scholarly journals Ivabradine added to usual care in patients with heart failure: a systematic review with meta-analysis and trial sequential analysis

2021 ◽  
pp. bmjebm-2021-111724
Author(s):  
Mathias Maagaard ◽  
Emil Eik Nielsen ◽  
Naqash Javaid Sethi ◽  
Ning Liang ◽  
Si-Hong Yang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Usual Care ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
All Cause Mortality

ObjectivesTo assess the beneficial and harmful effects of adding ivabradine to usual care in participants with heart failure.DesignA systematic review with meta-analysis and trial sequential analysis.Eligibility criteriaRandomised clinical trials comparing ivabradine and usual care with usual care (with or without) placebo in participants with heart failure.Information sourcesMedline, Embase, CENTRAL, LILACS, CNKI, VIP and other databases and trial registries up until 31 May 2021.Data extractionPrimary outcomes were all-cause mortality, serious adverse events and quality of life. Secondary outcomes were cardiovascular mortality, myocardial infarction and non-serious adverse events. We performed meta-analysis of all outcomes. We used trial sequential analysis to control risks of random errors, the Cochrane risk of bias tool to assess the risks of systematic errors and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of the evidence.ResultsWe included 109 randomised clinical trials with 26 567 participants. Two trials were at low risk of bias, although both trials were sponsored by the company that developed ivabradine. All other trials were at high risk of bias. Meta-analyses and trial sequential analyses showed that we could reject that ivabradine versus control reduced all-cause mortality (risk ratio (RR)=0.94; 95% CI 0.88 to 1.01; p=0.09; high certainty of evidence). Meta-analysis and trial sequential analysis showed that ivabradine seemed to reduce the risk of serious adverse events (RR=0.90; 95% CI 0.87 to 0.94; p<0.00001; number needed to treat (NNT)=26.2; low certainty of evidence). This was primarily due to a decrease in the risk of ‘cardiac failure’ (RR=0.83; 95% CI 0.71 to 0.97; p=0.02; NNT=43.9), ‘hospitalisations’ (RR=0.89; 95% CI 0.85 to 0.94; p<0.0001; NNT=36.4) and ‘ventricular tachycardia’ (RR=0.59; 95% CI 0.43 to 0.82; p=0.001; NNT=212.8). However, the trials did not describe how these outcomes were defined and assessed during follow-up. Meta-analyses showed that ivabradine increased the risk of atrial fibrillation (RR=1.19; 95% CI 1.04 to 1.35; p=0.008; number needed to harm (NNH)=116.3) and bradycardia (RR=3.95; 95% CI 1.88 to 8.29; p=0.0003; NNH=303). Ivabradine seemed to increase quality of life on the Kansas City Cardiomyopathy Questionnaire (KCCQ) (mean difference (MD)=2.92; 95% CI 1.34 to 4.50; p=0.0003; low certainty of evidence), but the effect size was small and possibly without relevance to patients, and on the Minnesota Living With Heart Failure Questionnaire (MLWHFQ) (MD=−5.28; 95% CI −6.60 to −3.96; p<0.00001; very low certainty of evidence), but the effects were uncertain. Meta-analysis showed no evidence of a difference between ivabradine and control when assessing cardiovascular mortality and myocardial infarction. Ivabradine seemed to increase the risk of non-serious adverse events.Conclusion and relevanceHigh certainty evidence shows that ivabradine does not seem to affect the risks of all-cause mortality and cardiovascular mortality. The effects on quality of life were small and possibly without relevance to patients on the KCCQ and were very uncertain for the MLWHFQ. The effects on serious adverse events, myocardial infarction and hospitalisation are uncertain. Ivabradine seems to increase the risk of atrial fibrillation, bradycardia and non-serious adverse events.PROSPERO registration number: CRD42018112082.

scholarly journals Effects of adding ivabradine to usual care in patients with angina pectoris: a systematic review of randomised clinical trials with meta-analysis and Trial Sequential Analysis

