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Objectives Evaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era. Methods Between 2012 and 2019, 3232 ART-naive PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time. Results Mean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens. Conclusions There is heterogeneity between regimens in weight gain following ART initiation among previously ART-naive PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

BACKGROUND Rates of stroke are higher in people living with HIV compared with age-matched uninfected individuals. Causes of elevated stroke risk, including the role of viremia, are poorly defined. METHODS Between 1 January 2006 and 31 December 2014, we identified incident strokes among people living with HIV on antiretroviral therapy at five sites across the United States. We considered three parameterizations of viral load (VL) including (1) baseline (most recent VL before study entry), (2) time-updated, and (3) cumulative VL (copy-days/mL of virus). We used Cox proportional hazards models to estimate hazard ratios (HRs) for stroke risk comparing the 75th percentile ("high VL") to the 25th percentile ("low VL") of baseline and time-updated VL. We used marginal structural Cox models, with most models adjusted for traditional stroke risk factors, to estimate HRs for stroke associated with cumulative VL. RESULTS Among 15,974 people living with HIV, 139 experienced a stroke (113 ischemic; 18 hemorrhagic; eight were unknown type) over a median follow-up of 4.2 years. Median baseline VL was 38 copies/mL (interquartile interval: 24, 3,420). High baseline VL was associated with increased risk of both ischemic (HR: 1.3; 95% CI = 0.96-1.7) and hemorrhagic stroke (HR: 3.1; 95% CI = 1.6-5.9). In time-updated models, high VL was also associated with an increased risk of any stroke (HR: 1.8; 95% CI = 1.4-2.3). We observed no association between cumulative VL and stroke risk. CONCLUSIONS Our findings are consistent with the hypothesis that elevated HIV VL may increase stroke risk, regardless of previous VL levels.

Marijuana use among all age groups has been increasing, including among older adults aged ≥65 years. There is a lack of epidemiologic data examining arrhythmia risk among users of marijuana. We evaluated cross-sectional associations between current and past marijuana smoking and arrhythmias among 1485 participants from the Multiethnic Study of Atherosclerosis who underwent extended ambulatory electrocardiographic monitoring with the Zio Patch XT. Outcomes included premature atrial contractions, runs of supraventricular tachycardia, premature ventricular contractions, and runs of nonsustained ventricular tachycardia (NSVT). Compared with never users, participants reporting current use of marijuana (n = 40, 3%) had more supraventricular tachycardia/day (adjusted geometric mean ratio [GMR] 1.42, 95% confidence interval [CI] 0.87 to 2.32), more premature atrial contractions/hour (GMR 1.22, 95% CI 0.72, 2.13), and more NSVT/day (GMR 1.28, 95% CI 0.95 to 1.73); although, CIs overlapped 1. Additionally, more frequent marijuana use was associated with more runs of NSVT/day (GMR 1.56, 95% CI 1.13, 2.17). In conclusion, our results suggest that current marijuana use may be associated with a greater burden of arrhythmias. There is a need for additional research, mainly using a prospective design, to clarify if marijuana use causes atrial and ventricular arrhythmias or other cardiovascular complications among older adults.

Mechanistic studies are needed to understand how rotating shift work perturbs metabolic processing. We collected plasma samples (n = 196) from 49 males, rotating car factory shift workers at the beginning and end of a night-shift (22:00-06:00 h) and day-shift (06:00 h-14:00 h). Samples underwent targeted LC-MS/MS metabolomics and concentrations of 130 metabolites were log2-transformed and pareto-scaled. An elastic net selected the most influential metabolites for linear mixed models examining within-person variation in metabolite levels at night-shift end (06:00 h) compared to day-shift start (06:00 h). Quantitative enrichment analysis explored differentially enriched biological pathways between sample time points. We included 20 metabolites (amino acids, biogenic amines, acylcarnitines, glycerophospholipids) in mixed models. Night-shift was associated with changes in concentrations of arginine (geometric mean ratio [GMR] 2.30, 95%CI 1.25, 4.23), glutamine (GMR 2.22, 95%CI 1.53, 3.24), kynurenine (GMR 3.22, 95%CI 1.05, 9.87), lysoPC18:2 (GMR 1.86, 95%CI 1.11, 3.11), lysoPC20:3 (GMR 2.48, 95%CI 1.05, 5.83), PCaa34:2 (GMR 2.27, 95%CI 1.16, 4.44), and PCae38:5 (GMR 1.66, 95%CI 1.02, 2.68). Tryptophan metabolism, glutathione metabolism, alanine metabolism, glycine and serine metabolism, and urea cycle were pathways differing between shifts. Night shift work was associated with changes in metabolites and the perturbation of metabolic and biochemical pathways related to a variety of health outcomes.

