Multiarm studies and how to handle them in a meta-analysis: A tutorial

This tutorial focuses on multiarm studies. We will explain what multiarm studies are and how to include data from them in a meta-analysis

Safety of topical corticosteroids in atopic eczema:an umbrella review

Objective: An umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema .Methods: Embase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews searched until 7th November 2018 and Epistemonikos until 2nd March 2021. Reviews were included if they assessed safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality assessed using AMSTAR-2. PROSPERO registration: CRD42018079409. Results: 38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up usually short (2-4 weeks). Key findings: TCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4%-5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased. TCS versus topical calcineurin inhibitors (TCIs): Meta-analysis showed higher relative risk of skin-thinning with TCS (RR 4.86, 95% CI 1.06-22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin-thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).Conclusions: We found no evidence of harm when TCS used intermittently “as required” to treat flares or “weekend therapy” to prevent flares. However, long-term safety data was limited

Different strategies for using topical corticosteroids in people with eczema

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To establish the effectiveness and safety of different ways of using topical corticosteroids in people with eczema

Psychological and educational interventions for managing eczema

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. 1. To assess the clinical outcomes of psychological and educational interventions in children and adults with eczema. 2. To summarise the availability and principal findings of relevant economic evaluations

Strategies for using topical corticosteroids in children and adults with eczema

Background Eczema is a common skin condition. Although topical corticosteroids (TCS) have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. Objectives To establish the effectiveness and safety of different ways of using TCS for treating eczema. Search methods We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT). Five clinical trial registers were also searched. Bibliographies from included studies were checked to identify further trials. Selection criteria Randomised controlled trials in adults and children with eczema comparing at least two strategies of TCS use. Placebo comparisons were excluded, other than for studies evaluating proactive versus reactive treatment

Strategies for using topical corticosteroids in children and adults with eczema.

BACKGROUND: Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. OBJECTIVES: To establish the effectiveness and safety of different ways of using topical corticosteroids for treating eczema. SEARCH METHODS: We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT) and five clinical trials registers. We checked bibliographies from included trials to identify further trials. SELECTION CRITERIA: Randomised controlled trials in adults and children with eczema that compared at least two strategies of topical corticosteroid use. We excluded placebo comparisons, other than for trials that evaluated proactive versus reactive treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, with GRADE certainty of evidence for key findings. Primary outcomes were changes in clinician-reported signs and relevant local adverse events. Secondary outcomes were patient-reported symptoms and relevant systemic adverse events. For local adverse events, we prioritised abnormal skin thinning as a key area of concern for healthcare professionals and patients. MAIN RESULTS: We included 104 trials (8443 participants). Most trials were conducted in high-income countries (81/104), most likely in outpatient or other hospital settings. We judged only one trial to be low risk of bias across all domains. Fifty-five trials had high risk of bias in at least one domain, mostly due to lack of blinding or missing outcome data. Stronger-potency versus weaker-potency topical corticosteroids Sixty-three trials compared different potencies of topical corticosteroids: 12 moderate versus mild, 22 potent versus mild, 25 potent versus moderate, and 6 very potent versus potent. Trials were usually in children with moderate or severe eczema, where specified, lasting one to five weeks. The most reported outcome was Investigator Global Assessment (IGA) of clinician-reported signs of eczema. We pooled four trials that compared moderate- versus mild-potency topical corticosteroids (420 participants). Moderate-potency topical corticosteroids probably result in more participants achieving treatment success, defined as cleared or marked improvement on IGA (52% versus 34%; odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41 to 3.04; moderate-certainty evidence). We pooled nine trials that compared potent versus mild-potency topical corticosteroids (392 participants). Potent topical corticosteroids probably result in a large increase in number achieving treatment success (70% versus 39%; OR 3.71, 95% CI 2.04 to 6.72; moderate-certainty evidence). We pooled 15 trials that compared potent versus moderate-potency topical corticosteroids (1053 participants). There was insufficient evidence of a benefit of potent topical corticosteroids compared to moderate topical corticosteroids (OR 1.33, 95% CI 0.93 to 1.89; moderate-certainty evidence). We pooled three trials that compared very potent versus potent topical corticosteroids (216 participants). The evidence is uncertain with a wide confidence interval (OR 0.53, 95% CI 0.13 to 2.09; low-certainty evidence). Twice daily or more versus once daily application We pooled 15 of 25 trials in this comparison (1821 participants, all reported IGA). The trials usually assessed adults and children with moderate or severe eczema, where specified, using potent topical corticosteroids, lasting two to six weeks. Applying potent topical corticosteroids only once a day probably does not decrease the number achieving treatment success compared to twice daily application (OR 0.97, 95% CI 0.68 to 1.38; 15 trials, 1821 participants; moderate-certainty evidence). Local adverse events Within the trials that tested 'treating eczema flare-up' strategies, we identified only 26 cases of abnormal skin thinning from 2266 participants (1% across 22 trials). Most cases were from the use of higher-potency topical corticosteroids (16 with very potent, 6 with potent, 2 with moderate and 2 with mild). We assessed this evidence as low certainty, except for very potent versus potent topical corticosteroids, which was very low-certainty evidence.  Longer versus shorter-term duration of application for induction of remission No trials were identified. Twice weekly application (weekend, or 'proactive therapy') to prevent relapse (flare-ups) versus no topical corticosteroids/reactive application Nine trials assessed this comparison, generally lasting 16 to 20 weeks. We pooled seven trials that compared weekend (proactive) topical corticosteroids therapy versus no topical corticosteroids (1179 participants, children and adults with a range of eczema severities, though mainly moderate or severe). Weekend (proactive) therapy probably results in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio (RR) 0.43, 95% CI 0.32 to 0.57; 7 trials, 1149 participants; moderate-certainty evidence). Local adverse events We did not identify any cases of abnormal skin thinning in seven trials that assessed skin thinning (1050 participants) at the end of treatment. We assessed this evidence as low certainty. Other comparisons  Other comparisons included newer versus older preparations of topical corticosteroids (15 trials), cream versus ointment (7 trials), topical corticosteroids with wet wrap versus no wet wrap (6 trials), number of days per week applied (4 trials), different concentrations of the same topical corticosteroids (2 trials), time of day applied (2 trials), topical corticosteroids alternating with topical calcineurin inhibitors versus topical corticosteroids alone (1 trial), application to wet versus dry skin (1 trial) and application before versus after emollient (1 trial). No trials compared branded versus generic topical corticosteroids and time between application of emollient and topical corticosteroids. AUTHORS' CONCLUSIONS: Potent and moderate topical corticosteroids are probably more effective than mild topical corticosteroids, primarily in moderate or severe eczema; however, there is uncertain evidence to support any advantage of very potent over potent topical corticosteroids. Effectiveness is similar between once daily and twice daily (or more) frequent use of potent topical corticosteroids to treat eczema flare-ups, and topical corticosteroids weekend (proactive) therapy is probably better than no topical corticosteroids/reactive use to prevent eczema relapse (flare-ups). Adverse events were not well reported and came largely from low- or very low-certainty, short-term trials. In trials that reported abnormal skin thinning, frequency was low overall and increased with increasing potency. We found no trials on the optimum duration of treatment of a flare, branded versus generic topical corticosteroids, and time to leave between application of topical corticosteroids and emollient. There is a need for longer-term trials, in people with mild eczema

