five studies and methylprednisolone acetate in one study. Both treatment modalities were applied as injections in all studies (Table 2 ).

In the study of Ahuja et al., one group of patients was given bilateral intralesional injections with 10 mg/ml of triamcinolone acetonide (TA), and another group was given bilateral intralesional injections of autologous PRP. The injections were given weekly for eight weeks. The injections in both groups were given after a field block local anesthetic with a vasoconstrictor. 0.5 ml of either corticosteroid or PRP was injected per 1cm 2 of the involved mucosa. Significant reduction in the mean pain scores and the mean lesion size was observed in both groups, but the comparative p values were found to be insignificant [ 26 ].

In the study conducted by El Ghareeb et al., PRP Injections were given at four points of the lesion’s periphery (superior, inferior, left, and right) in one group, and intralesional injection of triamcinolone acetonide as multiple 0.2-ml injections at 1-cm intervals in the other group. 40 mg/ml of TA was mixed with 1 ml of lidocaine 2%, and the final concentration of TA was 20 mg/ml. The injection was performed for both groups every two weeks for two months. There were no statistically significant differences between the studied groups in pain score (NRS) after treatment [ 27 ].

In the study conducted by Hijazi et al., two groups of patients received intralesional injections of either PRP or 40 mg/ml of TA. 0.5 ml of each treatment was injected per 1 cm 2 of the ulcerated mucosa. The injections in both groups were applied after a field block with Mepivacaine 3% anesthetic without vasoconstrictor. The patients in both groups received injections once a week for four weeks. There was no statistical significance when comparing the two groups regarding pain and clinical score or remission [ 28 ].

In the split-mouth study conducted by Al-Hallak et al., patients received an intralesional injection of 1 ml of PRF on one side and an intralesional injection of 0.5 ml of triamcinolone acetonide (40 mg/ml) on the other side. The control side (TA) injections were done 15 days after finishing the treatment of the study side (PRF). Both treatments were applied once a week for four weeks. There was no significant difference between the groups regarding the pain score [ 29 ].

In the split-mouth study conducted by Bennardo et al., the test side received 1 mL of PRF injection, and the control side received 0.5 ml of triamcinolone acetonide (40 mg/ml). The treatments were applied once a week for a month. For each patient, experimentation lasted eight weeks. Both treatments effectively reduced the lesions’ extension and improved symptoms. However, no statistically significant difference was observed comparing changes in lesion extension and pain modification between the two protocols [ 30 ].

In the split-mouth study by Saglam et al., one side received 40 mg/ml of methylprednisolone acetate injections, and the other side received PRP injections. Methylprednisolone acetate was injected at four different points into the subepithelial tissue underlying the lesion and adjacent to the normal mucosa. Each injection was 0.2 mL per session. PRF was injected at four different points at the periphery of the lesion. The treatments were applied in four sessions at 15-day intervals. The intergroup comparison showed no significant difference between the PRF and corticosteroid groups regarding VAS-pain values and Thongprasom score [ 31 ].

Assessing the risk of bias

According to the RoB2 tool, out of six RCT studies, four showed a low risk of bias, whereas the other two showed some concerns (Fig. 2 ). Randomization of the samples wasn’t clearly indicated in one study (26), and two studies didn’t mention the blindness of the assessor [ 27 , 29 ].

( A ) The risk of bias for each study; ( B ) Risk of bias in each domain, based on Cochrane risk of bias tool 2

Meta-analysis

All of the six studies were included in the meta-analysis. Clinical parameters before the treatment and after the follow-up period were compared. There was no significant difference in the pooled estimate SMD of pain decline in patients receiving APCs in comparison with topical steroids (SMD = 0.17 (95% CI: -0.47 to 0.81); I 2 = 63.6%) (Fig. 3 ). Meta-analysis showed that the SMD of Thongprasom score in patients receiving APCs was lower than the corticosteroid groups, with no significant effect size. (SMD= -2.88 (95% CI: -5.51 to -0.25); I 2 = 91.7%) (Fig. 4 ). Since there were less than ten studies in each meta-analysis subgroup analysis and assessment of publication bias were not conducted.

