scholarly journals Drug treatments for covid-19: living systematic review and network meta-analysis

BMJ ◽  
2020 ◽  
pp. m2980 ◽  
Author(s):  
Reed AC Siemieniuk ◽  
Jessica J Bartoszko ◽  
Long Ge ◽  
Dena Zeraatkar ◽  
Ariel Izcovich ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Standard Care ◽  
Interferon Beta ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Drug Discontinuation ◽  
Duration Of Symptoms ◽  
Risk Of Death ◽  
The Impact

Abstract Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. Conclusion Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 ( BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.

scholarly journals Prophylaxis against covid-19: living systematic review and network meta-analysis

BMJ ◽  
2021 ◽  
pp. n949
Author(s):  
Jessica J Bartoszko ◽  
Reed A C Siemieniuk ◽  
Elena Kum ◽  
Anila Qasim ◽  
Dena Zeraatkar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Standard Care ◽  
Meta Analysis ◽  
A Priori ◽  
Credible Interval ◽  
Risk Of Bias ◽  
World Health ◽  
Drug Discontinuation ◽  
Randomised Trials

Abstract Objective To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. Design Living systematic review and network meta-analysis. Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. Study selection Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. Methods Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results The first iteration of this living network meta-analysis includes nine randomised trials—six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. Conclusions Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. Systematic review registration This review was not registered. The protocol established a priori is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

scholarly journals Prophylaxis for covid-19: living systematic review and network meta-analysis

2021 ◽  
Author(s):  
Jessica J Bartoszko ◽  
Reed AC Siemieniuk ◽  
Elena Kum ◽  
Anila Qasim ◽  
Dena Zeraatkar ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Effects ◽  
Standard Care ◽  
Randomized Trials ◽  
Meta Analysis ◽  
A Priori ◽  
Credible Interval ◽  
Risk Of Bias ◽  
Drug Discontinuation ◽  
Drug Prophylaxis

AbstractObjectiveTo determine and compare the effects of drug prophylaxis on severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (covid-19).DesignLiving systematic review and network meta-analysis.Data sourcesWHO covid-19 database, a comprehensive multilingual source of global covid-19 literature to 19 January 2021, and six additional Chinese databases to 20 January 2021.Study selectionRandomized trials in which people at risk of covid-19 were randomized to drug prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.MethodsAfter duplicate data abstraction, we conducted random-effects bayesian network meta-analysis. We assessed risk of bias of the included studies using a modification of the Cochrane risk of bias 2.0 tool and assessed the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach.ResultsThe first iteration of this living network meta-analysis includes nine randomized trials – six addressing hydroxychloroquine (6,059 participants), one addressing ivermectin combined with iota-carrageenan (234 participants) and two addressing ivermectin alone (540 participants), all compared to standard care or placebo. Hydroxychloroquine has no important effect on admission to hospital (risk difference (RD) 1 fewer per 1,000, 95% credible interval (CrI) 3 fewer to 4 more, high certainty) or mortality (RD 1 fewer per 1,000, 95% CrI 2 fewer to 3 more, high certainty). Hydroxychloroquine probably has no important effect on laboratory-confirmed infection (RD 2 more per 1,000, 95% CrI 18 fewer to 28 more, moderate certainty), probably increases adverse effects leading to drug discontinuation (RD 19 more per 1,000, 95% CrI 1 fewer to 70 more, moderate certainty) and may have no important effect on suspected, probable or laboratory-confirmed infection (RD 15 fewer per 1,000, 95% CrI 64 fewer to 41 more, low certainty). Due to serious risk of bias and very serious imprecision – and thus very low certainty evidence, the effects of ivermectin combined with iota-carrageenan on laboratory-confirmed infection (RD 52 fewer per 1,000, 95% CrI 58 fewer to 37 fewer), and ivermectin alone on laboratory-confirmed infection (RD 50 fewer per 1,000, 95% CrI 59 fewer to 16 fewer) and suspected, probable or laboratory-confirmed infection (RD 159 fewer per 1,000, 95% CrI 165 fewer to 144 fewer) remain uncertain.ConclusionHydroxychloroquine prophylaxis does not have an important effect on hospital admission and mortality, probably increases adverse effects, and probably does not have an important effect on laboratory-confirmed SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, we are highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection.Systematic review registrationThis review was not registered. The protocol established a priori is included as a supplement.FundingThis study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).Readers’ noteThis article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