Artificial light at night (ALAN) exposure is associated with the disruption of human circadian processes. Through numerous pathophysiological mechanisms such as melatonin dysregulation, it is hypothesised that ALAN exposure is involved in asthma and allergy, mental illness, and cancer outcomes. There are numerous existing studies considering these relationships; however, a critical appraisal of available evidence on health outcomes has not been completed. Due to the prevalence of ALAN exposure and these outcomes in society, it is critical that current evidence of their association is understood. Therefore, this systematic scoping review will aim to assess the association between ALAN exposure and asthma and allergy, mental health, and cancer outcomes. This systematic scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. We will search bibliographic databases, registries, and references. We will include studies that have described potential sources of ALAN exposure (such as shift work or indoor and outdoor exposure to artificial light); have demonstrated associations with either allergic conditions (including asthma), mental health, or cancer-related outcomes; and are published in English in peer-reviewed journals. We will conduct a comprehensive literature search, title and abstract screening, full-text review, and data collection and analysis for each outcome separately. This study will be partially funded by a non-exclusive research grant from Synergy Respiratory & Cardiac Care (to Paige Lacy), and internal research support from Apollo Gleneagles Hospital (to Saibal Moitra). Ana Adan and Jose Francisco Navarro are supported by the grant PID2020-117767GB-I00 of the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033). Hannah Durrington is supported by a Medical Research Council Clinician Scientist Fellowship (MRC-CSF-MR/V029460/1).

Introduction: Cardiovascular risk factors are associated with cognitive decline and dementia. Brain magnetic resonance imaging (MRI) provides sensitive measurement of cerebral atrophy and small vessel disease, reflecting multiple pathologies leading to dementia. However, large brain MRI studies include primarily white participants. We investigated associations in the diverse Multi-Ethnic Study of Atherosclerosis (MESA). Hypothesis: Cardiovascular and sociodemographic risk factors are associated with brain morphology and white matter injury in a racially and ethnically diverse population. Methods: In MESA, brain MRI was performed in 2018-2019 with automated measurement of total brain volume, gray and white matter (GM, WM) volume, and measures of WM injury including WM lesion volume, WM fractional anisotropy, and WM apparent diffusion coefficient. In cross-sectional analyses, we assessed the association of race/ethnicity with MRI measures, with and without adjustment for cardiovascular risk factors, education, and socioeconomic status. In a multivariable model, we assessed the association of cardiovascular risk factors with brain MRI measures. All analyses of volumes, including WM lesion volume, were adjusted for total intracranial volume. Results: MRI data were complete in 1,051 participants; 40% were white, 15% Chinese-American, 25% African-American, and 20% Hispanic. Mean (standard deviation, SD) age was 73 (8) years and 53% of participants were women. Adjusted for age and sex, African-American participants had slightly greater total brain and WM volume than white participants. Adjusted for age and sex, African-American participants had on average more WM injury than whites as measured by higher WM lesion volume (46.7% higher, 95% CI: 19.9, 79.4%) and lower fractional anisotropy (-0.20 SD, 95% CI: -0.34, -0.05); these associations were attenuated after additional adjustment for cardiovascular risk factors and socioeconomic status (24.3% higher WM lesion volume, 95% CI: 0.0, 54.3; -0.06 SD fractional anisotropy, 95% CI: -0.22, 0.09). Conversely, all non-white race/ethnic groups had slightly less WM injury than white participants as estimated by apparent diffusion coefficient. Overall, greater age, diabetes, current smoking, high systolic blood pressure, and treated hypertension were strongly associated with more WM injury; in addition, age and diabetes were strongly associated with lower brain volumes. Conclusions: We found little evidence of differences in measures of brain atrophy and WM injury by race/ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. Findings of differences by race/ethnicity in apparent diffusion coefficient are intriguing and need further investigation. Consistent with previous studies, age, diabetes, current smoking and hypertension were strongly and consistently associated with WM injury.

