Sensitivity analyses allowed more appropriate and reliable meta-analysis conclusions for multiple outcomes when missing data was present

Schools are promising sites for the delivery of prevention and early intervention programs to reduce child and adolescent anxiety. It is unclear whether universal or targeted approaches are most effective. This review and meta-analysis examines the effectiveness of school-based indicated interventions and was registered with PROSPERO [CRD42018087628].MEDLINE, EMBASE, PsycINFO and the Cochrane Library were searched for randomised controlled trials comparing indicated school programs for child and adolescent anxiety to active or inactive control groups. Twenty original studies, with 2076 participants, met the inclusion criteria and 18 were suitable for meta-analysis. Sub-group and sensitivity analyses explored intervention intensity, delivery agent and control type. A small beneficial effect was found for indicated programs compared to controls on self-reported anxiety symptoms at post-test (g = -0.28, CI = -0.50, -0.05, k= 18). The small effect was maintained at 6 (g = -0.35, CI= -0.58, -0.13, k = 9) and 12 months (g = -0.24, CI = -0.48, 0.00, k = 4). Based on two studies, >12 month effects were very small (g = -0.01, CI= -0.38, 0.36). No differences were found based on intervention intensity, delivery agent and control type. There was evidence of publication bias and a relatively high risk of contamination in studies. Findings support the value of school based indicated programs for child and adolescent anxiety. Effects at 12 months outperform many universal programs. High quality, randomised controlled and pragmatic trials are needed, with attention control groups and beyond 12 month diagnostic assessments are needed.

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Systematic review and meta-analysis of the prevalence of depressive symptoms, dysthymia and major depressive disorders among homeless people

BMJ Open ◽

10.1136/bmjopen-2020-040061 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040061

Author(s):

Getinet Ayano ◽

Asmare Belete ◽

Bereket Duko ◽

Light Tsegay ◽

Berihun Assefa Dachew

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Depressive Disorders ◽

Meta Analysis ◽

Random Effect ◽

Homeless People ◽

Sensitivity Analyses ◽

Prevalence Rates ◽

Major Depressive ◽

Major Depressive Disorders

ObjectivesTo assess the global prevalence estimates of depressive symptoms, dysthymia and major depressive disorders (MDDs) among homeless people.DesignSystematic review and meta-analysis.Data sourcesDatabases including PubMed, Scopus and Web of Science were systematically searched up to February 2020 to identify relevant studies that have reported data on the prevalence of depressive symptoms, dysthymia and MDDs among homeless people.Eligibility criteriaOriginal epidemiological studies written in English that addressed the prevalence of depressive problems among homeless people.Data extraction and synthesisA random-effect meta-analysis was performed to pool the prevalence estimated from individual studies. Subgroup and sensitivity analyses were employed to compare the prevalence across the groups as well as to identify the source of heterogeneities. The Joanna Briggs Institute’s quality assessment checklist was used to measure the study quality. Cochran’s Q and the I2 test were used to assess heterogeneity between the studies.ResultsForty publications, including 17 215 participants, were included in the final analysis. This meta-analysis demonstrated considerably higher prevalence rates of depressive symptoms 46.72% (95% CI 37.77% to 55.90%), dysthymia 8.25% (95% CI 4.79% to 11.86%), as well as MDDs 26.24% (95% CI 21.02% to 32.22%) among homeless people. Our subgroup analysis showed that the prevalence of depressive symptoms was high among younger homeless people (<25 years of age), whereas the prevalence of MDD was high among older homeless people (>50 years of age) when compared with adults (25–50 years).ConclusionThis review showed that nearly half, one-fourth and one-tenth of homeless people are suffering from depressive symptoms, dysthymia and MDDs, respectively, which are notably higher than the reported prevalence rates in the general population. The findings suggest the need for appropriate mental health prevention and treatment strategies for this population group.

