AbstractObjectiveTo develop an instrument to evaluate the credibility of anchor based minimal important differences (MIDs) for outcome measures reported by patients, and to assess the reliability of ...the instrument.DesignInstrument development and reliability study.Data sourcesInitial criteria were developed for evaluating the credibility of anchor based MIDs based on a literature review (Medline, Embase, CINAHL, and PsycInfo databases) and the experience of the authors in the methodology for estimation of MIDs. Iterative discussions by the team and pilot testing with experts and potential users facilitated the development of the final instrument.ParticipantsWith the newly developed instrument, pairs of masters, doctoral, or postdoctoral students with a background in health research methodology independently evaluated the credibility of a sample of MID estimates.Main outcome measuresCore credibility criteria applicable to all anchor types, additional criteria for transition rating anchors, and inter-rater reliability coefficients were determined.ResultsThe credibility instrument has five core criteria: the anchor is rated by the patient; the anchor is interpretable and relevant to the patient; the MID estimate is precise; the correlation between the anchor and the outcome measure reported by the patient is satisfactory; and the authors select a threshold on the anchor that reflects a small but important difference. The additional criteria for transition rating anchors are: the time elapsed between baseline and follow-up measurement for estimation of the MID is optimal; and the correlations of the transition rating with the baseline, follow-up, and change score in the patient reported outcome measures are satisfactory. Inter-rater reliability coefficients (ĸ) for the core criteria and for one item from the additional criteria ranged from 0.70 to 0.94. Reporting issues prevented the evaluation of the reliability of the three other additional criteria for the transition rating anchors.ConclusionsResearchers, clinicians, and healthcare policy decision makers can consider using this instrument to evaluate the design, conduct, and analysis of studies estimating anchor based minimal important differences.
Background
Many studies have assessed the quality of news reports about the effects of health interventions, but there has been no systematic review of such studies or meta-analysis of their results. ...We aimed to fill this gap (PROSPERO ID: CRD42018095032).
Methods
We included studies that used at least one explicit, prespecified and generic criterion to assess the quality of news reports in print, broadcast, or online news media, and specified the sampling frame, and the selection criteria and technique. We assessed criteria individually for inclusion in the meta-analyses, excluding inappropriate criteria and criteria with inadequately reported results. We mapped and grouped criteria to facilitate evidence synthesis. Where possible, we extracted the proportion of news reports meeting the included criterion. We performed meta-analyses using a random effects model to estimate such proportions for individual criteria and some criteria groups, and to characterise heterogeneity across studies.
Results
We included 44 primary studies in the qualitative summary, and 18 studies and 108 quality criteria in the meta-analyses. Many news reports gave an unbalanced and oversimplified picture of the potential consequences of interventions. A limited number mention or adequately address conflicts of interest (22%; 95% CI 7%-49%) (low certainty), alternative interventions (36%; 95% CI 26%-47%) (moderate certainty), potential harms (40%; 95% CI 23%-61%) (low certainty), or costs (18%; 95% CI 12%-28%) (moderate certainty), or quantify effects (53%; 95% CI 36%-69%) (low certainty) or report absolute effects (17%; 95% CI 4%-49%) (low certainty).
Discussion
There is room for improving health news, but it is logically more important to improve the public's ability to critically appraise health information and make judgements for themselves.
