Influence of light at night on allergic diseases: a systematic review and meta-analysis.

BACKGROUND: Allergic diseases impose a significant global disease burden, however, the influence of light at night exposure on these diseases in humans has not been comprehensively assessed. We aimed to summarize available evidence considering the association between light at night exposure and major allergic diseases through a systematic review and meta-analysis. METHODS: We completed a search of six databases, two registries, and Google Scholar from inception until December 15, 2023, and included studies that investigated the influence of artificial light at night (ALAN, high vs. low exposure), chronotype (evening vs. morning chronotype), or shift work (night vs. day shift work) on allergic disease outcomes (asthma, allergic rhinitis, and skin allergies). We performed inverse-variance random-effects meta-analyses to examine the association between the exposures (ALAN exposure, chronotype, or shiftwork) and these allergic outcomes. Stratification analyses were conducted by exposure type, disease type, participant age, and geographical location along with sensitivity analyses to assess publication bias. RESULTS: We included 12 publications in our review. We found that exposure to light at night was associated with higher odds of allergic diseases, with the strongest association observed for ALAN exposure (OR: 1.88; 95% CI: 1.04 to 3.39), followed by evening chronotype (OR: 1.35; 95% CI: 0.98 to 1.87) and exposure to night shift work (OR: 1.33; 95% CI: 1.06 to 1.67). When analyses were stratified by disease types, light at night exposure was significantly associated with asthma (OR: 1.62; 95% CI: 1.19 to 2.20), allergic rhinitis (OR: 1.89; 95% CI: 1.60 to 2.24), and skin allergies (OR: 1.11; 95% CI: 1.09 to 1.91). We also found that the association between light at night exposure and allergic diseases was more profound in youth (OR: 1.63; 95% CI: 1.07 to 2.48) than adults (OR: 1.30; 95% CI: 1.03 to 1.63). Additionally, we observed significant geographical variations in the association between light at night exposure and allergic diseases. CONCLUSIONS: Light at night exposure was associated with a higher prevalence of allergic diseases, both in youth and adults. More long-term epidemiological and mechanistic research is required to understand the possible interactions between light at night and allergic diseases.

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Characterization of the internal working-life exposome using minimally and non-invasive sampling methods - a narrative review.

During recent years, we are moving away from the 'one exposure, one disease'-approach in occupational settings and towards a more comprehensive approach, taking into account the totality of exposures during a life course by using an exposome approach. Taking an exposome approach however is accompanied by many challenges, one of which, for example, relates to the collection of biological samples. Methods used for sample collection in occupational exposome studies should ideally be minimally invasive, while at the same time sensitive, and enable meaningful repeated sampling in a large population and over a longer time period. This might be hampered in specific situations e.g., people working in remote areas, during pandemics or with flexible work hours. In these situations, using self-sampling techniques might offer a solution. Therefore, our aim was to identify existing self-sampling techniques and to evaluate the applicability of these techniques in an occupational exposome context by conducting a literature review. We here present an overview of current self-sampling methodologies used to characterize the internal exposome. In addition, the use of different biological matrices was evaluated and subdivided based on their level of invasiveness and applicability in an occupational exposome context. In conclusion, this review and the overview of self-sampling techniques presented herein can serve as a guide in the design of future (occupational) exposome studies while circumventing sample collection challenges associated with exposome studies.

Chronic obstructive pulmonary disease and the risk for myocardial infarction by type in people with HIV.

OBJECTIVES: The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI). DESIGN: We utilized data from five sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, a multisite observational study. METHODS: Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and at least 90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI. RESULTS: Among 12 046 PWH, 945 had COPD. Overall, 309 PWH had an MI: 58% had T1MI ( N  = 178) and 42% T2MI ( N  = 131). In adjusted models, COPD was associated with a significantly increased risk of all MI [adjusted hazard ratio (aHR) 2.68 (95% confidence interval (CI) 1.99-3.60)] even after including self-reported smoking [aHR 2.40 (95% CI 1.76-3.26)]. COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use. CONCLUSION: COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed.

Metabolic profiling of night shift work - The HORMONIT study.

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.

Disruption of cellular immune response among male rotating night shift workers in Spain- The HORMONIT study.

