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The CRB-65 score is a clinical prediction rule that grades the severity of community-acquired pneumonia in terms of 30-day mortality. AimThe study sought to validate CRB-65 and assess its clinical value in community and hospital settings. Design of studySystematic review and meta-analysis of validation studies of CRB-65. Medline (1966 to June 2009), Embase (1988 to November 2008, British Nursing Index (BNI) and PsychINFO were searched, using a diagnostic accuracy search filter combined with subject-specific terms. The derived (index) rule was used as a predictive model and applied to all validation studies. Comparison was made between the observed and predicted number of deaths stratified by risk group (low, intermediate, and high) and setting of care (community or hospital). Pooled results are presented as risk ratios (RRs) in terms of over-prediction (RR>1) or under-prediction (RR<1) of 30-day mortality. Method ResultsFourteen validation studies totalling 397 875 patients are included. CRB-65 performs well in hospitalised patients, particularly in those classified as intermediate (RR 0.91, 95% confidence interval [CI] = 0.71 to 1.17) or high risk (RR 1.01, 95% CI = 0.87 to 1.16). In community settings, CRB-65 over-predicts the probability of 30-day mortality across all strata of predicted risk, low (RR 9.41, 95% CI = 1.75 to 50.66), intermediate (RR 4.84, 95% CI = 2.61 to 8.69), and high (RR 1.58, 95% CI = 0.59 to 4.19). ConclusionCRB-65 performs well in stratifying severity of pneumonia and resultant 30-day mortality in hospital settings. In community settings, CRB-65 appears to over-predict the probability of 30-day mortality across all strata of predicted risk. Caution is needed when applying CRB-65 to patients in general practice. Keywordsgeneral practice; meta-analysis; pneumonia; prognosis; severity of illness index. INTRODUCTIONCommunity-acquired pneumonia (CAP) has an annual incidence of 5-11 per 1000, accounting for 5-12% of all cases of adult lower respiratory tract infection managed by GPs.1 Appropriate management for patients with suspected CAP must be determined by GPs at initial presentation, particularly with regard to whether or not to manage a patient in the community or refer them to hospital.2 The proportion of adults with CAP who require hospital admission in the UK varies between 22% and 42%.1 This proportion varies in other countries, possibly due to differing structures of primary and secondary healthcare systems.

Aims The aim of this study was to examine the effect of dapagliflozin on the incidence of ventricular arrhythmias and sudden death in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results In a post hoc analysis of DAPA-HF, we examined serious adverse event reports related to ventricular arrhythmias or cardiac arrest, in addition to adjudicated sudden death. The effect of dapagliflozin, compared with placebo, on the composite of the first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest, or sudden death was examined using Cox proportional hazards models. A serious ventricular arrhythmia was reported in 115 (2.4%) of the 4744 patients in DAPA-HF (ventricular fibrillation in 15 patients, ventricular tachycardia in 86, ‘other’ ventricular arrhythmia/tachyarrhythmia in 12, and torsade de pointes in 2 patients). A total of 206 (41%) of the 500 cardiovascular deaths occurred suddenly. Eight patients survived resuscitation from cardiac arrest. Independent predictors of the composite outcome (first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest or sudden death), ranked by chi-square value, were log-transformed N-terminal pro-B-type natriuretic peptide, history of ventricular arrhythmia, left ventricular ejection fraction, systolic blood pressure, history of myocardial infarction, male sex, body mass index, serum sodium concentration, non-white race, treatment with dapagliflozin, and cardiac resynchronization therapy. Of participants assigned to dapagliflozin, 140/2373 patients (5.9%) experienced the composite outcome compared with 175/2371 patients (7.4%) in the placebo group [hazard ratio 0.79 (95% confidence interval 0.63–0.99), P = 0.037], and the effect was consistent across each of the components of the composite outcome. Conclusions Dapagliflozin reduced the risk of any serious ventricular arrhythmia, cardiac arrest, or sudden death when added to conventional therapy in patients with HFrEF. Clinical trial registration  ClinicalTrials.gov unique identifier: NCT03036124 (DAPA-HF).

Aim Anaemia is common in heart failure and associated with worse outcomes. We examined the effect of dapagliflozin on correction of anaemia in patients with heart failure (HF) and reduced ejection fraction in DAPA‐HF. We also analysed the effect of dapagliflozin on outcomes, according to anaemia status at baseline. Methods and results Anaemia was defined at baseline as a haematocrit <39% in men and <36% in women. Resolution of anaemia was defined as two consecutive haematocrit measurements above these thresholds at any time during follow‐up. The primary outcome was a composite of worsening HF (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized in DAPA‐HF, 4691 had a haematocrit available at baseline, of which 1032 were anaemic (22.0%). The rate of the primary outcome was higher in patients with anaemia (16.1 per 100 person‐years) compared with those without (12.9 per 100 person‐years). Anaemia was corrected in 62.2% of patients in the dapagliflozin group, compared with 41.1% of patients in the placebo group. The effect of dapagliflozin on the primary outcome was consistent in anaemic compared with non‐anaemic patients [hazard ratio (HR) 0.68, 95% confidence interval (CI) 0.52–0.88 vs. HR 0.76, 95% CI 0.65–0.89; interaction P = 0.44]. Similar findings were observed for cardiovascular death, HF hospitalization, and all‐cause mortality. Patients with resolution of anaemia had better outcomes than those in which anaemia persisted. Conclusion Patients with anaemia had worse outcomes in DAPA‐HF. Dapagliflozin corrected anaemia more often than placebo and improved outcomes, irrespective of anaemia status at baseline.