Crisaborole Ointment, 2%, for Treatment of Patients with Mild-to-Moderate Atopic Dermatitis:Systematic Literature Review and Network Meta-Analysis

The authors would like to replace 2 small sections of the published manuscript that refer to a qualitative review of safety data for included studies (together with an associated safety table), to provide some further clarifications on these safety data and to include some quantitative updates for rates

The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis

Background This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George’s Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations. Methods A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance. Results Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant. Conclusions The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships, results were in the expected direction with few exceptions. The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies

A systematic review of the association between delayed appropriate therapy and mortality among patients hospitalized with infections due to Klebsiella pneumoniae or Escherichia coli: how long is too long?

Abstract Background Temporal relationships between the time to appropriate antibiotic therapy and outcomes are not well described. Methods A systematic literature review and meta-analysis was performed to examine this relationship in patients hospitalized with Klebsiella pneumoniae or Escherichia coli infections. Results Twenty identified studies contained data for patients who received delayed appropriate therapy (DAT) versus appropriate antibiotic therapy for these pathogens. Of the 20 included studies, the majority (19/20) focused on patients with bloodstream infections, and only 1 study evaluated patients with pneumonia. When all DAT results were combined (any delay > 24 h from culture collection or any delay after culture and susceptibility reporting [C& SR]), there was an increased risk of mortality (odds ratio [OR], 1.60 [95% CI, 1.25–2.50]). The risk of mortality was greater when DAT > 48 h from culture collection or DAT > C&SR results were combined (OR, 1.76 [95% CI, 1.27–2.44]). Conclusions Our findings suggest there is a need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early, relatively aggressive and comprehensive, antibiotic therapy, especially among patients with bloodstream infections due to K. pneumoniae or E. coli

The relation of self-efficacy measures to sport performance : a meta-analytic review

Une méta-analyse de 45 travaux de recherche montre une corrélation moyenne entre sentiment de compétence et performance sportive de .38. Etant donné l'hétérogénéité des résultats, d'autres analyses ont été effectuées pour évaluer leur validité

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer:a network meta-analysis

Background: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with agents - other than docetaxel - that are approved second-line treatments for non-small-cell lung cancer. Methods: The relative efficacy of nintedanib plus docetaxel versus second-line agents was evaluated by conducting a network meta-analysis of progression-free survival and overall survival. Results: Nine suitable studies were identified. The estimated probability of nintedanib plus docetaxel being the best treatment with regard to overall survival was 70% (versus 16% for pemetrexed, 10% for docetaxel and 3% for erlotinib). Results for progression-free survival were similar. Conclusion: In patients with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient group

Handling related publications reporting real-world evidence in network meta-analysis: a case study in multiple sclerosis

Aim: The presence of two or more publications that report on overlapping patient cohorts poses a challenge for quantitatively synthesizing real-world evidence (RWE) studies. Thus, we evaluated eight approaches for handling such related publications in network meta-analyses (NMA) of RWE studies.Methods: Bayesian NMAs were conducted to estimate the annualized relapse rate (ARR) of disease -modifying therapies in multiple sclerosis. The NMA explored the impact of hierarchically selecting one pivotal study from related publications versus including all of them while adjusting for correlations.Results: When selecting one pivotal study from related publications, the ARR ratios were mostly similar regardless of the pivotal study selected. When including all related publications, there were shifts in the point estimates and the statistical significance. Conclusion: An a priori hierarchy should guide the selection among related publications in NMAs of RWE. Sensitivity analyses modifying the hierarchy should be considered for networks with few or small studies.Plain language summary What is this article about? Real-world evidence (RWE) studies are increasingly recognized as important data source in guiding clinical care and regulatory submissions. However, when synthesizing the evidence originating from RWE studies, different analyses of the same data source are identified often. To avoid the double-counting of patients in network meta-analysis, we investigated different approaches for synthesizing the evidence from such related publications. What were the results? When selecting a single pivotal publication by prioritizing different selection criteria (sample size, number of therapies evaluated, type of publication, or follow-up time), results were fairly similar. In the scenarios that included all related publications (instead of selecting single pivotal study), the overall conclusions sometimes changed inappropriately, even when correcting for correlations between publications. What do the results mean? When analyzing RWE data in a network meta-analysis, we recommend establishing selection criteria for choosing pivotal publications prior to quantitatively synthesizing the evidence from RWE studies. Tweetable abstract: This study in multiple sclerosis examines approaches for handling related publications in network meta-analyses of real-world evidence and recommends establishing an a priori hierarchy for selection

AbobotulinumtoxinA Doses in Upper and Lower Limb Spasticity: A Systematic Literature Review

International audienceDisabling limb spasticity can result from stroke, traumatic brain injury or other disorders causing upper motor neuron lesions such as multiple sclerosis. Clinical studies have shown that abobotulinumtoxinA (AboBoNT-A) therapy reduces upper and lower limb spasticity in adults. However, physicians may administer potentially inadequate doses, given the lack of consensus on adjusting dose according to muscle volume, the wide dose ranges in the summary of product characteristics or cited in the published literature, and/or the high quantity of toxin available for injection. Against this background, a systematic literature review based on searches of MEDLINE and Embase (via Ovid SP) and three relevant conferences (2018 to 2020) was conducted in November 2020 to examine AboBoNT-A doses given to adults for upper or lower limb muscles affected by spasticity of any etiology in clinical and real-world evidence studies. From the 1781 unique records identified from the electronic databases and conference proceedings screened, 49 unique studies represented across 56 publications (53 full-text articles, 3 conference abstracts) were eligible for inclusion. Evidence from these studies suggested that AboBoNT-A dose given per muscle in clinical practice varies considerably, with only a slight trend toward a relationship between dose and muscle volume. Expert-based consensus is needed to inform recommendations for standardizing AboBoNT-A treatment initiation doses based on muscle volume