Introduction: Preliminary studies suggest that night shift work is associated with a desynchronization of rhythmic immune markers, possibly explaining the increased risk of infection, cardiometabolic disorders, and cancer in shift workers. Methods: This study included 51 male rotating shift workers from a car industry in Barcelona, Spain, sampled twice toward the end of a 3-week night shift (22:00-06:00 h) and a 3-week day shift (06:00-14:00 h) rotation. We collected four blood samples per worker, at the start and end of each shift. We measured 27 cytokines, chemokines and growth factors in plasma samples by luminex using the Cytokine Human Magnetic 30-Plex Panel LHC6003M and applied linear mixed models to examine within-person associations between shift work and analytes' concentrations, comparing samples taken at 06:00 h on a day and night shift. We also conducted a factor analysis using analyte concentrations from all 4 time points for each individual to identify common factors and determine if these factors were altered by shift work. Results: We observed lower levels of 15 analytes in the night shift compared to the day shift including cytokines (pro-inflammatory TNF-α, IL-2R; anti-inflammatory IL1-RA; Th1 IL-2, Th2 IL-4 and Th17 Il-17), chemokines (IP-10, MIP-1α, MIP-1ß, RANTES) and growth factors (EGF, G-CSF, HGF, VEGF, FGF). In a factor analysis, three factors were identified. The main factor (Factor 1), explaining 57% of the variance and including IL-1ß, IL-12, IL-15, MIP-1α, MIP-1ß, EGF and FGF; and another factor (Factor 3) explaining 10% of the variance and including the Th1 cytokine IL-12, were inversely associated with the night shift (coefficient: -0.17, 95%CI -0.32 to -0.01 and coefficient: -0.22, 95%CI -0.38, -0.06, for Factors 1 and 3, respectively). Our results indicate that night shift disrupts the levels of several immune markers, which could contribute to the increased risk of infections and cancer reported in night shift workers. Conclusion: Night shift is associated with disruption of multiple immune response pathways.

Association of time of breakfast and nighttime fasting duration with breast cancer risk in the multicase-control study in Spain.

Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer.

The Influence of Artificial Light at Night on Asthma and Allergy, Mental Health, and Cancer Outcomes: A Systematic Scoping Review Protocol.

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.

Self-reported marijuana use and cardiac arrhythmias (from the Multiethnic Study of Atherosclerosis).

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.

Applying the exposome concept to working life health: The EU EPHOR project.

Exposures at work have a major impact on noncommunicable diseases (NCDs). Current risk reduction policies and strategies are informed by existing scientific evidence, which is limited due to the challenges of studying the complex relationship between exposure at work and outside work and health. We define the working life exposome as all occupational and related nonoccupational exposures. The latter includes nonoccupational exposures that may be directly or indirectly influenced by or interact with the working life of the individual in their relation to health. The Exposome Project for Health and Occupational Research aims to advance knowledge on the complex working life exposures in relation to disease beyond the single high exposure-single health outcome paradigm, mapping and relating interrelated exposures to inherent biological pathways, key body functions, and health. This will be achieved by combining (1) large-scale harmonization and pooling of existing European cohorts systematically looking at multiple exposures and diseases, with (2) the collection of new high-resolution external and internal exposure data. Methods and tools to characterize the working life exposome will be developed and applied, including sensors, wearables, a harmonized job exposure matrix (EuroJEM), noninvasive biomonitoring, omics, data mining, and (bio)statistics. The toolbox of developed methods and knowledge will be made available to policy makers, occupational health practitioners, and scientists. Advanced knowledge on working life exposures in relation to NCDs will serve as a basis for evidence-based and cost-effective preventive policies and actions. The toolbox will also enable future scientists to further expand the working life exposome knowledge base.

Association of Brain Volumes and White Matter Injury With Race, Ethnicity, and Cardiovascular Risk Factors: The Multi-Ethnic Study of Atherosclerosis.

Background Cardiovascular risk factors are associated with cognitive decline and dementia. Magnetic resonance imaging provides sensitive measurement of brain morphology and vascular brain injury. However, associations of risk factors with brain magnetic resonance imaging findings have largely been studied in White participants. We investigated associations of race, ethnicity, and cardiovascular risk factors with brain morphology and white matter (WM) injury in a diverse population. Methods and Results In the Multi-Ethnic Study of Atherosclerosis, measures were made in 2018 to 2019 of total brain volume, gray matter and WM volume, and WM injury, including WM hyperintensity volume and WM fractional anisotropy. We assessed cross-sectional associations of race and ethnicity and of cardiovascular risk factors with magnetic resonance imaging measures. Magnetic resonance imaging data were complete in 1036 participants; 25% Black, 15% Chinese-American, 19% Hispanic, and 41% White. Mean (SD) age was 72 (8) years and 53% were women. Although WM injury was greater in Black than in White participants in a minimally adjusted model, additional adjustment for cardiovascular risk factors and socioeconomic status each attenuated this association, rendering it nonsignificant. Overall, greater average WM hyperintensity volume was associated with older age and current smoking (69% greater vs never smoking); lower fractional anisotropy was additionally associated with higher diastolic blood pressure, use of antihypertensive medication, and diabetes. Conclusions We found no statistically significant difference in measures of WM injury by race and ethnicity after adjustment for cardiovascular risk factors and socioeconomic status. In all racial and ethnic groups, older age, current smoking, hypertension, and diabetes were strongly associated with WM injury.

