Background
Electroconvulsive therapy (ECT) involves the induction of a seizure by the administration of an electrical stimulus via electrodes usually placed bilaterally on the scalp and was ...introduced as a treatment for schizophrenia in 1938. However, ECT is a controversial treatment with concerns about long‐term side effects such a memory loss. Therefore, it is important to determine its clinical efficacy and safety for people with schizophrenia who are not responding to their treatment.
Objectives
Our primary objective was to assess the effects (benefits and harms) of ECT for people with treatment‐resistant schizophrenia.
Our secondary objectives were to determine whether ECT produces a differential response in people: who are treated with unilateral compared to bilateral ECT; who have had a long (more than 12 sessions) or a short course of ECT; who are given continuation or maintenance ECT; who are diagnosed with well‐defined treatment‐resistant schizophrenia as opposed to less rigorously defined treatment‐resistant schizophrenia (who would be expected to have a greater affective component to their illness).
Search methods
We searched the Cochrane Schizophrenia Group's Study‐Based Register of Trials including clinical trial registries on 9 September 2015 and 4 August 2017. There were no limitations on language, date, document type, or publication status for the inclusion of records in the register. We also inspected references of all the included records to identify further relevant studies.
Selection criteria
Randomised controlled trials investigating the effects of ECT in people with treatment‐resistant schizophrenia.
Data collection and analysis
Two review authors independently extracted data. For binary outcomes, we calculated the risk ratio (RR) and its 95% confidence intervals (CIs), on an intention‐to‐treat basis. For continuous data, we estimated the mean difference (MD) between the groups and its 95% CIs. We employed the fixed‐effect model for all analyses. We assessed risk of bias for the included studies and created 'Summary of findings' tables using the GRADE framework.
Main results
We included 15 studies involving 1285 participants (1264 completers with an average age of 18 to 46 years) with treatment‐resistant schizophrenia. We rated most studies (14/15, 93.3%) as at high risk of bias due to issues related to the blinding of participants and personnel. Our main outcomes of interest were: (i) clinically important response to treatment; (ii) clinically important change in cognitive functioning; (iii) leaving the study early; (iv) clinically important change in general mental state; (v) clinically important change in general functioning; (vi) number hospitalised; and (vii) death. No trial reported data on death.
The included trials reported useable data for four comparisons: ECT plus standard care compared with sham‐ECT added to standard care; ECT plus standard care compared with antipsychotic added to standard care; ECT plus standard care compared with standard care; and ECT alone compared with antipsychotic alone.
For the comparison ECT plus standard care versus sham‐ECT plus standard care, only average endpoint BPRS (Brief Psychiatric Rating Scale) scores from one study were available for mental state; no clear difference between groups was observed (short term; MD 3.60, 95% CI ‐3.69 to 10.89; participants = 25; studies = 1; very low‐quality evidence). One study reported data for service use, measured as number readmitted; there was a clear difference favouring the ECT group (short term; RR 0.29, 95% CI 0.10 to 0.85; participants = 25; studies = 1; low‐quality evidence).
When ECT plus standard care was compared with antipsychotics (clozapine) plus standard care, data from one study showed no clear difference for clinically important response to treatment (medium term; RR 1.23, 95% CI 0.95 to 1.58; participants = 162; studies = 1; low‐quality evidence). Clinically important change in mental state data were not available, but average endpoint BPRS scores were reported. A positive effect for the ECT group was found (short‐term BPRS; MD ‐5.20, 95% CI ‐7.93 to ‐2.47; participants = 162; studies = 1; very low‐quality evidence).
When ECT plus standard care was compared with standard care, more participants in the ECT group had a clinically important response (medium term; RR 2.06, 95% CI 1.75 to 2.42; participants = 819; studies = 9; moderate‐quality evidence). Data on clinically important change in cognitive functioning were not available, but data for memory deterioration were reported. Results showed that adding ECT to standard care may increase the risk of memory deterioration (short term; RR 27.00, 95% CI 1.67 to 437.68; participants = 72; studies = 1; very low‐quality evidence). There were no clear differences between groups in satisfaction and acceptability of treatment, measured as leaving the study early (medium term; RR 1.18, 95% CI 0.38 to 3.63; participants = 354; studies = 3; very low‐quality evidence). Only average endpoint scale scores were available for mental state (BPRS) and general functioning (Global Assessment of Functioning). There were clear differences in scores, favouring ECT group for mental state (medium term; MD ‐11.18, 95% CI ‐12.61 to ‐9.76; participants = 345; studies = 2; low‐quality evidence) and general functioning (medium term; MD 10.66, 95% CI 6.98 to 14.34; participants = 97; studies = 2; very low‐quality evidence).
