David Rigau

The quality of clinical practice guidelines over the last two decades: a systematic review of guideline appraisal studies

Background Despite the increasing number of manuals on how to develop clinical practice guidelines (CPGs) there remain concerns about their quality. The aim of this study was to review the quality of CPGs across a wide range of healthcare topics published since 1980. Methods The authors conducted a literature search in MEDLINE to identify publications assessing the quality of CPGs with the Appraisal of Guidelines, Research and Evaluation (AGREE) instrument. For the included guidelines in each study, the authors gathered data about the year of publication, institution, country, healthcare topic, AGREE score per domain and overall assessment. Results In total, 42 reviews were selected, including a total of 626 guidelines, published between 1980 and 2007, with a median of 25 CPGs. The mean scores were acceptable for the domain ‘Scope and purpose’ (64%; 95% CI 61.9 to 66.4) and ‘Clarity and presentation’ (60%; 95% CI 57.9 to 61.9), moderate for domain ‘Rigour of development’ (43%; 95% CI 41.0 to 45.2), and low for the other domains (‘Stakeholder involvement’ 35%; 95% CI 33.9 to 37.5, ‘Editorial independence’ 30%; 95% CI 27.9 to 32.3, and ‘Applicability’ 22%; 95% CI 20.4 to 23.9). From those guidelines that included an overall assessment, 62% (168/270) were recommended or recommended with provisos. There was a significant improvement over time for all domains, except for ‘Editorial independence.’ Conclusions This review shows that despite some increase in quality of CPGs over time, the quality scores as measured with the AGREE Instrument have remained moderate to low over the last two decades. This finding urges guideline developers to continue improving the quality of their products. International collaboration could help increasing the efficiency of the process.

Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis.

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.

Interferon-γ Release Assays for the Diagnosis of Tuberculosis and Tuberculosis Infection in HIV-Infected Adults: A Systematic Review and Meta-Analysis

Background Despite the widespread use of interferon-γ release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients remains unclear. We conducted a comprehensive systematic review to contribute to the evidence-based practice in HIV-infected people. Methodology/Principal Findings We searched MEDLINE, Cochrane, and Biomedicine databases to identify articles published between January 2005 and July 2011 that assessed QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-SPOT®.TB (T-SPOT.TB) in HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis and incident active tuberculosis, and the proportion of indeterminate results. The search identified 38 evaluable studies covering a total of 6514 HIV-infected participants. The pooled sensitivity and specificity for tuberculosis were 61% and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T-SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low-intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were also higher in patients with CD4+ T-cell count <200 (11.6% for QFT-GIT and 11.4% for T-SPOT.TB) than in those with CD4+ T-cell count ≥200 (3.1% for QFT-GIT and 7.9% for T-SPOT.TB). Conclusions/Significance IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults. While their predictive value for incident active tuberculosis is modest, a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the factors associated with indeterminate results will help to optimize the use of IGRAs in clinical practice, particularly in resource-limited countries with a high prevalence of HIV-coinfection.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no “gold standard” reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia. International ERS guidelines recommend a combination of tests to diagnose primary ciliary dyskinesia http://ow.ly/sJhH304InBN

European Respiratory Society guidelines for the management of adult bronchiectasis

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines. The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature. A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy. These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes. The publication of the first ERS guidelines for bronchiectasis http://ow.ly/wQSO30dU0nE

Efficacy of whole body vibration exercise in older people: a systematic review

Purpose: The aim of this study was to perform a systematic review of the literature on whole body vibration programs in older population and a meta-analysis of randomized controlled clinical trials. Method: A search was conducted in MEDLINE, EMBASE, CENTRAL, CINAHL and PsychINFO databases. We included randomized controlled trials evaluating the efficacy and safety of whole body vibration training in older populations compared to conventional exercise or control groups that assessed balance, muscle strength, falls, bone mineral density and adverse events. Results: Sixteen trials met the inclusion criteria. Comparing the vibration and the control group, we found that vibration significantly improved knee muscle isometric strength (18.30 Nm, 95% CI 7.95–28.65), muscle power (10.44  W, 95% CI 2.85–18.03) and balance control (Tinetti test: 4.5 points, 95% CI 0.95–8.11). Comparison with a conventional exercise showed that the only significant difference was bone mineral density in the femoral neck (0.04 g/cm–2, 95% CI 0.02–0.07). There were no serious complications in most of studies. Conclusion: Whole body vibration training may improve strength, power and balance in comparison with a control group, although these effects are not apparent when compared with a group that does conventional exercise. Implications for Rehabilitation Physical exercise is effective for improving balancing and walking, muscle strength in the legs, and cardiovascular resistance, and decreasing the risk of falling in older persons. Whole body vibration training can decrease the risk of falling related to muscle weakness or balance disorders in older people when compared with a control group, although these effects are not apparent when compared with a conventional exercise. Evidence is not conclusive to assess the effect of whole body vibration training on the incidence of falls. Safety concerns related to whole body vibration have not been identified.

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline

This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Forces questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation. The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available. New guideline on the management of #COPD exacerbations from @ERStalk and @atscommunity http://ow.ly/Pvtr307YCMu

Blinding of Outcomes in Trials of Orthopaedic Trauma: An Opportunity to Enhance the Validity of Clinical Trials

BACKGROUND Blinding personnel in randomized controlled trials is an important strategy to minimize bias and increase the validity of the results. Trials of surgical interventions present blinding challenges not seen in drug trials. How often orthopaedic trauma investigators undertake blinding, and the frequency with which they could potentially utilize blinding, remains uncertain. METHODS We conducted a systematic review of all randomized controlled trials of orthopaedic trauma published from 1995 to 2004. Two reviewers assessed each trial for eligibility and extracted data regarding its characteristics, outcomes, reporting of blinding, and feasibility of blinding. RESULTS We included 171 unique randomized controlled trials spanning a variety of body regions and interventions. The most commonly reported outcomes were clinical (e.g., mortality or wound infection; 91% of trials), radiographic (83%), patient-reported (66%), and physiological results (e.g., range of motion; 56%). Less than 10% of the trials in each category reported the use of blinded outcome assessors. This contrasted with blinding that investigators could have accomplished: blinding was feasible with use of simple methods such as independent assessors, concealed incisions, and masked radiographs for 89% of clinical assessors, 89% of radiographic assessors, 96% of physiological assessors, and 35% of patient-reported assessors. CONCLUSIONS Trials in orthopaedic trauma typically measure many outcomes requiring judgment, but the individuals assessing those outcomes are seldom blinded. Investigators have the opportunity to enhance the validity of future clinical trials by incorporating simple blinding techniques.

The validity of recommendations from clinical guidelines: a survival analysis

Background: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. Methods: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan–Meier method. Results: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9–4.4 yr). We retrieved 39 136 references (range 3343–14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9–97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). Interpretation: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT)

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention. ERS/ESICM/ESCMID/ALAT evidence-based recommendations for HAP/VAP diagnosis, treatment and prevention http://ow.ly/dGhv30dAVoa