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BackgroundParticipation and active engagement in meaningful activities support the emotional and physical well-being of older adults. In 2020, the onset of the COVID-19 pandemic altered lives, including the ability to participate in meaningful activities. This study compared meaningful activity engagement before and at the beginning of the COVID-19 pandemic in a nationally representative, diverse sample >65 years between 2015 and 2020.MethodsWe described the proportions and characteristics of National Health and Aging Trends Study participants and their engagement in four activities: visiting friends or family, attending religious services, participating in clubs/classes/other organized activities, and going out for enjoyment. We used mixed effects logistic regressions to compare probabilities of activity engagement before 2020 and in 2020, adjusting for age, sex, functional status, income, geographic region, anxiety-depression, and transportation issues.ResultsOf 6815 participants in 2015, the mean age was 77.7 (7.6) years; 57% of participants were female; 22% were Black, 5% Hispanic, 2% were American Indian, and 1% were Asian; 20% had disability; and median income was $33,000. Participation in all four activities remained consistent between 2015 and 2019 and declined in 2020. Significant differences existed in attending religious services (p

Background: Racial and ethnic minoritized people with dementia (PWD) are at high risk of disenrollment from hospice, yet little is known about the relationship between hospice quality and racial disparities in disenrollment among PWD. Objective: To assess the association between race and disenrollment between and within hospice quality categories in PWD. Design/Setting/Subjects: Retrospective cohort study of 100% Medicare beneficiaries 65+ enrolled in hospice with a principal diagnosis of dementia, July 2012-December 2017. Race and ethnicity (White/Black/Hispanic/Asian and Pacific Islander [AAPI]) was assessed with the Research Triangle Institute (RTI) algorithm. Hospice quality was assessed with the publicly-available Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey item on overall hospice rating, including a category for hospices exempt from public reporting (unrated). Results: The sample included 673,102 PWD (mean age 86, 66% female, 85% White, 7.3% Black, 6.3% Hispanic, 1.6% AAPI) enrolled in 4371 hospices nationwide. Likelihood of disenrollment was higher in hospices in the lowest quartile of quality ratings (vs. highest quartile) for both White (adjusted odds ratio [AOR] 1.12 [95% confidence interval 1.06-1.19]) and minoritized PWD (AOR range 1.2-1.3) and was substantially higher in unrated hospices (AOR range 1.8-2.0). Within both low- and high-quality hospices, minoritized PWD were more likely to be disenrolled compared with White PWD (AOR range 1.18-1.45). Conclusions: Hospice quality predicts disenrollment, but does not fully explain disparities in disenrollment for minoritized PWD. Efforts to improve racial equity in hospice should focus both on increasing equity in access to high-quality hospices and improving care for racial minoritized PWD in all hospices.

IntroductionFunctional outcomes during non-small cell lung cancer (NSCLC) treatment are critically important to older adults. Yet, data on physical function and which measures best capture functional change remain limited.Materials and methodsThis multisite, mixed methods cohort study recruited adults ≥65 years with advanced NSCLC starting systemic treatment (i.e., chemotherapy, immunotherapy, and/or targeted therapy) with non-curative intent. Participants underwent serial geriatric assessments prior to starting treatment and at one, two, four, and six months, which included the Karnofsky Performance Scale (KPS, range: 0-100%), instrumental activities of daily living (IADL, range: 0-14), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Physical Functioning subscale (EORTC QLQ-C30 PF, range: 0-100), and Life-Space Assessment (LSA, range: 0-120). For all measures, higher scores represent better functioning. In a qualitative substudy, 20 patients completed semi-structured interviews prior to starting treatment and at two and six months to explore how treatment affected their daily functioning. We created joint displays for each interview participant that integrated their longitudinal KPS, IADL, EORTC QLQ-C30 PF, and LSA scores with patient quotes describing their function.ResultsAmong 87 patients, median age was 73 years (range 65-96). Mean pretreatment KPS score was 79% (standard deviation [SD] 13), EORTC QLQ-C30 PF was 69 (SD 23), and LSA was 67 (SD 28); median IADL was 13 (interquartile range [IQR] 10-14). At two months after treatment initiation, 70% of patients experienced functional decline on at least one measure, with only 13% of these patients recovering at six months. At two and six months, decline in LSA was the most common (48% and 35%, respectively). Joint displays revealed heterogeneity in how well each quantitative measure of physical function captured the qualitative patient experience.DiscussionFunctional decline during NSCLC treatment is common among older adults. LSA is a useful measure to detect subtle functional decline that may be missed by other measures. Given heterogeneity in how well each quantitative measure captures changes in physical function, there is value to including more than one functional measure in geriatric oncology research studies.