Summary
The association between rare coding loss‐of‐function (LOF) mutations in the melanocortin receptor 3 (MC3R) gene and human obesity is controversial. To fill this gap of knowledge, we performed ...a systematic review and meta‐analysis of genetic association studies in all ages and ethnicities. Two reviewers independently performed risk of bias assessment and extracted data. We searched Medline, Embase, Web of Science Core Collection, BIOSIS Preview, CINAHL, ProQuest Dissertations & Theses, and reference lists of relevant studies. All case‐control, cross‐sectional, prospective, and retrospective studies that evaluated prevalence of rare (less than 1% frequency) coding partial/complete LOF mutations in MC3R among individuals with obesity and normal weight were included. Our systematic search identified 1925 references relevant to the present review. Six studies were deemed eligible. Meta‐analysis of 2969 individuals with obesity and 2572 with normal weight showed a positive association between rare heterozygous coding partial/complete LOF mutations in MC3R and obesity in children and adults of European, North African, and Asian ancestries (odds ratio = 3.07; 95% CI, 1.48‐7.00; P = 4.2 × 10−3). Our data demonstrates that rare partial/complete LOF mutations in the coding region of MC3R confer three‐time increased risk of obesity in humans, and implies that rare genetic variants with intermediate effects contribute to the missing heritability of obesity.
Objective
To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication ...recommendations.
Methods
Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.
Results
Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.
Conclusion
Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.
Objective
To provide guidance for the management of gout, including indications for and optimal use of urate‐lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication ...recommendations.
Methods
Fifty‐seven population, intervention, comparator, and outcomes questions were developed, followed by a systematic literature review, including network meta‐analyses with ratings of the available evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and patient input. A group consensus process was used to compose the final recommendations and grade their strength as strong or conditional.
Results
Forty‐two recommendations (including 16 strong recommendations) were generated. Strong recommendations included initiation of ULT for all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first‐line ULT, including for those with moderate‐to‐severe chronic kidney disease (CKD; stage >3); using a low starting dose of allopurinol (≤100 mg/day, and lower in CKD) or febuxostat (<40 mg/day); and a treat‐to‐target management strategy with ULT dose titration guided by serial serum urate (SU) measurements, with an SU target of <6 mg/dl. When initiating ULT, concomitant antiinflammatory prophylaxis therapy for a duration of at least 3–6 months was strongly recommended. For management of gout flares, colchicine, nonsteroidal antiinflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) were strongly recommended.
Conclusion
Using GRADE methodology and informed by a consensus process based on evidence from the current literature and patient preferences, this guideline provides direction for clinicians and patients making decisions on the management of gout.
ObjectivesTo identify credible anchor-based minimal important differences (MIDs) for patient-reported outcome measures (PROMs) relevant to a BMJ Rapid Recommendations addressing subacromial ...decompression surgery for shoulder pain.DesignSystematic review.Outcome measuresEstimates of anchor-based MIDs, and their credibility, for PROMs judged by the parallel BMJ Rapid Recommendations panel as important for informing their recommendation (pain, function and health-related quality of life (HRQoL)).Data sourcesMEDLINE, EMBASE and PsycINFO up to August 2018.Study selection and review methodsWe included original studies of any intervention for shoulder conditions reporting estimates of anchor-based MIDs for relevant PROMs. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria. Six reviewers, working in pairs, independently extracted data from eligible studies using a predesigned, standardised, pilot-tested extraction form and independently assessed the credibility of included studies using an MID credibility tool.ResultsWe identified 22 studies involving 5562 patients that reported 74 empirically estimated anchor-based MIDs for 10 candidate instruments to assess shoulder pain, function and HRQoL. We identified MIDs of high credibility for pain and function outcomes and of low credibility for HRQoL. We offered median estimates for the systematic review team who applied these MIDs in Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence summaries and in their interpretations of results in the linked systematic review addressing the effectiveness of surgery for shoulder pain.ConclusionsOur review provides anchor-based MID estimates, as well as a rating of their credibility, for PROMs for patients with shoulder conditions. The MID estimates inform the interpretation for a linked systematic review and guideline addressing subacromial decompression surgery for shoulder pain, and could also prove useful for authors addressing other interventions for shoulder problems.PROSPERO registration numberCRD42018106531.
This is the second version (first update) of the living systematic review, replacing the previous version (available as a data supplement). When citing this paper please consider adding the version ...number and date of access for clarity.
To 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).
Living systematic review and network meta-analysis (NMA).