For the comparison ECT alone versus antipsychotics (flupenthixol) alone, only average endpoint scale scores were available for mental state and general functioning. Mental state scores were similar between groups (medium‐term BPRS; MD ‐0.93, 95% CI ‐6.95 to 5.09; participants = 30; studies = 1; very low‐quality evidence); general functioning scores were also similar between groups (medium‐term Global Assessment of Functioning; MD ‐0.66, 95% CI ‐3.60 to 2.28; participants = 30; studies = 1; very low‐quality evidence).
Authors' conclusions
Moderate‐quality evidence indicates that relative to standard care, ECT has a positive effect on medium‐term clinical response for people with treatment‐resistant schizophrenia. However, there is no clear and convincing advantage or disadvantage for adding ECT to standard care for other outcomes. The available evidence was also too weak to indicate whether adding ECT to standard care is superior or inferior to adding sham‐ECT or other antipsychotics to standard care, and there was insufficient evidence to support or refute the use of ECT alone. More good‐quality evidence is needed before firm conclusions can be made.
Objective
To systematically review the methodological assessment tools for pre‐clinical and clinical studies, systematic review and meta‐analysis, and clinical practice guideline.
Methods
We searched ...PubMed, the Cochrane Handbook for Systematic Reviews of Interventions, Joanna Briggs Institute (JBI) Reviewers Manual, Centre for Reviews and Dissemination, Critical Appraisal Skills Programme (CASP), Scottish Intercollegiate Guidelines Network (SIGN), and the National Institute for Clinical Excellence (NICE) up to May 20th, 2014. Two authors selected studies and extracted data; quantitative analysis was performed to summarize the characteristics of included tools.
Results
We included a total of 21 assessment tools for analysis. A number of tools were developed by academic organizations, and some were developed by only a small group of researchers. The JBI developed the highest number of methodological assessment tools, with CASP coming second. Tools for assessing the methodological quality of randomized controlled studies were most abundant. The Cochrane Collaboration's tool for assessing risk of bias is the best available tool for assessing RCTs. For cohort and case‐control studies, we recommend the use of the Newcastle‐Ottawa Scale. The Methodological Index for Non‐Randomized Studies (MINORS) is an excellent tool for assessing non‐randomized interventional studies, and the Agency for Healthcare Research and Quality (ARHQ) methodology checklist is applicable for cross‐sectional studies. For diagnostic accuracy test studies, the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool is recommended; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias tool is available for assessing animal studies; Assessment of Multiple Systematic Reviews (AMSTAR) is a measurement tool for systematic reviews/meta‐analyses; an 18‐item tool has been developed for appraising case series studies, and the Appraisal of Guidelines, Research and Evaluation (AGREE)‐II instrument is widely used to evaluate clinical practice guidelines.
Conclusions
We have successfully identified a variety of methodological assessment tools for different types of study design. However, further efforts in the development of critical appraisal tools are warranted since there is currently a lack of such tools for other fields, e.g. genetic studies, and some existing tools (nested case‐control studies and case reports, for example) are in need of updating to be in line with current research practice and rigor. In addition, it is very important that all critical appraisal tools remain subjective and performance bias is effectively avoided.
Meta-analysis is a statistical method with the ability to increase the power for statistical inference, while it may still face the problem of being underpowered. In this study, we investigated the ...power to detect certain true effects for published meta-analyses of rare events.
We extracted data from the Cochrane Database of Systematic Reviews for meta-analyses of rare events from January 2003 to May 2018. We retrospectively estimated the power to detect a 10–50% relative risk reduction (RRR) of eligible meta-analyses. The proportion of meta-analyses achieved a sufficient power (≥0.8) were estimated.