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Association of UCP1 and UCP2 variants with diabetic retinopathy susceptibility in type-2 diabetes mellitus patients: a meta-analysis

BMC Ophthalmology ◽

10.1186/s12886-021-01838-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xujia Liu ◽

Zehua Jiang ◽

Guihua Zhang ◽

Tsz Kin Ng ◽

Zhenggen Wu

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Fixed Effects ◽

Literature Search ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Fixed Effects Models ◽

Type 2 Dm ◽

Subgroup Analyses

Abstract Background Genetic association of uncoupling proteins (UCPs) variants with the susceptibility of diabetic retinopathy (DR) in diabetes mellitus (DM) patients has been reported but with controversy. Here we aimed to conduct a meta-analysis to confirm the association of different UCPs variants with DR. Methods Three databases (Medline Ovid, Embase Ovid and CENTRAL) were applied in the literature search. Five genetic models, including allelic, homozygous, heterozygous, dominant and recessive models, were evaluated. Odds ratios (OR) were estimated under the random or fixed-effects models. Subgroup analyses, publication bias and sensitivity analyses were also conducted. Results Eleven studies on 2 UCPs variants (UCP1 rs1800592 and UCP2 rs659366) were included. Our meta-analysis showed that UCP1 rs1800592 was not associated with DR in type-2 DM patients, and UCP2 rs659366 also showed no association with DR. In the subgroup analyses on the stage of DR, allele G of UCP1 rs1800592 significantly increased the susceptibility of proliferative diabetic retinopathy (PDR) in type-2 DM patients in the allelic (OR = 1.26, P = 0.03) and homozygous models (OR = 1.60, P = 0.04). Subgroup analysis on ethnicity did not found any significant association of rs1800592 and rs659366 with DR. Conclusion Our meta-analysis confirmed the association of UCP1 rs1800592 variant with PDR in patients with type-2 DM, suggesting its potential as a genetic marker for PDR prediction in population screening.

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Dealing with Missing Data in an IPD Meta‐Analysis

Individual Participant Data Meta‐Analysis ◽

10.1002/9781119333784.ch18 ◽

2021 ◽

pp. 499-524

Author(s):

Thomas P.A. Debray ◽

Kym I.E. Snell ◽

Matteo Quartagno ◽

Shahab Jolani ◽

Karel G.M. Moons ◽

...

Keyword(s):

Missing Data ◽

Meta Analysis

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Incidence, risk factors and prognostic effect of imaging right ventricular involvement in patients with COVID-19: a dose–response analysis protocol for systematic review

BMJ Open ◽

10.1136/bmjopen-2021-049866 ◽

2021 ◽

Vol 11 (5) ◽

pp. e049866

Author(s):

Chenghui Zhou ◽

Baohui Lou ◽

Hui Li ◽

Xin Wang ◽

Hushan Ao ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Right Ventricular ◽

Dose Response ◽

Meta Analysis ◽

Adult Patients ◽

Sensitivity Analyses ◽

Prognostic Effect ◽

All Cause Mortality ◽

Incidence Risk

IntroductionEmerging evidence has shown that COVID-19 infection may result in right ventricular (RV) disturbance and be associated with adverse clinical outcomes. The aim of this meta-analysis is to summarise the incidence, risk factors and the prognostic effect of imaging RV involvement in adult patients with COVID-19.MethodsA systematical search will be performed in PubMed, EMBase, ISI Knowledge via Web of Science and preprint databases (MedRxiv and BioRxiv) (until October 2021) to identify all cohort studies in adult patients with COVID-19. The primary outcome will be the incidence of RV involvement (dysfunction and/or dilation) assessed by echocardiography, CT or MRI. Secondary outcomes will include the risk factors for RV involvement and their association with all-cause mortality during hospitalisation. Additional outcomes will include the RV global or free wall longitudinal strain (RV-GLS or RV-FWLS), tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC) and RV diameter. Univariable or multivariable meta-regression and subgroup analyses will be performed for the study design and patient characteristics (especially acute or chronic pulmonary embolism and pulmonary hypertension). Sensitivity analyses will be used to assess the robustness of our results by removing each included study at one time to obtain and evaluate the remaining overall estimates of RV involvement incidence and related risk factors, association with all-cause mortality, and other RV parameters (RV-GLS or RV-FWLS, TAPSE, S’, FAC and RV diameter). Both linear and cubic spline regression models will be used to explore the dose–response relationship between different categories (>2) of RV involvement and the risk of mortality (OR or HR).Ethics and disseminationThere was no need for ethics approval for the systematic review protocol according to the Institutional Review Board/Independent Ethics Committee of Fuwai Hospital. This meta-analysis will be disseminated through a peer-reviewed journal for publication.PROSPERO registration numberCRD42021231689.

