Objective: Although life stress and adversity have emerged as risk factors for mental health problems and cognitive impairment among older adults, prior studies on this topic have been cross-sectional and based on relatively homogeneous samples. To address these issues, we examined prospective associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in a nationally representative, longitudinal sample of older adults in the U.S. Method: We analyzed data from the Health and Retirement Study (1992-2016). The sample included 3,496 individuals (59.9% female), aged ≥64 years old (M age=76.0 ±7.6 years). We used the individual-level panel data and ordinary least squares regressions to estimate associations between childhood and adulthood adversities and later-life depression, anxiety, and cognitive impairment. Results: Many participants experienced a significant early life (38%) or adulthood (79%) stressor. Second, experiencing a childhood adversity was associated with a 17.4% increased risk of experiencing an adulthood adversity. Finally, childhood and adulthood adversities both prospectively predicted more symptoms of late-life depression, anxiety, and cognitive impairment. Discussion: These findings are among the first to demonstrate prospective associations between lifetime adversity and symptoms of depression, anxiety, and cognitive impairment in older adults. Screening for lifetime stressors may thus help health care professionals and policymakers identify individuals who could benefit from interventions designed to reduce stress and enhance resilience.

Introduction Real-world data on Omalizumab (OMA) and Mepolizumab (MEPO) can inform their use in severe asthma (SA). We studied patients in the Wessex AsThma CoHort of difficult asthma (WATCH) to: 1. Phenotypically compare OMA or MEPO treated patients against a SA, non-biologic group (SNB). 2. Assess clinical responses to OMA and MEPO. 3. Assess the spectrum of responses to these biologics. Methods We retrospectively phenotyped biologic naïve patients from WATCH (N=478) commenced on OMA (N=105) or MEPO (N=62) compared to SNB (N=178). Biologic response was gauged using standard criteria and response features were identified using logistic regression. Results OMA and MEPO patients were phenotypically distinct. Both drugs significantly reduced exacerbations, acute healthcare encounters (emergency department or hospital admissions), maintenance oral corticosteroid dose, and improved Asthma Control Questionnaire 6 (ACQ6) scores. OMA patients with more exacerbations at baseline (P=0.024), less acute healthcare encounters (P=0.050), and no anxiety (P=0.008) were more likely to respond to it. Lower baseline ACQ6 was independently associated with higher odds of MEPO response (P=0.007). Combined (OMA or MEPO) non-responders had significantly more psychological co-morbidities and worse baseline subjective disease markers compared to responder groups. Current criteria used to measure trial outcomes for MEPO, but not OMA, missed some modalities of response. Conclusion In a difficult asthma cohort, OMA and MEPO were used for distinct SA phenotypes, yet both were multidimensionally efficacious. Among these phenotypes, some clinical features associated with response were identified which emphasized the importance of addressing treatable traits when considering biologic therapy.

Background It has been hypothesized that epigenomic modifications such as genomic methylation changes are an intermediate step linking environmental exposures with allergic disease development. Associations between individual DNA methylation CpG sites and allergic diseases have been reported, but they have not been assessed regarding their joint predictive capability. Methods Data were obtained from 240 children of the German LISA cohort. Blood-based DNA methylation was measured at six and ten years. Aeroallergen sensitization, at least RAST class 1, was measured in blood at six, ten and 15 years. We calculated six methylation risk scores (MRS) for allergy-related phenotypes based on available publications and assessed their performance both cross-sectionally and prospectively. Dose-response associations between aeroallergen sensitization and MRS, their correlation and mapping of common hits were evaluated. Results All six atopy-related MRS were highly correlated (r>0.86) and seven CpGs were included in more than one MRS. Cross-sectionally, we observed an 80% increased risk for aeroallergen sensitization at six years with an increased risk score by one standard deviation (best MRS: relative risk = 1.81, 95% confidence interval = [1.43; 2.27]). Significant associations were also seen at ten years and in prospective models, though the effect of the latter was attenuated when only including participants not sensitized at baseline. A clear dose-response relationship with RAST classes of aeroallergen sensitization could be established cross-sectionally, but not prospectively. Conclusion We found good classification and prediction capabilities of calculated allergy-related MRS, particularly cross-sectionally for the allergy prevalence, underlining the relevance of altered gene-regulation in allergic diseases.