Purpose: High blood pressure (BP) is a well-known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. We evaluated whether longitudinal measures of BP were associated with subclinical arrhythmias after adjustment for more conventional BP measures such as a single cross-sectional BP value. Methods: This study included 1,256 Multi-Ethnic Study of Atherosclerosis (MESA) and 1,948 Atherosclerosis Risk in Communities study (ARIC) participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically-detected cardiovascular disease, including AF. Using BP measurements from six exams (2000-2018 in MESA, 1987-2017 in ARIC), we examined cross-sectional BP at the most recent exam, individual long-term mean BP from exams 1-5, BP trend during exams 1-5, and visit-to-visit variability during exams 1-5 in systolic BP (SBP) and pulse pressure (PP) for each participant. Logistic regression models were used to examine BP exposures in relation to subclinical AF and linear regression models were used to examine BP exposures in relation to frequency of supraventricular ectopy. Models adjusted for participant demographics, height, weight, diabetes, antihypertensive medication use and cross-sectional BP. Results from each study were combined with inverse variance-weighted meta-analysis. Results: At Exam 6, the mean age was 73 years in MESA and 79 years in ARIC, and 4% had subclinical AF. A 10 mmHg higher cross-sectional SBP and a 10 mmHg higher cross-sectional PP were associated with less AF (odds ratio [OR] SBP 0.86, 95% confidence interval [CI] 0.76, 0.96 and OR PP 0.73, 95% CI 0.63, 0.84). In contrast, a 4 mmHg higher visit-to-visit variability in SBP was associated with a greater prevalence of subclinical AF (OR 1.20, 95% CI 1.02, 1.38) and with a greater frequency of premature atrial contractions/hour (8%, 95% CI 1%, 15%). For PP as well, a 4 mmHg higher visit-to-visit variability was associated with a greater prevalence of AF (OR 1.18, 95% CI 1.00-1.37). In addition, a 10 mmHg higher long-term mean PP was associated with a greater prevalence of subclinical AF (OR 1.36, 95% CI 1.08-1.70). Conclusion: Our results indicate that information on BP assessed longitudinally for several years, especially visit-to-visit BP variability, is associated with a greater prevalence of subclinical atrial arrhythmias, while cross-sectional BP values alone were not associated with a greater prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

Background High blood pressure (BP) is a well‐known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi‐Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000–2018 in MESA and 1987–2017 in ARIC study), we calculated individual long‐term mean, trend, and detrended visit‐to‐visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance‐weighted meta‐analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit‐to‐visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02–1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01–1.15). For pulse pressure as well, higher visit‐to‐visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00–1.37). In addition, higher long‐term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08–1.70). Conclusions Antecedent visit‐to‐visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

