Effect of Conventional Chemotherapy in Patients With Neuroendocrine Tumours: A Systematic Review

Abstract Background: Neuroendocrine tumours (NETs) are a wide-ranging group of neoplasms originating from neuroendocrine cells. In 2014 NETs incidence was 7 per 100000 people annually. The purpose of this systematic review is to evaluate the safety and efficacy of various types of chemotherapeutic agents on gastroenteropancreatic NETs (GEP NETs) and to determine which type of chemotherapy is the most effective for different tumour types, with minimum adverse events. To our knowledge, this study is the first systematic review that compares several types of chemotherapy and evaluates their safety and efficacy on GEP NETs. Methods: The study followed recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines on reporting systematic reviews. The literature search for this systematic review was conducted using the following databases and search engines: Cochrane library, EMBASE, Google Scholar, PubMed, and Web of Science, from 1963 to 2020. Results: The review comprised 26 observational studies, and 5 randomized controlled trials (RCTs). The total number of subjects included in this study was 1783. Our study showed that the most effective treatment for Grade 3 NETs and Grade 3 neuroendocrine carcinomas was cisplatin/etoposide. Furthermore, capecitabin/temozolomide therapy has been shown to be most effective in Grade 1 and Grade 2 NETs. Conclusion: Therapy with two chemotherapeutic agents has been shown to be more effective than monotherapy and therapy with three chemotherapeutic agents. Unfortunately, our study has limitations and we urgently need RCTs or larger observational studies that will contain all the necessary efficacy and safety tools, and thus provide answers to our clinical questions.

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Artificial Intelligence-Aid Colonoscopy Vs. Conventional Colonoscopy for Polyp and Adenoma Detection: A Systematic Review of 7 Discordant Meta-Analyses

Frontiers in Medicine ◽

10.3389/fmed.2021.775604 ◽

2022 ◽

Vol 8 ◽

Author(s):

Hui Pan ◽

Mingyan Cai ◽

Qi Liao ◽

Yong Jiang ◽

Yige Liu ◽

...

Keyword(s):

Artificial Intelligence ◽

Systematic Review ◽

Systematic Reviews ◽

Detection Rate ◽

Conventional Colonoscopy ◽

Cochrane Library ◽

High Quality ◽

Decision Algorithm ◽

Adenoma Detection ◽

Meta Analyses

Objectives: Multiple meta-analyses which investigated the comparative efficacy and safety of artificial intelligence (AI)-aid colonoscopy (AIC) vs. conventional colonoscopy (CC) in the detection of polyp and adenoma have been published. However, a definitive conclusion has not yet been generated. This systematic review selected from discordant meta-analyses to draw a definitive conclusion about whether AIC is better than CC for the detection of polyp and adenoma.Methods: We comprehensively searched potentially eligible literature in PubMed, Embase, Cochrane library, and China National Knowledgement Infrastructure (CNKI) databases from their inceptions until to April 2021. Assessment of Multiple Systematic Reviews (AMSTAR) instrument was used to assess the methodological quality. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used to assess the reporting quality. Two investigators independently used the Jadad decision algorithm to select high-quality meta-analyses which summarized the best available evidence.Results: Seven meta-analyses met our selection criteria finally. AMSTAR score ranged from 8 to 10, and PRISMA score ranged from 23 to 26. According to the Jadad decision algorithm, two high-quality meta-analyses were selected. These two meta-analyses suggested that AIC was superior to CC for colonoscopy outcomes, especially for polyp detection rate (PDR) and adenoma detection rate (ADR).Conclusion: Based on the best available evidence, we conclude that AIC should be preferentially selected for the route screening of colorectal lesions because it has potential value of increasing the polyp and adenoma detection. However, the continued improvement of AIC in differentiating the shape and pathology of colorectal lesions is needed.

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What Are We Measuring When We Evaluate Digital Interventions for Improving Lifestyle? A Scoping Meta-Review

Frontiers in Public Health ◽

10.3389/fpubh.2021.735624 ◽

2022 ◽

Vol 9 ◽

Author(s):

Rodolfo Castro ◽

Marcelo Ribeiro-Alves ◽

Cátia Oliveira ◽

Carmen Phang Romero ◽

Hugo Perazzo ◽

...