ObjectivesTo examine how people living with dementia at home engage in meaningful activities, a critical component of quality of life.DesignEthnographic study design using semistructured interviews, participant-observation, and ethnographic analysis.Setting and participantsHome setting. People living with dementia were recruited through 3 geriatrics programs in the San Francisco Bay Area, along with 1 primary live-in care partner for each. Participants were purposively sampled to maximize heterogeneity of dementia severity and life experience.MeasurementsWe asked participants to self-identify and report meaningful activity engagement prior to dementia onset and during the study period using a structured questionnaire, semistructured dyadic interviews, and observed engagement in activities. Home visits were audio-recorded, transcribed, and inductively analyzed using thematic analysis.ResultsTwenty-one people living with dementia (mean age 84 years, 38% women) and 20 care partners (59 years, 85% women), including 40% professionals, 35% spouse/partners, and 15% adult children. Overarching theme: specific activities changed over time but underlying sources of meaning and identity remained stable. As dementia progressed, meaningful activity engagement took 3 pathways. Pathway 1: Activities continued with minimal adaptation when engagement demanded little functional or cognitive ability (eg, watching football on TV). Pathway 2: care partners adapted or replaced activities when engagement required greater functional or cognitive abilities (eg, traveling overseas). This pathway was associated with caregiving experience, nursing training, and strong social support structures. Pathway 3: care partners discontinued meaningful activity engagement. Discontinuation was associated with severe caregiver burden, coupled with illness, injury, or competing caregiving demands severe enough to impact their ability to facilitate activities.Conclusions and implicationsFor people living with dementia at home, underlying sources of meaning and identity remains stable despite changes in meaningful activity engagement. Many of the factors associated with adaptation vs discontinuation over time are modifiable and can serve as targets for intervention.

BackgroundOlder adults are increasingly admitted to the ICU, and those with disabilities, dementia, frailty, and multimorbidity are vulnerable to adverse outcomes. Little is known about how pre-existing geriatric conditions have changed over time.Research questionHow have changes in disability, dementia, frailty, and multimorbidity in older adults admitted to the ICU changed from 1998 through 2015?Study design and methodsMedicare-linked Health and Retirement Survey (HRS) data identifying patients 65 years of age and older admitted to an ICU between 1998 and 2015. ICU admission was the unit of analysis. Year of ICU admission was the exposure. Disability, dementia, frailty, and multimorbidity were identified based on responses to HRS surveys before ICU admission. Disability represented the need for assistance with ≥ 1 activity of daily living. Dementia used cognitive and functional measures. Frailty included deficits in ≥ 2 domains (physical, nutritive, cognitive, or sensory function). Multimorbidity represented ≥ 3 self-reported chronic diseases. Time trends in geriatric conditions were modeled as a function of year of ICU admission and were adjusted for age, sex, race or ethnicity, and proxy interview status.ResultsAcross 6,084 ICU patients, age at admission increased from 77.6 years (95% CI, 76.7-78.4 years) in 1998 to 78.7 years (95% CI, 77.5-79.8 years) in 2015 (P < .001 for trend). The adjusted proportion of ICU admissions with pre-existing disability rose from 15.5% (95% CI, 12.1%-18.8%) in 1998 to 24.0% (95% CI, 18.5%-29.6%) in 2015 (P = .001). Rates of dementia did not change significantly (P = .21). Frailty increased from 36.6% (95% CI, 30.9%-42.3%) in 1998 to 45.0% (95% CI, 39.7%-50.2%) in 2015 (P = .04); multimorbidity rose from 54.4% (95% CI, 49.2%-59.7%) in 1998 to 71.8% (95% CI, 66.3%-77.2%) in 2015 (P < .001).InterpretationRates of pre-existing disability, frailty, and multimorbidity in older adults admitted to ICUs increased over time. Geriatric principles need to be deeply integrated into the ICU setting.

BackgroundUnderstanding life expectancy can help persons with dementia, their care partners, and policymakers plan for what lies ahead. We sought to determine life expectancy and predictors of mortality for community-dwelling persons with dementia and severe disability.MethodsUsing the National Health and Aging Trends Study (NHATS) linked to Medicare claims, we identified community-dwelling respondents age 65+ who entered NHATS in 2011 with dementia and severe disability (defined as three impairments in activities of daily living), or who subsequently met criteria for dementia and then severe disability. We estimated time to death based on the timing of meeting severe disability criteria. We conducted parametric survival analyses using a Gompertz distribution to calculate risk of death and predicted median time to death. Predictors included demographic, functional, clinical characteristics, and behavioral symptoms (assessed among NHATS respondents with proxy interviews).ResultsAmong 842 community-dwelling persons with dementia and severe disability, 80.5% died during the study period. After adjusting for age and gender, overall predicted median time to death was 1.7 years (25th percentile 0.6, 75th percentile 3.8 years). Six notable characteristics were associated with shorter life expectancy: 1) older age (90+), with a predicted median time to death of 1.0 year (0.4, 2.1); 2) being bedbound, 1.1 years (0.4, 2.3); 3) being homebound, 1.2 years (0.5, 2.6); 4) having comorbid cancer, 1.2 years (0.5, 2.6); 5) unintended weight loss, 1.4 years (0.5, 3.1); and 6) comorbid depression, 1.5 years (0.6, 3.3).ConclusionsCommunity-dwelling persons with dementia and severe disability lived a median of 1.7 years. Clinicians can use the study findings to provide anticipatory guidance to patients and care partners, and policymakers to inform design of longitudinal supportive services.