Open Heart ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. e001288
Author(s):  
Mathias Maagaard ◽  
Emil Eik Nielsen ◽  
Naqash Javaid Sethi ◽  
Liang Ning ◽  
Si-hong Yang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angina Pectoris ◽  
Adverse Events ◽  
Sequential Analysis ◽  
Randomised Clinical Trials ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
All Cause Mortality ◽  
Artery Disease

ObjectiveTo determine the impact of ivabradine on outcomes important to patients with angina pectoris caused by coronary artery disease.MethodsWe conducted a systematic review. We included randomised clinical trials comparing ivabradine versus placebo or no intervention for patients with angina pectoris due to coronary artery disease published prior to June 2020. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Cochrane methodology, Trial Sequential Analysis, Grading of Recommendations Assessment, Development, and Evaluation, and our eight-step procedure. Primary outcomes were all-cause mortality, serious adverse events and quality of life.ResultsWe included 47 randomised clinical trials enrolling 35 797 participants. All trials and outcomes were at high risk of bias. Ivabradine compared with control did not have effects when assessing all-cause mortality (risk ratio [RR] 1.04; 95% CI 0.96 to 1.13), quality of life (standardised mean differences −0.05; 95% CI −0.11 to 0.01), cardiovascular mortality (RR 1.07; 95% CI 0.97 to 1.18) and myocardial infarction (RR 1.03; 95% CI 0.91 to 1.16). Ivabradine seemed to increase the risk of serious adverse events after removal of outliers (RR 1.07; 95% CI 1.03 to 1.11) as well as the following adverse events classified as serious: bradycardia, prolonged QT interval, photopsia, atrial fibrillation and hypertension. Ivabradine also increased the risk of non-serious adverse events (RR 1.13; 95% CI 1.11 to 1.16). Ivabradine might have a statistically significant effect when assessing angina frequency (mean difference (MD) 2.06; 95% CI 0.82 to 3.30) and stability (MD 1.48; 95% CI 0.07 to 2.89), but the effect sizes seemed minimal and possibly without any relevance to patients, and we identified several methodological limitations, questioning the validity of these results.ConclusionOur findings do not support that ivabradine offers significant benefits on patient important outcomes, but rather seems to increase the risk of serious adverse events such as atrial fibrillation and non-serious adverse events. Based on current evidence, guidelines need reassessment and the use of ivabradine for angina pectoris should be reconsidered.PROSPERO registration numberCRD42018112082.

scholarly journals Psychotherapy versus treatment as usual and other control interventions in children and adolescents with overweight and obesity: a protocol for systematic review with meta-analysis and Trial Sequential Analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e036058
Author(s):  
Rajeeb Rashid ◽  
Laura Condon ◽  
Christian Gluud ◽  
Janus C Jakobsen ◽  
Jane Lindschou ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Children And Adolescents ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Overweight And Obesity ◽  
Trial Sequential Analysis ◽  
Serious Adverse Events ◽  
Treatment As Usual

IntroductionThe prevalence of children with overweight and obesity is increasing worldwide. Multicomponent interventions incorporating diet, physical activity and behavioural change have shown limited improvement to body mass index (BMI). However, the impact of psychotherapy is poorly explored. This systematic review aims to assess the effects of psychotherapeutic approaches for children with all degrees of overweight.Methods and analysisWe will include randomised clinical trials involving children and adolescents between 0 and 18 years with overweight and obesity, irrespective of publication type, year, status or language up to April 2020. Psychotherapy will be compared with no intervention; wait list control; treatment as usual; sham psychotherapy or pharmaceutical placebo. The following databases will be searched: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, Embase, PsycINFO, PubMed, Web of Science, CINAHL and LILACS. Primary outcomes will be BMI z-score, quality of life measured by a validated scale and proportion of patients with serious adverse events. Secondary outcomes will be body weight, self-esteem, anxiety, depression and proportion of patients with non-serious adverse events. Exploratory outcomes will be body fat, muscle mass and serious adverse events. Study inclusion, data extraction and bias risk assessments will be conducted independently by at least two authors. We will assess risk of bias according to Cochrane guidelines and the Cochrane Effective Practice and Organisation of Care guidance. We will use meta-analysis and control risks of random errors with Trial Sequential Analysis. The quality of the evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation Tool. The systematic review will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines.Ethics and disseminationAs individual patient data will not be included, we do not require ethics approval. This review will be published in a peer review journal.PROSPERO registration numberCRD42018086458.