scholarly journals Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

2021 ◽  
Author(s):  
Dena Zeraatkar ◽  
Ellen Cusano ◽  
Juan Pablo Diaz Martinez ◽  
Anila Qasim ◽  
Sophia O Mangala ◽  
...  
Keyword(s):  
Systematic Review ◽  
Standard Care ◽  
Meta Analysis ◽  
Analysis Data ◽  
Risk Of Bias ◽  
Risk Of Death ◽  
Study Selection ◽  
Receptor Blockers ◽  
Meta Analyses ◽  
Grade Approach

Objective: To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design: Systematic review and network meta-analysis Data sources: WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection: Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results: We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias 2.0 tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion: IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness.

Mortality Benefit From the Passive Leg Raise Maneuver in Guiding Resuscitation of Septic Shock Patients: A Systematic Review and Meta-Analysis of Randomized Trials

2021 ◽  
pp. 088506662110197
Author(s):  
Moosa Azadian ◽  
Suyee Win ◽  
Amir Abdipour ◽  
Carolyn Krystal Kim ◽  
H. Bryant Nguyen
Keyword(s):  
Systematic Review ◽  
Septic Shock ◽  
Fluid Resuscitation ◽  
Standard Care ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Time Interval ◽  
Eligibility Criteria ◽  
Significant Difference ◽  
Passive Leg Raise

Background: Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. Methods: This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. Results: We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. Conclusion: Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.

scholarly journals Racecadotril for acute diarrhoea in children: systematic review and meta-analyses

2015 ◽  
Vol 101 (3) ◽  
pp. 234-240 ◽  
Author(s):  
Morris Gordon ◽  
Anthony Akobeng
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Methodological Quality ◽  
Data Extraction ◽  
Meta Analysis ◽  
Acute Diarrhoea ◽  
Risk Of Bias ◽  
Duration Of Symptoms ◽  
Duration Of Illness ◽  
Significant Difference

ObjectiveRacecadotril is an antisecretory agent that can prevent fluid/electrolyte depletion from the bowel as a result of acute diarrhoea without affecting intestinal motility. An up-to-date systematic review is indicated to summarise the evidence on racecadotril for the treatment of acute diarrhoea in children.DesignA Cochrane format systematic review of randomised controlled trials (RCTs). Data extraction and assessment of methodological quality were performed independently by two reviewers. Methodological quality was assessed using the Cochrane risk of bias tool.PatientsChildren with acute diarrhoea, as defined by the primary studies.InterventionsRCTs comparing racecadotril with placebo or other interventions.Main outcome measursDuration of illness, stool output/volume and adverse events.ResultsSeven RCTs were included, five comparing racecadotril with placebo or no intervention, one with pectin/kaolin and one with loperamide. Moderate to high risk of bias was present in all studies. There was no significant difference in efficacy or adverse events between racecadotril and loperamide. A meta-analysis of three studies with 642 participants showed significantly shorter duration of symptoms with racecadotril compared with placebo (mean difference −53.48 h, 95% CI −65.64 to −41.33). A meta-analysis of five studies with 949 participants showed no significant difference in adverse events between racecadotril and placebo (risk ratio 0.99, 95% CI 0.73 to 1.34).ConclusionsThere is some evidence that racecadotril is more effective than placebo or no intervention in reducing the duration of illness and stool output in children with acute diarrhoea. However, the overall quality of the evidence is limited due to sparse data, heterogeneity and risk of bias. Racecadotril appears to be safe and well tolerated.

scholarly journals The Effect of Anakinra in Hospitalized Patients with COVID-19: An Updated Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (19) ◽  
pp. 4462
Author(s):  
Konstantinos G. Kyriakoulis ◽  
Anastasios Kollias ◽  
Garyphallia Poulakou ◽  
Ioannis G. Kyriakoulis ◽  
Ioannis P. Trontzas ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Interleukin 1 ◽  
Severe Pneumonia ◽  
Hospitalized Patients ◽  
Current Evidence ◽  
Adjusted Risk ◽  
Risk Of Death ◽  
The Impact