Meta-analysis of standardized mean difference of pain

Meta-analysis of standardized mean difference of Thongprasom score

This systematic review evaluated APCs as an alternative to topical steroids for managing symptomatic OLP. Lichen planus is an inflammatory disorder of the skin and mucous membranes with no known cause [ 32 ]. The currently available treatments only decrease the symptoms [ 33 ]. A variety of therapeutic options are used for the management of OLP, including corticosteroids, immunosuppressive agents (Cyclosporin, Azathioprine, and mycophenolate mofetil), and immunomodulatory agents (thalidomide and levamisole) [ 34 ].

Platelet concentrates (PCs), represented mainly by platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), are autologous biological blood-derived products that may combine plasma/platelet-derived bioactive components, together with fibrin-forming protein able to create a natural three-dimensional scaffold. These products are safely used in clinical applications due to the autologous-derived source and the minimally invasive application procedure [ 35 ]. Autologous platelet concentrates have been used in medicine and dentistry for regenerative procedures and seem mainly to promote soft-tissue wound healing by delivering more than natural concentrations of autologous growth factors [ 36 ].

APCs contain growth factors and cytokines. The local release of growth factors and cytokines contained in platelet alpha granules accelerates tissue repair and promotes wound healing. This effect is boosted upon combination with the fibrinolytic system, which is crucial for complete regeneration [ 37 ].

The pathogenesis of OLP is influenced by various cellular mechanisms that are mediated by various cytokines. Tumor necrosis factor α, IL-1, and IL-4 play a significant role in disease progression [ 8 ]. PRP promotes the production of anti-inflammatory cytokines. These cytokines help the activated macrophages regulate the effect of pro-inflammatory cytokines. Anti-inflammatory cytokines regulate inflammation by interacting with soluble cytokine receptors and cytokine inhibitors [ 37 ]. Furthermore, Oxidative stress might have a role in the development of OLP [ 39 ]. It has been shown that PRP treatment can prevent oxidative damage by activating nuclear factor type 2, which, leads to increased signaling of antioxidant response elements [ 40 ].

Concerning the recurrence of the lesions and the treatment side effects, most of the studies reported no/mild symptoms of recurrence and no/mild side effects for either treatment modality. In the study of Ahuja et al., during follow-up for the next two months after treatment, the patients treated with PRP showed no or less recurrence, with only one patient out of 10 showing mild erythema and slight burning in the 15th week. In the corticosteroid group, three patients out of ten showed recurrences of the lesion during follow-up with increased pain and erythema compared to the 8th week. Also, there were mild side effects noted in two patients in the steroid group, but none of the patients treated with PRP reported any adverse effects [ 26 ]. In the split-mouth study of Al-Hallak et al., only two patients (16.7%) described mild symptoms of recurrence on both sides of the buccal mucosa [ 29 ]. In the study conducted by Hijazi et al., the remission score after three months of follow-up showed no significant difference between TA and PRP [ 28 ]. In the split-mouth study conducted by Saglam et al., no systemic side effects were reported for PRF or methylprednisolone acetate during the injections or the follow-up period [ 31 ]. In the study conducted by El Ghareeb et al., there was a significant increase in the frequency of side effects, especially pain, among patients who received PRP compared to those treated with steroids; this is in contrast with the other two studies that used PRP. This contrast may be due to lower injection intervals in this study and the dilution of TA with lidocaine as a local anesthetic. Also, there was a significant increase in recurrence rate among patients treated by PRP compared to TA; they suggested that this may be explained by the consumption of growth factors at the site of the lesion after a short period or by the immunosuppressive action of corticosteroids lasting for a long time [ 27 ].

The platelets’ function is not limited to hemostasis, but they have regenerative potential. PRP is a concentrated mixture of growth factors and cytokines that can influence inflammation, cell proliferation, stem cell migration, tissue repair, and angiogenesis [ 41 ]. Although the exact pathogenesis of OLP hasn’t been identified, it has been shown that many cytokines and inflammatory processes have an important role [ 42 ]. Therefore, it can be predictable that APCs might be useful in OLP’s management.