scholarly journals Ursodeoxycholic Acid: Efficacy and Safety in the Treatment of Nonalcoholic Fatty Liver Disease (Meta-Analysis)

2018 ◽  
Vol 73 (5) ◽  
pp. 294-305 ◽  
Author(s):  
Сhavdar S. Pavlov ◽  
Daria L. Varganova ◽  
Marianna C. Semenistaia ◽  
Ekatherina A. Kuznetsova ◽  
Anna A. Usanova ◽  
...  
Keyword(s):  
Liver Disease ◽  
Adverse Events ◽  
Ursodeoxycholic Acid ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Trial Sequential Analysis ◽  
Quality Of Evidence ◽  
Bias Risk

Вackground: Non-alcoholic liver disease (NAFLD) is a widely spread disease that needs an effective and safe treatment strategy. One of pharmacological treatments for people with NAFLD is ursodeoxycholic acid (UDCA). The use of UDCA is pathogenetically justified because of its cytoprotective, antiapoptotic, antioxidant, and hypoglycemic properties. Aim: Our meta-analysis (M-A) aimed to assess the benefits and harms of UDCA in people with NAFLD. Material and methods: We identified trials through electronic searches in the Cochrane Hepato-Biliary (CHB) Controlled Trials Register, CENTRAL, MEDLINE, Embase, SCI, LILACS, eLibrary (May 2018). We considered for inclusion randomised clinical trials (RCTs) assessing URSO versus placebo/no intervention in adult participants with NAFLD. We allowed co-interventions in the trial groups if they were similar. We followed Cochrane methodology, CHB Group methodology using Review Manager 5 and Trial Sequential Analysis to perform meta-analysis (M-A), assessed bias risk of the trials, quality of evidence using GRADE. Results: Four RCT, at high bias risk, low quality of evidence, provided data for analysis: 254 participants at different stages of NAFLD received oral UDCA (median of 18 months), 256 ― placebo/no intervention; age 18 to 75 years. We found no evidence of effect on mortality (there were no deaths) and on histological parameters such as steatosis (MD -0.13; CI -0.40−0.13; participants 323; trials 3; I2=43%), fibrosis (MD 0.00; CI -0.00−0.22; participants 323; trials 3; I2=0%), and inflammation (MD -0.05; CI -0.20−0.10; participants 325; trials 3; I2=0%). Also we found no evidence for significant influence of UDCA on occurrence of serious adverse events (RR 1.45, 95% CI 0.65−3.21; participants 292; trials 2; I2=0%), adverse events (RR 1.52, 95% CI 0.73−3.16; participants 510; trials 4; I2=36%) neither with traditional M-A (random-effects), nor with TSA SAE (CI 0.56−2.91; participants 292; trials 2; I2=0%, D2=0%), AE (CI 0.77–2.21; participants 510; trials 4; I2=0%, D2=0%). There was no evidence of effect on cytolysis, but beneficial effect of UDCA on cholestasis (GGTP) (data from two trials only) (р0.0001). We found no data on quality of life. All the trials were funded by the industry. Conclusion: Based on the small number of trials at high risk of bias, low quality, despite the safety profile observed with our M-A, we can neither recommend nor reject the use of UDCA for people with NAFLD. Further trials with low risk of bias and high quality are required to assess the benefits and harms of UDCA. 

scholarly journals Traction Therapy for Cervical Radicular Syndrome is Statistically Significant but not Clinically Relevant for Pain Relief. A Systematic Literature Review with Meta-Analysis and Trial Sequential Analysis