Background Most studies of stroke in people living with HIV (PLWH) do not use verified stroke diagnoses, are small, and/or do not differentiate stroke types and subtypes. Setting CNICS, a U.S. multisite clinical cohort of PLWH in care. Methods We implemented a centralized adjudication stroke protocol to identify stroke type, subtype, and precipitating conditions identified as direct causes including infection and illicit drug use in a large diverse HIV cohort. Results Among 26,514 PLWH, there were 401 strokes, 75% of which were ischemic. Precipitating factors such as sepsis or same-day cocaine use were identified in 40% of ischemic strokes. Those with precipitating factors were younger, had more severe HIV disease, and fewer traditional stroke risk factors such as diabetes and hypertension. Ischemic stroke subtypes included cardioembolic (20%), large vessel atherosclerosis (13%), and small vessel (24%) ischemic strokes. Individuals with small vessel strokes were older, were more likely to have a higher current CD4 cell count than those with cardioembolic strokes and had the highest mean blood pressure of the ischemic stroke subtypes. Conclusion Ischemic stroke, particularly small vessel and cardioembolic subtypes, were the most common strokes among PLWH. Traditional and HIV-related risk factors differed by stroke type/subtype. Precipitating factors including infections and drug use were common. These results suggest that there may be different biological phenomena occurring among PLWH and that understanding HIV-related and traditional risk factors and in particular precipitating factors for each type/subtype may be key to understanding, and therefore preventing, strokes among PLWH.

BackgroundAnemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy (ART) era is lacking.MethodsWithin a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010–3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin ResultsThis retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range [IQR] 4.3–7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR.ConclusionBecause anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.

Purpose: Opioids and gabapentinoids may have adverse cardiovascular effects. We evaluated whether these medications were associated with incident clinically-detected atrial fibrillation (AF) or monitor-detected supraventricular ectopy (SVE), including premature atrial contractions (PACs) and supraventricular tachycardia (SVT). Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study that enrolled 6,814 Americans without clinically-detected cardiovascular disease (CVD) in 2000-2002. At the 2016-2018 examination, a subset of participants received extended ambulatory electrocardiographic (ECG) monitoring with a device that records up to 14 days of continuous data. Longitudinal analyses investigated time-varying medication exposures at 5 exams (through 2012) and the risk of incident clinically-detected AF through 2015 using Cox proportional hazards regression models. Cross-sectional analyses investigated medication exposures at the 2016-2018 examination and the risk of monitor-detected SVE using linear and logistic regression models. Methods: The longitudinal cohort included 6,652 participants. Opioid and gabapentenoid use increased over time (Figure). During 12.4 years of mean follow-up, 961 participants (14.4%) experienced incident AF. Opioid use and gabapentinoid use were not associated with the risk of incident AF compared with no use. The cross-sectional analysis included 1,435 participants with ECG monitoring. Compared with non-use, gabapentinoid use was associated with an 84% greater count of PACs/hour (95% CI, 25%-171%) and with a 44% greater average number of runs of SVT/day (95% CI, 3%-100%) but not with a higher odds of SVT. No associations were found with use of opioids in cross-sectional analyses. Conclusions: In this study, gabapentinoid use was associated with more SVE. Given the rapid increase in gabapentinoid use, additional studies are needed to clarify whether these medications increase the risk of CVD complications.

Background: Among people living with HIV (PLWH), elevated plasma HIV RNA (viral load, [VL]), indicative of increased inflammation, may be associated with greater risk of stroke. Methods: Among adult PLWH receiving clinical care at six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites across the U.S. from January 2006 through January 2015, first ischemic or hemorrhagic stroke was identified from adjudicated clinical events. We considered baseline and time-updated VL. Baseline viral load was defined as the most recent viral load before 2006 or at CNICS cohort entry (if after 2006). Cox proportional hazards models were used to assess the relationship between baseline VL and time-updated VL and stroke. We estimated hazard ratios for risk of stroke (all stroke, and ischemic and hemorrhagic stroke separately) comparing the 75 th percentile of VL (“high VL”) to the 25 th percentile (“low VL”). All models were adjusted for age, sex, race/ethnicity, CNICS site, diabetes, treated hypertension, statin use, smoking, nadir CD4, BMI, hepatitis C virus coinfection, and baseline ART use. The hemorrhagic stroke model was also adjusted for FIB-4. Results: Among 16,648 PLWH over an average follow-up of 4.7 years, there were 146 total strokes (119 ischemic; 19 hemorrhagic). At baseline, the median VL was 41 copies/mL (IQR: 24, 3860). Individuals with high baseline VL were 1.57 times more likely to have a stroke than individuals with low baseline VL (95% CI: 1.22, 2.04). In addition, high baseline VL was associated with increased risk of ischemic stroke (HR: 1.48; 95% CI: 1.11, 1.97) and hemorrhagic stroke (HR: 2.5; 95% CI: 1.25, 4.98). The HR for all strokes comparing high VL and low VL individuals using time-updated VL was 1.84 (95% CI: 1.42-2.40). Conclusion: Our findings suggest that higher VL is associated with stroke risk after adjusting for traditional stroke risk factors, and may have a greater impact on incidence of hemorrhagic stroke. In addition to reducing HIV-related morbidity and mortality, improving HIV care may also reduce stroke risk.