Studies of genome regulation routinely use high-throughput DNA sequencing approaches to determine where specific proteins interact with DNA, and they rely on DNA amplification and short-read sequencing, limiting their quantitative application in complex genomic regions. To address these limitations, we developed directed methylation with long-read sequencing (DiMeLo-seq), which uses antibody-tethered enzymes to methylate DNA near a target protein's binding sites in situ. These exogenous methylation marks are then detected simultaneously with endogenous CpG methylation on unamplified DNA using long-read, single-molecule sequencing technologies. We optimized and benchmarked DiMeLo-seq by mapping chromatin-binding proteins and histone modifications across the human genome. Furthermore, we identified where centromere protein A localizes within highly repetitive regions that were unmappable with short sequencing reads, and we estimated the density of centromere protein A molecules along single chromatin fibers. DiMeLo-seq is a versatile method that provides multimodal, genome-wide information for investigating protein-DNA interactions.

BackgroundThe effects of extracranial hemorrhage (ECH), or bleeding outside the brain, are often considered transient. Yet, there are few data on the long-term and functional consequences of ECH.ObjectiveDefine the association of ECH hospitalization with functional independence and survival in a nationally representative cohort of older adults.DesignLongitudinal cohort study.Settings and participantsData from the Health and Retirement Study from 1995 to 2016, a nationally representative, biennial survey of older adults. Adults aged 66 and above with Medicare linkage and at least 12 months of continuous Medicare Part A and B enrollment.InterventionHospitalization for ECH.Main outcomes and measuresAdjusted odds ratios and predicted likelihood of independence in all activities of daily living (ADLs), independence in all instrumental activities of daily living (IADLs) and extended nursing home stay. Adjusted hazard ratio and predicted likelihood for survival.ResultsIn a cohort of 6719 subjects (mean age 77, 59% women) with average follow-up time of 8.3 years (55,767 person-years), 736 (11%) were hospitalized for ECH. ECH was associated with a 15% increase in ADL disability, 15% increase in IADL disability, 8% increase in nursing home stays, and 4% increase in mortality. After ECH, subjects became disabled and died at the same annual rate as pre-ECH but never recovered to pre-ECH levels of function. In conclusion, hospitalization for ECH was associated with significant and durable declines in independence and survival. Clinical and research efforts should incorporate the long-term harms of ECH into decision-making and strategies to mitigate these effects.

Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment. A total of 429 subjects (858 samples across 2 time points) from three male military cohorts were included in the analyses. We conducted two different meta-analyses to answer two different scientific questions: one to identify a DNAm profile of PTSS using a random effects model including both time points for each subject, and the other to identify a DNAm profile of change in PTSS conditioned on pre-deployment DNAm. Four CpGs near four genes (F2R, CNPY2, BAIAP2L1, and TBXAS1) and 88 differentially methylated regions (DMRs) were associated with PTSS. Change in PTSS after deployment was associated with 15 DMRs, of those 2 DMRs near OTUD5 and ELF4 were also associated with PTSS. Notably, three PTSS-associated CpGs near F2R, BAIAP2L1 and TBXAS1 also showed nominal evidence of association with change in PTSS. This study, which identifies PTSD-associated changes in genes involved in oxidative stress and immune system, provides novel evidence that epigenetic differences are associated with PTSS.

ContextPhthalates may disrupt maternal-fetal-placental endocrine pathways, affecting pregnancy outcomes and child development. Placental corticotropin releasing hormone (pCRH) is critical for healthy pregnancy and child development, but understudied as a target of endocrine disruption.ObjectiveTo examine phthalate metabolite concentrations (as mixtures and individually) in relation to pCRH.DesignSecondary data analysis from a prospective cohort study.SettingPrenatal clinics in Tennessee, USA.Patients1018 pregnant women (61.4% non-Hispanic Black, 32% non-Hispanic White, 6.6% other) participated in the CANDLE study and provided data. Inclusion criteria included: low-medical-risk singleton pregnancy, age 16-40, and gestational weeks 16-29.InterventionNone.Main outcome measuresPlasma pCRH at two visits (mean gestational ages 23.0 and 31.8 weeks) and change in pCRH between visits (ΔpCRH).ResultsIn weighted quantile sums (WQS) regression models, phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.07, 95 %CI: 0.02, 0.11) but lower pCRH at Visit 2 (β = -0.08, 95 %CI: -0.14, -0.02). In stratified analyses, among women with gestational diabetes (n = 59), phthalate mixtures were associated with lower pCRH at Visit 1 (β = -0.17, 95 %CI: -0.35, 0.0006) and Visit 2 (β = -0.35, 95 %CI: -0.50, -0.19), as well as greater ΔpCRH (β = 0.16, 95 %CI: 0.07, 0.25). Among women with gestational hypertension (n = 102), phthalate mixtures were associated with higher pCRH at Visit 1 (β = 0.20, 95 %CI: 0.03, 0.36) and Visit 2 (β = 0.42; 95 %CI: 0.19, 0.64) and lower ΔpCRH (β = -0.17, 95 %CI: -0.29, -0.06). Significant interactions between individual phthalate metabolites and pregnancy complications were observed.ConclusionsPhthalates may impact placental CRH secretion, with differing effects across pregnancy. Differences in results between women with and without gestational diabetes and gestational hypertension suggest a need for further research examining whether women with pregnancy complications may be more vulnerable to endocrine-disrupting effects of phthalates.