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Mindfulness-based and acceptance-based programmes in the treatment of obsessive–compulsive disorder: a study protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2021-050329 ◽

2021 ◽

Vol 11 (6) ◽

pp. e050329

Author(s):

Johannes Julian Bürkle ◽

Johannes Caspar Fendel ◽

Stefan Schmidt

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Obsessive Compulsive Disorder ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Secondary Outcome ◽

Controlled Trials ◽

Obsessive Compulsive ◽

Compulsive Disorder

IntroductionCognitive–behavioural therapy (CBT) with exposure and response prevention is the recommended standard for the treatment of obsessive–compulsive disorder (OCD). However, a high proportion of patients refuse this treatment, do not respond or relapse shortly after treatment. Growing evidence suggests that mindfulness-based and acceptance-based programmes (MABPs) are an effective option for the treatment of OCD. This systematic review and meta-analysis will examine the effectiveness of MABPs in treating OCD. We also aimed to explore potential moderators of the programmes’ effectiveness.Methods and analysisWe will systematically search MEDLINE, Embase, PsycINFO, PSYINDEX, Web of Science, CINAHL and Cochrane Register of Controlled Trials (no language restrictions) for studies that evaluate the effect of MABPs on patients with OCD. We will conduct backward and forward citation searches of included studies and relevant reviews and contact corresponding authors. The primary outcome will be pre-post intervention change in symptom severity. A secondary outcome will be change in depressive symptoms. Two reviewers will independently screen the records, extract the data and rate the methodological quality of the studies. We will include both controlled and uncontrolled trials. Randomised controlled trials will be meta-analysed, separately assessing between-group effects. A second meta-analysis will assess the within-group effect of all eligible studies. We will explore moderators and sources of heterogeneity such as the specific programme, study design, changes in depressive symptoms, hours of guided treatment, control condition and prior therapy (eg, CBT) using metaregression and subgroup analyses. We will perform sensitivity analyses using follow-up data. A narrative synthesis will also be pursued. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to assess the quality of the evidence.Ethics and disseminationEthical approval is not required. Results will be published in peer-reviewed journals and presented at international conferences.

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Risk of dementia in gout and hyperuricaemia: a meta-analysis of cohort studies

BMJ Open ◽

10.1136/bmjopen-2020-041680 ◽

2021 ◽

Vol 11 (6) ◽

pp. e041680

Author(s):

Shu-Yue Pan ◽

Rui-Juan Cheng ◽

Zi-Jing Xia ◽

Qiu-Ping Zhang ◽

Yi Liu

Keyword(s):

Cohort Studies ◽

Quality Assessment ◽

Publication Bias ◽

Data Extraction ◽

Meta Analysis ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Crystal Formation ◽

Medical Subject Headings ◽

Eligibility Criteria

ObjectivesGout, characterised by hyperuricaemia with monosodium urate crystal formation and inflammation, is the most common inflammatory arthritis in adults. Recent studies have found that elevated uric acid levels are related to the occurrence of dementia. We conducted a study to investigate the association between dementia and gout or hyperuricaemia.DesignSystematic review and meta-analysis of cohort studies.Data sourcesStudies were screened from inception to 28 June 2019 by searching Medline, Embase and the Cochrane Library databases.Eligibility criteriaCohort studies comparing the risk of dementia in patients with gout and hyperuricaemia versus non-gout and non-hyperuricaemia controls were enrolled.Data extraction and analysisTwo reviewers separately selected studies and extracted data using the Medical Subject Headings without restriction on languages or countries. The adjusted HRs were pooled using the DerSimonian and Laird random effects model. Sensitivity analyses were conducted to evaluate the stability of the results. Publication bias was evaluated using Egger’s and Begg’s tests. Quality assessment was performed according to the Newcastle-Ottawa Scale.ResultsFour cohort studies that met the inclusion criteria were included in our meta-analysis. We found that gout and hyperuricaemia did not increase the risk of dementia, with a pooled HR of 0.94 (95% CI 0.69 to 1.28), but might decrease the risk of Alzheimer’s disease (AD), with a pooled HR of 0.78 (95% CI 0.64 to 0.95). There was little evidence of publication bias. Quality assessment of the included studies was high (range: 6–8 points).ConclusionsOur study shows that gout and hyperuricaemia do not increase the risk of dementia. However, gout and hyperuricaemia might have a protective effect against AD. Due to the limited number of research articles, more investigations are needed to demonstrate the potential relationship between dementia and gout or hyperuricaemia.