We identified 4,177 meta-analyses. The median power to detect 10%, 30%, and 50% RRR were 0.06 (interquartile range IQR: 0.05 to 0.06), 0.08 (IQR: 0.06 to 0.15), and 0.17 (IQR: 0.10 to 0.42), respectively); the corresponding proportion of meta-analyses that reached sufficient power were 0.32%, 3.68%, and 11.81%. Meta-analyses incorporating data from more studies had higher probability to achieve a sufficient power (rate ratio = 2.49, 95% CI: 1.76, 3.52, P < 0.001).
Most of the meta-analyses of rare events in Cochrane systematic reviews were underpowered. Future meta-analysis of rare events should report the power of the results to support informative conclusions.
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To systematically review the available evidence on the effects (benefits and harms) of DPP‐4 inhibitors, GLP‐1 ...receptor agonists, and SGLT‐2 inhibitors in people with established CVD, using network meta‐analysis.
Background
Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase‐4 inhibitors (DPP4i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and ...sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first‐line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP‐1RA and SGLT2i may exert positive effects on patients with known CVD.
Objectives
To systematically review the available evidence on the benefits and harms of DPP4i, GLP‐1RA, and SGLT2i in people with established CVD, using network meta‐analysis.
Search methods
We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status.
Selection criteria
We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP‐1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non‐fatal myocardial infarction, fatal and non‐fatal stroke, all‐cause mortality, hospitalisation for heart failure (HF), and safety outcomes.
Data collection and analysis
Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta‐analyses and network meta‐analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope.
Main results
We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta‐analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP‐1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow‐up duration.
1. DPP4i versus placebo
Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high‐certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high‐certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high‐certainty evidence), and all‐cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high‐certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate‐certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low‐certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate‐certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate‐certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate‐certainty evidence).
2. GLP‐1RA versus placebo
Our findings indicate that GLP‐1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high‐certainty evidence), all‐cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high‐certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high‐certainty evidence). GLP‐1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate‐certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high‐certainty evidence). GLP‐1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low‐certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low‐certainty evidence). We are uncertain about the effect of GLP‐1RA on hypoglycaemia and bone fractures.
3. SGLT2i versus placebo
This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate‐certainty evidence), all‐cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate‐certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high‐certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high‐certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate‐certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate‐certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate‐certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high‐certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low‐certainty evidence).
4. Network meta‐analysis
Because we failed to identify direct comparisons between each class of the agents, findings from our network meta‐analysis provided limited novel insights. Almost all findings from our network meta‐analysis agree with those from the standard meta‐analysis. GLP‐1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate‐certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta‐analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all‐cause mortality.
Authors' conclusions
Findings from both standard and network meta‐analyses of moderate‐ to high‐certainty evidence suggest that GLP‐1RA and SGLT2i are likely to reduce the risk of CVD mortality and all‐cause mortality in people with established CVD; high‐certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate‐certainty evidence likely supports the use of GLP‐1RA to reduce fatal and non‐fatal stroke. Future studies conducted in the non‐diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose‐lowering effects.
Background
Cardiac surgery is performed worldwide. Most types of cardiac surgery are performed using cardiopulmonary bypass (CPB). Cardiac surgery performed with CPB is associated with morbidities. ...CPB needs an extracorporeal circulation that replaces the heart and lungs, and performs circulation, ventilation, and oxygenation of the blood. The lower limit of mean blood pressure to maintain blood flow to vital organs increases in people with chronic hypertension. Because people undergoing cardiac surgery commonly have chronic hypertension, we hypothesised that maintaining a relatively high blood pressure improves desirable outcomes among the people undergoing cardiac surgery with CPB.
Objectives
To evaluate the benefits and harms of higher versus lower blood pressure targets during cardiac surgery with CPB.
Search methods
We used standard, extensive Cochrane search methods. The latest search of databases was November 2021 and trials registries in January 2020.
Selection criteria
We included randomised controlled trials (RCTs) comparing a higher blood pressure target (mean arterial pressure 65 mmHg or greater) with a lower blood pressure target (mean arterial pressure less than 65 mmHg) in adults undergoing cardiac surgery with CPB.
