Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis

Background Previous studies hypothesized that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19. Methods We performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation in both models. In the first model we performed a pair-matched propensity score model between those under active and non-active use of ADT. To the second model we initially performed a multivariate backward elimination process to select variables to a final inverse-weight adjusted with double robust estimation model. Results We analyzed 199 PC patients with COVID-19 that received ADT. In total, 52.3% (95/199) of our patients were less than 75 years old, 78.4% (156/199) were on active ADT, and most were using a GnRH analog (80.1%; 125/156). Most of patients were in palliative treatment (89.9%; 179/199). Also, 63.3% of our cohort died from COVID-19. Forty-eight patients under active ADT were pair matched against 48 controls (non-active ADT). All patients (199) were analyzed in the double robust model. ADT active use were not protective factor in both inverse-weight based propensity score (OR 0.70, 95% CI 0.38–1.31, P = 0.263), and pair-matched propensity score (OR 0.67, 95% CI 0.27–1.63, P = 0.374) models. We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT, with important reductions in the differences after the adjustments. Conclusions The active use of ADT was not associated with a reduced risk of death in patients with COVID-19.

Effects of Metoprolol on Periprocedural Myocardial Infarction After Percutaneous Coronary Intervention (Type 4a MI): An Inverse Probability of Treatment Weighting Analysis

Background: Metoprolol is the most used cardiac selective β-blocker and has been recommended as a mainstay drug in the management of acute myocardial infarction (AMI). However, the evidence supporting this regimen in periprocedural myocardial infarction (PMI) is limited.Methods: This study identified 860 individuals who suffered PMI following percutaneous coronary intervention (PCI) procedure and median followed up for 3.2 years. Subjects were dichotomized according to whether they received chronic oral sustained-release metoprolol succinate following PMI. After inverse probability of treatment weighting (IPTW) adjustment, logistic regression analysis, Kaplan-Meier curve, and Cox regression analysis were performed to estimate the effects of metoprolol on major adverse cardiovascular events (MACEs) which composed of cardiac death, myocardial infarction (MI), stroke, and revascularization. Moreover, an exploratory analysis was performed according to hypertension, cardiac troponin I (cTnI) elevation, and cardiac function. A double robust adjustment was used for sensitivity analysis.Results: Among enrolled PMI subjects, 456 (53%) patients received metoprolol treatment and 404 (47%) patients received observation. After IPTW adjustment, receiving metoprolol was found to reduce the subsequent 3-year risk of MACEs by nearly 7.1% [15 vs. 22.1%, absolute risk difference (ARD) = 0.07, number needed to treat (NNT) = 14, relative risk (RR) = 0.682]. In IPTW-adjusted Cox regression analyses, receiving metoprolol was related to a reduced risk of MACEs (hazard ratio [HR] = 0.588, 95%CI [0.385–0.898], P = 0.014) and revascularization (HR = 0.538, 95%CI [0.326–0.89], P = 0.016). Additionally, IPTW-adjusted logistic regression analysis showed that receiving metoprolol reduced the risk of MI at the third year (odds ratio [OR] = 0.972, 95% CI [0.948–997], P = 0.029). Exploratory analysis showed that the protective effect of metoprolol was more pronounced in subgroups of hypertension and cTnI elevation ≥1,000%, and was remained in patients without cardiac dysfunction. The benefits above were consistent when double robust adjustments were performed.Conclusion: In the real-world setting, receiving metoprolol treatment following PCI-related PMI has decreased the subsequent risk of MACEs, particularly the risk of recurrent MI and revascularization.

High-dimensional semi-supervised learning: in search of optimal inference of the mean

A fundamental challenge in semi-supervised learning lies in the observed data’s disproportional size when compared with the size of the data collected with missing outcomes. An implicit understanding is that the dataset with missing outcomes, being significantly larger, ought to improve estimation and inference. However, it is unclear to what extent this is correct. We illustrate one clear benefit: root-n inference of the outcome’s mean is possible while only requiring a consistent estimation of the outcome, possibly at a rate slower than root-n. This is achieved by a novel k-fold cross-fitted, double robust estimator. We discuss both linear and nonlinear outcomes. Such an estimator is particularly suited for models that naturally do not admit root-n consistency, such as high-dimensional, nonparametric, or semiparametric models. We apply our methods to the heterogeneous treatment effects.

