scholarly journals Assessing the impact of human trampling on vegetation: a systematic review and meta-analysis of experimental evidence

2014 ◽  
Author(s):  
Oliver L. Pescott ◽  
Gavin Stewart
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Plant Communities ◽  
Life Form ◽  
Conservation Management ◽  
Meta Analysis ◽  
Vegetation Recovery ◽  
Management Decisions ◽  
Natural Habitats ◽  
The Impact

Vegetation trampling resulting from recreation can adversely impact natural habitats, leading to the loss of vegetation and the degradation of plant communities. A considerable primary literature exists on this topic, therefore it is important to assess whether this accumulated evidence can be used to reach general conclusions concerning vegetation vulnerability to inform conservation management decisions. Experimental trampling studies on a global scale were retrieved using a systematic review methodology and synthesised using random effects meta-analysis. The relationships between vegetation recovery and each of initial vegetation resistance, trampling intensity, time for recovery, Raunkiaer life-form (perennating bud position), and habitat were tested using random effects multiple meta-regressions and subgroup analyses. The systematic search yielded 304 studies; of these, nine reported relevant randomized controlled experiments, providing 188 vegetation recovery effect sizes for analysis. The synthesis indicated there was significant heterogeneity in the impact of trampling on vegetation recovery. This was related to resistance and recovery time, and the interactions of these variables with Raunkiaer life-form, but was not strongly dependent on the intensity of the trampling experienced. The available evidence suggests that vegetation dominated by hemicryptophytes and geophytes recovers from trampling to a greater extent than vegetation dominated by other life-forms. Variation in effect within the chamaephyte, hemicryptophyte and geophyte life-form sub-groups was also explained by the initial resistance of vegetation to trampling, but not by trampling intensity. Intrinsic properties of plant communities appear to be the most important factors determining the response of vegetation to trampling disturbance. Specifically, the dominant Raunkiaer life-form of a plant community accounts for more variation in the resilience of communities to trampling than the intensity of the trampling experienced, suggesting that simple assessments based on this trait could guide decisions concerning sustainable access to natural areas. Methodological and reporting limitations must be overcome before more disparate types of evidence can be synthesised; this would enable more reliable extrapolation to non-study situations, and a more comprehensive understanding of how assessments of intrinsic plant traits can be used to underpin conservation management decisions concerning access.

scholarly journals Assessing the impact of human trampling on vegetation: a systematic review and meta-analysis of experimental evidence

2014 ◽  
Author(s):  
Oliver L. Pescott ◽  
Gavin Stewart
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Plant Communities ◽  
Life Form ◽  
Conservation Management ◽  
Meta Analysis ◽  
Vegetation Recovery ◽  
Management Decisions ◽  
Natural Habitats ◽  
The Impact

Vegetation trampling resulting from recreation can adversely impact natural habitats, leading to the loss of vegetation and the degradation of plant communities. A considerable primary literature exists on this topic, therefore it is important to assess whether this accumulated evidence can be used to reach general conclusions concerning vegetation vulnerability to inform conservation management decisions. Experimental trampling studies on a global scale were retrieved using a systematic review methodology and synthesised using random effects meta-analysis. The relationships between vegetation recovery and each of initial vegetation resistance, trampling intensity, time for recovery, Raunkiaer life-form (perennating bud position), and habitat were tested using random effects multiple meta-regressions and subgroup analyses. The systematic search yielded 304 studies; of these, nine reported relevant randomized controlled experiments, providing 188 vegetation recovery effect sizes for analysis. The synthesis indicated there was significant heterogeneity in the impact of trampling on vegetation recovery. This was related to resistance and recovery time, and the interactions of these variables with Raunkiaer life-form, but was not strongly dependent on the intensity of the trampling experienced. The available evidence suggests that vegetation dominated by hemicryptophytes and geophytes recovers from trampling to a greater extent than vegetation dominated by other life-forms. Variation in effect within the chamaephyte, hemicryptophyte and geophyte life-form sub-groups was also explained by the initial resistance of vegetation to trampling, but not by trampling intensity. Intrinsic properties of plant communities appear to be the most important factors determining the response of vegetation to trampling disturbance. Specifically, the dominant Raunkiaer life-form of a plant community accounts for more variation in the resilience of communities to trampling than the intensity of the trampling experienced, suggesting that simple assessments based on this trait could guide decisions concerning sustainable access to natural areas. Methodological and reporting limitations must be overcome before more disparate types of evidence can be synthesised; this would enable more reliable extrapolation to non-study situations, and a more comprehensive understanding of how assessments of intrinsic plant traits can be used to underpin conservation management decisions concerning access.