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Knowledge of blood donation and associated factors in Ethiopia: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-044343 ◽

2021 ◽

Vol 11 (7) ◽

pp. e044343

Author(s):

Addisu Getie ◽

Adam Wondmieneh ◽

Melaku Bimerew ◽

Getnet Gedefaw ◽

Asmamaw Demis

Keyword(s):

Systematic Review ◽

Associated Factors ◽

Blood Donation ◽

Meta Analysis ◽

Educational Status ◽

Sensitivity Analyses ◽

Cross Sectional ◽

Level Of Knowledge ◽

Cross Sectional Studies ◽

Study Participants

ObjectiveTo assess the level of knowledge about blood donation and associated factors in Ethiopia.DesignSystematic review and meta-analysis.MethodsBoth published and unpublished cross-sectional studies on the level of knowledge about blood donation in Ethiopia were included. Articles from different databases such as PubMed/MEDLINE, HINARI, EMBASE, Scopus, Google Scholar and African Journals Online were searched. Cochrane I2 statistics were used to check for heterogeneity. Subgroup and sensitivity analyses of evidence of heterogeneity were carried out. Egger’s test with funnel plot was conducted to investigate publication bias.ResultTwenty cross-sectional studies with a total of 8338 study participants (4712 men and 3626 women) were included. The overall nationwide level of knowledge about blood donation was 56.57% (95% CI 50.30 to 62.84). Being in secondary school and above (adjusted OR=3.12; 95% CI 2.34 to 4.16) and being male (adjusted OR=1.81; 95% CI 1.44 to 2.28) were the factors associated with level of knowledge about blood donation.ConclusionMore than half of the study participants were knowledgeable about blood donation. Sex and educational status were the factors significantly associated with level of knowledge about blood donation in Ethiopia. Therefore, there is a need for education and dissemination of information about blood donation among the general population to build adequate knowledge and maintain regular blood supply.

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Interventional radiology versus operative management for splenic injuries: a study protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-028172 ◽

2019 ◽

Vol 9 (8) ◽

pp. e028172

Author(s):

Masahiro Kashiura ◽

Noritaka Yada ◽

Kazuma Yamakawa

Keyword(s):

Systematic Review ◽

Interventional Radiology ◽

Meta Analysis ◽

Operative Management ◽

Sensitivity Analyses ◽

Definitive Treatment ◽

Controlled Trials ◽

Cochrane Central Register ◽

Statistical Heterogeneity ◽

Non Operative Management

IntroductionOver the past decades, the treatment for blunt splenic injuries has shifted from operative to non-operative management. Interventional radiology such as splenic arterial embolisation generally increases the success rate of non-operative management. However, the type of intervention, such as the first definitive treatment for haemostasis (interventional radiology or surgery) in blunt splenic injuries is unclear. Therefore, we aim to clarify whether interventional radiology improves mortality in patients with blunt splenic trauma compared with operative management by conducting a systematic review and meta-analysis.Methods and analysisWe will search the following electronic bibliographic databases to retrieve relevant articles for the literature review: Medline, Embase and the Cochrane Central Register of Controlled Trials. We will include controlled trials and observational studies published until September 2018. We will screen search results, assess the study population, extract data and assess the risk of bias. Two review authors will extract data independently, and discrepancies will be identified and resolved through a discussion with a third author where necessary. Data from eligible studies will be pooled using a random-effects meta-analysis. Statistical heterogeneity will be assessed by using the Mantel-Haenszel χ² test and the I² statistic, and any observed heterogeneity will be quantified using the I² statistic. We will conduct sensitivity analyses according to several factors relevant for the heterogeneity.Ethics and disseminationOur study does not require ethical approval as it is based on the findings of previously published articles. This systematic review will provide guidance on selecting a method for haemostasis of splenic injuries and may also identify knowledge gaps that could direct further research in the field. Results will be disseminated through publication in a peer-reviewed journal and presentations at relevant conferences.PROSPERO registration numberCRD42018108304.

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1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1426 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S639-S640

Author(s):

L W Preston Church

Keyword(s):

Plasmodium Falciparum ◽

Random Effects ◽

Normal Saline ◽

Meta Analysis ◽

Laboratory Data ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sensitivity Analyses ◽

Double Blind ◽

Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age > 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

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