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Digital Health ◽

Research Priorities ◽

Lifestyle Changes ◽

Cochrane Library ◽

Delivery Methods ◽

Intermediate Outcomes ◽

Scoping Reviews ◽

Meta Analyses

Background: Lifestyle Medicine (LM) aims to address six main behavioral domains: diet/nutrition, substance use (SU), physical activity (PA), social relationships, stress management, and sleep. Digital Health Interventions (DHIs) have been used to improve these domains. However, there is no consensus on how to measure lifestyle and its intermediate outcomes aside from measuring each behavior separately. We aimed to describe (1) the most frequent lifestyle domains addressed by DHIs, (2) the most frequent outcomes used to measure lifestyle changes, and (3) the most frequent DHI delivery methods.Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-ScR) Extension for Scoping Reviews. A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Web of Science for publications since 2010. We included systematic reviews and meta-analyses of clinical trials using DHI to promote health, behavioral, or lifestyle change.Results: Overall, 954 records were identified, and 72 systematic reviews were included. Of those, 35 conducted meta-analyses, 58 addressed diet/nutrition, and 60 focused on PA. Only one systematic review evaluated all six lifestyle domains simultaneously; 1 systematic review evaluated five lifestyle domains; 5 systematic reviews evaluated 4 lifestyle domains; 14 systematic reviews evaluated 3 lifestyle domains; and the remaining 52 systematic reviews evaluated only one or two domains. The most frequently evaluated domains were diet/nutrition and PA. The most frequent DHI delivery methods were smartphone apps and websites.Discussion: The concept of lifestyle is still unclear and fragmented, making it hard to evaluate the complex interconnections of unhealthy behaviors, and their impact on health. Clarifying this concept, refining its operationalization, and defining the reporting guidelines should be considered as the current research priorities. DHIs have the potential to improve lifestyle at primary, secondary, and tertiary levels of prevention—but most of them are targeting clinical populations. Although important advances have been made to evaluate DHIs, some of their characteristics, such as the rate at which they become obsolete, will require innovative research designs to evaluate long-term outcomes in health.

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Evidence-Based Medicine, Systematic Reviews, and Guidelines in Interventional Pain Management: Part 6. Systematic Reviews and Meta-Analyses of Observational Studies

January 2018 - Pain Physician ◽

10.36076/ppj.2009/12/819 ◽

2008 ◽

Vol 5;12 (5;9) ◽

pp. 819-850

Author(s):

Laxmaiah Manchikanti

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Evidence Based Medicine ◽

Observational Studies ◽

Meta Analysis ◽

Evidence Based ◽

Confounding Bias ◽

Meta Analyses ◽

Based Medicine

Observational studies provide an important source of information when randomized controlled trials (RCTs) cannot or should not be undertaken, provided that the data are analyzed and interpreted with special attention to bias. Evidence-based medicine (EBM) stresses the examination of evidence from clinical research and describes it as a shift in medical paradigm, in contrast to intuition, unsystematic clinical experience, and pathophysiologic rationale. While the importance of randomized trials has been created by the concept of the hierarchy of evidence in guiding therapy, much of the medical research is observational. The reporting of observational research is often not detailed and clear enough with insufficient quality and poor reporting, which hampers the assessment of strengths and weaknesses of the study and the generalizability of the mixed results. Thus, in recent years, progress and innovations in health care are measured by systematic reviews and meta-analyses. A systematic review is defined as, “the application of scientific strategies that limit bias by the systematic assembly, clinical appraisal, and synthesis of all relevant studies on a specific topic.” Meta-analysis usually is the final step in a systematic review. Systematic reviews and meta-analyses are labor intensive, requiring expertise in both the subject matter and review methodology, and also must follow the rules of EBM which suggests that a formal set of rules must complement medical training and common sense for clinicians to integrate the results of clinical research effectively. While expertise in the review methods is important, the expertise in the subject matter and technical components is also crucial. Even though, systematic reviews and meta-analyses, specifically of RCTs, have exploded, the quality of the systematic reviews is highly variable and consequently, the opinions reached of the same studies are quite divergent. Numerous deficiencies have been described in methodologic assessment of the quality of the individual articles. Consequently, observational studies can provide an important complementary source of information, provided that the data are analyzed and interpreted in the context of confounding bias to which they are prone. Appropriate systematic reviews of observational studies, in conjunction with RCTs, may provide the basis for elimination of a dangerous discrepancy between the experts and the evidence. Steps in conducting systematic reviews of observational studies include planning, conducting, reporting, and disseminating the results. MOOSE, or Meta-analysis of Observational Studies in Epidemiology, a proposal for reporting contains specifications including background, search strategy, methods, results, discussion, and conclusion. Use of the MOOSE checklist should improve the usefulness of meta-analysis for authors, reviewers, editors, readers, and decision-makers. This manuscript describes systematic reviews and meta-analyses of observational studies. Authors frequently utilize RCTs and observational studies in one systematic review; thus, they should also follow the reporting standards of the Quality of Reporting of Meta-analysis (QUOROM) statement, which also provides a checklist. A combined approach of QUOROM and MOOSE will improve reporting of systematic reviews and lead to progress and innovations in health care. Key words: Observational studies, evidence-based medicine, systematic reviews, metaanalysis, randomized trials, case-control studies, cross-sectional studies, cohort studies, confounding bias, QUOROM, MOOSE