The role of immunomodulatory agents in the treatment of hospitalized patients with COVID-19 has been of increasing interest. Anakinra, an interleukin-1 inhibitor, has been shown to offer significant clinical benefits in patients with COVID-19 and hyperinflammation. An updated systematic review and meta-analysis regarding the impact of anakinra on the outcomes of hospitalized patients with COVID-19 was conducted. Studies, randomized or non-randomized with adjustment for confounders, reporting on the adjusted risk of death in patients treated with anakinra versus those not treated with anakinra were deemed eligible. A search was performed in PubMed/EMBASE databases, as well as in relevant websites, until 1 August 2021. The meta-analysis of six studies that fulfilled the inclusion criteria (n = 1553 patients with moderate to severe pneumonia, weighted age 64 years, men 66%, treated with anakinra 50%, intubated 3%) showed a pooled hazard ratio for death in patients treated with anakinra at 0.47 (95% confidence intervals 0.34, 0.65). A meta-regression analysis did not reveal any significant associations between the mean age, percentage of males, mean baseline C-reactive protein levels, mean time of administration since symptoms onset among the included studies and the hazard ratios for death. All studies were considered as low risk of bias. The current evidence, although derived mainly from observational studies, supports a beneficial role of anakinra in the treatment of selected patients with COVID-19.

scholarly journals What Is the Impact of Ambulatory Vital Sign Monitoring on Deterioration Detection and Related Clinical Outcomes in Hospitalised Patients: a Systematic Review and Meta-analysis.

2021 ◽  
Author(s):  
Carlos Morgado Areia ◽  
Christopher Biggs ◽  
Mauro Santos ◽  
Neal Thurley ◽  
Stephen Gerry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Outcomes ◽  
Standard Care ◽  
Meta Analysis ◽  
Ambulatory Monitoring ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Monitoring Systems ◽  
Hospitalised Patients ◽  
The Impact

Abstract Background: Timely recognition of the deteriorating inpatient remains challenging. Ambulatory monitoring systems (AMS) may augment current monitoring practices. However, there are many challenges to implementation in the hospital environment, and evidence describing the clinical impact of AMS on deterioration detection and patient outcome remains unclear. Objective: To assess the impact of vital signs monitoring on detection of deterioration and related clinical outcomes in hospitalised patients using ambulatory monitoring systems, in comparison with standard care.Methods: A systematic search was conducted in August 2020 using MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL and Health Technology Assessment databases, as well as grey literature. Studies comparing the use of AMS against standard care for deterioration detection and related clinical outcomes in hospitalised patients were included. Deterioration related outcomes (primary) included unplanned intensive care admissions, rapid response team or cardiac arrest activation, total and major complications rate. Other clinical outcomes (secondary) included in-hospital mortality and hospital length of stay. Exploratory outcomes included alerting system parameters and clinical trial registry information. Results: Of 8706 citations, 10 studies with different designs met the inclusion criteria, of which 7 were included in the meta-analyses. Overall study quality was moderate. The meta-analysis indicated that the AMS, when compared with standard care, was associated with a reduction in intensive care transfers (risk ratio, RR, 0.87; 95% confidence interval, CI, 0.66 to 1.15), rapid response or cardiac arrest team activation (RR, 0.84; 95% CI 0.69 to 1.01), total (RR, 0.77; 95% CI 0.44 to 1.32) and major (RR, 0.55; 95% CI 0.24 to 1.30) complications prevalence. There was also association with reduced mortality (RR, 0.48; 95% CI 0.18 to 1.29) and hospital length of stay (mean difference, MD, -0.09; 95% CI -0.43 to 0.44). However, none were statistically significant.Conclusion: This systematic review indicates that implementation of AMS may have a positive impact on early deterioration detection and associated clinical outcomes, but differing design/quality of available studies and diversity of outcomes measures limits a definite conclusion. Our narrative findings suggested that alarms should be adjusted to minimise false alerts and promote rapid clinical action in response to deterioration.PROSPERO Registration number: CRD42020188633

scholarly journals Effect of dose administration aids on adherence to self-administered medications: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e030536
Author(s):  
Kanika Chaudhri ◽  
Madeleine Kearney ◽  
Richard O Day ◽  
Anthony Rodgers ◽  
Emily Atkins
Keyword(s):  
Systematic Review ◽  
Health Outcomes ◽  
Meta Analysis ◽  
Study Participant ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Dose Administration ◽  
Common Solution ◽  
The Impact

