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Miguel Angel Martinez-García,1,2 David Rigau,3 Miriam Barrecheguren,2,4 Alberto García-Ortega,1 Alexa Nuñez,2,4 Grace Oscullo Yepez,1 Marc Miravitlles2,4 1Pneumology Department, Hospital Universitario y Politécnico La Fe, Valencia, Spain; 2CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 3Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 4Pneumology Department, Hospital Universitari Vall d´Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, Barcelona, SpainCorrespondence: Marc Miravitlles, University Hospital Vall d’Hebron, Department of Pneumology, Vall d’Hebron Barcelona Hospital Campus, Pg Vall d’Hebron 119-129, Barcelona, 08036, Spain, Email marcm@separ.esBackground: Chronic bronchial infection is frequent in chronic obstructive pulmonary disease (COPD), but the impact of the isolation of pathogenic bacteria, and in particular Pseudomonas aeruginosa (PA) in respiratory samples on the prognosis of COPD is unclear.Methods: We conducted a systematic review of prognostic studies including patients with isolation of PA in sputum in stable state or during exacerbations of COPD. The main outcomes were all-cause mortality, respiratory mortality, and number and severity of future exacerbations. Data were expressed as hazard ratio (HR) (95% confidence interval [CI]) whenever possible.Results: Of 2773 studies, eight were finally included (23,228 individuals). The mean age ranged from 65.5 to 73 years. Six studies reported data for all-cause mortality. The adjusted risk of death was almost double in patients with PA isolation (HR 1.95, 95% CI, 1.34 to 2.84; quality of evidence moderate). Patients with PA isolation showed a three times higher adjusted risk of readmission at 30 days after discharge (OR 3.60, 95% CI, 3.60 to 12.03, 1 study; quality of evidence very low), and more than double adjusted risk of death and hospitalization at two years (HR 2.80, 95% CI, 2.20 to 3.56, 1 study; quality of evidence very low).Conclusion: There is moderate certainty that the isolation of PA in sputum is associated with an adjusted increased risk of death in patients with COPD.Keywords: COPD, prognosis, outcomes, mortality, exacerbations, bronchial infection, bronchial colonization

Background: A major challenge in updating clinical guidelines is to efficiently identify new, relevant evidence. We evaluated the efficiency and feasibility of two new approaches: the development of restrictive search strategies using PubMed Clinical Queries for MEDLINE and the use of the PLUS (McMaster Premium Literature Service) database. Methods: We evaluated a random sample of recommendations from a national guideline development program and identified the references that would potentially trigger an update (key references) using an exhaustive approach. We designed restrictive search strategies using the minimum number of Medical Subject Headings (MeSH) terms and text words required from the original exhaustive search strategies and applying broad and narrow filters. We developed PLUS search strategies, matching Medical Subject Headings (MeSH) and Systematized Nomenclature of Medicine (SNOMED) terms with guideline topics. We compared the number of key references retrieved by these approaches with those retrieved by the exhaustive approach. Results: The restrictive approach retrieved 68.1 % fewer references than the exhaustive approach (12,486 versus 39,136), and identified 89.9 % (62/69) of key references and 88 % (22/25) of recommendation updates. The use of PLUS retrieved 88.5 % fewer references than the exhaustive approach (4,486 versus 39,136) and identified substantially fewer key references (18/69, 26.1 %) and fewer recommendation updates (10/25, 40 %). Conclusions: The proposed restrictive approach is a highly efficient and feasible method to identify new evidence that triggers a recommendation update. Searching only in the PLUS database proved to be a suboptimal approach and suggests the need for topic-specific tailoring. [ABSTRACT FROM AUTHOR]

Background: The efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder (ADHD) shows wide between-study variability, which yields heterogeneous results in meta-analysis. The reasons for this variability have not been comprehensively investigated.Objectives: To determine the influence of treatment-related covariates of methylphenidate for adults with ADHD by means of meta-analysis. Clinical and methodological moderators and clinical trial reporting quality were also collected to control for their potential confounding effect.Methods: We searched for randomized, placebo-controlled clinical trials investigating the efficacy of methylphenidate for adults with ADHD. The study outcome was the efficacy of methylphenidate for reducing ADHD symptom severity. Treatment-related covariates included dose, type of drug-release formulation (formulations with a continuous drug release vs those with a non-continuous drug release), dose regimen (fixed vs flexible) and treatment length. Clinical (presence of co-morbid substance use disorders [SUD]) and methodological (design and rater) covariates were also collected, in addition to clinical trial reporting quality. The standardized mean difference (SMD) was calculated for each study. The analysis of the influence of methylphenidate effect modifiers was performed by means of random-effects meta-regression.Results: Eighteen studies were included. Dose, type of formulation and SUD appeared to modify the efficacy of methylphenidate in the bivariate analysis. These variables were included in a multivariate meta-regression, which showed that methylphenidate, at an average dose of 57.4 mg/day, delivered by means of non-continuous-release formulations, had a moderate effect on ADHD symptoms compared with placebo (SMD 0.57-0.58). A dose-response relationship was found, indicating that efficacy could be increased by SMD 0.11-0.12 for every 10 mg increment of methylphenidate. Continuous-release formulations and co-morbid SUD appeared to reduce the efficacy of methylphenidate. Nevertheless, the effect of treatment formulation may have been confounded by co-morbid SUD, since all studies using this continuous-release formulation were conducted in dual ADHD-SUD patients. No residual heterogeneity was found.Conclusions: This study shows that methylphenidate improves ADHD symptoms in adults in a dose-dependent fashion. The efficacy of methylphenidate appears to be reduced in patients with co-morbid SUD. It is unclear whether methylphenidate efficacy is influenced by the type of formulation, because the effect of this covariate is confounded by that of co-morbid SUD. [ABSTRACT FROM AUTHOR]