Trajectories of intimate partner violence and their relationship to stress among young women in South Africa: An HPTN 068 study.

BACKGROUND: One in four South African women will experience intimate partner violence (IPV) in their lifetime, potentially increasing their biological stress. In South Africa, limited IPV and stress research has utilized multiple timepoints or examined modifying factors. Cash transfers (CTs) are associated with reduced IPV and stress and may be an intervention target. AIMS: We used data-driven methods to identify longitudinal IPV trajectory groups among South African adolescent girls and young women (AGYW), estimate each group's association with stress, and assess modification by a CT. METHODS: A total of 2,183 South African AGYW ages 13 to 24 years from the HIV Prevention Trials Network 068 study were randomized to a CT or control group. Physical IPV was measured five times (2011-2017), and stress was captured once (2018-2019). Stress measures included the Cohen Stress Scale and stress biomarkers (C-reactive protein (CRP), cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1)). Group-based trajectory modeling identified IPV trajectories; ordinal logistic regression estimated the association between trajectory group and stress. RESULTS: A two-group quadratic trajectory model was identified (higher trajectory group = 26.7% of AGYW; lower trajectory group = 73.3%). In both groups, the probability of IPV increased from ages 13 to 17 years before declining in early adulthood. However, the higher group's probability peaked later and declined gradually. The higher trajectory group was associated with an increased odds of elevated CRP (OR: 1.41, 95% CI [1.11, 1.80]), but not with other stress measures. The CT modified the relationship with CMV: a positive association was observed among the usual care arm (OR: 1.59, 95% CI [1.11, 2.28]) but not the CT arm (OR: 0.85, 95% CI [0.61, 1.19]). CONCLUSIONS: Sustained IPV risk during adolescence was associated with elevated CRP in young adulthood. The relationship between IPV and elevated CMV was attenuated among those receiving a CT, suggesting that CTs could possibly reduce biological stress due to IPV.

The Sociodemographic and Lifestyle Correlates of Epigenetic Aging in a Nationally Representative U.S. Study of Younger Adults.

Importance: Epigenetic clocks represent molecular evidence of disease risk and aging processes and have been used to identify how social and lifestyle characteristics are associated with accelerated biological aging. However, most of this research is based on older adult samples who already have measurable chronic disease. Objective: To investigate whether and how sociodemographic and lifestyle characteristics are related to biological aging in a younger adult sample across a wide array of epigenetic clock measures. Design: Nationally representative prospective cohort study. Setting: United States (U.S.). Participants: Data come from the National Longitudinal Study of Adolescent to Adult Health, a national cohort of adolescents in grades 7-12 in U.S. in 1994 followed for 25 years over five interview waves. Our analytic sample includes participants followed-up through Wave V in 2016-18 who provided blood samples for DNA methylation (DNAm) testing (n=4237) at Wave V. Exposure: Sociodemographic (sex, race/ethnicity, immigrant status, socioeconomic status, geographic location) and lifestyle (obesity status, exercise, tobacco, and alcohol use) characteristics. Main Outcome: Biological aging assessed from blood DNAm using 16 epigenetic clocks when the cohort was aged 33-44 in Wave V. Results: While there is considerable variation in the mean and distribution of epigenetic clock estimates and in the correlations among the clocks, we found sociodemographic and lifestyle factors are more often associated with biological aging in clocks trained to predict current or dynamic phenotypes (e.g., PhenoAge, GrimAge and DunedinPACE) as opposed to clocks trained to predict chronological age alone (e.g., Horvath). Consistent and strong associations of faster biological aging were found for those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use. Conclusions and Relevance: Our study found important social and lifestyle factors associated with biological aging in a nationally representative cohort of younger-aged adults. These findings indicate that molecular processes underlying disease risk can be identified in adults entering midlife before disease is manifest and represent useful targets for interventions to reduce social inequalities in heathy aging and longevity. Key Points: Question: Are epigenetic clocks, measures of biological aging developed mainly on older-adult samples, meaningful for younger adults and associated with sociodemographic and lifestyle characteristics in expected patterns found in prior aging research?Findings: Sociodemographic and lifestyle factors were associated with biological aging in clocks trained to predict morbidity and mortality showing accelerated aging among those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use.Meaning: Age-related molecular processes can be identified in younger-aged adults before disease manifests and represent potential interventions to reduce social inequalities in heathy aging and longevity.