Data collection and analysis
We used standard Cochrane methods. Primary outcomes were 1. acute kidney injury, 2. cognitive deterioration, and 3. all‐cause mortality. Secondary outcomes were 4. quality of life, 5. acute ischaemic stroke, 6. haemorrhagic stroke, 7. length of hospital stay, 8. renal replacement therapy, 9. delirium, 10. perioperative transfusion of blood products, and 11. perioperative myocardial infarction. We used GRADE to assess certainty of evidence.
Main results
We included three RCTs with 737 people compared a higher blood pressure target with a lower blood pressure target during cardiac surgery with CPB. A high blood pressure target may result in little to no difference in acute kidney injury (risk ratio (RR) 1.30, 95% confidence interval (CI) 0.81 to 2.08; I² = 72%; 2 studies, 487 participants; low‐certainty evidence), cognitive deterioration (RR 0.82, 95% CI 0.45 to 1.50; I² = 0%; 2 studies, 389 participants; low‐certainty evidence), and all‐cause mortality (RR 1.33, 95% CI 0.30 to 5.90; I² = 49%; 3 studies, 737 participants; low‐certainty evidence). No study reported haemorrhagic stroke. Although a high blood pressure target may increase the length of hospital stay slightly, we found no differences between a higher and a lower blood pressure target for the other secondary outcomes.
We also identified one ongoing RCT which is comparing a higher versus a lower blood pressure target among the people who undergo cardiac surgery with CPB.
Authors' conclusions
A high blood pressure target may result in little to no difference in patient outcomes including acute kidney injury and mortality. Given the wide CIs, further studies are needed to confirm the efficacy of a higher blood pressure target among those who undergo cardiac surgery with CPB.
Meta-analyses of rare events often generate unstable results, and selective reporting of the results may mislead the health care decision. Developing a synthesis plan for rare events in protocol may ...help to formulate the reporting. We aim to investigate whether existing protocols specified methods to deal with rare events.
Protocols (not including Cochrane protocols) for systematic reviews of health care interventions focused on the safety registered in PROSPERO were included. The proportion of protocols that specified methods to deal with rare events and the detailed methods were summarized. We compared the difference of proportions (PD) across different settings.
We identified 1,004 eligible protocols, of which, 119 (11.85%, 95% confidence interval (CI): 9.92%, 14.01%) specified methods to deal with rare events. The three most commonly planned methods were the Mantel–Haenszel, Peto's odds ratio, and continuity correction. Protocols planned a quantitative analysis (PD = 0.07, 95% CI: 0.02, 0.12; P = 0.004) and listed safety as a primary outcome (PD = 0.07, 95% CI: 0.01, 0.12; P = 0.018) were more likely to specify methods to deal with rare events.
Protocols for systematic reviews of intervention safety seldom specified methods to deal with rare events. Future systematic reviewers should provide a detailed and rigorous synthesis plan for rare events in their protocols.
Background
People with heart failure report various symptoms and show a trajectory of periodic exacerbations and recoveries, where each exacerbation event may lead to death. Current clinical practice ...guidelines indicate the importance of discussing future care strategies with people with heart failure. Advance care planning (ACP) is the process of discussing an individual's future care plan according to their values and preferences, and involves the person with heart failure, their family members or surrogate decision‐makers, and healthcare providers. Although it is shown that ACP may improve discussion about end‐of‐life care and documentation of an individual's preferences, the effects of ACP for people with heart failure are uncertain.
Objectives
To assess the effects of advance care planning (ACP) in people with heart failure compared to usual care strategies that do not have any components promoting ACP.
Search methods
We searched CENTRAL, MEDLINE, Embase, CINAHL, Social Work s, and two clinical trials registers in October 2019. We checked the reference lists of included studies. There were no restrictions on language or publication status.
Selection criteria
We included randomised controlled trials (RCTs) that compared ACP with usual care in people with heart failure. Trials could have parallel group, cluster‐randomised, or cross‐over designs. We included interventions that implemented ACP, such as discussing and considering values, wishes, life goals, and preferences for future medical care. The study participants comprised adults (18 years of age or older) with heart failure.