World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 4 March 2022.
Randomised trials in which people at risk of covid-19 were allocated to prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles.
After 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.
The second iteration of this living NMA includes 32 randomised trials which enrolled 25 147 participants and addressed 21 different prophylactic drugs; adding 21 trials (66%), 18 162 participants (75%) and 16 (76%) prophylactic drugs. Of the 16 prophylactic drugs analysed, none provided convincing evidence of a reduction in the risk of laboratory confirmed SARS-CoV-2 infection. For admission to hospital and mortality outcomes, no prophylactic drug proved different than standard care or placebo. Hydroxychloroquine and vitamin C combined with zinc probably increase the risk of adverse effects leading to drug discontinuation—risk difference for hydroxychloroquine (RD) 6 more per 1000 (95% credible interval (CrI) 2 more to 10 more); for vitamin C combined with zinc, RD 69 more per 1000 (47 more to 90 more), moderate certainty evidence.
Much of the evidence remains very low certainty and we therefore anticipate future studies evaluating drugs for prophylaxis may change the results for SARS-CoV-2 infection, admission to hospital and mortality outcomes. Both hydroxychloroquine and vitamin C combined with zinc probably increase adverse effects.
This review was not registered. The protocol established a priori is included as a supplement.
This study was supported by the Canadian Institutes of Health Research (grant CIHR-IRSC:0579001321).
Abstract
We aimed to assess the impact of allocation concealment and blinding on the results of coronavirus disease 2019 (COVID-19) trials, using the World Health Organization COVID-19 database (to ...February 2022). We identified 488 randomized trials comparing drug therapeutics with placebo or standard care in patients with COVID-19. We performed random-effects meta-regressions comparing the results of trials with and without allocation concealment and blinding of health-care providers and patients. We found that, compared with trials with allocation concealment, trials without allocation concealment may estimate treatments to be more beneficial for mortality, mechanical ventilation, hospital admission, duration of hospitalization, and duration of mechanical ventilation, but results were imprecise. We did not find compelling evidence that, compared with trials with blinding, trials without blinding produce consistently different results for mortality, mechanical ventilation, and duration of hospitalization. We found that trials without blinding may estimate treatments to be more beneficial for hospitalizations and duration of mechanical ventilation. We did not find compelling evidence that COVID-19 trials in which health-care providers and patients are blinded produce different results from trials without blinding, but trials without allocation concealment estimate treatments to be more beneficial compared with trials with allocation concealment. Our study suggests that lack of blinding may not always bias results but that evidence users should remain skeptical of trials without allocation concealment.
The objective of the study was to develop an inventory summarizing all anchor-based minimal important difference (MID) estimates for patient-reported outcome measures (PROMs) available in the medical ...literature.
We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Patient-Reported Outcome and Quality of Life Instruments Database internal library (January 1989–October 2018). We included primary studies empirically calculating an anchor-based MID estimate for any PROM in adults and adolescents. Pairs of reviewers independently screened and selected studies, extracted data, and evaluated the credibility of the MIDs.
We identified 585 eligible studies, the majority conducted in Europe (n = 211) and North America (n = 179), reporting 5,324 MID estimates for 526 distinct PROMs. Investigators conducted their studies in the context of patients receiving surgical (n = 105, 18%), pharmacological (n = 85, 15%), rehabilitation (n = 65, 11%), or a combination of interventions (n = 194, 33%). Of all MID estimates, 59% (n = 3,131) used a global rating of change anchor. Major credibility limitations included weak correlation (n = 1,246, 23%) or no information regarding the correlation (n = 3,498, 66%) between the PROM and anchor and imprecision in the MID estimate (n = 2,513, 47%).
A large number of MIDs for assisting in the interpretation of PROMs exist. The MID inventory will facilitate the use of MID estimates to inform the interpretation of the magnitude of treatment effects in clinical research and guideline development.
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