PURPOSE Opioids, gabapentinoids, and nonsteroidal anti-inflammatory drugs (NSAIDs) may have adverse cardiovascular effects. We evaluated whether these medications were associated with incident clinically detected atrial fibrillation (AF) or monitor-detected supraventricular ectopy (SVE), including premature atrial contractions (PACs) and supraventricular tachycardia (SVT). METHODS We used data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study that enrolled 6814 Americans without clinically detected cardiovascular disease in 2000 to 2002. At the 2016 to 2018 examination, 1557 individuals received ambulatory electrocardiographic (ECG) monitoring. Longitudinal analyses investigated time-varying medication exposures at the first five exams (through 2011) in relation to incident clinically detected AF through 2015 using Cox proportional hazards regression models. Cross-sectional analyses investigated medication exposures at 2016 to 2018 examination and the risk of monitor-detected SVE using linear regression models. RESULTS The longitudinal cohort included 6652 participants. During 12.4 years of mean follow-up, 982 participants (14.7%) experienced incident clinically detected AF. Use of opioids, gabapentinoids, and NSAIDs were not associated with incident AF. The cross-sectional analysis included 1435 participants with ECG monitoring. Gabapentinoid use was associated with an 84% greater average frequency of PACs/hour (95% CI, 25%-171%) and a 44% greater average number of runs of SVT/day (95% CI, 3%-100%). No associations were found with use of opioids or NSAIDs in cross-sectional analyses. CONCLUSIONS In this study, gabapentinoid use was associated with SVE. Given the rapid increase in gabapentinoid use, additional studies are needed to clarify whether these medications cause cardiovascular complications.

Objective To examine associations between post-diagnosis use of antihypertensive (AH) medications including thiazide diuretics (TDs), angiotensin converting enzyme inhibitors (ACEIs), beta blockers (BBs) [both non-selective (NSBBs) and selective (SBBs)] and calcium channel blockers (CCBs) and ovarian cancer-specific survival. Methods This cohort study used SEER-Medicare data on 2195 women 66+ years of age who were diagnosed with ovarian cancer during 2007–2012 and who survived for at least 12 months. Use of an AH class was defined as two or more fills during the year after diagnosis. Ovarian cancer-specific death was assessed starting one year after diagnosis and continued through the end of 2013. Associations between AH use and ovarian cancer-specific mortality were assessed using Cox proportional hazard models, comparing users of a given class of AH to non-AH users. Results Overall, 718 (33%), 690 (31%), 521 (24%), 154 (7%) of women used a TD, ACEI, BB, or CCB, respectively, with some women (48%) using more than one class of drug. Ovarian cancer-specific mortality was found to be lower among women who used an ACEI (adjusted hazard ratio [aHR] 0.76, 95% confidence interval [CI] 0.63–0.92), a TD (aHR 0.82, 95%CI 0.68–0.99), or a NSBB (aHR 0.60, 95%CI 0.43–0.83), but no such association was seen in women who took a SBB or CCB. Conclusion We observed that women who took certain forms of an AH medication during the year following a diagnosis of ovarian cancer were thereafter at a relatively reduced risk of dying from their disease. However, the potential for residual confounding by disease severity argues for a cautious interpretation.