Data collection and analysis
Two review authors independently extracted outcome data from the included studies, and assessed their risk of bias. We contacted trial authors when we needed to obtain missing information.
Main results
We included nine RCTs (1242 participants and 426 surrogate decision‐makers) in this review. The meta‐analysis included seven studies (876 participants). Participants' mean ages ranged from 62 to 82 years, and 53% to 100% of the studies' participants were men. All included studies took place in the US or the UK.
Only one study reported concordance between participants' preferences and end‐of‐life care, and it enrolled people with heart failure or renal disease. Owing to one study with small sample size, the effects of ACP on concordance between participants' preferences and end‐of‐life care were uncertain (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.91 to 1.55; participants = 110; studies = 1; very low‐quality evidence). It corresponded to an assumed risk of 625 per 1000 participants receiving usual care and a corresponding risk of 744 per 1000 (95% CI 569 to 969) for ACP. There was no evidence of a difference in quality of life between groups (standardised mean difference (SMD) 0.06, 95% CI –0.26 to 0.38; participants = 156; studies = 3; low‐quality evidence). However, one study, which was not included in the meta‐analysis, showed that the quality of life score improved by 14.86 points in the ACP group compared with 11.80 points in the usual care group.
Completion of documentation by medical staff regarding discussions with participants about ACP processes may have increased (RR 1.68. 95% CI 1.23 to 2.29; participants = 92; studies = 2; low‐quality evidence). This corresponded to an assumed risk of 489 per 1000 participants with usual care and a corresponding risk of 822 per 1000 (95% CI 602 to 1000) for ACP. One study, which was not included in the meta‐analysis, also showed that ACP helped to improve documentation of the ACP process (hazard ratio (HR) 2.87, 95% CI 1.09 to 7.59; participants = 232).
Three studies reported that implementation of ACP led to an improvement of participants' depression (SMD –0.58, 95% CI –0.82 to –0.34; participants = 278; studies = 3; low‐quality evidence). We were uncertain about the effects of ACP on the quality of communication when compared to the usual care group (MD –0.40, 95% CI –1.61 to 0.81; participants = 9; studies = 1; very low‐quality evidence). We also noted an increase in all‐cause mortality in the ACP group (RR 1.32, 95% CI 1.04 to 1.67; participants = 795; studies = 5).
The studies did not report participants' satisfaction with care/treatment and caregivers' satisfaction with care/treatment.
Authors' conclusions
ACP may help to increase documentation by medical staff regarding discussions with participants about ACP processes, and may improve an individual's depression. However, the quality of the evidence about these outcomes was low. The quality of the evidence for each outcome was low to very low due to the small number of studies and participants included in this review. Additionally, the follow‐up periods and types of ACP intervention were varied. Therefore, further studies are needed to explore the effects of ACP that consider these differences carefully.
AbstractObjectiveThe objective of the study was to systematically survey the methodological literature and collect suggested criteria for assessing the credibility of effect modification and ...associated rationales. Study Design and SettingWe searched MEDLINE, Embase, and WorldCat up to March 2018 for publications providing guidance for assessing the credibility of effect modification identified in randomized trials or meta-analyses. Teams of two investigators independently identified eligible publications and extracted credibility criteria and authors’ rationale, reaching consensus through discussion. We created a taxonomy of criteria that we iteratively refined during data abstraction. ResultsWe identified 150 eligible publications that provided 36 criteria and associated rationales. Frequent criteria included significant test for interaction ( n = 54), a priori hypothesis ( n = 49), providing a causal explanation ( n = 47), accounting for multiplicity ( n = 45), testing a small number of effect modifiers ( n = 38), and prespecification of analytic details ( n = 39). For some criteria, we found more than one rationale; some criteria were connected through a common rationale. For some criteria, experts disagreed regarding their suitability (e.g., added value of stratified randomization; trustworthiness of biologic rationales). ConclusionMethodologists have expended substantial intellectual energy providing criteria for critical appraisal of apparent effect modification. Our survey highlights popular criteria, expert agreement and disagreement, and where more work is needed, including testing criteria in practice.
This is a protocol for a Cochrane Review (intervention). The objectives are as follows:
To assess the effectiveness and safety of vitamin A for preventing acute LRTIs in children up to seven years of ...age.
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