BackgroundIn the United States, dementia specialty centers affiliated with centers of excellence for research hold promise as locations to develop innovative, holistic care in care systems otherwise siloed by discipline or payer.ObjectiveWe conducted foundational research to inform development of patient-and family-centered palliative care interventions for dementia specialty centers.MethodsWe interviewed persons living with dementia (PLWD), current, and former care partners (CP) recruited from a specialty dementia clinic and purposively selected for variation across disease syndrome and stage. A framework method of thematic analysis included coding, analytic matrices, and pattern mapping.Results40 participants included 9 PLWD, 16 current CPs, and 15 former CPs of decedents; 48% impacted by Alzheimer's disease dementia. While help from family, support groups and adult day centers, paid caregiving, and sensitive clinical care were invaluable to PLWD, CPs, or both, these supports were insufficient to navigate the extensive challenges. Disease-oriented sources of distress included symptoms, functional impairment and falls, uncertainty and loss, and inaccessible care. Social and relational challenges included constrained personal and professional opportunities. The obligation and toll of giving or receiving caregiving were challenging. Clinical care challenges for PLWD and/or CPs included care fragmentation, insufficient guidance to inform planning and need for expert interdisciplinary clinical care at home.ConclusionFindings highlight the breadth and gravity of gaps, which surpass the disciplinary focus of either behavioral neurology or palliative care alone. Results can inform the development of novel interventions to add principles of geriatrics and neuropalliative care to dementia care.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous endocrine-disrupting combustion by-products that have been linked to preterm birth. One possible mechanism is through disruption of placental corticotropin releasing hormone (pCRH), a key hormone implicated in parturition. As an extension of recent research identifying pCRH as a potential target of endocrine disruption, we examined maternal PAH exposure in relation to pCRH in a large, diverse sample. Participants, drawn from the CANDLE cohort, part of the ECHO-PATHWAYS Consortium, completed study visits at 16-29 weeks (V1) and 22-39 weeks (V2) gestation (n=812). Seven urinary mono-hydroxylated PAH metabolites (OH-PAHs) were measured at V1 and serum pCRH at V1 and V2. Associations between individual log-transformed OH-PAHs (as well as two summed PAH measures) and log(pCRH) concentrations across visits were estimated using mixed effects models. Minimally-adjusted models included gestational age and urinary specific gravity, while fully-adjusted models also included sociodemographic characteristics. We additionally evaluated effect modification by pregnancy complications, fetal sex, and maternal childhood trauma history. We observed associations between 2-OH-Phenanthrene (2-OH-PHEN) and rate of pCRH change that persisted in fully adjusted models (β=0.0009, 0.00006, 0.0017), however, positive associations with other metabolites (most notably 3-OH-Phenanthrene and 1-Hydroxypyrene) were attenuated after adjustment for sociodemographic characteristics. Associations tended to be stronger at V1 compared to V2 and we observed no evidence of effect modification by pregnancy complications, fetal sex, or maternal childhood trauma history. In conclusion, we observed modest evidence of association between OH-PAHs, most notably 2-OH-PHEN, and pCRH in this sample. Additional research using serial measures of PAH exposure is warranted, as is investigation of alternative mechanisms that may link PAHs and timing of birth, such as inflammatory, epigenetic, or oxidative stress pathways.

BackgroundMaintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown.MethodsThis mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA

BackgroundThe Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood.MethodsThis multicenter observational cohort study will enroll at least 600 patients

BackgroundParkinson's disease (PD) complexity poses challenges for individuals with Parkinson's, providers, and researchers. A recent multisite randomized trial of a proactive, telephone-based, nurse-led care management intervention - Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS) - demonstrated improved PD care quality. Implementation details and supportive stakeholder feedback were subsequently published. To inform decisions on dissemination, CHAPS Model components require evaluations of their fidelity to the Chronic Care Model and to their implementation. Additionally, assessment is needed on whether CHAPS addresses care challenges cited in recent literature.MethodsThese analyses are based on data from a subset of 140 intervention arm participants and other CHAPS data. To examine CHAPS Model fidelity, we identified CHAPS components corresponding to the Chronic Care Model's six essential elements. To assess implementation fidelity of these components, we examined data corresponding to Hasson's modified implementation fidelity framework. Finally, we identified challenges cited in current Parkinson's care management literature, grouped these into themes using open card sorting techniques, and examined CHAPS data for evidence that CHAPS met these challenges.ResultsAll Chronic Care Model essential elements were addressed by 17 CHAPS components, thus achieving CHAPS Model fidelity. CHAPS implementation fidelity was demonstrated by adherence to content, frequency, and duration with partial fidelity to telephone encounter frequency. We identified potential fidelity moderators for all six of Hasson's moderator types. Through card sorting, four Parkinson's care management challenge themes emerged: unmet needs and suggestions for providers (by patient and/or care partner), patient characteristics needing consideration, and standardizing models for Parkinson's care management. CHAPS activities and stakeholder perceptions addressed all these themes.ConclusionsCHAPS, a supportive nurse-led proactive Parkinson's care management program, improved care quality and is designed to be reproducible and supportive to clinicians. Findings indicated CHAPS Model fidelity occurred to the Chronic Care Model and fidelity to implementation of the CHAPS components was demonstrated. Current Parkinson's care management challenges were met through CHAPS activities. Thus, dissemination of CHAPS merits consideration by those responsible for implementing changes in clinical practice and reaching people in need.Trial registrationClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.

Predictions of xenobiotic hepatic clearance in humans using in vitro-to-in vivo extrapolation methods are frequently inaccurate and problematic. Multiple strategies are being pursued to disentangle responsible mechanisms. The objective of this work is to evaluate the feasibility of using insights gained from independent virtual experiments on two model systems to begin unraveling responsible mechanisms. The virtual culture is a software analog of hepatocytes in vitro, and the virtual human maps to hepatocytes within a liver within an idealized model human. Mobile objects (virtual compounds) map to amounts of xenobiotics. Earlier versions of the two systems achieved quantitative validation targets for intrinsic clearance (virtual culture) and hepatic clearance (virtual human). The major difference between the two systems is the spatial organization of the virtual hepatocytes. For each pair of experiments (virtual culture, virtual human), hepatocytes are configured the same. Probabilistic rules govern virtual compound movements and interactions with other objects. We focus on highly permeable virtual compounds and fix their extracellular unbound fraction at one of seven values (0.05-1.0). Hepatocytes contain objects that can bind and remove compounds, analogous to metabolism. We require that, for a subset of compound properties, per-hepatocyte compound exposure and removal rates during culture experiments directly predict corresponding measures made during virtual human experiments. That requirement serves as a cross-system validation target; we identify compound properties that enable achieving it. We then change compound properties, ceteris paribus, and provide model mechanism-based explanations for when and why measures made during culture experiments under- (or over-) predict corresponding measures made during virtual human experiments. The results show that, from the perspective of compound removal, the organization of hepatocytes within virtual livers is more efficient than within cultures, and the greater the efficiency difference, the larger the underprediction. That relationship is noteworthy because most in vitro-to-in vivo extrapolation methods abstract away the structural organization of hepatocytes within a liver. More work is needed on multiple fronts, including the study of an expanded variety of virtual compound properties. Nevertheless, the results support the feasibility of the approach and plan.

BackgroundEvidence-based interventions addressing loneliness and social isolation are needed, including among low-income, community-dwelling older adults of diverse racial and ethnic backgrounds. Our objective was to assess the effect of a peer intervention in addressing loneliness, isolation, and behavioral health needs in this population.MethodsWe conducted a mixed-method, two-year longitudinal study of a peer-outreach intervention in 74 low-income older adults recruited via an urban senior center in San Francisco. Structured participant surveys were conducted at baseline and every 6 months for up to 2 years. Outcomes included loneliness (3-item UCLA loneliness scale), social interaction (10-item Duke index), self-perceived socializing barriers (range: 0-10), and depression (PHQ-2 screen). Data were analyzed using mixed-effects linear and logistic regression adjusted for age and gender. Qualitative, semi-structured interviews with participants (N = 15) and peers (N = 6) were conducted in English and Spanish and analyzed thematically.ResultsParticipants were on average 71 years old (range: 59-96 years), with 58% male, 15% LGBT, 18% African American, 19% Latinx, 8% Asian, 86% living alone, and 36% with an ADL impairment. On average, 43 contact visits (IQR: 31-97 visits) between participants and peers occurred over the first year. Loneliness scores decreased by, on average, 0.8 points over 24 months (p = 0.015). Participants reported reduced depression (38%-16%, p

BackgroundBiological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.ResultsLeveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.ConclusionThis study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