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The Effectiveness of Telemedicine Solutions for the Management of Type 2 Diabetes: A Systematic Review, Meta-Analysis, and Meta-Regression

Journal of Diabetes Science and Technology ◽

10.1177/19322968211064633 ◽

2021 ◽

pp. 193229682110646

Author(s):

Stine Hangaard ◽

Sisse H. Laursen ◽

Jonas D. Andersen ◽

Thomas Kronborg ◽

Peter Vestergaard ◽

...

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Sufficient Information ◽

Meta Regression ◽

Meta Analyses

Background: Previous systematic reviews have aimed to clarify the effect of telemedicine on diabetes. However, such reviews often have a narrow focus, which calls for a more comprehensive systematic review within the field. Hence, the objective of the present systematic review, meta-analysis, and meta-regression is to evaluate the effectiveness of telemedicine solutions versus any comparator without the use of telemedicine on diabetes-related outcomes among adult patients with type 2 diabetes (T2D). Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We considered telemedicine randomized controlled trials (RCT) including adults (≥18 years) diagnosed with T2D. Change in glycated hemoglobin (HbA1c, %) was the primary outcome. PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials (CENTRAL) were searched on October 14, 2020. An overall treatment effect was estimated using a meta-analysis performed on the pool of included studies based on the mean difference (MD). The revised Cochrane risk-of-bias tool was applied and the certainty of evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: The final sample of papers included a total of 246, of which 168 had sufficient information to calculate the effect of HbA1c%. The results favored telemedicine, with an MD of −0.415% (95% confidence interval [CI] = −0.482% to −0.348%). The heterogeneity was great (I2 = 93.05%). A monitoring component gave rise to the higher effects of telemedicine. Conclusions: In conclusion, telemedicine may serve as a valuable supplement to usual care for patients with T2D. The inclusion of a telemonitoring component seems to increase the effect of telemedicine.

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Improving the usefulness of evidence concerning the effectiveness of implementation strategies for knowledge products in primary healthcare: Protocol for a series of systematic reviews

10.21203/rs.2.23906/v2 ◽

2020 ◽

Author(s):

Hervé Tchala Vignon Zomahoun ◽

José Massougbodji ◽

André Bussières ◽

Aliki Thomas ◽

Dahlia Kairy ◽

...