scholarly journals High burden of acute kidney injury in COVID-19 pandemic: systematic review and meta-analysis

2020 ◽  
pp. jclinpath-2020-207023
Author(s):  
Camila Barbosa Oliveira ◽  
Camilla Albertina Dantas Lima ◽  
Gisele Vajgel ◽  
Antonio Victor Campos Coelho ◽  
Paula Sandrin-Garcia
Keyword(s):  
Systematic Review ◽  
Acute Kidney Injury ◽  
Critically Ill ◽  
Random Effects ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Random Effects Model ◽  
Risk Of Death ◽  
Meta Analyses ◽  
The Impact

AimsHospitalised patients with COVID-19 have a variable incidence of acute kidney injury (AKI) according to studies from different nationalities. The present systematic review and meta-analysis describes the incidence of AKI, need for renal replacement therapy (RRT) and mortality among patients with COVID-19-associated AKI.MethodsWe systematically searched electronic database PubMed, SCOPUS and Web of Science to identify English articles published until 25 May 2020. In case of significant heterogeneity, the meta-analyses were conducted assuming a random-effects model.ResultsFrom 746 screened publications, we selected 21 observational studies with 15 536 patients with COVID-19 for random-effects model meta-analyses. The overall incidence of AKI was 12.3% (95% CI 7.3% to 20.0%) and 77% of patients with AKI were critically ill (95% CI 58.9% to 89.0%). The mortality among patients with AKI was 67% (95% CI 39.8% to 86.2%) and the risk of death was 13 times higher compared with patients without AKI (OR=13.3; 95% CI 6.1 to 29.2). Patients with COVID-19-associated AKI needed for RRT in 23.4% of cases (95% CI 12.6% to 39.4%) and those cases had high mortality (89%–100%).ConclusionThe present study evidenced an incidence of COVID-19-associated AKI higher than previous meta-analysis. The majority of patients affected by AKI were critically ill and mortality rate among AKI cases was high. Thus, it is extremely important for health systems to be aware about the impact of AKI on patients’ outcomes in order to establish proper screening, prevention of additional damage to the kidneys and adequate renal support when needed.

Systematic Review and Meta-Analysis of the Association Between Transfusion Independence (TI) and Overall Survival (OS) in Patients (pts) with Myelodysplastic Syndromes (MDS)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1934-1934
Author(s):  
Sue Harnan ◽  
Shijie Ren ◽  
Tim Gomersall ◽  
Emma Everson-Hock ◽  
Anthea Sutton ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Lower Risk ◽  
Research Funding ◽  
Meta Analysis ◽  
Type A ◽  
Type B ◽  
Risk Of Death ◽  
Meta Regression ◽  
The Impact

