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Overlap weighting, using weights defined as the probability of receiving the opposite treatment, is a relatively new, alternative propensity score-based weighting technique used to adjust for confounding when estimating causal treatment effects. It has preferable properties compared to inverse probability of treatment weighting, such as exact covariate balance, safeguards against extreme weights and emphasis on medical equipoise, where treatment decisions are most uncertain. In this article, we introduce the overlap weighting methodology, compare it to inverse probability of treatment weighting and provide some strategies for assessing weighting impact, through an applied example of hospital mortality. When the propensity score distributions have large separation, inverse probability of treatment weighting has been shown to produce biased and less efficient estimates of the treatment effect, making overlap weighting a preferred method in such cases. [ABSTRACT FROM AUTHOR]

Background The impact of remdesivir (RDV) on mortality rates in coronavirus disease 2019 (COVID-19) is controversial, and the mortality effect in subgroups of baseline disease severity has been incompletely explored. The purpose of this study was to assess the association of RDV with mortality rates in patients with COVID-19. Methods In this retrospective cohort study we compared persons receiving RDV with those receiving best supportive care (BSC). Patients hospitalized between 28 February and 28 May 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection were included with the development of COVID-19 pneumonia on chest radiography and hypoxia requiring supplemental oxygen or oxygen saturation ≤94% with room air. The primary outcome was overall survival, assessed with time-dependent Cox proportional hazards regression and multivariable adjustment, including calendar time, baseline patient characteristics, corticosteroid use, and random effects for hospital. Results A total of 1138 patients were enrolled, including 286 who received RDV and 852 treated with BSC, 400 of whom received hydroxychloroquine. Corticosteroids were used in 20.4% of the cohort (12.6% in RDV and 23% in BSC). Comparing persons receiving RDV with those receiving BSC, the hazard ratio (95% confidence interval) for death was 0.46 (.31–.69) in the univariate model (P <.001) and 0.60 (.40–.90) in the risk-adjusted model (P =.01). In the subgroup of persons with baseline use of low-flow oxygen, the hazard ratio (95% confidence interval) for death in RDV compared with BSC was 0.63 (.39–1.00; P =.049). Conclusion Treatment with RDV was associated with lower mortality rates than BSC. These findings remain the same in the subgroup with baseline use of low-flow oxygen. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The St. Jude Medical Silzone heart valve had a silver-impregnated sewing ring designed to reduce the incidence of prosthetic valve endocarditis. Recruitment to the randomized AVERT study comparing Silzone valves with non-Silzone Control valves was stopped because of an increased risk of reoperation for paravalvular leak, but patient follow-up continues. Determining the time-related risk profile of the Silzone valve is important for helping physicians manage the approximately 28,000 patients currently alive with a Silzone valve. Methods: Between 1998 and 2000, 403 Silzone and 404 Control patients were enrolled in AVERT. As of July 2005, there were 1819 Silzone and 1842 Control patient-years of follow-up (mean 4.5, median 5.1 years). Analysis emphasized the use and interpretation of hazard functions, since they are more meaningful than event-free percentages to currently surviving patients. To this end, instead of Cox regression, which estimates the hazard ratio, assuming it is constant over time, we employed primarily Aalen additive regression, which measures the hazard difference, and produces a plot of it over time. We assessed the risks of major paravalvular leak, endocarditis, bleeding and thrombo-embolism. Results: The Silzone valve had a higher initial risk of major paravalvular leak than Control in the mitral (p =0.02) position, but not in the aortic (p =0.42) position. Analysis of this risk using additive regression, with all valve positions combined, showed that the initial risk due to Silzone lost statistical significance by 2 years and disappeared by 4 years after implant. In the mitral position, the Silzone valve had a higher initial risk of thrombo-embolism plus bleeding than Control; this risk also lost statistical significance by 2 years and subsided to zero by 4 years. The risks for death and endocarditis were similar for Slizone and Control valves. Conclusions: The additional risks of the Silzone valve, compared to Control, diminish over time and disappear by 4 years after implant. The minimum time after implant of the patients currently alive with Silzone is now well beyond 5 years; thus, these current patients now have a risk profile similar to that of patients with a standard St. Jude valve. [Copyright &y& Elsevier]

