The study was supported by Novartis.

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Background: Poor health-related quality of life (HRQL) is common in heart failure (HF), but there are few data on HRQL in HF and the association between HRQL and mortality outside Western countries. Methods: We used the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 to record HRQL in 23,291 HF patients from 40 countries in 8 different world regions in the Global Congestive Heart Failure study (G-CHF). We compared standardized KCCQ-12-summary scores (SS; adjusted for age, sex and markers of HF severity) between regions (0-100, higher=better HRQL). We used multivariable Cox regression with adjustment for 15 variables to assess the association between KCCQ-12-SS and the composite of all-cause death, of HF hospitalization and each component over a median follow-up of 1.6 years. Results: The mean age was 65 years, 61% were men, 40% had NYHA class III-IV symptoms, and 46% had left ventricular ejection fraction (EF) ≥40%. Average HRQL differed between regions (lowest in Africa [39.5 SE±0.3], highest in Western Europe [62.5±0.4]). There were 4,460 (19%) deaths, 3,885 (17%) HF hospitalizations and 6,949 (30%) had either event. Lower KCCQ-12-SS was associated with higher risk of all outcomes, the adjusted hazard ratio (HR) for each 10-unit KCCQ-12-SS decrement was 1.18 (95% CI 1.17-1.20) for death. Although this association was observed in all regions, it was less marked in South Asia, South America and Africa (weakest association in South Asia, HR 1.08 [95% CI 1.03-1.14], strongest in Eastern Europe HR 1.31 [95% CI [1.21-1.42], interaction p<0.0001). Lower HRQL predicted death in both those with NYHA class I-II and III-IV symptoms (HR 1.17 [95% CI 1.14-1.19] and HR 1.14 [95% CI [1.12-1.17], interaction p=0.13) and was a stronger predictor for the composite outcome in NYHA class I-II vs. III-IV (HR 1.15 [95% CI 1.13-1.17] vs. 1.09 [95% CI [1.07-1.11], interaction p<0.0001). HR for death was greater in EF ≥40 vs. <40% (HR 1.23 [95% CI 1.20-1.26] and HR 1.15 [95% 1.13-1.17], interaction p<0.0001). Conclusions: HRQL is a strong and independent predictor of all-cause death and HF hospitalization across all geographic regions, in mildly and severe symptomatic HF and among those with preserved and reduced EF. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03078166

Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods:We randomised 2970 patients from 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were ≥45 years of age were eligible. Patients were randomly assigned to accelerated surgery (goal of surgery within 6 hours of diagnosis; 1487 patients) or standard care (1483 patients). The co-primary outcomes were 1.) mortality, and 2.) a composite of major complications (i.e., mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Outcome adjudicators were masked to treatment allocation, and patients were analysed according to the intention-to-treat principle; ClinicalTrials.gov, NCT02027896. Findings:The median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] 4-9) in the accelerated-surgery group and 24 hours (IQR 10-42) in the standard-care group, p<0.0001. Death occurred in 140 patients (9%) assigned to accelerated surgery and 154 patients (10%) assigned to standard care; hazard ratio (HR) 0.91, 95% CI 0.72-1.14; absolute risk reduction (ARR) 1%, 95% CI -1-3%; p=0.40. The primary composite outcome occurred in 321 patients (22%) randomised to accelerated surgery and 331 patients (22%) randomised to standard care; HR 0.97, 95% CI 0.83-1.13; ARR 1%, 95% CI -2-3%; p=0.71.Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared to standard care.

Received the first dose of study drug 4612 (97.0) (96.7) Received the second dose of the study drug 4586 (96.4) (96.5) Received both doses of the study drug 4581 (96.3) (96.3) no. = number; % = percentage

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Ethanol extract of Pisonia aculeata (EPA) was evaluated for hepatoprotective and antioxidant activities in rats. The plant extract (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against carbon tetrachloride (CCl 4) -induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of P. aculeata against CCl 4 -induced hepatotoxicity in rats.