Sociodemographic patterns in biomarkers of aging in the Add Health cohort.

Biomarkers in population health research serve as indicators of incremental physiological deterioration and contribute to our understanding of mechanisms through which social disparities in health unfold over time. Yet, few population-based studies incorporate biomarkers of aging in early midlife, when disease risks may emerge and progress across the life course. We describe the distributions of several biomarkers of inflammation and neurodegeneration and their variation by sociodemographic characteristics using blood samples collected during Wave V of the National Longitudinal Study of Adolescent to Adult Health (ages 33-44 years). Higher mean levels of inflammatory and neurodegenerative biomarkers were associated with greater socioeconomic disadvantage. For example, the neurodegenerative markers, Neurofilament Light Chain and total Tau proteins were higher among lower income groups, though the relationship was not statistically significant. Similarly, proinflammatory marker Tumor Necrosis Factor-α (TNF-α) levels were higher among those with lower education. Significant differences in the mean levels of other proinflammatory markers were observed by race/ethnicity, sex, census region, BMI, and smoking status. These descriptive findings indicate that disparities in biomarkers associated with aging are already evident among young adults in their 30s and attention should focus on age-related disease risk earlier in the life course.

The association between incarceration and housing insecurity and advanced immune age during late life.

Emerging evidence suggests that psychosocial stress ages the immune system. Accordingly, immune aging may be an important potential mechanism linking psychosocial stress to aging-related decline and disease. Incarceration and housing insecurity represent severe and complex experiences of a multitude of psychosocial stressors, including discrimination, violence, and poverty. In this study, we investigated the association between incarceration and/or housing insecurity and advanced immune age in adults aged 55 and older. Our sample was derived from the Health and Retirement Survey (HRS), with n = 7003 individuals with valid housing insecurity data and n = 7523 with valid incarceration data. From 2016 Venous Blood Study data, we assessed immune aging using a comprehensive set of immune markers including inflammatory markers (IL-6, CRP, s-TNFR1), markers of viral control (CMV IgG antibodies), and ratios of T cell phenotypes (CD8+:CD4+, CD+ Memory: Naïve, CD4+ Memory: Naïve, CD8+ Memory: Naïve ratios). We found that both incarceration and housing insecurity were strongly associated with more advanced immune aging as indicated by increased inflammation, reduced viral control, and reduction in naïve T cells relative to memory T cells. Given that those who experienced incarceration, housing insecurity, and/or are racialized minorities were less likely to be included in this study, our results likely underestimated these associations. Despite these limitations, our study provided strong evidence that experiencing incarceration and/or housing insecurity may accelerate the aging of the immune system.

Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study.