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Primary Healthcare ◽

Healthcare Delivery ◽

Implementation Strategies ◽

Psychosocial Health ◽

Performance Outcomes ◽

Cochrane Library ◽

Eligibility Criteria ◽

Meta Analyses

Abstract Background: The literature on the implementation of knowledge products is extensive. However, this literature is still difficult to interpret for policymakers and other stakeholders when faced with choosing implementation strategies likely to bring about successful change in their health systems. This work has the particularity to examine the scope of this literature, and to clarify the effectiveness of implementation strategies for different knowledge products. Consequently, we aim to: 1) determine the strengths and weaknesses of existing literature overviews; 2) produce a detailed portrait of the literature on implementation strategies for various knowledge products; and 3) assess the effectiveness of implementation strategies for each knowledge product identified and classify them.Methods: We will use a three-phase approach consisting of a critical analysis of existing literature overviews, a systematic review of systematic reviews, and a series of systematic reviews and meta-analyses. We will follow the Cochrane Methodology for each of three phases. Our eligibility criteria are defined following a PICOS approach: Population, individuals or stakeholders participating in healthcare delivery, specifically, healthcare providers, caregivers, and end users; Intervention, any type of strategy aiming to implement a knowledge product including, but not limited to, a decision support tool, a clinical practice guideline, a policy brief, or a decision-making tool, a one-pager, or a health intervention; Comparison, any comparator will be considered; Outcomes, Phases 1 and 2 – any outcome related to implementation strategies including, but not limited to, the measures of adherence/fidelity to the use of knowledge products, their acceptability, adoption, appropriateness, feasibility, adaptability, implementation costs, penetration/reach and sustainability; Phase 3 – any additional outcome related to patients (psychosocial, health behavioral, and clinical outcomes) or healthcare professionals (behavioral and performance outcomes); Setting, primary healthcare has to be covered. We will search MEDLINE (Ovid), EMBASE, Web of Science, PsycINFO, CINAHL, and the Cochrane Library from their inception onwards. For each phase, two reviewers will independently perform the selection of studies, data extraction, and assess their methodological quality. We will analyze extracted data, and perform narrative syntheses, and meta-analyses when possible.Discussion: Our results could inform not only the overviews’ methodology, but also the development of an online platform for the implementation strategies of knowledge products. This platform could be useful for stakeholders in implementation science.Systematic review registration: Protocol registered on Open science Framework, https://osf.io/hqbx8

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The Psychological and Physical Effects of Forests on Human Health: A Systematic Review of Systematic Reviews and Meta-Analyses

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041770 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1770

Author(s):

Marita Stier-Jarmer ◽

Veronika Throner ◽

Michaela Kirschneck ◽

Gisela Immich ◽

Dieter Frisch ◽

...

Keyword(s):

Mental Health ◽

Systematic Review ◽

Systematic Reviews ◽

Grey Literature ◽

Primary School Children ◽

Cochrane Library ◽

Therapeutic Effects ◽

Physical Effects ◽

Randomised Controlled ◽

Meta Analyses

Background: The aim of this systematic review of systematic reviews was to identify, summarise, and synthesise the available evidence of systematic reviews (SRs) and meta-analyses (MAs) on the preventative and therapeutic psychological and physical effects of forest-based interventions. Methods: Both bibliographic databases and grey literature sources were searched for SRs and MAs published until May 2020. Eight databases were searched for relevant articles: MEDLINE, Embase, Web of Science, Cochrane Library, PsycInfo, CiNii, EBSCO, and Scopus. Grey literature was sourced from Google Scholar and other web-based search tools. SRs and MAs that included randomised controlled (RCT), non-randomised controlled (NRCT), and non-controlled trials (NCT) on health-related effects of forest-based interventions were eligible if they had searched at least two databases. The methodological quality of eligible reviews was assessed by AMSTAR-2. Results: We evaluated 11 systematic reviews covering 131 different primary intervention studies, mostly from Asian countries, three of which included supplementary meta-analyses. The quality assessment resulted in moderate confidence in the results of two reviews, low confidence in six, and critically low confidence in three. The results of the eight moderate and low-rated reviews indicated that forest-based interventions are beneficial to the cardiovascular system, immune system, and mental health (in the areas of stress, depression, anxiety, and negative emotions). Evidence for the effectiveness of forest-based interventions on metabolic parameters in adults, the severity of atopic dermatitis in children and adolescents, and social skills and sociality in healthy primary school children was weak. Discussion/Conclusions: Evidence suggests beneficial therapeutic effects of forest-based interventions on hypertension, stress, and mental-health disorders, such as depression and anxiety. Changes in immunological and inflammatory parameters after forest therapy should be verified in bio-geographically native forests. In the future, more attention should be paid to careful planning, implementation, and reporting of primary studies and to systematic reviews on the effects of forest-based interventions.

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Association between climate conditions and osteoarthritis: protocol for a systematic review and meta-analysis

10.21203/rs.3.rs-859153/v1 ◽

2021 ◽

Author(s):

Lin Wang ◽

Qinguang Xu ◽

Yan Chen ◽

Yan Xue ◽

Ding Jiang ◽

...