The potential for immortal time bias is pervasive in epidemiologic studies with left truncation or time-varying exposures. Unlike other biases in epidemiologic research (e.g., measurement bias, confounding due to unmeasured factors, and selection based on unmeasured predictors of the outcome), immortal time bias can and should be avoided by the correct assignment of person-time during follow up. However, even when handing person-time correctly, allowing late entry into a study or into an exposure group can open the door to more insidious sources of bias, some of which we explore here. Clear articulation of the study question, including the treatment plans of interest, can provide navigation around these sources of bias and elucidate the assumptions needed for inference given the available data. Here, we use simulated data to illustrate the assumptions required under various approaches to estimate the effect of a time-varying treatment and describe how these assumptions relate to the assumptions necessary to estimate single sample rates and risks in settings with censoring and truncation.

Background Epidemiologic studies often use diagnosis codes to identify dementia outcomes. It remains unknown to what extent cognitive screening test results add value in identifying dementia cases in big data studies leveraging electronic health record (EHR) data. We examined test scores from EHR data and compared results with dementia algorithms. Methods This retrospective cohort study included patients 60+ years of age from Kaiser Permanente Washington (KPWA) during 2013–2018 and the Veterans Health Affairs (VHA) during 2012–2015. Results from the Mini Mental State Examination (MMSE) and the Saint Louis University Mental Status Examination (SLUMS) cognitive screening exams, were classified as showing dementia or not. Multiple dementia algorithms were created using combinations of diagnosis codes, pharmacy records, and specialty care visits. Correlations between test scores and algorithms were assessed. Results 3,690 of 112,917 KPWA patients and 2,981 of 102,981 VHA patients had cognitive test results in the EHR. In KPWA, dementia prevalence ranged from 6.4%-8.1% depending on the algorithm used and in the VHA, 8.9%–12.1%. The algorithm which best agreed with test scores required ≥2 dementia diagnosis codes in 12 months; at KPWA, 14.8% of people meeting this algorithm had an MMSE score, of whom 65% had a score indicating dementia. Within VHA, those figures were 6.2% and 77% respectively. Conclusions Although cognitive test results were rarely available, agreement was good with algorithms requiring ≥2 dementia diagnosis codes, supporting the accuracy of this algorithm. Implications These scores may add value in identifying dementia cases for EHR-based research studies.

Background: It has been suggested that the likelihood of survival among women with ovarian cancer could be increased by postdiagnosis statin use. This study examines the potential association between postdiagnosis statin use and cancer-specific mortality among women with ovarian cancer. Methods: This cohort study used SEER-Medicare data on women ≥66 years of age diagnosed with ovarian cancer during 2007 to 2012 who were enrolled in Medicare parts A, B, and D during the year after diagnosis. Statin use was defined as two or more fills for a statin during the year after diagnosis. Ovarian cancer–specific death was assessed starting 1 year after diagnosis. Marginal structural Cox models were used, adjusting for the inverse probability of treatment weighting and censoring weighting. Treatment weights and censoring weights were calculated using logistic regression models with a priori–defined covariates. Results: Among 2,195 women with ovarian cancer, 489 (22%) used statins within 1 year after their diagnosis. Over a mean follow-up of 2.2 years, 796 (36%) women died from ovarian cancer. The adjusted HR for ovarian cancer mortality comparing statin users to nonusers was 0.74 (95% confidence interval, 0.61–0.91). Conclusions: Findings from this and prior work suggest statin use following a diagnosis with ovarian cancer is associated with a lower risk of cancer death. Impact: Because, in most women, statin administration has limited side effects, a randomized trial of statins among patients with ovarian cancer may be warranted.

Purpose The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested. Methods This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model. Results Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]). Conclusions No association was observed between PPI use and fracture risk among older adults.