IntroductionForgetting to take a medication is the most common reason for non-adherence to self-administered medication. Dose administration aids (DAAs) are a simple and common solution to improve unintentional non-adherence for oral tablets. DAAs can be in the form of compartmentalised pill boxes, automated medication dispensing devices, blister packs and sachets packets. This protocol aims to outline the methods that will be used in a systematic review of the current literature to assess the impact of DAAs on adherence to medications and health outcomes.Methods and analysisRandomised controlled trials will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL and the Cochrane Library, from the beginning of each database until January 2020. Two reviewers will independently screen studies and extract data using the standardised forms. Data extracted will include general study information, characteristics of the study, participant characteristics, intervention characteristics and outcomes. Primary outcome is to assess the effects of DAAs on medication adherence. Secondary outcome is to evaluate the changes in health outcomes. The risk of bias will be ascertained by two reviewers in parallel using The Cochrane Risk of Bias Tool. A meta-analysis will be performed if data are homogenous.Ethics and disseminationEthics approval will not be required for this study. The results of the review described within this protocol will be disseminated through publication in a peer-reviewed journal and relevant conference presentations.PROSPERO registration numberCRD42018096087

scholarly journals Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e024886 ◽  
Author(s):  
Klaus Munkholm ◽  
Asger Sand Paludan-Müller ◽  
Kim Boesen
Keyword(s):  
Systematic Review ◽  
Clinical Study ◽  
Effect Size ◽  
Meta Analysis ◽  
Evidence Base ◽  
Risk Of Bias ◽  
Depression Symptom ◽  
Meta Analyses ◽  
The Impact ◽  
Clinical Study Reports

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.

The impact of time to adjuvant chemotherapy (AC) on survival in colorectal cancer (CRC): A systematic review and meta-analysis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
J. J. Biagi ◽  
M. Raphael ◽  
W. D. King ◽  
W. Kong ◽  
W. J. Mackillop ◽  
...  
Keyword(s):  
Systematic Review ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Publication Bias ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Risk Of Death ◽  
The Impact ◽  
The Relationship

364 Background: The optimal timing from CRC surgery to initiation of AC is unknown. We report a systematic review and meta-analysis to determine the relationship between time to adjuvant chemotherapy (TTAC) and survival. Methods: A systematic review of literature was done to identify studies that described the relationship between TTAC and survival. Studies were only included if the distribution of relevant prognostic factors was adequately described, and either comparative groups were balanced or results adjusted for the prognostic factors. Hazard ratio (HR) and TTAC for overall survival (OS) and disease free survival (DFS) from each study were converted to a regression coefficient (β) and standard error (SE) corresponding to a continuous representation per 4 weeks of TTAC. The adjusted β from individual studies were combined using a fixed-effect model. Inverse-variance (1/SE2) was used to weight individual studies. The possible effect of publication bias was investigated using the trim and fill approach. Results: We identified 9 eligible studies involving 14,357 patients (4 published articles, 5 abstracts). Two studies were randomized trials and 7 were cohort studies. Six studies reported TTAC as a binary variable and 3 reported TTAC as ≥3 categories. An estimate of HR for OS was derived from all 9 studies and estimate for DFS was derived from 5 studies. Meta-analysis demonstrated that a 4-week increase in TTAC was associated with a significant decrease in both OS (HR = 1.12, 95% CI 1.09-1.15), and DFS (HR = 1.15, 95% CI 1.11-1.20). The analysis showed no significant heterogeneity among studies. These TTAC associations remained significant after analysis for potential publication bias, and when the analysis was repeated excluding the two studies of largest weight. Conclusions: This study demonstrates a 12% increase in the risk of death for each 4 week of delay in the start of AC for CRC. These findings indicate the need for clinicians and health systems managers to take the steps necessary to keep TTAC as short as reasonably achievable. In addition, our results suggest there may be some benefit to AC after a 3-month TTAC delay. No significant financial relationships to disclose.

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