Importance: People who complete more education live longer lives with better health. New evidence suggests that these benefits operate through a slowed pace of biological aging. If so, measurements of the pace of biological aging could offer intermediate end points for studies of how interventions to promote education will affect healthy longevity. Objective: To test the hypothesis that upward educational mobility is associated with a slower pace of biological aging and increased longevity. Design, Setting, and Participants: This prospective cohort study analyzed data from 3 generations of participants in the Framingham Heart Study: (1) the original cohort, enrolled beginning in 1948; (2) the Offspring cohort, enrolled beginning in 1971; and (3) the Gen3 cohort, enrolled beginning in 2002. A 3-generation database was constructed to quantify intergenerational educational mobility. Mobility data were linked with blood DNA-methylation data collected from the Offspring cohort in 2005 to 2008 (n = 1652) and the Gen3 cohort in 2009 to 2011 (n = 1449). Follow-up is ongoing. Data analysis was conducted from June 2022 to November 2023 using data obtained from the National Institutes of Health database of Genotypes and Phenotypes (dbGaP). Exposure: Educational mobility was measured by comparing participants' educational outcomes with those of their parents. Main Outcomes and Measures: The pace of biological aging was measured from whole-blood DNA-methylation data using the DunedinPACE epigenetic clock. For comparison purposes, the analysis was repeated using 4 other epigenetic clocks. Survival follow-up was conducted through 2019. Results: This study analyzed data from 3101 participants from the Framingham Heart Study; 1652 were in the Offspring cohort (mean [SD] age, 65.57 [9.22] years; 764 [46.2%] male) and 1449 were in the Gen3 cohort (mean [SD] age, 45.38 [7.83] years; 691 [47.7%] male). Participants who were upwardly mobile in educational terms tended to have slower pace of aging in later life (r = -0.18 [95% CI, -0.23 to -0.13]; P < .001). This pattern of association was similar across generations and held in within-family sibling comparisons. There were 402 Offspring cohort participants who died over the follow-up period. Upward educational mobility was associated with lower mortality risk (hazard ratio, 0.89 [95% CI, 0.81 to 0.98]; P = .01). Slower pace of aging accounted for approximately half of this association. Conclusions and Relevance: This cohort study's findings support the hypothesis that interventions to promote educational attainment may slow the pace of biological aging and promote longevity. Epigenetic clocks have potential as near-term outcome measures of intervention effects on healthy aging. Experimental evidence is needed to confirm findings.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Magnitude and Durability of the Antibody Response to mRNA-Based Vaccination Among SARS-CoV-2 Seronegative and Seropositive Health Care Personnel.

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

An Early and Unequal Decline: Life Course Trajectories of Cognitive Aging in the United States.

Objectives: Cognitive aging is a lifelong process with implications for Alzheimer's disease and dementia. This study aims to fill major gaps in research on the natural history of and social disparities in aging-related cognitive decline over the life span. Methods: We conducted integrative data analysis of four large U.S. population-based longitudinal studies of individuals aged 12 to 105 followed over two decades and modeled age trajectories of cognitive function in multiple domains. Results: We found evidence for the onset of cognitive decline in the 4th decade of life, varying gender differences with age, and persistent disadvantage among non-Hispanic Blacks, Hispanics, and those without college education. We further found improvement in cognitive function across 20th century birth cohorts but widening social inequalities in more recent cohorts. Discussion: These findings advance an understanding of early life origins of dementia risk and invite future research on strategies for promoting cognitive health for all Americans.

Does biological age mediate the relationship between childhood adversity and depression? Insights from the Detroit Neighborhood Health Study.

The link between childhood adversity and adulthood depression is well-established; however, the underlying mechanisms are still being explored. Recent research suggests biological age may mediate the relationship between childhood adversity and depression in later life. This study examines if biological age mediates the relationship between childhood adversity and depression symptoms using an expanded set of biological age measures in an urban population-based cohort. Data from waves 1-3 of the Detroit Neighborhood Health Study (DNHS) were used in this analysis. Questions about abuse during childhood were coded to form a childhood adversity score similar to the Adverse Childhood Experience measure. Multiple dimensions of biological age, defined as latent variables, were considered, including systemic biological age (GrimAge, PhenoAge), epigenetic age (Horvath, SkinBlood), and immune age (cytomegalovirus, herpes simplex virus type 1, C-reactive protein, interleukin-6). Depression symptoms, modeled as a latent variable, were captured through the Patient Health Questionnaire-9 (PHQ-9). Models were adjusted for age, gender, race, parent education, and past depressive symptoms. Total and direct effects of childhood adversity on depression symptoms and indirect effects mediated by biological age were estimated. For total and direct effects, we observed a dose-dependent relationship between cumulative childhood adversity and depression symptoms, with emotional abuse being particularly influential. However, contrary to prior studies, in this sample, we found few direct effects of childhood adversity on biological age or biological age on depression symptoms and no evidence of mediation through the measures of biological age considered in this study. Further research is needed to understand how childhood maltreatment experiences are embodied to influence health and wellness.

