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Purpose: Alpha-1 blockers, often used to treat benign prostatic hyperplasia (BPH), have been hypothesized to prevent COVID-19 complications by minimising cytokine storm release. The proposed treatment based on this hypothesis currently lacks support from reliable real-world evidence, however. We leverage an international network of large-scale healthcare databases to generate comprehensive evidence in a transparent and reproducible manner. Methods: In this international cohort study, we deployed electronic health records from Spain (SIDIAP) and the United States (Department of Veterans Affairs, Columbia University Irving Medical Center, IQVIA OpenClaims, Optum DOD, Optum EHR). We assessed association between alpha-1 blocker use and risks of three COVID-19 outcomes--diagnosis, hospitalization, and hospitalization requiring intensive services--using a prevalent-user activecomparator design. We estimated hazard ratios using state-of-the-art techniques to minimize potential confounding, including large-scale propensity score matching/stratification and negative control calibration. We pooled database-specific estimates through random effects meta-analysis. Results: Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our metaanalytic HR estimates being 1.02 (95% CI: 0.92-1.13) for diagnosis, 1.00 (95% CI: 0.89-1.13) for hospitalization, and 1.15 (95% CI: 0.71-1.88) for hospitalization requiring intensive services. Conclusion: We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers--further research is needed to identify effective therapies for this novel disease. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are commonly used in the elderly despite limited efficacy and safety data from randomised controlled trials. Observational comparative safety studies of antipsychotics vary, which may be due to confounding. Objective: To compare the characteristics of typical and atypical antipsychotic initiators. Methods: Using the Australian Government Department of Veterans' Affairs claims dataset, we compared patient and prescribing physician characteristics and health care utilisation between atypical and typical antipsychotic initiators. Significant independent predictors of use were calculated using a multivariate log-binomial model. Results: Compared to patients initiated on typical antipsychotics (N=10,966), patients initiated on atypical antipsychotics (N=9,239) were less likely to be male (Relative Risk (RR)=0.91,95% CI 0.89-0.94) and have prior dispensing of morphine (RR=0.53, 95% CI 0.49-0.57) and oral corticosteroids (RR=0.86, 95% CI 0.81-0.91) and to have been hospitalised for myocardial infarction or pneumonia. Patients initiated on atypical antipsychotics were more likely to be in aged care (RR=1.08, 95% CI 1.05-1.12), to be prescribed the medicine by their usual doctor (RR=1.12, 95% CI 1.09-1.16) and have prior dispensing of anticholinesterases (RR = 1.19, 95% CI 1.151.23), antidepressants (RR = 1.18 95% CI 1.15-1.22) and anti-parkinson medications (RR=1.30, 95% CI 1.25-1.36). Conclusions: Differences between typical and atypical antipsychotic initiators indicate the potential for confounding in observational studies. Future pharmacoepidemiogical research in Australia, investigating the adverse events of antipsychotics, should consider the variables identified in this study to control for confounding. Key words: antipsychotic agents, aged, veterans, dementia, confounding factors. doi: 10.1111/j.1753-6405.2010.00613.x

Importance: There remains a lack of randomized trials investigating aspirin monotherapy for symptomatic venous thromboembolism (VTE) prophylaxis following total hip arthroplasty (THA) or total knee arthroplasty (TKA).Objective: To determine whether aspirin was noninferior to enoxaparin in preventing symptomatic VTE after THA or TKA.Design, Setting, and Participants: Cluster-randomized, crossover, registry-nested trial across 31 hospitals in Australia. Clusters were hospitals performing greater than 250 THA or TKA procedures annually. Patients (aged ≥18 years) undergoing hip or knee arthroplasty procedures were enrolled at each hospital. Patients receiving preoperative anticoagulation or who had a medical contraindication to either study drug were excluded. A total of 9711 eligible patients were enrolled (5675 in the aspirin group and 4036 in the enoxaparin group) between April 20, 2019, and December 18, 2020. Final follow-up occurred on August 14, 2021.Interventions: Hospitals were randomized to administer aspirin (100 mg/d) or enoxaparin (40 mg/d) for 35 days after THA and for 14 days after TKA. Crossover occurred after the patient enrollment target had been met for the first group. All 31 hospitals were initially randomized and 16 crossed over prior to trial cessation.Main Outcomes and Measures: The primary outcome was symptomatic VTE within 90 days, including pulmonary embolism and deep venous thrombosis (DVT) (above or below the knee). The noninferiority margin was 1%. Six secondary outcomes are reported, including death and major bleeding within 90 days. Analyses were performed by randomization group.Results: Enrollment was stopped after an interim analysis determined the stopping rule was met, with 9711 patients (median age, 68 years; 56.8% female) of the prespecified 15 562 enrolled (62%). Of these, 9203 (95%) completed the trial. Within 90 days of surgery, symptomatic VTE occurred in 256 patients, including pulmonary embolism (79 cases), above-knee DVT (18 cases), and below-knee DVT (174 cases). The symptomatic VTE rate in the aspirin group was 3.45% and in the enoxaparin group was 1.82% (estimated difference, 1.97%; 95% CI, 0.54%-3.41%). This failed to meet the criterion for noninferiority for aspirin and was significantly superior for enoxaparin (P = .007). Of 6 secondary outcomes, none were significantly better in the enoxaparin group compared with the aspirin group.Conclusions and Relevance: Among patients undergoing hip or knee arthroplasty for osteoarthritis, aspirin compared with enoxaparin resulted in a significantly higher rate of symptomatic VTE within 90 days, defined as below- or above-knee DVT or pulmonary embolism. These findings may be informed by a cost-effectiveness analysis.Trial Registration: ANZCTR Identifier: ACTRN12618001879257. [ABSTRACT FROM AUTHOR]

Objective: To measure the association between major causes of mortality and tobacco use; and the association between major causes of mortality and alcohol use, after adjusting for tobacco use. Method: Employees of Australian Institute of Petroleum member companies were enrolled in the cohort in four industry-wide surveys between 1981 and 1999. Mortality of 16,547 men was determined up to 31 December 2001 and cancer incidence to 31 December 2000. Relative mortality and cancer incidence rates were computed for smoking categories compared with never smokers, and for alcohol consumption compared with total abstainers. Results: The highest category of smoking, more than 30 cigarettes per day, was associated with more than a threefold increase in all-cause mortality, a 60% increase in cancer incidence, a 43-fold increase in lung cancer incidence, and a more than fourfold increase in mortality from ischaemic heart disease. There were only four cancers in lifelong non-smokers. Moderate alcohol consumption provided a protective effect from death from all causes combined, relative to nil or low consumption, and relative to heavy alcohol consumption. The main contributor to the protective effect was protection against death from ischaemic heart disease. Conclusions: Lifelong avoidance of tobacco and moderate alcohol consumption confer significant improvements on life expectancy.

Assisting patients to deal with loss is a major, yet unrecognized, role of general practitioners. Although instruments exist for measuring grief resulting from a given loss, such as bereavement, none exists that detects and measures grief from any loss. This study describes the development of the Grief Diagnostic Instrument for this purpose in general practice patients. Evaluation showed it to be a concise, valid, reliable and sensitive measure, and acceptable to general practice patients. The instrument investigates and measures grief from multiple losses rather than a single loss compared to other grief scales. Suggestions have been made for further validation studies. Its use in future grief research and clinical practice are described.