Abstract: Objective: Logistic regression is most often used to produce a cardiac operative risk model. But the logistic equation requires a computer to solve. Thus, simple additive models have been derived from logistic models by adding the odds ratios or modified coefficients. However, this simplification has no statistical justification, and the additive scores do not equal the original logistic probabilities. Methods: The EuroSCORE risk model is a very successful and widely used cardiac surgery risk model and it comes in both an additive and a full logistic version. We applied the EuroSCORE model to the 28,337 cardiac surgeries in the Providence Health System Cardiovascular Study Group database. The discrimination of the models was assessed by the c index. The comparison of the mortality predictions of the logistic and the additive model are mostly descriptive and graphical. Results: Theoretical considerations would predict that the additive model greatly underestimates the risk for the higher risk patients, and clinical data confirm this fact. For the 23,463 (83%) cases with complete data, the predicted mortality was 8.3% by the logistic model and 5.4% by the additive model. The discrimination (c index) of the additive (0.794) and logistic (0.791) models was equally good. A modified additive score is proposed (the mean of the logistic predicted mortality for each original additive score) which could be provided as a look-up table along with the scoring sheet. Conclusions: The additive EuroSCORE gives excellent discrimination, as good as the logistic risk model, but it greatly underestimates the risk of high-risk patients, compared to the logistic. The logistic equation should be used to predicate the mortality when possible. If this is not feasible, a modified additive score could be employed at the bedside. But the logistic should always be used for comparison of providers and for research publications. [Copyright &y& Elsevier]

Objective: To attempt to reconcile reports containing contradictory findings with the St. Jude Medical Silzone heart valve. Methods: Major leak and thromboembolism data were extracted from available Silzone valve studies. Linearized rates were used to summarize and compare the events rates among the studies. Results: The Artificial Valve Endocarditis Reduction Trial (AVERT) study reported significant higher rate of major leak and the Cardiff Embolic Risk Factor Study (CERFS) reported significant higher rate of thromboembolism with Silzone compared to non-Silzone valves. But, current updates of these studies show a diminution of these differences. Three other comparative studies reported no difference between Silzone and non-Silzone valves, and three single arm studies reported acceptable results with Silzone valves. Conclusion: The contradictory findings could be partly due to clinical and technical reasons. No new events have been reported since the original AVERT (major leak) and CERFS (mitral thromboembolism) publications. [Copyright &y& Elsevier]

Abstract: Objective: We evaluated video-assisted thoracic surgery (VATS) and open (OPEN) lobectomy for lung cancer and impact upon 6-month postoperative (postop) functional health status and quality of life. Methods: In this retrospective analysis of prospective, observational data, anatomic lobectomy with staging thoracic lymphadenectomy was performed with curative intent for lung cancer. OPEN consisted of either thoracotomy (TH) or median sternotomy (MS). Technique was selected on the basis of anatomic imperative (OPEN: larger or central; VATS smaller or peripheral tumours) and/or surgical skills (VATS lobectomy initiated in 2001). All patients completed the Short Form 36 Health Survey (SF36) and Ferrans and Powers quality-of-life index (QLI) preoperatively (preop) and 6 months postop. Results: A total of 241 patients underwent lobectomy (OPEN, 192; VATS, 49). OPEN included MS 128 and TH 64. Comparison of MS and TH patient demographics, co-morbidities, pulmonary variables, intra-operative variables, stage and cell type, postop complications and 6-month clinical outcomes found no differences, allowing grouping together into OPEN. The VATS group had better pulmonary function testing (PFT), more adenocarcinoma and lower stage. The VATS and OPEN groups did not differ regarding operating time, postop complications and operative or 6-month mortality. The VATS group had less blood loss, transfusion, intra-operative fluid administration and shorter length of stay. Comparing within each group''s preop to 6-month postop data, VATS patients were either the same or better in all SF36 categories (physical functioning, role functioning – physical, role functioning – emotional, social functioning, bodily pain, mental health, energy and general health). The OPEN group, however, was significantly worse in SF36 categories physical functioning, role functioning – physical and social functioning. The preop and 6 months postop VATS versus OPEN QLI scores were not different. At 6 months postop, hospital re-admission and use of pain medication was less in the VATS group. In addition, the VATS group had better preservation of preop performance status. Conclusions: VATS lobectomy for curative lung cancer resection appears to provide a superior functional health recovery compared with OPEN techniques. [Copyright &y& Elsevier]

