Ascertainment of cause-specific mortality in COPD - operations of the TORCH clinical endpoint Committee

Background: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. Methods: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. Results: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases ( = 0.80). COPD-relatedness was reproduced 84% of the time ( = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. Conclusion: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.

Decision making in childhood asthma exacerbation – a clinical judgement analysis

Background: Clinical decisions which impact directly on patient safety and quality of care are made during acute asthma attacks by individual doctors on the basis of their knowledge and experience. These include administration of systemic corticosteroids (CS), oral antibiotics, and admission to hospital. Clinical judgement analysis provides a methodology for comparing decisions between practitioners with different training and experience, and improving decision making. Methods: Stepwise linear regression was used to select clinical cues based on visual analogue scale assessments of the propensity of 62 clinicians to prescribe a short course of oral CS (decision 1), a course of antibiotics (decision 2), and/or admit to hospital (decision 3) for 60 â??paperâ?? patients. Results:When compared by specialty, paediatriciansâ?? models for decision 1 were more likely to include as a cue level of alertness (54% v. 16%); for decision 2 presence of crepitations (49% v. 16%), and less likely to include inhaled CS (8% v. 40%), respiratory rate (0% v. 24%), and air entry (70% v. 100%). When compared to other grades, the models derived for decision 3 by consultants/general practitioners were more likely to include wheeze severity as a cue (39% v. 6%). Conclusions: Clinicians differed in their use of individual cues and the number included in their models. Patient safety and quality of care will benefit from clarification of decision making strategies as general learning points during medical training, in the development of guidelines and care pathways, and by clinicians developing self-awareness of their own preferences.

Randomised controlled trial of home-based walking programmes at and below current recommended levels of exercise in sedentary adults

Objectives: To determine, using unsupervised walking programmes, the effects of exercise at a level lower than currently recommended to improve cardiovascular risk factors and functional capacity.

Relationship between Helicobacter pylori infection and gastric atrophy and the stages of the oesophageal inflammation, metaplasia, adenocarcinoma sequence: Results from the FINBAR case-control study.

Objective: A number of studies have shown an inverse association between infection with Helicobacter pylori and oesophageal adenocarcinoma (OAC). The mechanism of the apparent protection against OAC by H pylori infection and, in particular, the role of gastric atrophy is disputed. The relationship between all stages of the oesophageal inflammation, metaplasia, adenocarcinoma sequence and H pylori infection and gastric atrophy was explored. Methods: A case-control study involving 260 population controls, 227 OAC, 224 Barrett's oesophagus (BO) and 230 reflux oesophagitis (RO) patients recruited within Ireland was carried out. H pylori and CagA (cytotoxin-associated gene product A) infection was diagnosed serologically by western blot, and pepsinogen I and II levels were measured by enzyme immunoassay. Gastric atrophy was defined as a pepsinogen I/II ratio of <3. Results: H pylori seropositive was inversely associated with OAC, BO and RO; adjusted ORs (95% CIs), 0.49 (0.31 to 0.76), 0.35 (0.22 to 0.56) and 0.42 (0.27 to 0.65), respectively. Gastric atrophy was uncommon (5.3% of all subjects), but was inversely associated with non-junctional OAC, BO and RO; adjusted ORs (95% CIs), 0.34 (0.10 to 1.24), 0.23 (0.05 to 0.96) and 0.27 (0.08 to 0.88), respectively. Inverse associations between H pylori and the disease states remained in gastric atrophy-negative patients. Conclusion: H pylori infection and gastric atrophy are associated with a reduced risk of OAC, BO and RO. While use of the pepsinogen I/II ratio as a marker for gastric atrophy has limitations, these data suggest that although gastric atrophy is involved it may not fully explain the inverse associations observed with H pylori infection.