2020 ◽  
Vol 9 (11) ◽  
pp. 3389
Author(s):  
Claudio Colombo ◽  
Stefano Salvioli ◽  
Silvia Gianola ◽  
Greta Castellini ◽  
Marco Testa
Keyword(s):  
Sequential Analysis ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Treatment Modalities ◽  
Trial Sequential Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Quality Of Evidence ◽  
Radicular Syndrome

Aim: We aimed to investigate the effectiveness of traction therapy in reducing pain by performing a systematic review with meta-analysis. We also explore the best modality for administering traction to patients with cervical radicular syndrome (CRS). Methods: We searched the Medline, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) electronic databases. Two reviewers independently selected randomized controlled trials (RCTs) that compared traction in addition to other treatments versus the effectiveness of other treatments alone for pain outcome. We calculated the mean differences (MDs) and 95% confidence intervals (CIs). We used Cochrane’s tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to evaluate the quality of evidence and summarize the study conclusions. Results: A total of seven studies (589 patients), one with low risk of bias, were evaluated. An overall estimate of treatment modalities showed low evidence that adding traction to other treatments is statistically significant (MD −5.93 [95% CI, −11.81 to −0.04] P = 0.05 and I2 = 57%) compared to other treatments alone. The subgroup analyses were still statistically significant only for mechanical and continuous modalities. Conclusions: Overall analysis showed that, compared to controls, reduction in pain intensity after traction therapy was achieved in patients with cervical radiculopathy. However, the quality of evidence was generally low and none of these effects were clinically meaningful.

scholarly journals Efficacy and harms of convalescent plasma for treatment of hospitalized COVID-19 patients: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Alejandro Piscoya ◽  
Luis Ng-Sueng ◽  
Angela Parra del Riego ◽  
Renato Cerna-Viacava ◽  
Vinay Pasupuleti ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Improvement ◽  
Meta Analysis ◽  
Random Effect ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Quality Of Evidence ◽  
All Cause Mortality ◽  
Grade Methodology

IntroductionWe systematically reviewed benefits and harms of convalescent plasma (CP) in hospitalized COVID-19 patients.Material and methodsRandomized controlled trials (RCTs) and observational studies assessing CP effects on hospitalized, adult COVID-19 patients were searched until November 24, 2020. We assessed risk of bias (RoB) using Cochrane RoB 2.0 and ROBINS-I tools. Inverse variance random effect meta-analyses were performed. Quality of evidence was evaluated using GRADE methodology. Primary outcomes were all-cause mortality, clinical improvement, and adverse events.ResultsFive RCTs (n = 1067) and 6 cohorts (n = 881) were included. Three and 1 RCTs had some concerns and high RoB, respectively; and there was serious RoB in all cohorts. Convalescent plasma did not reduce all-cause mortality in RCTs of severe (RR = 0.60, 95% CI: 0.33–1.10) or moderate (RR = 0.60, 95% CI: 0.09–3.86) COVID-19 vs. standard of care (SOC); CP reduced all-cause mortality vs. SOC in cohorts (RR = 0.66, 95% CI: 0.49–0.91). Convalescent plasma did not reduce invasive ventilation vs. SOC in moderate disease (RR = 0.85, 95% CI: 0.47–1.55). In comparison to placebo + SOC, CP did not affect all-cause mortality (RR = 0.75, 95% CI: 0.48–1.16) or clinical improvement (HR = 1.07, 95% CI: 0.82–1.40) in severe patients. Adverse and serious adverse events were scarce, similar between CP and controls. Quality of evidence was low or very low for most outcomes.ConclusionsIn comparison to SOC or placebo + SOC, CP did not reduce all-cause mortality in RCTs of hospitalized COVID-19 patients. Convalescent plasma did not have an effect on other clinical or safety outcomes. Until now there is no good quality evidence to recommend CP for hospitalized COVID-19 patients.

scholarly journals Nutritional Status in Patients with Acute heart failure: A systematic review and meta-analysis with trial sequential analysis