Abstract Introduction: MDS are a diverse group of haematological disorders affecting bone marrow function and necessitating frequent blood transfusions. A number of studies, from retrospective cohort and registry analyses to randomized controlled trials (RCTs), have shown transfusion status to impact OS in MDS. While transfusion status is considered a prognostic indicator in MDS, no systematic review has been conducted to consolidate and analyze all available evidence to date. This systematic review and meta-analysis is the first to assess the association between TI and OS, and also considers patient risk and acquisition of TI post treatment. Methods: Comprehensive electronic searches were conducted in five key bibliographic databases. Relevant conference proceedings were searched electronically, experts were contacted, grey literature (national and international guidelines, unpublished and unindexed studies) was searched online, and the reference lists of relevant reviews and guidelines were checked. The protocol was published a priori on PROSPERO (ID CRD42014007264). Studies which recruited adults aged ≥ 18 years with confirmed MDS, and reported OS for TI versus transfusion-dependent (TD) pts were included. Any expression of OS and any definition of transfusion status (x transfusions per unit time) were acceptable. RCTs, cohort studies, consecutive case series ≥ 10 cases, before-after studies and case-control studies were eligible for inclusion. Where a hazard ratio (HR) was expressed for TD vs. TI, the ratio was converted by dividing 1 by the reported HR to obtain HR for TI vs. TD. A narrative synthesis and a random effects meta-analysis were conducted. The meta-analysis synthesised the multivariate HR for OS of TI compared with TD pts from non-overlapping cohorts. A random effects meta-regression assessed whether the effect of being TI on OS depends on the risk group (according to IPSS or WHO criteria) of the included pts. Results: Searches identified 1821 titles of which 89 were included, representing 60 separate analyses. Study quality (by the Quality in Prognosis Studies [QUIPS] criteria) was moderate overall, with some limitations in reporting of attrition, correction of confounders, and patient spectrum. Three types of studies were identified: a) recruited TD and TI pts and compared OS between groups (n = 45); b) recruited TD only, and compared those who became TI to those who remained TD after treatment (n = 8); c) recruited TD only, compared those with high transfusion burden to those with low (n = 7). Amongst type a studies (n = 45), TI was consistently associated with an OS benefit whether results were expressed as HRs or as other metrics such as mean survival. In a meta-analysis of all eligible type a studies (n = 11) a 57% decrease in the risk of death compared with TD pts (HR 0.43; 95% credible interval (CrI) 0.31 to 0.56) was estimated. When considering the impact of the risk category of pts through meta-regression (lower-risk and all-risk cohorts only; no higher-risk cohorts were eligible for inclusion), the coefficient of the interaction term was estimated to be HR 1.33 (95% CrI 0.6 to 2.98), which suggested that the magnitude of the benefit for pts being TI on OS was higher for all-risk groups. However, this effect was inconclusive. A meta-analysis of type b studies was not possible as study cohorts overlapped. The multivariate HR in the 3 type b studies which reported this ranged from 0.53 to 0.36, indicating a mortality reduction between 47% and 64% associated with acquisition of TI. Studies reporting other metrics also reported TI pts fared better. A meta-analysis of type c studies was neither planned nor conducted. All studies reported that pts with fewer transfusions per unit time demonstrated better OS than those with more, regardless of the high/low transfusion burden cut point used. Conclusion: A number of studies have previously suggested that MDS pts who are TI have better survival relative to those who are TD, but no meta-analysis has been conducted to date. Our findings revealed a consistent, substantial reduction in mortality among TI pts when compared with TD pts confirming the positive TI-OS association. A meta-regression analysis indicated that the impact of TI was higher in all-risk cohorts versus lower-risk cohorts, but this effect was not conclusive. A similar association was seen for those who acquired TI through treatment (Figure 1). Figure 1 Figure 1. Disclosures Harnan: Celgene Ltd: Research Funding. Ren:Celgene: Research Funding. Gomersall:Celgene Corporation: Research Funding. Everson-Hock:Celgene Ltd: Research Funding. Dhanasiri:Celgene Corp: Employment, Equity Ownership. Kulasekararaj:Celgene: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau.

scholarly journals The Potential Role of Previous Physical Exercise Program to Reduce Seizure Susceptibility: A Systematic Review and Meta-Analysis of Animal Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Ricardo Mario Arida ◽  
Adrielle Andrade Passos ◽  
Alexandre Lebedev Graciani ◽  
João Angelo Ferres Brogin ◽  
Mayara de Almeida Lima Ribeiro ◽  
...  
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Physical Exercise ◽  
Random Effects ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Exercise Programs ◽  
The Impact

Background: Clinical and pre-clinical studies indicate a reduction in seizure frequency as well as a decrease in susceptibility to subsequently evoked seizures after physical exercise programs. In contrast to the influence of exercise after epilepsy previously established, various studies have been conducted attempting to investigate whether physical activity reduces brain susceptibility to seizures or prevents epilepsy. We report a systematic review and meta-analysis of different animal models that addressed the impact of previous physical exercise programs to reduce seizure susceptibility.Methods: We included animal model (rats and mice) studies before brain insult that reported physical exercise programs compared with other interventions (sham, control, or naïve). We excluded studies that investigated animal models after brain insult, associated with supplement nutrition or drugs, that did not address epilepsy or seizure susceptibility, ex vivo studies, in vitro studies, studies in humans, or in silico studies. Electronic searches were performed in the MEDLINE (PubMed), Web of Science (WOS), Scopus, PsycINFO, Scientific Electronic Library Online (SciELO) databases, and gray literature, without restrictions to the year or language of publication. We used SYRCLE's risk of bias tool and CAMARADES checklist for study quality. We performed a synthesis of results for different types of exercise and susceptibility to seizures by random-effects meta-analysis.Results: Fifteen studies were included in the final analysis (543 animals), 13 of them used male animals, and Wistar rats were the most commonly studied species used in the studies (355 animals). The chemoconvulsants used in the selected studies were pentylenetetrazol, penicillin, kainic acid, pilocarpine, and homocysteine. We assessed the impact of study design characteristics and the reporting of mitigations to reduce the risk of bias. We calculated a standardized mean difference effect size for each comparison and performed a random-effects meta-analysis. The meta-analysis included behavioral analysis (latency to seizure onset, n = 6 and intensity of motor signals, n = 3) and electrophysiological analysis (spikes/min, n = 4, and amplitude, n = 6). The overall effect size observed in physical exercise compared to controls for latency to seizure onset was −130.98 [95% CI: −203.47, −58.49] (seconds) and the intensity of motor signals was −0.40 [95% CI: −1.19, 0.40] (on a scale from 0 to 5). The largest effects were observed in electrophysiological analysis for spikes/min with −26.96 [95% CI: −39.56, −14.36], and for spike amplitude (μV) with −282.64 [95% CI: −466.81, −98.47].Discussion:Limitations of evidence. A higher number of animal models should be employed for analyzing the influence of exerciseon seizure susceptibility. The high heterogeneity in our meta-analysis is attributable to various factors, including the number of animals used in each study and the limited number of similar studies. Interpretation. Studies selected in this systematic review and meta-analysis suggest that previous physical exercise programs can reduce some of the main features related to seizure susceptibility [latency seizure onset, spikes/min, and spike amplitude (μV)] induced by the administration of different chemoconvulsants.Systematic Review Registration: PROSPERO, identifier CRD42021251949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251949.