APCs may help patients with normal, impaired, and slower or incomplete healing by accelerating recovery. However, infection is one of the major contributors to delayed healing and tissue regeneration [ 43 ]. It has been suggested that using APCs as a drug delivery system, by combination with different molecules, such as antibiotics, can be useful [ 44 ]. Bennardo et al. reported that PRF could be loaded with antibiotics, and the drug is later released with antimicrobial effects [ 45 ]. Moreover, in vitro, research studied the effect of the addition of PRP to corticosteroids in chondrocytes and reported that the addition of PRP can significantly reduce the cytotoxic effects of corticosteroids [ 45 ].

Corticosteroids are the most commonly used medication for OLP due to their anti-inflammatory effects, nevertheless they are not definitive cures and only act in reducing the symptoms [ 47 ]. APCs however, could release various growth factors which endorse tissue repair, cell migration, angiogenesis, and tissue regeneration [ 48 ]. Additionally, APCs actively increase the proliferation of endothelial cells and fibroblasts [ 49 ]. Therefore it might be suggested that APCs could locally reverse the OLP lesions. The development of an effective three-dimensional fibrin scaffold following the administration of plasma rich in growth factors could facilitate healing, and guiding cell populations to their position and function [ 50 ]. More research is needed to evaluate the long term and probably definitive treatment effects of these preparations.

This review showed that platelet concentrates have the potential to alleviate the symptoms of OLP, have low side effects, and have a low rate of symptom recurrence. The results of treating OLP with APCs are comparable to topical steroids, and they have the advantage of lower side effects, such as oral candidiasis, which is seen with corticosteroids. Therefore, they can be suggested to be used, especially in patients who don’t respond well to topical steroids. Furthermore, future research is needed on using APCs as drug delivery systems for corticosteroids. Although there wasn’t enough information to compare the PRP with PRF, PRF may have a faster clinical response than PRP in managing OLP. Further studies are needed to compare these two materials.

This review had some limitations, such as the limited number of studies that have compared APCs and topical steroids, and as a result, the small size of the total sample, the heterogenicity of the outcomes, or the measurement scales of certain outcomes in different studies and the different time intervals of injections in the studies. Also, the follow-up times were different, which could affect the outcome results.

Within the limitations of our study, APCs could be effective in treating oral lichen planus and have comparable results with topical steroids. However, they have no superiority over topical steroids regarding the reduction of pain and clinical appearance. Furthermore, the higher expenses of APCs should be considered when choosing between these two treatment modalities. Future studies with larger sample sizes and longer follow-ups are recommended. Furthermore, it is suggested to conduct studies to reach a standard treatment protocol regarding the duration and intervals for using APCs in OLP patients.

APCs were found to decrease the size of lesions, Thongprasom score, and pain in OLP patients; However, no significant differences were found between APCs and topical steroids. Thus, APCs could be considered as an alternative treatment to topical steroids. However, the results should be interpreted cautiously due to the high heterogenicity between the studies and a limited number of patients. Further well-designed prospective randomized clinical trials with large sample sizes and longer follow-ups are recommended.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Acknowledgements

The authors would like to thank the statistical support of the “Clinical Research Development Unit of Al-Zahra Hospital” Tabriz University of Medical Sciences.

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KK contributed to the conception of the study and reviewed the identified articles for eligibility, extracted data and assessed the risk of bias; BA screened the articles, extracted data and assessed the risk of bias and drafted the manuscript; MHS conducted the systematic search in databases and revised the manuscript; HA performed the meta-analysis and revised the manuscript; All the authors have read and approved the final manuscript.

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Azizi, B., Katebi, K., Azizi, H. et al. Comparison of autologous platelet concentrates and topical steroids on oral lichen planus: a systematic review and meta-analysis. BMC Oral Health 24 , 674 (2024). https://doi.org/10.1186/s12903-024-04443-y

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Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials

Ji, Mengjia
Feng, Junfei
Liu, Guirong

Objectives To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). Methods We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. Results Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. Conclusions A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.