2021 ◽  
Author(s):  
Jihane Belayachi ◽  
Imane Katir ◽  
Rhita Nechba Bennis ◽  
Naoufel Madani ◽  
Redouane Abouqal
Keyword(s):  
Heart Failure ◽  
Nutritional Status ◽  
Quality Assessment ◽  
Publication Bias ◽  
Acute Heart Failure ◽  
Sequential Analysis ◽  
Meta Analysis ◽  
Trial Sequential Analysis ◽  
All Cause Mortality

AbstractA critical review of the prognosis impact of malnutrition in patients admitted with acute heart failure (AHF) has never been performed. We systematically reviewed the observational epidemiology literature to determine the all-cause mortality (ACM) in undernourished patients with acute heart failure or at risk of malnutrition through a meta-analysis of observational studies.A systemic search using PubMed, Scopus, and Web of Science was done for articles reporting an association between malnutrition and mortality in patient with acute heart failure published before December 2019. Original data from observational cohort studies in patients with acute heart failure at baseline, and with nutritional state evaluation at admission using screening, or assessment tools. The outcome of interest was mortality independent of the timeframe for follow up. The characteristics of the included study were collected. Data quality assessment using the Newcastle Ottawa Quality Assessment Scale. The hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted. For the meta-analysis, a random-effects model was considered.Heterogeneity between studies was assessed using Cochran Q statistics and I2 statistics. Subgroup analyses were used to identify the source of heterogeneity. A sensitive analysis was performed to reflect the influence of the individual data set on the pooled HR. Publication bias was detected using the Doi plot and Luis Furuya-Kanamori asymmetry index (LFK index). The influence of potential publication bias on results was explored by using the trim-and-fill procedure. To assess the risks of random errors, trial sequential analysis (TSA) was performed.Seven studies were eligible for review and meta-analysis. There were 9053 participants and over 1536 events occurred. The prevalence of malnutrition varied from 33% to 78.8%. Mean follow-up varied between 189 and 951 days. ACM rates varied between 7% and 42.6%. Nutritional status is significantly associated with mortality in patients with AHF (Pooled HR=1.15;95%CI[1.08-1.23]). Considerable between-study heterogeneity was observed (I2=83%, P=0.001). Heterogeneity was partially explained by the different tools used to screen malnutrition risk, and follow-up durations used by the included studies. There was evidence of major publication bias regarding the risk of malnutrition-related to ACM. The obtained LFK index was 6.12 and suggests major asymmetry. The recalculated pooled HR that incorporates the hypothetical missing studies is 1.15; 95%CI (1.08-1.22). However, the accumulating number of participants and the required information size has not yet been achieved. Then, the trial sequential monitoring boundary is inconclusive.This first meta-analysis of the association between nutritional status in patients with acute heart failure and all-cause mortality indicated that malnutrition risk in a patient with acute heart failure was associated with increased all-cause mortality. The prognosis impact of malnutrition is real despite heterogeneity in tools and cut off for defining malnutrition and mean follow up duration. This review underlines the peremptory need for multicenter studies, for uniform guidelines for assessing nutritional status, and for reporting guidelines for prognostic studies in an acute cardiovascular setting. Better nutritional practice to improve patient care is emphasized in international and national health care guidelines.

scholarly journals Self-determination theory interventions versus usual care in people with diabetes: a protocol for a systematic review with meta-analysis and trial sequential analysis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anne Sophie Mathiesen ◽  
Mette Juel Rothmann ◽  
Vibeke Zoffmann ◽  
Janus Christian Jakobsen ◽  
Christian Gluud ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Usual Care ◽  
Patient Engagement ◽  
Sequential Analysis ◽  
Self Determination Theory ◽  
Risk Of Bias ◽  
Self Determination ◽  
Trial Sequential Analysis

