These guidelines offer a rapid method to assess disease severity and to treat primary focal hyperhidrosis according to severity.

Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions. Objective: We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 inhibitor upadacitinib in patients with moderate to severe atopic dermatitis. Methods: In the 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries (ClinicalTrials.gov, NCT02925117; ongoing, not recruiting), adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to oncedaily upadacitinib oral monotherapy 7.5, 15, or 30 mg or placebo. The primary end point was percentage improvement in Eczema Area and Severity Index from baseline at week 16. Efficacy was analyzed by intention-to-treat in all randomized patients. Safety was analyzed in all randomized patients who received study medication, based on actual treatment. Results: Patients (N 5 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n 5 42; placebo, n 5 41); 166 were analyzed for safety (each upadacitinib group, n 5 42; placebo, n 5 40). The mean (SE) primary efficacy end point was 39% (6.2%), 62% (6.1%), and 74% (6.1%) for the upadacitinib 7.5-, 15-, and 30-mg groups, respectively, versus 23% (6.4%) for placebo (P 5 .03, <.001, and <.001). Serious adverse events occurred in 4.8% (2 of 42), 2.4% (1 of 42), and 0% (0 of 42) of upadacitinib groups (vs 2.5% [1 of 40] for placebo). Conclusions: A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.

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Topic Primary open angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. Clinical Relevance Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). While topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. Methods We included randomized controlled trials that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. Results We included 114 randomized controlled trials with data from 20,275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in mmHg at 3 months, ordered from the most to least effective drugs were: bimatoprost 5·61 (4·94; 6·29), latanoprost 4·85 (4·24; 5·46), travoprost 4·83 (4·12; 5·54), levobunolol 4·51 (3·85; 5·24), tafluprost 4·37 (2·94; 5·83), timolol 3·7 (3·16; 4·24), brimonidine 3·59 (2·89; 4·29), carteolol 3·44 (2·42; 4·46), levobetaxolol 2·56 (1·52; 3·62), apraclonidine 2·52 (0·94; 4·11), dorzolamide 2·49 (1·85; 3·13), brinzolamide 2·42 (1·62; 3·23), betaxolol 2·24 (1·59; 2·88), and unoprostone 1·91 (1·15; 2·67). Conclusions All active first-line drugs are effective compared to placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost should be considered in selecting a drug for a given patient.

Summary Bayesian statistical approaches to mixed treatment comparisons (MTCs) are becoming more popular due to their flexibility and interpretability. Many randomized clinical trials report multiple outcomes with possible inherent correlations. Moreover, MTC data are typically sparse (though richer than standard meta-analysis, comparing only two treatments) and researchers often choose study arms based upon which treatments emerge as superior in previous trials. In this paper, we summarize existing hierarchical Bayesian methods for MTCs with a single outcome, and introduce novel Bayesian approaches for multiple outcomes simultaneously, rather than in separate MTC analyses. We do this by incorporating partially observed data and its correlation structure between outcomes through contrast- and arm-based parameterizations that consider any unobserved treatment arms as missing data to be imputed. We also extend the model to apply to all types of generalized linear model outcomes, such as count or continuous responses. We offer a simulation study under various missingness mechanisms (e.g., MCAR, MAR, and MNAR) providing evidence that our models outperform existing models in terms of bias, MSE, and coverage probability, then illustrate our methods with a real MTC dataset. We close with a discussion of our results, several contentious issues in MTC analysis, and a few avenues for future methodological development.

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Objective: To identify variations in outcomes and results across reports of randomized clinical trials (RCTs). Study Design and Setting: Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., journal articles) and nonpublic (e.g., clinical study reports) sources by 2015. We prespecified outcome domains. From each source, we collected ''outcomes'' (i.e., domain, measure, metric, method of aggregation, and time point); ''treatment effect'' (i.e., outcome plus the methods of analysis [e.g., how missing data were handled]); and results (i.e., numerical contrasts of treatment and comparison groups). We assessed whether results included sufficient information for meta-analysis.Results: We found 21 gabapentin (68 public, 6 nonpublic reports) and seven quetiapine RCTs (46 public, 4 nonpublic reports). For four (gabapentin) and seven (quetiapine) prespecified outcome domains, RCTs reported 214 and 81 outcomes by varying four elements. RCTs assessed 605 and 188 treatment effects by varying the analysis of those outcomes. RCTs reported 1,230 and 661 meta-analyzable results, 305 (25%) and 109 (16%) in public reports.Conclusion: RCTs included hundreds of outcomes and results; a small proportion were in public reports. Trialists and meta-analysts may cherry-pick what they report from multiple sources of RCT information. Ó 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The antithrombotic treatment of patients with atrial fibrillation (AF) and coronary artery disease, in particular with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), poses a significant treatment dilemma in clinical practice.OBJECTIVE To study the safety and efficacy of different antithrombotic regimens using a network meta-analysis of randomized controlled trials in this population.DATA SOURCES PubMed, EMBASE, EBSCO, and Cochrane databases were searched to identify randomized controlled trials comparing antithrombotic regimens.STUDY SELECTION Four randomized studies were included (n = 10 026; WOEST, PIONEER AF-PCI, RE-DUAL PCI, and AUGUSTUS). DATA EXTRACTION AND SYNTHESISThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used in this systematic review and network meta-analysis between 4 regimens using a Bayesian random-effects model. A pre hoc statistical analysis plan was written, and the review protocol was registered at PROSPERO. Data were analyzed between November 2018 and February 2019. MAIN OUTCOMES AND MEASURESThe primary safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding; secondary safety outcomes were combined TIMI major and minor bleeding, trial-defined primary bleeding events, intracranial hemorrhage, and hospitalization. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE); secondary efficacy outcomes were individual components of MACE. RESULTSThe overall prevalence of ACS varied from 28% to 61%. The mean age ranged from 70 to 72 years; 20% to 29% of the trial population were women; and most patients were at high risk for thromboembolic and bleeding events. Compared with a regimen of vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT; P2Y 12 inhibitor plus aspirin), the odds ratios (ORs) for TIMI major bleeding were 0.58 (95% CI, 0.31-1.08) for VKA plus P2Y 12 inhibitor, 0.49 (95% CI, 0.30-0.82) for non-VKA oral anticoagulant (NOAC) plus P2Y 12 inhibitor, and 0.70 (95% CI, 0.38-1.23) for NOAC plus DAPT. Compared with VKA plus DAPT, the ORs for MACE were 0.96 (95% CI, 0.60-1.46) for VKA plus P2Y 12 inhibitor, 1.02 (95% CI, 0.71-1.47) for NOAC plus P2Y 12 inhibitor, and 0.94 (95% CI, 0.60-1.45) for NOAC plus DAPT. CONCLUSIONS AND RELEVANCEA regimen of NOACs plus P2Y 12 inhibitor was associated with less bleeding compared with VKAs plus DAPT. Strategies omitting aspirin caused less bleeding, including intracranial bleeding, without significant difference in MACE, compared with strategies including aspirin. Our results support the use of NOAC plus P2Y 12 inhibitor as the preferred regimen post-percutaneous coronary intervention for these high-risk patients with AF. A regimen of VKA plus DAPT should generally be avoided.