ObjectiveTo determine the availability of palliative care programs in long-term acute care hospitals (LTACHs) DESIGN: Cross-sectional analysis using the 2016 American Hospital Association (AHA) Annual Survey.Setting and participantsLTACHs in the United States.MethodWe used descriptive analyses to compare the prevalence of palliative care programs in LTACHs across the United States in 2016. For LTACHs without a program, we also examined palliative care physician capacity in regions where those LTACHs resided to evaluate if expertise existed in those regions.ResultsOne-third (36.5%) of 405 LTACHs (50.6% response rate) self-reported having a palliative care program. Among LTACHs without palliative care, 42.4% were in regions with the highest palliative care physician capacity nationwide.Conclusions and implicationsLTACHs care for patients with serious and prolonged illnesses, many of whom would benefit from palliative care. Despite this, our study finds that specialty palliative care is limited in LTACHs. The limited palliative care availability in LTACHs is mismatched with the needs of this seriously ill population. Greater focus on increasing palliative care in LTACHs is essential and may be feasible as 40% of LTACHs without a palliative care program were located in regions with the highest palliative care physician capacity.

Background People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear. Methods and Results This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant's first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)-defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow-up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04-1.25), adjusting for possible confounders. In analyses with time-varying CD4 and HIV viral load, people living with HIV with CD4 counts 500 copies/mL (HR, 1.70; 95% CI, 1.46-1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts >500 cells/mm3 (HR, 1.03; 95% CI, 0.90-1.18) or HIV viral load

Cases of seroconversion on pre-exposure prophylaxis (PrEP) should be carefully investigated, given their public health implications and rarity. We report a case of transmitted drug resistance causing seroconversion on PrEP in spite of high adherence, confirmed with dried blood spot and segmental hair drug-level testing and single-genome sequencing.

BackgroundOlder adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability have not been previously characterized. Our objective was to determine long-term function among older adults with AF and the relative contribution of stroke.MethodsWe used data from the nationally representative Health and Retirement Study (1992-2014) with participants ≥65 years with incident AF. We examined the association of incident stroke with three outcomes: independence with activities of daily living (ADL), instrumental activities of daily living (IADL), and residence outside a nursing home (community-dwelling). We fit logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimated the contribution of strokes to the overall population burden of disability using the method of recycled predictions.ResultsAmong 3530 participants (median age 79 years, 53% women), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for comorbidities, annually, ADL independence decreased by 4.4%, IADL independence decreased by 3.9%, and community dwelling decreased by 1.2% (p

Background and objectiveMost methods for developing clinical prognostic models focus on identifying parsimonious and accurate models to predict a single outcome; however, patients and providers often want to predict multiple outcomes simultaneously. As an example, for older adults one is often interested in predicting nursing home admission as well as mortality. We propose and evaluate a novel predictor-selection computing method for multiple outcomes and provide the code for its implementation.MethodsOur proposed algorithm selected the best subset of common predictors based on the minimum average normalized Bayesian Information Criterion (BIC) across outcomes: the Best Average BIC (baBIC) method. We compared the predictive accuracy (Harrell's C-statistic) and parsimony (number of predictors) of the model obtained using the baBIC method with: 1) a subset of common predictors obtained from the union of optimal models for each outcome (Union method), 2) a subset obtained from the intersection of optimal models for each outcome (Intersection method), and 3) a model with no variable selection (Full method). We used a case-study data from the Health and Retirement Study (HRS) to demonstrate our method and conducted a simulation study to investigate performance.ResultsIn the case-study data and simulations, the average Harrell's C-statistics across outcomes of the models obtained with the baBIC and Union methods were comparable. Despite the similar discrimination, the baBIC method produced more parsimonious models than the Union method. In contrast, the models selected with the Intersection method were the most parsimonious, but with worst predictive accuracy, and the opposite was true in the Full method. In the simulations, the baBIC method performed well by identifying many of the predictors selected in the baBIC model of the case-study data most of the time and excluding those not selected in the majority of the simulations.ConclusionsOur method identified a common subset of variables to predict multiple clinical outcomes with superior balance between parsimony and predictive accuracy to current methods.

BackgroundDiet quality is a risk factor for chronic disease and mortality. Differential DNA methylation across the epigenome has been associated with chronic disease risk. Whether diet quality is associated with differential methylation is unknown. This study assessed whether diet quality was associated with differential DNA methylation measured across 445 548 loci in the Women's Health Initiative (WHI) and the TwinsUK cohort.DesignThe discovery cohort consisted of 4355 women from the WHI. The replication cohort consisted of 571 mono- and dizygotic twins from the TwinsUK cohort. DNA methylation was measured in whole blood using the Illumina Infinium HumanMethylation450 Beadchip. Diet quality was assessed using the Alternative Healthy Eating Index 2010 (AHEI-2010). A meta-analysis, stratified by study cohort, was performed using generalized linear models that regressed methylation on AHEI-2010, adjusting for cell composition, chip number and location, study characteristics, principal components of genetic relatedness, age, smoking status, race/ethnicity and body mass index (BMI). Statistical significance was defined as a false discovery rate < 0.05. Significant sites were tested for replication in the TwinsUK cohort, with significant replication defined by P

