Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

Marshall Joffe's Contributions to Causal Inference, Biostatistics, and Epidemiology.

We pay tribute to Marshall Joffe, PhD, and his substantial contributions to the field of causal inference with focus in biostatistics and epidemiology. By compiling narratives written by us, his colleagues, we not only present highlights of Marshall's research and their significance for causal inference but also offer a portrayal of Marshall's personal accomplishments and character. Our discussion of Marshall's research notably includes (but is not limited to) handling of posttreatment variables such as noncompliance, employing G-estimation for treatment effects on failure-time outcomes, estimating effects of time-varying exposures subject to time-dependent confounding, and developing a causal framework for case-control studies. We also provide a description of some of Marshall's unpublished work, which is accompanied by a bonus anecdote. We discuss future research directions related to Marshall's research. While Marshall's impact in causal inference and the world outside of it cannot be wholly captured by our words, we hope nonetheless to present some of what he has done for our field and what he has meant to us and to his loved ones.

Learning Optimal Dynamic Treatment Regimes from Longitudinal Data.

Studies often report estimates of the average treatment effect (ATE). While the ATE summarizes the effect of a treatment on average, it does not provide any information about the effect of treatment within any individual. A treatment strategy that uses an individual's information to tailor treatment to maximize benefit is known as an optimal dynamic treatment rule (ODTR). Treatment, however, is typically not limited to a single point in time; consequently, learning an optimal rule for a time-varying treatment may involve not just learning the extent to which the comparative treatments' benefits vary across the characteristics of individuals, but also learning the extent to which the comparative treatments' benefits vary as relevant circumstances evolve within an individual. The goal of this paper is to provide a tutorial for estimating ODTR from longitudinal observational and clinical trial data for applied researchers. We describe an approach that uses a doubly-robust unbiased transformation of the conditional average treatment effect. We then learn a time-varying ODTR for when to increase buprenorphine-naloxone (BUP-NX) dose to minimize return-to-regular-opioid-use among patients with opioid use disorder. Our analysis highlights the utility of ODTRs in the context of sequential decision making: the learned ODTR outperforms a clinically defined strategy.

Disease activity trajectories in juvenile dermatomyositis from childhood to adulthood.

OBJECTIVES: To assess whether there are identifiable subgroups of disease activity trajectory in a population of juvenile dermatomyositis (JDM) patients-followed throughout childhood and into adulthood-and determine factors that predict those trajectory groupings. METHODS: This is a retrospective, longitudinal inception cohort of patients with idiopathic inflammatory myopathies, largely JDM. We sought to identify baseline factors that predict membership into different groups (latent classes) of disease activity trajectory. RESULTS: A total of 172 patients (64% females), with median age at diagnosis of 7.7 years, were analyzed. We studied 4,725 visits (1,471 patient-years). We identified 3 latent classes of longitudinal disease activity, as measured by the modified disease activity score (DASm), with distinct class trajectories predicted by DASm at baseline, and by the changes of DASm from either baseline to 3 months or baseline to 6 months (early response to therapy). In the analysis in which DASm at baseline and the changes of DASm from baseline to 6 months are included as predictors, Class 1 (10%) has persistently high disease activity, Class 2 (34%) is characterized by moderate disease activity, and Class 3 (56%) is characterized by individuals with a high early disease activity but an apparently good response to treatment and long-term low disease activity. CONCLUSION: High early disease activity, and treatment resistance in the first few months, predict a more chronic longitudinal course of JDM.

Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

Within-individual relationships between mother-to-infant bonding and postpartum depressive symptoms: a longitudinal study.