Keyword(s):

Systematic Review ◽

Observational Studies ◽

Data Extraction ◽

Meta Analysis ◽

Weather Conditions ◽

Cochrane Library ◽

Climate Conditions ◽

Relative Risks ◽

Newcastle Ottawa Scale ◽

Meta Analyses

Abstract Background Osteoarthritis (OA) is the most common form of arthritis, causing by multiple factors. It has long been a belief that arthritis pain is influenced by the weather. However, scientific studies have documented inconsistent results. To date, neither systematic review nor meta-analysis of existing findings has comprehensively considered their relations. The present study will critically appraise and synthesize the existing evidence from observational studies that examined the relationship between certain climate conditions and OA. Methods and design: This protocol will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. There are no restrictions on the study date or publication status for searches in the Cochrane Library, EMBASE, Web of Science, PubMed, and other relative databases. All eligible observational studies will be included, with weather conditions as effect factors and OA symptom or imaging abnormality as outcomes. Two reviewers will be responsible for data extraction and analysis. Risk of bias and quality appraisal will be performed for the included studies using Newcastle-Ottawa Scale (NOS). Meta-analysis will be conducted using Rev Man V.5.3 with the associations between weather conditions and OA presented by odds ratios (ORs), relative risks (RRs), hazard ratios (HRs) and the 95% confidence intervals (CIs). Results This systematic review and meta-analysis will present the overall association between weather conditions and OA. The association of climate factors influencing OA incidence or progression would be further illustrated in subgroup analysis depending on whether that has been extensively described in the literature. Discussion This study will provide the analysis evidence on the effect of meteorological factors on OA. In an approach of dealing with weather conditions, the results will benefit the daily management of OA.

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Inexpensive Systemic Inflammatory Biomarkers in Ovarian Cancer: An Umbrella Systematic Review of 17 Prognostic Meta-Analyses

Frontiers in Oncology ◽

10.3389/fonc.2021.694821 ◽

2021 ◽

Vol 11 ◽

Author(s):

Khalid El Bairi ◽

Ouissam Al Jarroudi ◽

Said Afqir

Keyword(s):

Systematic Review ◽

Ovarian Cancer ◽

Systematic Reviews ◽

Observational Studies ◽

Inflammatory Biomarkers ◽

Current Evidence ◽

Class Iii ◽

Poor Overall Survival ◽

Meta Analyses

The association of several inflammation-based biomarkers [lymphocyte-to-monocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios (LMR, NLR, and PLR, respectively)] with the survival of epithelial ovarian cancer (EOC) patients has been extensively investigated in several systematic reviews and meta-analyses (MAs) of observational studies. The aim of this umbrella systematic review is to appraise all available results in published MAs that explored the association between these biomarkers and EOC outcomes. An umbrella systematic review of the current evidence for systemic inflammatory biomarkers in the peripheral blood of EOC patients was performed by searching several databases including PubMed/Medline and Web of Science. The quality of the MAs was appraised using the AMSTAR-2 tool as well as other qualitative criteria. The evidence was graded from convincing (Class I) to weak (Class IV). Our umbrella review appraised 17 MAs of retrospective studies (range: 7–16) with a number of enrolled patients ranging from 1,636 to 4,910 patients in each MA. All these MAs demonstrated that pretreatment high NLR and PLR, as well as low LMR, were independent predictors of poor overall survival and progression-free survival in EOC. Nearly all published MAs were conducted by Chinese researchers (16/17) and were redundant in their character. Another issue in these MAs is the absence of prior PROSPERO database registration as well as the earlier exclusion of the gray literature. On the other hand, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE)-based reporting guidelines were used in nine out of the 17 MAs. A good number of MAs have transparently provided funding acknowledgment. The AMSTAR-2-based assessment showed low quality in 11 out of the 17 reviewed MAs. This negative rating was largely due to the absence of critical domains. Finally, all evaluated MAs were rated as Class III or IV (suggestive and weak, respectively). Despite the power of MAs in increasing sampling and precision, the quality of the current non-randomized evidence on this topic is still weak.Systematic Review RegistrationPROSPERO, identifier CRD42020201493.

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Surgical treatment for cryptoglandular and Crohn’s perianal fistulas: Protocol of an umbrella review

PLoS ONE ◽

10.1371/journal.pone.0251460 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251460

Author(s):

Zubing Mei ◽

Qin Feng ◽

Peixin Du ◽

Bin Li ◽

Chenyang Fang ◽

...