Virologic outcomes of people living with human immunodeficiency virus who started antiretroviral treatment on the same-day of diagnosis in Ethiopia: A multicenter observational study

Introduction There have been tremendous achievements in scaling-up antiretroviral therapy (ART) for treatment of human immunodeficiency virus (HIV), following universal “test and treat” policy implementation in low- and middle-income countries. However, its effects on virologic outcomes is not yet well investigated. We compared low viral load status in people living with HIV between those who were initiated on ART on the same-day and after 7 days of being diagnosed with HIV infection. Methods We conducted a retrospective cohort study of persons age ≥15 years-old who were newly diagnosed and started on ART between October 2016 and July 2018 at 11 public health facilities in northwest Ethiopia. Exposure was initiation of ART on the same-day of HIV diagnosis. The outcome was low viral load at 12-months following ART initiation. We used double-robust estimator using inverse-probability-weighted regression adjustment to compare the groups. Results A total of 398 people who started ART on the same-day of HIV diagnosis and 479 people who started 7 days after the initial diagnosis were included in this study. By 12-months following ART initiation, 73.4% (292) in the same-day group vs 83.7% (401) in the >7 days group achieved low viral load (absolute difference = 10.3% (95% CI: 4.9%, 15.8%)). After adjusting for baseline and follow-up covariates, there was statistically significant difference in low viral load status (adjusted difference = 8.3% (95% CI: 3.5%, 13.0%)) between the same-day group and the >7 days group. Conclusions Achievement of low viral load by 12-months post-initiation of ART was not optimal among participants who started ART on the same-day of HIV diagnosis. Efforts should be made to reinforce treatment adherence while initiating same-day ART.

1321Marginal structural model of the causal role of hepatitis B vaccination in multiple sclerosis risk

Background There are conflicting reports regarding the association between uptake of recombinant vaccine against hepatitis B virus (HBV) and risk of multiple sclerosis (MS). Most cohort or case-control studies found no significant short- or long-term increase in MS risk after immunization. Whereas others reported a significant increase in MS risk within three years of HBV vaccination. The present matched case-control study was conducted to test the hypothesis whether recombinant HBV vaccination status is causally associated with MS risk using targeted maximum likelihood estimation (TMLE) that uses data-adaptive flexible machine learning algorithms to estimate the causal parameters. Methods Confirmed 110 MS incident cases and age (± 5 years), gender and nationality matched (1:1) 110 community controls were enrolled. A pre-tested structured questionnaire was used to collect the data on demographics, environmental factors, comorbidities, history of vaccinations through face-to-face interviews both from cases and controls. We implemented case-control-weighted TMLE – a double robust, multistep procedure to estimate causal relative risk (RR), marginal odds ratio (OR) and population attributable fraction. Results This study demonstrated a non-specific protective effect of HBV vaccine against MS risk as estimated by TMLE (causal RR 0.63, 95% CI: 0.45-0.90; p = 0.004; marginal OR 0.43; 95% CI: 0.18-0.67; p = 0.006). The population attributable fraction was 20% (95% CI: 6%, 34%; p = 0.014)) Conclusions Subject to inherent limitations of the case-control design, this study suggests a non-specific protective effect of recombinant HBV vaccination against MS risk. Future studies may contemplate to confirm these results. Key message Causal analysis showed a non-specific protective causal association between uptake of recombinant HBV vaccine and MS risk in the study population.

Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: A propensity score-based analysis.

5067 Background: Previous studies suggested that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19. Methods: We performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation, and for the outcome analysis we performed a multivariate backward elimination process to select variables to add to the propensity score model. Results: We analyzed 109 PC patients with COVID-19 that presented past or current use of ADT. In total, 52.8% of our patients were less than 75 years old, 44.0% (48/109) were in active ADT, and most were using a GnRH analog (73%, 35/48). Also, 63.3% of our cohort died from COVID-19. ADT active use were protective factor in our logistic regression model (OR 0.28, 95% CI 0.12–0.66, P = 0.0036). We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT. Then, when we performed a propensity score-based inverse weight double robust estimation model, we observed that ADT remained statistically associated with improved overall survival (average treatment effect [ATE] -0.26, 95% CI -0.45 to -0.08, P = 0.0058). Conclusions: The active use of ADT was associated with a reduced risk of death in patients with COVID-19.