Infection precaution adherence varies by potential exposure risks to SARS-CoV-2 and job role: Findings from a US medical center.

BACKGROUND: Infection precautions (IP) facilitate standardized and safe patient care. Research has demonstrated several barriers to IP adherence among health care personnel (HCP) but potential exposure risk to SARS-CoV-2 and job role has not been considered. METHODS: Researchers used self-reported baseline surveys with 191 HCPs at a university medical center to examine factors that may have affected IP adherence (eg, personal protective equipment [PPE] and hand hygiene errors) over the 2 weeks prior to the survey. Chi-square tests were used to determine if differences existed first, among job role and IP adherence, and second, the potential risk of exposure to SARS-CoV-2 and IP adherence. A binary logistic regression estimated if PPE nonadherence was associated with COVID-19 stress, job role, and potential exposure risk to SARS-CoV-2. RESULTS: PPE nonadherence varied by job role. Those in the Other group (ie, nonphysician/non-nursing HCP) reported significantly fewer errors (9.6%) compared to Physicians (26.5%) and Registered Nurses (33.3%). Hand/glove hygiene errors between COVID-19 patient rooms varied by job role. Respondents who had higher risks of exposure to SARS-CoV-2 were 5.74 times more likely to experience errors. CONCLUSIONS: The results provide implications for adopting systems-level approaches to support worker knowledge and engagement across job roles to improve IP adherence.

Peripheral immune function and Alzheimer's disease: a living systematic review and critical appraisal.

BACKGROUND: A growing body of literature examines the relationship between peripheral immune function and Alzheimer's Disease (AD) in human populations. Our living systematic review summarizes the characteristics and findings of these studies, appraises their quality, and formulates recommendations for future research. METHODS: We searched the electronic databases PubMed, PsycINFO, and Web of Science, and reviewed references of previous reviews and meta-analyses to identify human studies examining the relationship between any peripheral immune biomarkers and AD up to September 7th, 2023. We examined patterns of reported statistical associations (positive, negative, and null) between each biomarker and AD across studies. Evidence for each biomarker was categorized into four groups based on the proportion of studies reporting different associations: corroborating a positive association with AD, a negative association, a null association, and presenting contradictory findings. A modified Newcastle-Ottawa scale (NOS) was employed to assess the quality of the included studies. FINDINGS: In total, 286 studies were included in this review. The majority were cross-sectional (n = 245, 85.7%) and hospital-based (n = 248, 86.7%), examining relationships between 187 different peripheral immune biomarkers and AD. Cytokines were the most frequently studied group of peripheral immune biomarkers. Evidence supported a positive association with AD for six biomarkers, including IL-6, IL-1ß, IFN-γ, ACT, IL-18, and IL-12, and a negative association for two biomarkers, including lymphocytes and IL-6R. Only a small proportion of included studies (n = 22, 7.7%) were deemed to be of high quality based on quality assessment. INTERPRETATION: Existing research on peripheral immune function and AD exhibits substantial methodological variations and limitations, with a notable lack of longitudinal, population-based studies investigating a broad range of biomarkers with prospective AD outcomes. The extent and manner in which peripheral immune function can contribute to AD pathophysiology remain open questions. Given the biomarkers that we identified to be associated with AD, we posit that targeting peripheral immune dysregulation may present a promising intervention point to reduce the burden of AD.

Patterns and Life Course Determinants of Black-White Disparities in Biological Age Acceleration: A Decomposition Analysis.