BACKGROUND: Although the importance of the dynamic intra-individual relationship between mother-to-infant bonding and postpartum depressive symptoms has been widely recognized, the complex interplay between them is not well understood. Furthermore, the potential role of prenatal depressive symptoms and infant temperament in this relationship remains unclear. This study aims to examine the bidirectional influence of mother-to-infant bonding on postpartum depressive symptoms within individuals and to elucidate whether prenatal depressive symptoms and infant temperament would influence deviations from stable individual states. METHODS: Longitudinal data were collected from 433 women in early pregnancy. Of these, 360 participants completed the main questionnaires measuring impaired mother-to-infant bonding and postpartum depressive symptoms at least once during the postpartum period. Data were collected at early and late pregnancy and several postpartum time points: shortly after birth and at one, four, ten, and 18 months postpartum. We also assessed prenatal depressive symptoms and infant temperament. A random-intercept cross-lagged panel model was used. RESULTS: Within-individual variability in mother-to-infant bonding, especially anger and rejection, significantly predicted subsequent postpartum depressive symptoms. However, the inverse relationship was not significant. Additionally, prenatal depressive symptoms and difficult infant temperament were associated with greater within-individual variability in impaired mother-to-infant bonding and postpartum depressive symptoms. CONCLUSIONS: The present study demonstrated that the within-individual relationship between mother-to-infant bonding and postpartum depressive symptoms is likely non-bidirectional. The significance of the findings is underscored by the potential for interventions aimed at improving mother-to-infant bonding to alleviate postpartum depressive symptoms, suggesting avenues for future research and practice.

Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study.

INTRODUCTION: Cognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. METHODS: Fifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. RESULTS: BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. CONCLUSIONS: We found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Impulsivity as key bridge symptoms in cross-sectional and longitudinal networks of ADHD and ODD.

BACKGROUND: Impulsivity is viewed as key to attention-deficit/hyperactivity disorder (ADHD) and disruptive behavior disorders (DBD). Yet, to date, no work has provided an item-level analysis in longitudinal samples across the critical developmental period from childhood into adolescence, despite prior work suggesting items exhibit differential relevance with respect to various types of impairment. The current study conducted a novel longitudinal network analysis of ADHD and oppositional defiant disorder (ODD) symptoms between childhood and adolescence, with the important applied prediction of social skills in adolescence. METHODS: Participants were 310 children over-recruited for clinical ADHD issues followed longitudinally for six years in total with gold standard diagnostic procedures and parent and teacher ratings of symptoms and social outcomes. RESULTS: Findings from baseline, Year 3, and Year 6 suggested Difficulty waiting turn, Blurts, and Interrupts/intrudes were key bridge items across cross-sectional and longitudinal parent-reported DBD networks. Furthermore, shortened symptom lists incorporating these symptoms were stronger predictors of teacher-rated social skills 5 years later compared to total DBD scores. CONCLUSIONS: Such findings are consistent with the trait impulsivity theory of DBD and ADHD and may inform useful screening tools and personalized intervention targets for children at risk for DBD during adolescence.

Testing the interpersonal theory of suicide in adolescents: A multi-wave longitudinal study.

BACKGROUND: Suicide is a major public health crisis among youth. Several prominent theories, including the Interpersonal Theory of Suicide (IPTS), aim to characterize the factors leading from suicide ideation to action. These theories are largely based on findings in adults and require testing and elaboration in adolescents. METHODS: Data were examined from high-risk 13-18-year-old adolescents (N = 167) participating in a multi-wave, longitudinal study; 63% of the sample exhibited current suicidal thoughts or recent behaviors (n = 105). The study included a 6-month follow-up period with clinical interviews and self-report measures at each of the four assessments as well as weekly smartphone-based assessments of suicidal thoughts and behaviors. Regression and structural equation models were used to probe hypotheses related to the core tenets of the IPTS. RESULTS: Feelings of perceived burdensomeness were associated with more severe self-reported suicidal ideation (b = 0.58, t(158) = 7.64, p < .001). Similarly, burdensomeness was associated with more frequent ideation based on weekly smartphone ratings (b = 0.11, t(1460) = 3.41, p < .001). Contrary to IPTS hypotheses, neither feelings of thwarted belongingness, nor interactions between burdensomeness and thwarted belongingness were significantly associated with ideation (ps > .05). Only elevated depression severity was associated with greater odds of suicide events (i.e., suicide attempts, psychiatric hospitalizations, and/or emergency department visits for suicide concerns) during the follow-up period (OR = 1.83, t(158) = 2.44, p = .01). No effect of acquired capability was found. CONCLUSIONS: Perceptions of burdensomeness to others reflect a critical risk factor for suicidal ideation among high-risk adolescents. Null findings with other IPTS constructs may suggest a need to adopt more developmentally sensitive models or measures of interpersonal and acquired capability risk factors for youth. Refining methods and theoretical models of suicide risk may help improve the identification of high-risk cases and inform clinical intervention.