Abstract: Objective: This study aimed at calculating and comparing the long-term outcomes of patients after aortic valve replacement with the Carpentier-Edwards bovine pericardial and porcine supraannular bioprostheses using microsimulation. Methods: We conducted a meta-analysis of eight studies on the Carpentier-Edwards pericardial valves (2685 patients, 12,250 patient-years) and five studies on the supraannular valves (3796 patients, 20,127 patient-years) to estimate the occurrence rates of valve-related events. Eighteen-year follow-up data sets were used to construct age-dependent Weibull curves that described their structural valvular deterioration. The estimates were entered into a microsimulation model, which was used to calculate the outcomes of patients after aortic valve replacement. Results: The annual hazard rates for thrombo-embolism after aortic valve replacement were 1.35% and 1.76% for the pericardial and supraannular valves, respectively. For a 65-year-old male, median time to structural valvular deterioration was 20.1 and 22.2 years while the lifetime risk of reoperation due to structural valvular deterioration was 18.3% and 14.0%, respectively. The life expectancy of the patient was 10.8 and 10.9 years and event-free life expectancy 9.0 and 8.8 years, respectively. Conclusions: The microsimulation methodology provides insight into the prognosis of a patient after aortic valve replacement with any given valve type. Both the Carpentier-Edwards pericardial and supraannular valve types perform satisfactorily, especially in elderly patients, and show no appreciable difference in long-term outcomes when implanted in the aortic position. [Copyright &y& Elsevier]

Objective: Mechanical valves and bioprostheses are the commonly used devices in aortic valve replacement (AVR). Many patients with valvular disease also require concomitant coronary artery bypass grafting (CABG). We used a microsimulation model to provide insight into the outcomes of patients after AVR with mechanical valves and stented bioprostheses, with and without CABG, and to determine the age-thresholds or age crossover points in outcomes between the two valve types. Methods: We conducted a meta-analysis of published results after primary AVR with mechanical prostheses (nine reports, 4274 patients, 25,726 patient-years) and stented porcine bioprostheses (13 reports, 9007 patients, 54,151 patient-years) to estimate risks of valve-related events. A hazard ratio of 1.3 was used to incorporate the effect of CABG on long-term survival. Estimates were entered into a microsimulation model, which was then used to predict the outcomes of patients after AVR, with and without CABG. The model calculations were validated using a large data set from Portland, USA. Results: For a 65-year-old male without CABG, the life expectancy (LE) was 11.2 and 11.6 years and the event-free life expectancy (EFLE) was 8.2 and 8.9 years, respectively, after implantation with mechanical valves and bioprostheses. The lifetime risk of at least one valve-related event was 51 and 47%, respectively. The age crossover point between the two valve types, considering the above outcome parameters, was 59, 60 and 63 years, respectively. CABG reduced LE and consequently EFLE and lifetime risk of an event, but only minimally influenced the patient age crossover points. The model calculations showed good agreement with the Portland data. Conclusions: The currently recommended patient age for using a bioprosthesis (65 years) could be lowered further, irrespective of concomitant CABG. The trade-off between the reduced risks of bioprosthetic failure and of hemorrhage in mechanical valves, resulting from a lower LE, minimized the effect of CABG on the age crossover points between the two valve types. [Copyright &y& Elsevier]