Importance Cancer patients who use statins appear to have a substantially better survival than non-users in observational studies. However, this inverse association between statin use and mortality in cancer patients may be due to selection bias and immortal time bias. Objective We used observational data to emulate a randomized trial of statin initiation that is free of selection bias and immortal time bias. Design We used data on 17,372 cancer patients from the SEER-Medicare 2007-2009 database with complete follow-up until 2011. Individuals were duplicated, with each replicate assigned to either the strategy “statin initiation within 6 months of diagnosis” or “no statin initiation”. Replicates were censored when they stopped following their assigned strategy, and the potential selection bias was adjusted for via inverse-probability weighting. Hazard ratios (HR), cumulative incidences, and risk differences were calculated for all-cause mortality and cancer-specific mortality. We then compared our estimates with those obtained using the same analytic approaches as in previous observational studies. Setting The SEER-Medicare data is a linkage between 17 American cancer registries and claims files from Medicare and Medicaid in 12 states. Participants We included individuals with a new diagnosis of colorectal, breast, prostate, and bladder cancer who had not been prescribed statins for at least 6 months before cancer. Exposure Statin initiation within 6 months from cancer diagnosis. Main outcome measure Cancer-specific and all-cause mortality. Results The adjusted HR (95% CI) comparing statin initiation vs. no initiation was 1.00 (0.88-1.15) for cancer-specific mortality and 1.07 (0.93-1.21) for overall mortality. Cumulative incidence curves for each group were almost overlapping. On the contrary, the methods used by prior studies resulted in a strong inverse association between statin use and mortality. Conclusion and relevance After using methods that are not susceptible to selection bias from prevalent users and to immortal time bias, initiation of statins within 6 months of cancer diagnosis did not appear to improve 3-year cancer-specific or overall survival.

The clinical impact of coadministration of the oral SARS-CoV-2 protease inhibitor nirmatrelvir and the pharmacokinetic booster ritonavir among vaccinated populations is uncertain. This study emulated a clinical trial to assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages.

Objective: The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.Methods: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (,8), medium (8-9), or high (.9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.Results: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58). Conclusions:We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions. Neurology ® 2014;83:134-141 GLOSSARY cART 5 combined antiretroviral therapy; CI 5 confidence interval; CPE 5 CNS Penetration Effectiveness; ICD-9 5 International Classification of Diseases, ninth revision; NNRTI 5 nonnucleoside reverse transcriptase inhibitor.

BACKGROUND: Widespread lockdowns imposed during the coronavirus disease 2019 crisis may impact birth outcomes. OBJECTIVE: This study aimed to evaluate the association between the COVID-19 lockdown and the risk of adverse birth outcomes in Botswana. STUDY DESIGN: In response to the coronavirus disease 2019 crisis, Botswana enforced a lockdown that restricted movement within the country. We used data from an ongoing nationwide birth outcomes surveillance study to evaluate adverse outcomes (stillbirth, preterm birth, small-for-gestational-age fetuses, and neonatal death) and severe adverse outcomes (stillbirth, very preterm birth, very-small-forgestational-age fetuses, and neonatal death) recorded prelockdown