Background Emerging data suggest variability in susceptibility and outcome to COVID-19 infection. Identifying risk-factors associated with infection and outcomes in cancer patients is necessary to develop healthcare recommendations. Methods We analyzed electronic health records of the US Veterans Affairs healthcare system and assessed the prevalence of COVID-19 infection in cancer patients. We evaluated the proportion of cancer patients tested for COVID-19 who were positive, as well as outcome attributable to COVID-19, and stratified by clinical characteristics including demographics, comorbidities, cancer treatment and cancer type. All statistical tests are two-sided. Results Of 22914 cancer patients tested for COVID-19, 1794 (7.8%) were positive. The prevalence of COVID-19 was similar across age. Higher prevalence was observed in African-American (AA) (15.0%) compared to White (5.5%; P<.001) and in patients with hematologic malignancy compared to those with solid tumors (10.9% vs 7.8%; P<.001). Conversely, prevalence was lower in current smokers and patients who recently received cancer therapy (<6 months). The COVID-19 attributable mortality was 10.9%. Higher attributable mortality rates were observed in older patients, those with higher Charlson comorbidity score, and in certain cancer types. Recent (<6 months) or past treatment did not influence attributable mortality. Importantly, AA patients had 3.5-fold higher COVID-19 attributable hospitalization, however had similar attributable mortality as White patients. Conclusion Pre-existence of cancer affects both susceptibility to COVID-19 infection and eventual outcome. The overall COVID-19 attributable mortality in cancer patients is affected by age, comorbidity and specific cancer types, however, race or recent treatment including immunotherapy does not impact outcome.

Background The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty. Methods ICD-9 codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by two geriatricians. Using nationals cohort of Veterans ≥65 years old, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012-2018 were examined. Results The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97-98% were male, 78-79% were white, and the mean VA-FI was 0.20-0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality. Patients classified as frail (VA-FI ≥0.2) consistently had a hazard of death more than two-times higher than non-frail patients (VA-FI <0.1). Distributions of frailty and associations with mortality varied with and without linkage to CMS data and with different assessment periods for capturing deficits. Conclusions The updated VA-FI-10 maintains content validity, stability, and predictive validity for mortality in a contemporary cohort of Veterans ≥65 years old, and may be applied to ICD-9 and ICD-10 claims data to measure frailty.

Importance Most studies examining the association of prenatal antiretroviral exposures with congenital anomalies (CAs) in children born to HIV-infected women have been reassuring, but some suggest increased risk with specific antiretrovirals. Objectives To evaluate associations of in utero antiretroviral exposures with CAs in HIV-exposed uninfected children. Design prospective cohort study, the Pediatric HIV/AIDS Cohort Study (PHACS) Surveillance Monitoring of ART Toxicities (SMARTT) study. Setting 22 US medical centers Participants 2580 HIV-exposed, uninfected children enrolled in SMARTT between 2007–2012. Exposures First trimester exposure to any antiretroviral and to specific antiretroviral medications. Main Outcome The primary endpoint was a CA, based on clinician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate associations of CAs with first trimester antiretroviral exposures, adjusting for demographic and maternal characteristics. Results CAs occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI: 5.85–7.82%); there were 242 confirmed major CAs (72 musculoskeletal, 55 cardiovascular). The prevalence of CAs increased significantly in successive birth cohorts (3.8% for children born <2002 up to 8.3% for 2008–2010). In adjusted models, there was no association of first trimester exposures to any antiretroviral, to combination antiretroviral regimens, or to any drug class with CAs. No individual antiretroviral in the reverse transcriptase inhibitor drug classes was associated with increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir (adjusted odds ratio (aOR)=1.93, 95% confidence interval (CI):1.23,3.03) and for ritonavir used as a booster (aOR=1.52, 95%CI: 1.08,2.14). With first trimester atazanavir, risks were highest for skin and musculoskeletal CAs (aORs=5.24 and 2.55, respectively). Conclusions and Relevance Few individual antiretrovirals and no drug classes were associated with increased risk of CAs after adjustment for calendar year and maternal characteristics. While the overall risk remained low, there was a relative increase in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV use during pregnancy still outweigh such risks, although further studies are warranted.

The Pediatric HIV/AIDS Cohort Study's Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites between 2007 and 2011 that was designed to evaluate the safety of in utero antiretroviral drug exposure in children not infected with human immunodeficiency virus who were born to mothers who were infected. This ongoing study uses a "trigger-based" design; that is, initial assessments are conducted on all children, and only those meeting certain thresholds or "triggers" undergo more intensive evaluations to determine whether they have had an adverse event (AE). The authors present the estimated rates of AEs for each domain of interest in the Surveillance Monitoring of ART Toxicities Study. They also evaluated the efficiency of this trigger-based design for estimating AE rates and for testing associations between in utero exposures to antiretroviral drugs and AEs. The authors demonstrate that estimated AE rates from the trigger-based design are unbiased after correction for the sensitivity of the trigger for identifying AEs. Even without correcting for bias based on trigger sensitivity, the trigger approach is generally more efficient for estimating AE rates than is evaluating a random sample of the same size. Minor losses in efficiency when comparing AE rates between persons exposed and unexposed in utero to particular antiretroviral drugs or drug classes were observed under most scenarios.

Objective To evaluate the safety of in utero antiretroviral (ARV) exposure in children born to mothers with HIV, using a trigger-based design. Design The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in utero ARV drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting pre-defined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events (AEs). Methods AE “cases” were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various ARV exposures during pregnancy. Results Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any ARV regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case (RR=1.69, 95% CI:1.08–2.64) and didanosine plus stavudine (<1% exposed) with increased risk of both neurodevelopmental (RR=12.4, 95% CI:5.29–29.08) and language (RR=4.84, 95% CI:1.14–20.51) cases. Conclusions Our findings support current recommendations for combination ARV therapy during pregnancy, although higher risk of metabolic disorder with zidovudine exposure warrants further study.