Detecting adolescent depression through passive monitoring of linguistic markers in smartphone communication.

BACKGROUND: Cross sectional studies have identified linguistic correlates of major depressive disorder (MDD) in smartphone communication. However, it is unclear whether monitoring these linguistic characteristics can detect when an individual is experiencing MDD, which would facilitate timely intervention. METHODS: Approximately 1.2 million messages typed into smartphone social communication apps (e.g. texting, social media) were passively collected from 90 adolescents with a range of depression severity over a 12-month period. Sentiment (i.e. positive vs. negative valence of text), proportions of first-person singular pronouns (e.g. 'I'), and proportions of absolutist words (e.g. 'all') were computed for each message and converted to weekly aggregates temporally aligned with weekly MDD statuses obtained from retrospective interviews. Idiographic, multilevel logistic regression models tested whether within-person deviations in these linguistic features were associated with the probability of concurrently meeting threshold for MDD. RESULTS: Using more first-person singular pronouns in smartphone communication relative to one's own average was associated with higher odds of meeting threshold for MDD in the concurrent week (OR = 1.29; p = .007). Sentiment (OR = 1.07; p = .54) and use of absolutist words (OR = 0.99; p = .90) were not related to weekly MDD. CONCLUSIONS: Passively monitoring use of first-person singular pronouns in adolescents' smartphone communication may help detect MDD, providing novel opportunities for early intervention.

Developmental trajectories of child and adolescent emotional problems: associations with early adult alcohol use behaviors.

BACKGROUND: Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co-occurring conduct problems, developmental change/timing, sex differences, and potential confounds. METHODS: Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self-reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol-related problems) were self-reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences. RESULTS: Emotional problems had different associations with alcohol-related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol-related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males. CONCLUSIONS: Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex- and age-specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms.

Health, behavior, and social outcomes among offspring of parents with criminal convictions: a register-based study from Sweden.

BACKGROUND: There is currently insufficient understanding of the health and behavior of children whose parents engage in criminal behavior. We examined associations between parental criminal convictions and wide range of offspring health, behavioral, and social outcomes by age 18 in a large, national sample, aiming to get a comprehensive picture of the risks among children of offending parents. METHODS: We studied 1,013,385 individuals born in Sweden between 1987 and 1995, and their parents. Using data from several longitudinal nationwide registers, we investigated parental convictions and 85 offspring outcomes until the end of 2013, grouped into birth-related conditions, psychiatric and somatic disorders, accidents and injuries, mortality, school achievement, violent victimization, and criminality. Cox proportional hazards regression and logistic regression models were used to examine the associations. The role of genetic factors in intergenerational associations was studied in children-of-siblings analyses. We also examined the co-occurrence of multiple outcomes using Poisson regression. RESULTS: A total of 223,319 (22.0%) individuals had one parent convicted and 31,241 (3.1%) had both parents convicted during the first 18 years of their life. The strongest associations were found between parental convictions and offspring behavioral problems, substance use disorders, poor school achievement, violent victimization, and criminality, with an approximately 2 to 2.5-fold increased risk in children with one convicted parent and 3- to 4-fold increased risk in children with two convicted parents. The risks were particularly elevated among children of incarcerated parents with a history of violent convictions. The associations appeared to be at least partly explained by genetic influences. Parental convictions were also associated with an increased likelihood of experiencing multiple outcomes. CONCLUSIONS: Our findings help to calibrate the risks of a wide range of adverse outcomes associated with parental convictions and may be used to guide prevention efforts and identify key areas for future research.

Age effects on autism heritability and etiological stability of autistic traits.