scholarly journals Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Stephanie Antoun ◽  
Pierre Ellul ◽  
Hugo Peyre ◽  
Michelle Rosenzwajg ◽  
Pierre Gressens ◽  
...  
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Random Effects ◽  
Neurodevelopmental Disorders ◽  
Meta Analysis ◽  
Fetal Brain ◽  
First Trimester ◽  
Case Control ◽  
Increased Risk ◽  
The Impact

Abstract Background Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis. Methods Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801). Results We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case–control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12–1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13–95% CI: 1.02–1.26]. Limitations We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case–control). Conclusion Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).

scholarly journals Budesonide for Protein Losing Enteropathy in Patients with Fontan Circulation: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 11 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Jakrin Kewcharoen ◽  
Poemlarp Mekraksakit ◽  
Nath Limpruttidham ◽  
Chanavuth Kanitsoraphan ◽  
Nattawat Charoenpoonsiri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Random Effects ◽  
Meta Analysis ◽  
Fontan Procedure ◽  
Fontan Operation ◽  
Albumin Level ◽  
Random Effects Model ◽  
Protein Losing Enteropathy ◽  
Before And After ◽  
The Impact

Background: Recent studies have shown that oral budesonide can be used to improve albumin level in patients with protein-losing enteropathy (PLE) following Fontan procedure. However, there has never been a systematic review and meta-analysis to confirm this finding. We performed a systematic review and meta-analysis to explore the therapeutic effect of budesonide in patients with PLE post-Fontan procedure. Methods: We searched the databases of MEDLINE and EMBASE from inception to January 2019. Included studies were published studies that evaluate albumin level before and after budesonide therapy in patients with PLE following Fontan procedure. Data from each study were combined using the random-effects model. Results: Five studies with 36 post-Fontan operation patients with PLE were included. In random-effects model, there was a statistically significant difference in albumin level between before and after budesonide treatment (weighted mean difference = 1.28, 95% confidence interval: 0.76-1.79). No publication bias was observed on a funnel plot and Egger test with a P value of .676. Conclusions: The results of this systematic review and meta-analysis show that budesonide can be used to increase albumin level in patients with PLE following Fontan operation. Further studies may focus on the impact of outcome of budesonide in this population.

O-238 Preterm birth after recurrent pregnancy loss: A systematic review and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Wu ◽  
K Nichols ◽  
M Carwana ◽  
C Nicholas ◽  
C Maratta
Keyword(s):  
Systematic Review ◽  
Preterm Birth ◽  
Random Effects ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Meta Analysis ◽  
Population Exposure ◽  
Publication Date ◽  
History Of ◽  
The Impact

