Tadalafil in patients with chronic obstructive pulmonary disease:a randomised, double-blind, parallel-group, placebo-controlled trial

SummaryBackgroundPhosphodiesterase-5 (PDE5) inhibitors improve exercise capacity and quality of life in patients with idiopathic pulmonary arterial hypertension. However, whether such beneficial effects take place in selected populations with chronic obstructive pulmonary disease (COPD) remains uncertain. We aimed to assess the effects of tadalafil—a PDE5 inhibitor—on exercise capacity and quality of life in patients with COPD and mild pulmonary hypertension.MethodsWe did a randomised, double-blind, parallel-group, placebo-controlled trial at three centres in Scotland, UK, between Sept 1, 2010, and Sept 1, 2012. Patients with moderate to severe COPD were randomly assigned (1:1), via centralised randomisation with a computer-generated sequence and block sizes of four, to receive daily tadalafil 10 mg or placebo for 12 weeks. Patients, study investigators, outcome assessors, and those administering drugs were masked to group allocation. The primary endpoint was the mean placebo-corrected difference between the baseline and final 6 min walk distance after 12 weeks. We measured change in quality of life at baseline, 8 weeks, and 12 weeks, with standardised questionnaires. Analysis was per protocol and by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01197469.Findings120 patients were randomly assigned to receive tadalafil (n=60) or placebo (n=60), of whom 56 (93%) versus 57 (95%) completed the study. At 12 weeks the difference in 6 min walking distance between the tadalafil and placebo groups was 0·5 m (95% CI −11·6 to 12·5; p=0·937). We recorded no statistically significant changes in quality of life (between-group difference on the St George's Respiratory Questionnaire −2·64 [95% CI −6·43 to 1·15]; Research and Development version 1 short-form-36 4·08 [–1·35 to 9·52]; Minnesota Living with Heart Failure questionnaire −2·31 [–7·06 to 2·45]). 19 (32%) of 60 patients in the treatment group had dyspepsia; the severity of dyspepsia ranged from mild to severe, with four (21%) of 19 patients needing a proton-pump inhibitor. Five (8%) of 60 participants had dyspepsia in the placebo group. Headache was noted in 17 (28%) patients in the treatment group versus 5 (8%) in the placebo group, but was mild in all patients. Two (3%) patients in the treatment group had facial flushing, which resulted in one withdrawal. Other withdrawals within the tadalafil group happened after a transient ischaemic attack and two deaths (ruptured abdominal aortic aneurysm and pneumonia).InterpretationTadalafil does not improve exercise capacity or quality of life despite exerting pulmonary vasodilation.FundingChief Scientist Office for Scotland

Cardiovascular Effects of Switching from Tobacco Cigarettes to Electronic Cigarettes

The VESUVIUS (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use) trial was funded by the British Heart Foundation (grant PG/15/64/31681); and supported by Immunoassay Biomarker Core Laboratory, University of Dundee, the Tayside Medical Sciences Centre, and the NHS Tayside Smoking Cessation Service. The funder had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or in the decision to submit for publication. Dr. Donnan has received research grants from AbbVie, Shire, and Gilead Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.Peer reviewedPublisher PD

Implications of serial measurements of natriuretic peptides in heart failure: insights from BIOSTAT‐CHF

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A systematic approach to context-mapping to prepare for health interventions: development and validation of the SETTING-tool in four countries

Effectiveness of health interventions can be substantially impaired by implementation failure. Context-driven implementation strategies are critical for successful implementation. However, there is no practical, evidence-based guidance on how to map the context in order to design context-driven strategies. Therefore, this practice paper describes the development and validation of a systematic context-mapping tool. The tool was cocreated with local end-users through a multistage approach. As proof of concept, the tool was used to map beliefs and behaviour related to chronic respiratory disease within the FRESH AIR project in Uganda, Kyrgyzstan, Vietnam and Greece. Feasibility and acceptability were evaluated using the modified Conceptual Framework for Implementation Fidelity. Effectiveness was assessed by the degree to which context-driven adjustments were made to implementation strategies of FRESH AIR health interventions. The resulting Setting-Exploration-Treasure-Trail-to-Inform-implementatioN-strateGies (SETTING-tool) consisted of six steps: (1) Coset study priorities with local stakeholders, (2) Combine a qualitative rapid assessment with a quantitative survey (a mixed-method design), (3) Use context-sensitive materials, (4) Collect data involving community researchers, (5) Analyse pragmatically and/or in-depth to ensure timely communication of findings and (6) Continuously disseminate findings to relevant stakeholders. Use of the tool proved highly feasible, acceptable and effective in each setting. To conclude, the SETTING-tool is validated to systematically map local contexts for (lung) health interventions in diverse low-resource settings. It can support policy-makers, non-governmental organisations and health workers in the design of context-driven implementation strategies. This can reduce the risk of implementation failure and the waste of resource potential. Ultimately, this could improve health outcomes