BACKGROUND: Autism and autistic traits onset in childhood but persist into adulthood. Little is known about how genetic and environmental factors influence autism and autistic traits into adulthood. We aimed to determine age effects on the heritability of clinically diagnosed autism and the etiological stability of autistic traits from childhood to adulthood using twin methods. METHODS: From 23,849 twin pairs in the Swedish Twin Register born between 1959 and 2010, we identified 485 individuals (1.01%, 31.5% female) with a clinical autism diagnosis. We estimated and compared the relative contribution of genetic, shared, and nonshared environmental influences to autism in childhood and adulthood. We further used multivariate twin analysis with four measurement points among 1,348 twin pairs in the longitudinal Twin Study of Child and Adolescent Development to assess the phenotypic and etiological stability of autistic traits - measured with three scales from the Child Behavior Checklist - from childhood to adulthood. RESULTS: Autism heritability was comparable from childhood, (96% [95% CI, 76-99%]) to adulthood (87% [67-96%]). Autistic traits were moderately stable (phenotypic correlation = 0.35-0.61) from childhood to adulthood, and their heritability varied between 52 and 71%. We observed stable as well as newly emerging genetic influences on autistic traits from ages 8-9 to 19-20, and unique nonshared environmental influences at each age. CONCLUSIONS: Genetic factors are important for autism and autistic traits in adulthood and separate genetic studies in adults are warranted.

Concurrent and prospective associations between family socioeconomic status, social support and salivary diurnal and hair cortisol in adolescence.

BACKGROUND: Exposure to socioeconomic adversity is hypothesized to impact hypothalamic-pituitary-adrenal (HPA) axis activity and cortisol secretion, but existing evidence is inconsistent. Yet, few studies have investigated this association using a developmental approach that considers potential protective contextual factors. This study examined the role of stability and changes in family socioeconomic status (SES) in the prediction of multiple cortisol indicators and tested whether social support moderated these associations. METHODS: Participants were part of a population-based sample of twin pairs recruited at birth. Family SES was assessed in early childhood (ages 0-5) and mid-adolescence (age 14). Social support was assessed at ages 14 and 19. Diurnal cortisol (n = 569) was measured at age 14 at awakening, 30 min later, in the afternoon and evening over four non-consecutive days. Hair cortisol concentration (HCC, n = 704) was measured at age 19. All data were collected before the pandemic and multilevel regression models were conducted to account for the nested data structure. RESULTS: Youth exposed to lower family SES levels in childhood and mid-adolescence had a flatter diurnal slope and higher HCC compared with those who experienced upward socioeconomic mobility in mid-adolescence. Contrastingly, mid-adolescence SES showed no association with the diurnal slope or HCC for youth from higher-SES households in early childhood. Moreover, youth raised in higher-SES families in early childhood had a higher CAR in mid-adolescence if they reported greater social support in mid-adolescence. Social support also moderated the SES-cortisol association in mid-adolescence, with higher-SES youth showing higher awakening cortisol secretion when reporting more social support. CONCLUSIONS: Our findings support the hypothesis that early socioeconomic adversity sensitizes HPA axis activity to later socioeconomic disadvantage, which may bear consequences for socioemotional and behavioral functioning.

Changes in employment status over time in multiple sclerosis following a first episode of central nervous system demyelination, a Markov multistate model study.

BACKGROUND AND PURPOSE: Understanding predictors of changes in employment status among people living with multiple sclerosis (MS) can assist health care providers to develop appropriate work retention/rehabilitation programs. We aimed to model longitudinal transitions of employment status in MS and estimate the probabilities of retaining employment status or losing or gaining employment over time in individuals with a first clinical diagnosis of central nervous system demyelination (FCD). METHODS: This prospective cohort study comprised adults (aged 18-59 years) diagnosed with FCD (n = 237) who were followed for more than 11 years. At each review, participants were assigned to one of three states: unemployed, part-time, or full-time employed. A Markov multistate model was used to examine the rate of state-to-state transitions. RESULTS: At the time of FCD, participants with full-time employment had an 89% chance of being in the same state over a 1-year period, but this decreased to 42% over the 10-year follow-up period. For unemployed participants, there was a 92% likelihood of remaining unemployed after 1 year, but this probability decreased to 53% over 10 years. Females, those who progressed to clinically definite MS, those with a higher relapse count, and those with a greater level of disability were at increased risk of transitioning to a deteriorated employment state. In addition, those who experienced clinically significant fatigue over the follow-up period were less likely to gain employment after being unemployed. CONCLUSIONS: In our FCD cohort, we found a considerable rate of employment transition during the early years post-diagnosis. Over more than a decade of follow-up post-FCD, we found that females and individuals with a greater disability and a higher relapse count are at higher risk of losing employment.

Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort.

BACKGROUND: The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). METHODS: Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSA-Brasil (2008-2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017-2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models. RESULTS: Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05-1.38). CONCLUSIONS: Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups.

First implantable cardiac defibrillator insertions in New South Wales, 2005-2020: an analysis of linked administrative data.

OBJECTIVES: To determine the annual numbers of first ICD insertions in New South Wales during 2005-2020; to examine health outcomes for people who first received ICDs during this period. STUDY DESIGN: Retrospective cohort study; analysis of linked administrative health data. SETTING, PARTICIPANTS: All first insertions of ICDs in NSW, 2005-2020. MAIN OUTCOME MEASURES: Annual numbers of first ICD insertions, and of emergency department presentations and hospital re-admissions 30 days, 90 days, 365 days after first ICD insertions; all-cause and disease-specific mortality (to ten years after ICD insertion). RESULTS: During 2005-2020, ICDs were first inserted into 16 867 people (18.5 per 100 000 population); their mean age was 65.7 years (standard deviation, 13.5 years; 7376 aged 70 years or older, 43.7%), 13 214 were men (78.3%). The annual number of insertions increased from 791 in 2005 to 1256 in 2016; the first ICD insertion rate increased from 15.5 in 2005 to 18.9 per 100 000 population in 2010, after which the rate was stable until 2019 (19.8 per 100 000 population). Of the 16 778 people discharged alive from hospital after first ICD insertions, 54.4% presented to emergency departments within twelve months, including 1236 with cardiac arrhythmias (7.4%) and 434 with device-related problems (2.6%); 56% were re-admitted to hospital, including 1944 with cardiac arrhythmias (11.5%) and 2045 with device-related problems (12.1%). A total of 5624 people who received first ICDs during 2005-2020 (33.3%) died during follow-up (6.7 deaths per 100 person-years); the survival rate was 94.4% at one year, 76.5% at five years, and 54.2% at ten years. CONCLUSIONS: The annual number of new ICDs inserted in NSW has increased since 2005. A substantial proportion of recipients experience device-related problems that require re-admission to hospital. The potential harms of ICD insertion should be considered when assessing the likelihood of preventing fatal ventricular arrhythmia.

Estimating impacts of reducing acrylonitrile exposure on lung cancer mortality in an occupational cohort with the parametric g-formula.

OBJECTIVES: To inform the potential human carcinogenicity of acrylonitrile, we estimate associations between acrylonitrile exposures and lung cancer mortality in US workers with the objectives of (1) assessing potential for healthy worker survivor bias and (2) adjusting for this bias while assessing the expected lung cancer mortality under different hypothetical occupational exposure limits on acrylonitrile exposure using the parametric g-formula. METHODS: We used data from a cohort of 25 460 workers at facilities making or using acrylonitrile in the USA. We estimated HRs to quantify associations between employment and lung cancer mortality, and exposure and leaving employment. Using the parametric g-formula, we estimated cumulative lung cancer mortality at hypothetical limits on acrylonitrile exposure. RESULTS: Recent and current employment was associated with lung cancer, and exposure was associated with leaving employment, indicating potential for healthy worker survivor bias. Relative to no intervention, reducing the historical exposure under limits of 2.0, 1.0 and 0.45 parts per million would have been expected to reduce lung cancer mortality by age 90 by 4.46 (95% CI 0.78 to 8.15), 5.03 (95% CI 0.96 to 9.11) and 6.45 (95% CI 2.35 to 10.58) deaths per 1000 workers, respectively. A larger lung cancer mortality reduction would be expected under elimination of exposure: 7.21 (95% CI 2.72 to 11.70) deaths per 1000 workers. CONCLUSIONS: Healthy worker survivor bias likely led to underestimation of excess risk. Our results corroborate previous study findings of an excess hazard of lung cancer among the highest exposed workers.