Keyword(s):

Systematic Review ◽

Systematic Reviews ◽

Meta Analysis ◽

Cochrane Library ◽

Surgical Approaches ◽

Efficacy And Safety ◽

Umbrella Review ◽

Perianal Fistulas ◽

Surgical Options ◽

Meta Analyses

Introduction A high prevalence of cryptoglandular and Crohn’s perianal fistulas has been reported worldwide, and several surgical options are available for the management of anal fistula, with varying clinical efficacy. However, currently, the available evidence for the effectiveness of these surgical approaches are lacking and of concern in terms of the credibility and strength. The purpose of this study is to evaluate the credibility of the published systematic reviews and meta-analyses that assess the efficacy and safety of the surgical options for cryptoglandular and Crohn’s perianal fistulas through an umbrella review. Methods and analysis A systematic search in PubMed, Embase and Cochrane library will be performed from inception to December 2020 without any language restriction. We will include systematic reviews and meta-analyses that investigate the efficacy and safety of surgical approaches in the management of cryptoglandular and Crohn’s perianal fistulas. Two reviewers will independently screen search results through reading the titles or abstracts. Relevant information will be extracted from each eligible systematic review or meta-analysis. Based on random effects model summary estimates along with their p values, 95% prediction intervals, between-study heterogeneity, small-study effects and excess significance, we will classify the evidence from convincing (class I) to weak (class IV). Findings will be summarized using quantitative synthesis combined with a narrative approach. Cryptoglandular and Crohn’s perianal fistulas will be summarized separately. Two authors will independently perform the literature search, data extraction, and quality assessment of each included systematic review and meta-analysis. Any unresolved conflicts or doubts will be resolved by discussion or by consulting a senior author. The risk of bias of the systematic reviews will be assessed using a 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist. The strength of evidence for the included systematic reviews will be classified as "high", "moderate", "low", or "critically low" quality. Ethics and dissemination Ethics approval is not required as we will collect data from the published systematic reviews and meta-analyses without using individual patient data. The results of this umbrella review will be published in a peer-reviewed journal and will be presented at an anorectal disease conference. PROSPERO registration number CRD42020200754.

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Environmental assessment of cytotoxic drugs in healthcare settings: protocol for a systematic review and meta-analysis

Systematic Reviews ◽

10.1186/s13643-020-01494-4 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Laila Al Alawi ◽

Elpidoforos S. Soteriades ◽

Marilia Silva Paulo ◽

Linda Östlundh ◽

Michal Grivna ◽

...

Keyword(s):

Systematic Review ◽

Occupational Exposure ◽

Health Outcomes ◽

Systematic Reviews ◽

Environmental Contamination ◽

Meta Analysis ◽

Cytotoxic Drugs ◽

Cochrane Library ◽

Healthcare Settings ◽

Meta Analyses

Abstract Background Occupational exposure to cytotoxic drugs is associated with various unfavorable health outcomes. This protocol reports a methodology for a systematic review and meta-analysis that aims to systematically review the published literature and quantify the level of environmental contamination of healthcare settings with cytotoxic drugs. Methods This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol-2015 (PRISMA-P) guidelines. Six electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, CINAHL, and EMBASE) will be searched with no restrictions on publication period. Eligible studies will be identified and data will be extracted using a predefined data extraction form by at least two independent reviewers following best practice. Eligible studies should report calculated or calculable estimates on the proportion of positive samples tested for cytotoxic drugs and/or estimates on the concentration of the cytotoxic drug(s) in the tested samples. Risk of bias (RoB) will be assessed by using the RoB in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool, which developed by the World Health Organization (WHO) and International Labour Organization (ILO) for environmental and occupational health systematic reviews. The random-effects model will be used to perform meta-analyses. Discussion Occupational exposure to cytotoxic drugs is associated with short- and long-term adverse health outcomes. Following this protocol, the review to be carried out will be the first to fill an evidence gap on the environmental contamination of healthcare settings with cytotoxic drugs. The findings of this review will help in the understanding of the risk of occupational exposure of healthcare workers to cytotoxic drugs and facilitate the identification of priority areas for specific interventions. Ethics and dissemination The systematic review methodology does not require ethics approval due to the nature of the study design. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available. Systematic review registration PROSPERO CRD42020162780, dated July 14, 2020

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