Effects of robot-assisted percutaneous kyphoplasty on osteoporotic vertebral compression fractures: a systematic review and meta-analysis

Published: 07 June 2024
Volume 18 , article number 243 , ( 2024 )

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Haoqian Chen ORCID: orcid.org/0000-0002-1719-7247 1 ,
Xin Wang 3 &
Yanming Fu ORCID: orcid.org/0000-0002-4874-5306 3

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This study systemically reviewed the effects of robot-assisted percutaneous kyphoplasty (R-PKP) on the clinical outcomes and complications of patients with osteoporotic vertebral compression fracture (OVCF). The articles published from the establishment of the database to 19 April 2024 were searched in PubMed, The Cochrane Library, Web of Science, Embase, Scopus, China National Knowledge Infrastructure (CNKI), and Chinese biomedical literature service system (SinoMed). Meta-analysis was employed to evaluate the status of pain relief and complications between the control and R-PKP groups. Standardized mean difference (SMD) or mean difference (MD), risk ratios (RR), and 95% confidence interval (CI) were selected for analysis, and a common or random effect model was adopted to merge the data. Eight studies involving 773 patients with OCVFs were included. R-PKP could effectively Cobb’s angles (MD = −1.00, 95% CI −1.68 to −0.33, P = 0.0034), and decrease the occurrence of cement leakage (RR = 0.36, 95% CI 0.21 to 0.60, P < 0.0001). However, there was no significant effect on the results of visual analog scale (MD = −0.09, 95% CI −0.20 to 0.02, P = 0.1145), fluoroscopic frequency (SMD = 5.31, 95% CI −7.24 to 17.86, P = 0.4072), and operation time (MD = −0.72, 95% CI −7.47 to 6.03, P = 0.8342). R-PKP could significantly correct vertebral angle and reduce cement leakage. Thus, R-PKP maybe an effective choice for correction vertebral Angle and reducing postoperative complications, while its impact on relieving pain, decreasing fluoroscopic frequency, and shortening operation time need further exploration.

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Advantages of unilateral percutaneous kyphoplasty for osteoporotic vertebral compression fractures—a systematic review and meta-analysis

Efficacy and safety of robot-assisted versus fluoroscopy-assisted PKP or PVP for osteoporotic vertebral compression fractures: a systematic review and meta-analysis

Analysis of two minimally invasive procedures for osteoporotic vertebral compression fractures with intravertebral cleft: a systematic review and meta-analysis

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No datasets were generated or analysed during the current study.

Abbreviations

Osteoporotic vertebral compression fractures
Percutaneous kyphoplasty

Robot-assisted percutaneous kyphoplasty

Critical Analytical Skills Program checklist

Visual analog scale

Relative risk

Mean diference

Standardized mean diference

Standard deviations

Confdence interval

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Chen, H., Li, J., Wang, X. et al. Effects of robot-assisted percutaneous kyphoplasty on osteoporotic vertebral compression fractures: a systematic review and meta-analysis. J Robotic Surg 18 , 243 (2024). https://doi.org/10.1007/s11701-024-01996-6