Despite the prominence of the weathering hypothesis as a mechanism underlying racialized inequities in morbidity and mortality, the life course social and economic determinants of Black-White disparities in biological aging remain inadequately understood. This study uses data from the Health and Retirement Study (n = 6,782), multivariable regression, and Kitagawa-Blinder-Oaxaca decomposition to assess Black-White disparities across three measures of biological aging: PhenoAge, Klemera-Doubal biological age, and homeostatic dysregulation. It also examines the contributions of racial differences in life course socioeconomic and stress exposures and vulnerability to those exposures to Black-White disparities in biological aging. Across the outcomes, Black individuals exhibited accelerated biological aging relative to White individuals. Decomposition analyses showed that racial differences in life course socioeconomic exposures accounted for roughly 27% to 55% of the racial disparities across the biological aging measures, and racial disparities in psychosocial stress exposure explained 7% to 11%. We found less evidence that heterogeneity in the associations between social exposures and biological aging by race contributed substantially to Black-White disparities in biological aging. Our findings offer new evidence of the role of life course social exposures in generating disparities in biological aging, with implications for understanding age patterns of morbidity and mortality risks.

Intimate partner violence is associated with cytomegalovirus among young women in rural South Africa: An HPTN 068 analysis.

ABSTRACTStressful life circumstances (e.g. violence and poverty) have been associated with elevated biomarkers, including C-reactive protein (CRP), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1), among older adults in high-income settings. Yet, it remains unknown whether these relationships exist among younger populations in resource-limited settings. We therefore utilised a cohort of 1,279 adolescent girls and young women (AGYW) from the HIV Prevention Trials Network 068 study in rural South Africa to examine the associations between 6 hypothesized stressors (intimate partner violence (IPV), food insecurity, depression, socioeconomic status (SES), HIV, childhood violence) and 3 biomarkers that were measured using dried blood spots (CRP, CMV, and HSV-1). Ordinal logistic regression estimated the lagged and cross-sectional associations between each stressor and each biomarker. IPV was cross-sectionally associated with elevated CMV (OR = 2.45, 95% CI = 1.05,5.72), while low SES was cross-sectionally associated with reduced CMV (OR = 0.73, 95% CI = 0.58,0.93). AGYW with HIV had elevated biomarkers cross-sectionally (CRP: OR = 1.51, 95% CI = 1.08,2.09; CMV: OR = 1.86, 95% CI = 1.31,2.63; HSV-1: OR = 1.68, 95% CI = 1.17,2.41) and in a lagged analysis. The association between violence and CMV could help explain how violence results in stress and subsequently worse health among AGYW; however, additional research is needed to disentangle the longitudinal nature of IPV and stress.

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis.

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls.

Estimation of SARS-CoV-2 Seroprevalence in Central North Carolina: Accounting for Outcome Misclassification in Complex Sample Designs.

BACKGROUND: Population-based seroprevalence studies are crucial to understand community transmission of COVID-19 and guide responses to the pandemic. Seroprevalence is typically measured from diagnostic tests with imperfect sensitivity and specificity. Failing to account for measurement error can lead to biased estimates of seroprevalence. Methods to adjust seroprevalence estimates for the sensitivity and specificity of the diagnostic test have largely focused on estimation in the context of convenience sampling. Many existing methods are inappropriate when data are collected using a complex sample design. METHODS: We present methods for seroprevalence point estimation and confidence interval construction that account for imperfect test performance for use with complex sample data. We apply these methods to data from the Chatham County COVID-19 Cohort (C4), a longitudinal seroprevalence study conducted in central North Carolina. Using simulations, we evaluate bias and confidence interval coverage for the proposed estimator compared with a standard estimator under a stratified, three-stage cluster sample design. RESULTS: We obtained estimates of seroprevalence and corresponding confidence intervals for the C4 study. SARS-CoV-2 seroprevalence increased rapidly from 10.4% in January to 95.6% in July 2021 in Chatham County, North Carolina. In simulation, the proposed estimator demonstrates desirable confidence interval coverage and minimal bias under a wide range of scenarios. CONCLUSION: We propose a straightforward method for producing valid estimates and confidence intervals when data are based on a complex sample design. The method can be applied to estimate the prevalence of other infections when estimates of test sensitivity and specificity are available.