Abstract Background Existing self-management and behavioural interventions for diabetes vary widely in their content, and their sustained long-term effectiveness is uncertain. Autonomy supporting interventions may be a prerequisite to achieve ‘real life’ patient engagement and more long-term improvement through shared decision-making and collaborative goal setting. Autonomy supportive interventions aim to promote that the person with diabetes’ motivation is autonomous meaning that the person strives for goals they themselves truly believe in and value. This is the goal of self-determination theory and guided self-determination interventions. Self-determination theory has been reviewed but without assessing both benefits and harms and accounting for the risk of random errors using trial sequential analysis. The guided self-determination has not yet been systematically reviewed. The aim of this protocol is to investigate the benefits and harms of self-determination theory-based interventions versus usual care in adults with diabetes. Methods/design We will conduct the systematic review following The Cochrane Collaboration guidelines. This protocol is reported according to the PRISMA checklist. A comprehensive search will be undertaken in the CENTRAL, MEDLINE, EMBASE, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S and CPCI-SSH to identify relevant trials. We will include randomised clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory provided face-to-face or digitally by any healthcare professional in any setting. The primary outcomes will be quality of life, mortality, and serious adverse events. The secondary will be diabetes distress, depressive symptoms and adverse events not considered serious. Exploratory outcomes will be glycated haemoglobin and motivation. Outcomes will be assessed at the end of the intervention and at maximum follow-up. The analyses will be performed using Stata version 16 and trial sequential analysis. Two authors will independently screen, extract data from and perform risk of bias assessment of included studies using the Cochrane risk of bias tool. Certainty of the evidence will be assessed by GRADE. Discussion Self-determination theory interventions aim to promote a more autonomous patient engagement and are commonly used. It is therefore needed to evaluate the benefit and harms according to existing trials. Systematic review registration PROSPERO CRD42020181144

scholarly journals Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Franco De Crescenzo ◽  
Laura Amato ◽  
Fabio Cruciani ◽  
Luke P Moynihan ◽  
Gian Loreto D’Alò ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Pharmacological Intervention ◽  
Pharmacological Interventions ◽  
Serious Adverse Events ◽  
All Cause Mortality ◽  
Randomised Controlled

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs.Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low.Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

scholarly journals Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e014820 ◽  
Author(s):  
Jesper Krogh ◽  
Carsten Hjorthøj ◽  
Helene Speyer ◽  
Christian Gluud ◽  
Merete Nordentoft
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Adverse Events ◽  
Sequential Analysis ◽  
Trial Sequential Analysis ◽  
Depression Severity ◽  
Serious Adverse Events ◽  
Secondary Outcomes

ObjectivesTo assess the benefits and harms of exercise in patients with depression.DesignSystematic reviewData sourcesBibliographical databases were searched until 20 June 2017.Eligibility criteria and outcomesEligible trials were randomised clinical trials assessing the effect of exercise in participants diagnosed with depression. Primary outcomes were depression severity, lack of remission and serious adverse events (eg, suicide) assessed at the end of the intervention. Secondary outcomes were quality of life and adverse events such as injuries, as well as assessment of depression severity and lack of remission during follow-up after the intervention.ResultsThirty-five trials enrolling 2498 participants were included. The effect of exercise versus control on depression severity was −0.66 standardised mean difference (SMD) (95% CI −0.86 to −0.46; p<0.001; grading of recommendations assessment, development and evaluation (GRADE): very low quality). Restricting this analysis to the four trials that seemed less affected of bias, the effect vanished into −0.11 SMD (−0.41 to 0.18; p=0.45; GRADE: low quality). Exercise decreased the relative risk of no remission to 0.78 (0.68 to 0.90; p<0.001; GRADE: very low quality). Restricting this analysis to the two trials that seemed less affected of bias, the effect vanished into 0.95 (0.74 to 1.23; p=0.78). Trial sequential analysis excluded random error when all trials were analysed, but not if focusing on trials less affected of bias. Subgroup analyses found that trial size and intervention duration were inversely associated with effect size for both depression severity and lack of remission. There was no significant effect of exercise on secondary outcomes.ConclusionsTrials with less risk of bias suggested no antidepressant effects of exercise and there were no significant effects of exercise on quality of life, depression severity or lack of remission during follow-up. Data for serious adverse events and adverse events were scarce not allowing conclusions for these outcomes.Systematic review registrationThe protocol was published in the journalSystematic Reviews: 2015; 4:40.

Sign in / Sign up

Export Citation Format

Share Document