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Systematic reviews vs meta-analysis: what's the difference?
A systematic review is an article that synthesizes available evidence on a certain topic utilizing a specific research question, pre-specified eligibility criteria for including articles, and a systematic method for its production. Whereas a meta-analysis is a quantitative, epidemiological study design used to assess the results of articles ...
Meta‐analysis and traditional systematic literature reviews—What, why
There are several fundamental differences between traditional SLRs and meta-analysis, distinguishing these popular methods for accumulating knowledge in a research domain. ... Review Manager (RevMan) is a web-based software that manages the entire literature review process and meta-analysis. The meta-analyst uploads all studies to RevMan ...
Systematic Reviews and Meta-Analysis: A Guide for Beginners
Meta-analysis is a statistical tool that provides pooled estimates of effect from the data extracted from individual studies in the systematic review. The graphical output of meta-analysis is a forest plot which provides information on individual studies and the pooled effect. Systematic reviews of literature can be undertaken for all types of ...
Introduction to systematic review and meta-analysis
A systematic review collects all possible studies related to a given topic and design, and reviews and analyzes their results [ 1 ]. During the systematic review process, the quality of studies is evaluated, and a statistical meta-analysis of the study results is conducted on the basis of their quality. A meta-analysis is a valid, objective ...
Systematic Review VS Meta-Analysis
A meta-analysis can help iron out any inconsistencies in data, as long as the studies are similar. For instance, if your research is about the influence of the Mediterranean diet on diabetic people, between the ages of 30 and 45, but you only find a study about the Mediterranean diet in healthy people and another about the Mediterranean diet in ...
Systematic Reviews and Meta-analysis: Understanding the Best Evidence
Systematic reviews aim to identify, evaluate, and summarize the findings of all relevant individual studies over a health-related issue, thereby making the available evidence more accessible to decision makers. The objective of this article is to introduce the primary care physicians about the concept of systematic reviews and meta-analysis ...
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Similar to conducting a literature review, the search process of a ... Ferron J, Bunuan R, Van den Noortgate W (2017) Methods for dealing with multiple outcomes in meta-analysis: a comparison between averaging effect sizes, robust variance estimation and multilevel meta-analysis. ... Estimating the difference between published and unpublished ...
The difference between a systematic review and a meta-analysis
Each term refers to research about research, but there are important differences! A systematic review is a piece of work that asks a research question and then answers it by summarising the evidence that meets a set of pre-specified criteria. Some systematic reviews present their results using meta-analysis, a statistical method that combines ...
Difference Between Meta-Analysis and Systematic Literature Review
The differences between a meta-analysis and a systematic literature review are discussed, including advantages and drawback of each. ... literature reviews, meta-analysis and literature review, meta-analysis as topic, publication bias. Show all Show less. Online ISBN: 9781529685916
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Systematic reviews and meta-analyses lie on the top of the evidence hierarchy because they utilize explicit methods for literature search and retrieval of studies relevant to the review question as well as robust methodology for quality assessment of included studies and quantitative synthesis of results.
Systematic Reviews and Meta-Analysis: A Guide for Beginners
Meta-analysis is a statistical tool that provides pooled estimates of effect from the data extracted from individual studies in the systematic review. The graphical output of meta-analysis is a forest plot which provides information on individual studies and the pooled effect. Systematic reviews of literature can be undertaken for all types of ...
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Meta-analysis is a specialised type of systematic review which is quantitative and rigorous, often comparing data and results across multiple similar studies. This is a common approach in medical research where several papers might report the results of trials of a particular treatment, for instance. The meta-analysis then statistical ...
Literature Reviews and Meta Analysis
The overall goals of a meta-analysis are the same as any review which were noted earlier (i.e., critically evaluate and summarize a body of research, reach some conclusions about that research, and offer suggestions for future work). The unique feature of a meta-analysis is its ability to quantify the magnitude of the findings via the effect size.
What Is the Difference Between a Systematic Review and a Meta-analysis
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For journalists, literature reviews and meta-analyses are important tools for investigating public policy issues and fact-checking claims made by elected leaders, campus administrators and others. But to use them, reporters first need to know how to find them. And, as with any source of information, reporters also should be aware of the ...
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A meta-analysis is the use of statistical methods to summarize the results of a systematic review. Not every systematic review contains a meta-analysis. A meta-analysis may not be appropriate if the designs of the studies are too different, if there are concerns about the quality of studies, if the outcomes measured are not sufficiently similar ...
PDF Similarities and differences between literature reviews
A meta-analysis is a type of systematic review that summarises and compares data using statistical techniques. Aim/Definition. A scholarly literature review summarises evidence on a topic using a formal writing style and adopting qualitative data collection methods to select and interpret studies. Can involve some quantitative analysis.
Systematic Literature Review or Literature Review
The difference between literature review and systematic review comes back to the initial research question. Whereas the systematic review is very specific and focused, the standard literature review is much more general. The components of a literature review, for example, are similar to any other research paper.
Know the Difference between Literature Review, Systematic ...
The main difference between literature review, systematic review, and meta-analysis is the methodology used to identify, evaluate, and synthesize the available evidence. Literature reviews provide ...
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Comparing Integrative and Systematic Literature Reviews
A literature review is a systematic way of collecting and synthesizing previous research (Snyder, 2019).An integrative literature review provides an integration of the current state of knowledge as a way of generating new knowledge (Holton, 2002).HRDR is labeling Integrative Literature Review as one of the journal's four non-empirical research article types as in theory and conceptual ...
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