Comparison of capillary blood self-collection using the Tasso-SST device with venous phlebotomy for anti-SARS-CoV-2 antibody measurement.

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous total Ig and IgG specific antibody quantitative levels was high (Total Ig: Spearman ρ = 0.72, 95% CI (0.39,0.90); IgG: Spearman ρ = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.

Age, period and cohort-related trends in prescription opioid use in the USA, 1999-2018.

BACKGROUND: To provide insight into the longitudinal dynamics of opioid use throughout the overdose crisis, this study estimated the separate influences of age, period and cohort on prescription opioid use during 1999-2018 in the USA. METHODS: Data from 10 cycles of the cross-sectional National Health and Nutrition Examination Survey were used to conduct an age-period-cohort analysis of the prevalence of prescription opioid use (n=63 500 across 1999-2018). Temporal trends were graphically visualised. The median polish approach was used to estimate age, period and cohort-related effects on prescription opioid use. RESULTS: Prescription opioid use broadly increased across the lifespan, with steeper prevalence increases observed from young adulthood to mid-adulthood. Period-related variation was consistent with recognised nationwide declines in opioid prescribing. While there was no evidence of systematic cohort effects, compared with individuals born in 1951-1954, those born during 1963-1966 had greater prescription opioid use (prevalence ratio (PR)=1.23, 95% CI: 1.05 to 1.43), whereas the 1991-1994 and 1999-2002 cohorts had lower prescription opioid use (PR91-94=0.70, 95% CI: 0.50 to 0.98; PR99-02=0.72, 95% CI: 0.63 to 0.81). CONCLUSION: In the USA, longitudinal trends in prescription opioid use during 1999-2018 were predominantly driven by age and period influences. The cohort of youngest baby boomers experienced greater prescription opioid use, whereas recent-born cohorts have had lower use. As the overdose crisis continues evolving, such population-level characterisations of age, period and cohort dynamics are instrumental in understanding opioid use and can inform prevention and intervention approaches by identifying population groups more likely to use opioids who, thus, may also experience related outcomes.

Biological expressions of early life trauma in the immune system of older adults.

BACKGROUND: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. METHODS: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. FINDINGS: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (ß = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (ß = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. INTERPRETATION: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

Association between prenatal socioeconomic disadvantage, adverse birth outcomes, and inflammatory response at birth.

Prenatal socioeconomic disadvantage is associated with inflammation in mid- to late-life, yet whether a pro-inflammatory phenotype is present at birth and the role of adverse birth outcomes in this pathway remains unclear. We utilized data on prenatal socioeconomic disadvantage at the individual- (i.e., mother's and father's education level, insurance type, marital status, and Women, Infants, and Children benefit receipt) and census-tract level as well as preterm (< 37 weeks gestation) and small-for-gestational-age (SGA) (i.e., < 10th percentile of sex-specific birth weight for gestational age) birth status, and assessed inflammatory markers (i.e., C-reactive protein, serum amyloid p, haptoglobin, and α-2 macroglobulin) in archived neonatal bloodspots from a Michigan population-based cohort of 1000 neonates. Continuous latent variables measuring individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage were constructed and latent profile analysis was used to create a categorical inflammatory response variable (high versus low) based on continuous inflammatory marker levels. Structural equation models were used to estimate the total and direct effect of prenatal socioeconomic disadvantage on the inflammatory response at birth as well as indirect effect via preterm or SGA birth (among term neonates only), adjusting for mother's age, race/ethnicity, body mass index, smoking status, comorbidities, and antibiotic use/infection as well as grandmother's education level. There was a statistically significant total effect of both individual- and combined individual- and neighborhood-level prenatal socioeconomic disadvantage on high inflammatory response among all neonates as well as among term neonates only, and a positive but not statistically significant direct effect in both groups. The indirect effects via preterm and SGA birth were both negative, but not statistically significant. Our findings suggest prenatal socioeconomic disadvantage contributes to elevated neonatal inflammatory response, but via pathways outside of these adverse birth outcomes.