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.

ConclusionsIn the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort. KEY WORDSher2-positive breast cancer, survival, trastuzumab, adjuvant

Risk prediction scores are important tools to support clinical decision-making for patients with coronavirus disease (COVID-19). The objective of this paper was to validate the 4C mortality score, originally developed in the United Kingdom, for a Canadian population, and to examine its performance over time. We conducted an external validation study within a registry of COVID-19 positive hospital admissions in the Kitchener-Waterloo and Hamilton regions of southern Ontario between March 4, 2020 and June 13, 2021. We examined the validity of the 4C score to prognosticate in-hospital mortality using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals calculated via bootstrapping. The study included 959 individuals, of whom 224 (23.4%) died in-hospital. Median age was 72 years and 524 individuals (55%) were male. The AUC of the 4C score was 0.77, 95% confidence interval 0.79–0.87. Overall mortality rates across the pre-defined risk groups were 0% (Low), 8.0% (Intermediate), 27.2% (High), and 54.2% (Very High). Wave 1, 2 and 3 values of the AUC were 0.81 (0.76, 0.86), 0.74 (0.69, 0.80), and 0.76 (0.69, 0.83) respectively. The 4C score is a valid tool to prognosticate mortality from COVID-19 in Canadian hospitals and can be used to prioritize care and resources for patients at greatest risk of death.

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Purpose Corticosteroids are standard of care for patients with severe COVID-19. However, the optimal dose is uncertain. We compare higher doses of corticosteroids with lower doses in patients with COVID-19. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, MedRxiv, and Web of Science from inception to January 7, 2022, for trials that randomized patients with severe-to-critical COVID-19 to corticosteroids, standard care, or placebo. Reviewers, working in duplicate, screened references, extracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. We performed a dose-response meta-analysis and used the GRADE framework to assess the certainty of evidence. We present our results in absolute risk difference (RD) per 1000 with 95% confidence intervals (CI). Results We included 19 trials, with 9,609 patients. We show that, compared to lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (RD 14.8 fewer deaths per 1000 [95% CI 6.0 to 27.9 fewer]; moderate certainty), may reduce the need for mechanical ventilation (RD 10.4 fewer per 1000 [95% CI 19.2 fewer to 3.6 more]; low certainty) and may reduce risk of nosocomial infections (16.7 fewer infections per 1000 [95% CI 5.4 to 25.0 fewer]; low certainty). Conclusions Relatively higher doses of corticosteroids may be beneficial in patients with severe-to-critical COVID-19 without increasing the risk of nosocomial infections.