Abstract Study question What is the impact of recurrent pregnancy loss on the risk of preterm birth? Summary answer Women with RPL were found to be at increased odds of having preterm deliveries (<37 weeks gestation) in their subsequent live pregnancies. What is known already Recurrent pregnancy loss (RPL) occurs in up to 5% of all women with miscarriages. The emotional, physical, and financial burden associated with RPL is unequivocal, and over the years, much research has gone into the management of RPL. However, relatively little is known about the perinatal outcomes following RPL. Past research in the area reports conflicting data on the association between RPL and preterm birth (PTB) in a subsequent pregnancy. Study design, size, duration A systematic search was performed across thePubMed, EMBASE and Google Scholar databases for relevant studies published up until October 2020. Observational cohort and case-control studies comparing the risk of preterm birth (PTB) among women with and without a history of RPL were included. Effect estimates were pooled using a DerSimonian and Laird random-effects meta-analysis model. Study appraisal was performed using the Newcastle-Ottawa scale. Participants/materials, setting, methods We included studies where the study population consisted of women with a history of RPL (defined as 2 or more pregnancy losses), where the comparator group consisted of women without a history of RPL, and where the outcomes assessed included PTB (defined as birth prior to 37 completed weeks gestation). Two reviewers independently extracted data in duplicate. Publication date, population, exposure and outcome data were extracted. Main results and the role of chance A total of 12 retrospective observational studies met inclusion criteria, and were included in the systematic review and meta-analysis (N = 37,046 women with a history of RPL). Incidence of PTB among the RPL groups ranged from 5.8% to 19.6%, and from 1.5-14.0% in the non-RPL groups. A pooled OR of 1.59 with 95% CI 1.40-1.80 was observed in our random-effects meta-analysis with an I2 of 84%. Subgroup analyses were completed for the pooled risk of only 2 RPL (pooled odds ratio [OR] 1.35; 95% CI 1.08-1.69; I2=84.7%); ≥2 RPL (pooled OR 1.42; 95% CI 0.91-2.22; I2=68.9%); and ≥3 RPL (pooled OR 1.86; 95% CI 1.51-2.29; I2=79.5%). Limitations, reasons for caution Inconsistent adjustment for confounders and significant between-study heterogeneity were noted in this study. Wider implications of the findings Despite significant heterogeneity among studies, we found that women with a history of RPL had significantly higher odds of delivering preterm infants in their subsequent pregnancies. Trial registration number CRD 224763

scholarly journals Prevalence of asymptomatic or “silent” myocardial ischemia in diabetic patients: Protocol for a systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252511
Author(s):  
Christophe Dongmo Fokoua-Maxime ◽  
Eric Lontchi-Yimagou ◽  
Takeude Erwan Cheuffa-Karel ◽  
Tchana Loic Tchato-Yann ◽  
Simeon Pierre-Choukem
Keyword(s):  
Systematic Review ◽  
Myocardial Ischemia ◽  
Random Effects ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Silent Myocardial Ischemia ◽  
Cochrane Library ◽  
Diabetic Patients ◽  
Global Prevalence ◽  
The Impact

Introduction Myocardial ischemia (MI) is a top ranked cause of death among diabetic patients, yet it is mostly asymptomatic or “silent”. There is a need for summary epidemiologic measures on this highly lethal and unnoticeable complication of diabetes. The proposed systematic review and meta-analysis aims to estimate of the global prevalence of silent MI among diabetic patients. Methods and analysis This protocol was prepared according to the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) statement. The systematic review will include all observational studies published until March 23, 2021 and reporting on the prevalence of silent MI in diabetic patients. Electronic sources including MEDLINE(PubMed), Embase, Cochrane Library, and Web of Science will be searched for potentially eligible studies, restricted to only studies published in English. Two investigators will select studies and use a pre-pilot tested form to extract data. Further, they will independently perform a qualitative assessment of the risk of bias and overall quality of the selected studies, followed by a quantitative assessment using funnel plots and Egger’s tests. The heterogeneity between studies will be assessed with the Cochrane’s Q statistic, and the I2 statistic will measure the percentage of variation across studies that is due to their heterogeneity rather than chance; it will decide if a meta-analysis can be conducted. In case a meta-analysis cannot be conducted, a descriptive analysis will be performed. Otherwise, study-specific estimates will be pooled using either a fixed-effects or a random-effects model depending on the value of the I2 statistic. Subgroup and random effects meta-regression analyses will be used to further investigate the potential sources of heterogeneity. Finally, sensitivity analyses will be performed to measure the impact of low-quality studies on the results of the meta-analysis, and power calculations will determine the probability that we will detect a true effect if it does exist. Strengths and limitations of this study The intended review will provide an up-to-date summary of the global prevalence of silent MI in diabetic patients. We will conduct a thorough literature search for eligible studies, and we will use robust meta-analysis tools to provide reliable estimates of the global prevalence of silent MI in diabetic patients. Two major limitations could be: the predominance of clinical trials that might limit the generalizability of the findings, given that the strict inclusion criteria of these studies might have excluded other patients; the risk of type 1 error emanating from the high number of subgroup and sensitivity analyses. PROSPERO registration number CRD42019138136.

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