Relationship between social support and incident hypertension in the Jackson Heart Study: a cohort study.

OBJECTIVES: Social support may be an important mitigating factor against adverse cardiovascular outcomes by facilitating health-promoting behaviours or by buffering against the negative effects of stress. This study examined the association of social support with incident hypertension. DESIGN: Prospective cohort study. SETTING: We evaluated the association of social support with incident hypertension among participants in the Jackson Heart Study, a community-based cohort of African Americans. PARTICIPANTS: This study included African American adults, who were free of hypertension at baseline (2000-2004). Functional social support, structural social support and satisfaction with social support were assessed at baseline among 1516, 1240 and 1503 participants, respectively. OUTCOME MEASURES: Incident hypertension was assessed at follow-up examinations in 2005-2008 and 2009-2013. Incident hypertension was defined by the first visit with systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg or self-reported antihypertensive medication use. Multivariable Poisson regression was used to estimate the association of baseline social support with incident hypertension, adjusting for relevant confounders. RESULTS: At baseline, the mean age of participants was 50 years and 64% were men. During a median follow-up time of 6.9 years, 54% of participants developed hypertension. A high level of functional social support was associated with lower risk of incident hypertension (incident rate ratio 0.64, (95% CI 0.41 to 0.97)), compared with a low level of functional social support. Level of structural social support and satisfaction with social support were not associated with hypertension risk. CONCLUSIONS: These results suggest that greater functional support may be associated with a lower risk of incident hypertension.

Changes in melatonin and sex steroid hormone production among men as a result of rotating night shift work - the HORMONIT study.

OBJECTIVE: Data from real world settings on circadian disruption and subsequent hormone-related changes may explain the higher risk of hormone-dependent cancers among night shift workers.The present study examines the melatonin and sex steroid hormone levels among night shift workers. METHODS: We included 44 male, rotating shift workers from a car factory in Spain, sampled both at the end of a 3-week night shift (22:00-06:00 hrs) and a 3-week early morning shift (06:00-14:00 hrs). Participants collected all urine voids over 24-hours during each shift. Urinary concentrations of sex steroid hormones (estrogens, androgens and progestogens) and 6-sulfatoxymelatonin (aMT6s, major melatonin metabolite) were determined. Individual cosinor analysis was used to derive the acrophase (peak time) and area under the curve (total production). Linear mixed models examined intraindividual associations between night shift work and log-transformed 24-hour peak time and total production of hormones compared to early morning shift work. RESULTS: The acrophase was delayed during the night shift for aMT6s [geometric mean difference (GMD) 7.53 hrs, 95% confidence interval (CI) 4.46-10.60], androgens (eg, testosterone: GMD 6.83 hrs, 95% CI 0.34-13.32) and progestogens (eg, 17-hydroxyprogesterone: GMD 4.54 hrs, 95% CI 2.92-6.16) compared to the early morning shift. We found a higher production of adrenal androgen 11-oxoandrosterone/11-oxoetiocholanolone [geometric mean ratio (GMR) 1.43, 95% CI 1.12-1.81], and a lower production of adrenal progestogen 16-cysteinylprogesterone (GMR 0.79, 95% CI 0.67-0.93) during the night shift compared to the early morning shift levels. CONCLUSIONS: Night shift work was associated with melatonin and sex hormone-related changes in timing and total production, providing insight into the mechanistic path for its association with hormone-dependent cancer.

Longitudinal Measures of Blood Pressure and Subclinical Atrial Arrhythmias: The MESA and the ARIC Study.

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.

Types of Stroke Among People Living With HIV in the United States.

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.

HIV Viremia and Risk of Stroke Among People Living with HIV Who Are Using Antiretroviral Therapy.

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.

Brief Report: Weight Gain Following ART Initiation in ART-Naïve People Living With HIV in the Current Treatment Era.

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-naïve 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-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

Opioid, gabapentinoid, and nonsteroidal anti-inflammatory medication use and the risks of atrial fibrillation and supraventricular ectopy in the Multi-Ethnic Study of Atherosclerosis.

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.

Methods to identify dementia in the electronic health record: Comparing cognitive test scores with dementia algorithms.

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.