Skin care interventions in infants for preventing eczema and food allergy

BackgroundEczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy.ObjectivesPrimary objectiveTo assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infantsSecondary objectiveTo identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated withthe greatest treatment benefit or harm for both eczema and food allergy.Search methodsWe searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials.Selection criteriaRCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre‐existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow‐up was required.Data collection and analysisThis is a prospective individual participant data (IPD) meta‐analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E‐mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician‐assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen.Main resultsThis review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta‐analysis (range 2 to 9 studies per individual meta‐analysis).Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty‐five studies, including all those contributing data to meta‐analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta‐analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow‐up ranged from 24 hours to two years.We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data.Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate‐certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate‐certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE‐mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low‐certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low‐certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow’s milk, and may be unreliable due to significant over‐reporting of cow’s milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate‐certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low‐certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low‐certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk.Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy.Authors' conclusionsSkin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain.Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments

A process for prioritising systematic reviews in tinnitus

Objective: To develop an innovative prioritisation process to identify topics for new or updated systematic reviews of tinnitus research.Design: A two-stage prioritisation process was devised. First, a scoping review assessed the amount of randomized controlled trial-level evidence available. This enabled development of selection criteria for future reviews, aided the design of template protocol and suggested the scale of work that would be required to conduct these reviews. Second, using the pre-defined primary and secondary criteria, interventions were prioritised for systematic review.Study sample: Searches identified 1080 records. After removal of duplicates and out of scope works, 437 records remained for full data charting.Results: The process was tested, using subjective tinnitus as the clinical condition and using Cochrane as the systematic review platform. The criteria produced by this process identified three high priority reviews: (1) Sound therapy using amplification devices and/or sound generators; (2) Betahistine and (3) Cognitive behaviour therapy. Further secondary priorities were: (4) Gingko biloba, (5) Anxiolytics, (6) Hypnotics, (7) Antiepileptics and (8) Neuromodulation.Conclusions: A process was developed which successfully identified priority areas for Cochrane systematic reviews of interventions for subjective tinnitus. This technique could easily be transferred to other conditions and other types of systematic reviews.status: publishe