BackgroundGuidelines recommend that clinicians use clinical prediction models to estimate future risk to guide decisions. For example, predicted fracture risk is a major factor in the decision to initiate bisphosphonate medications. However, current methods for developing prediction models often lead to models that are accurate but difficult to use in clinical settings.ObjectiveThe objective of this study was to develop and test whether a new metric that explicitly balances model accuracy with clinical usability leads to accurate, easier-to-use prediction models.MethodsWe propose a new metric called the Time-cost Information Criterion (TCIC) that will penalize potential predictor variables that take a long time to obtain in clinical settings. To demonstrate how the TCIC can be used to develop models that are easier-to-use in clinical settings, we use data from the 2000 wave of the Health and Retirement Study (n=6311) to develop and compare time to mortality prediction models using a traditional metric (Bayesian Information Criterion or BIC) and the TCIC.ResultsWe found that the TCIC models utilized predictors that could be obtained more quickly than BIC models while achieving similar discrimination. For example, the TCIC identified a 7-predictor model with a total time-cost of 44 seconds, while the BIC identified a 7-predictor model with a time-cost of 119 seconds. The Harrell C-statistic of the TCIC and BIC 7-predictor models did not differ (0.7065 vs. 0.7088, P=0.11).ConclusionAccounting for the time-costs of potential predictor variables through the use of the TCIC led to the development of an easier-to-use mortality prediction model with similar discrimination.

There has been extensive discussion about gender gaps in representation and career advancement in the sciences. However, psychological science itself has yet to be the focus of discussion or systematic review, despite our field's investment in questions of equity, status, well-being, gender bias, and gender disparities. In the present article, we consider 10 topics relevant for women's career advancement in psychological science. We focus on issues that have been the subject of empirical study, discuss relevant evidence within and outside of psychological science, and draw on established psychological theory and social-science research to begin to chart a path forward. We hope that better understanding of these issues within the field will shed light on areas of existing gender gaps in the discipline and areas where positive change has happened, and spark conversation within our field about how to create lasting change to mitigate remaining gender differences in psychological science.

Some hospitals have faced a surge of patients with COVID-19, while others have not. We assessed whether COVID-19 burden (number of patients with COVID-19 admitted during April 2020 divided by hospital certified bed count) was associated with mortality in a large sample of US hospitals. Our study population included 14,226 patients with COVID-19 (median age 66 years, 45.2% women) at 117 hospitals, of whom 20.9% had died at 5 weeks of follow-up. At the hospital level, the observed mortality ranged from 0% to 44.4%. After adjustment for age, sex, and comorbidities, the adjusted odds ratio for in-hospital death in the highest quintile of burden was 1.46 (95% CI, 1.07-2.00) compared to all other quintiles. Still, there was large variability in outcomes, even among hospitals with a similar level of COVID-19 burden and after adjusting for age, sex, and comorbidities.

Student impressions formed during the first day of class can impact course satisfaction and performance. Despite its potential importance, little is known about how instructors format the first day of class. Here, we report on observations of the first day of class in 23 introductory science, technology, engineering, and math (STEM) courses. We first described how introductory STEM instructors structure their class time by characterizing topics covered on the first day through inductive coding of class videos. We found that all instructors discussed policies and basic information. However, a cluster analysis revealed two groups of instructors who differed primarily in their level of STEM content coverage. We then coded the videos with the noncontent Instructor Talk framework, which organizes the statements instructors make unrelated to disciplinary content into several categories and subcategories. Instructors generally focused on building the instructor-student relationship and establishing classroom culture. Qualitative analysis indicated that instructors varied in the specificity of their noncontent statements and may have sent mixed messages by making negatively phrased statements with seemingly positive intentions. These results uncovered variation in instructor actions on the first day of class and can help instructors more effectively plan this day by providing messages that set students up for success.

Providing safe and reliable sanitation services to the billions of people currently lacking them will require a multiplicity of approaches. Improving onsite wastewater treatment to standards enabling water reuse would reduce the need to transport waste and fresh water over long distances. Here, we describe a compact, automated system designed to treat the liquid fraction of blackwater for onsite water reuse that combines cross-flow ultrafiltration, activated carbon, and electrochemical oxidation. In laboratory testing, the system consistently produces effluent with 6 ≤ pH ≤ 9, total suspended solids (TSS) < 30 mg L-1, and chemical oxygen demand (COD) < 150 mg L-1. These effluent parameters were achieved across a wide range of values for influent TSS (61-820 mg L-1) and COD (384-1505 mg L-1), demonstrating a robust system for treating wastewater of varying strengths. A preliminary techno-economic analysis (TEA) was conducted to elucidate primary cost drivers and prioritize research and development pathways toward commercial feasibility. The ultrafiltration system is the primary cost driver, contributing to >50% of both the energy and maintenance costs. Several scenario parameters showed an outsized impact on costs relative to technology parameters. Specific technological improvements for future prototype development are discussed.

Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur.

BackgroundA recent nurse-led proactive care management intervention, Care Coordination for Health Promotion and Activities in Parkinson Disease (CHAPS), improved care quality when compared to usual care in a randomized controlled trial. Therefore, stakeholder (patient participants, nurse care managers, and Parkinson disease (PD) specialists) perceptions of key intervention components merit evaluation to inform decisions about dissemination.MethodsThis multi-site study occurred in five southwest United States Veterans Health Administration medical centers. Stakeholders were surveyed on their perceptions of CHAPS including the CHAPS Assessment, CHAPS nurse care managers, the Siebens Domain Management Model™ (a practical clinical model), and the Siebens Health Care Notebook (Notebook) (self-care tool). Participants' electronic medical records were abstracted for perceptions of the Notebook. Statistical analysis software was used to provide summary statistics; open card sorting methodology was used to identify themes and attributes in qualitative data including usability of some components.ResultsParticipants, overall, highly rated their medication self-management, acknowledged some challenges with the CHAPS self-care tools, reported knowledge of PD specialist follow-up and PD red flags, and rated CHAPS nurse care managers as helpful. Nurse care manager responses indicated the CHAPS Assessment and Program highly facilitated care of their patients. Most all PD specialists would refer other patients to CHAPS. Nurse care manager and PD specialist responses indicated improved participant management of their PD. Three themes emerged in participant perceptions of the Notebook: Notebook Assets (e.g., benefits and features-liked); Deferring Notebook Review (e.g., no time to review); and Reasons for Not Using (e.g., participant preference). Shared attributes regarding the Siebens Domain Management Model and Notebook usability, reported by nurse care managers, were user-friendly, person/patient-centered, and organized. Some challenges to their use were also reported.ConclusionsOverall, stakeholder perceptions of the proactive nurse-led CHAPS intervention indicated its value in the care of individuals with PD. Responses about the CHAPS Assessment, Siebens Domain Management Model, and Notebook self-care tool signified their usefulness. Stakeholders' constructive suggestions indicated their engagement in CHAPS. These findings support CHAPS dissemination and contribute to research in care management.Trial registrationClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.

BackgroundEpigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whether DNA methylation profiles are associated with the development of PTSD. A total of 123 PTSD cases and 143 trauma-exposed controls were included in the analyses. The Psychiatric Genomics Consortium (PGC) PTSD EWAS QC pipeline was used on all cohorts, and results were combined using a sample size weighted meta-analysis in a two-stage design. In stage one, we jointly analyzed data of two new cohorts (N = 126 and 78) for gene discovery, and sought to replicate significant findings in a third, previously published cohort (N = 62) to assess the robustness of our results. In stage 2, we aimed at maximizing power for gene discovery by combining all three cohorts in a meta-analysis.ResultsStage 1 analyses identified four CpG sites in which, conditional on pre-deployment DNA methylation, post-deployment DNA methylation was significantly associated with PTSD status after epigenome-wide adjustment for multiple comparisons. The most significant (intergenic) CpG cg05656210 (p = 1.0 × 10-08) was located on 5q31 and significantly replicated in the third cohort. In addition, 19 differentially methylated regions (DMRs) were identified, but failed replication. Stage 2 analyses identified three epigenome-wide significant CpGs, the intergenic CpG cg05656210 and two additional CpGs located in MAD1L1 (cg12169700) and HEXDC (cg20756026). Interestingly, cg12169700 had an underlying single nucleotide polymorphism (SNP) which was located within the same LD block as a recently identified PTSD-associated SNP in MAD1L1. Stage 2 analyses further identified 12 significant differential methylated regions (DMRs), 1 of which was located in MAD1L1 and 4 were situated in the human leukocyte antigen (HLA) region.ConclusionsThis study suggests that the development of combat-related PTSD is associated with distinct methylation patterns in several genomic positions and regions. Our most prominent findings suggest the involvement of the immune system through the HLA region and HEXDC, and MAD1L1 which was previously associated with PTSD.

BackgroundA recent nurse-led, telephone-administered 18-month intervention, Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS), was tested in a randomized controlled trial and improved care quality. Therefore, intervention details on nurse care manager activity (types and frequencies) and participant actions are needed to support potential dissemination. Activities include nurse care manager use of a holistic organizing framework, identification of Parkinson's disease (PD)-related problems/topics, communication with PD specialists and care coordination, participant coaching, and participant self-care actions including use of a notebook self-care tool.MethodsThis article reports descriptive data on the CHAPS intervention. The study setting was five sites in the Veterans Affairs Healthcare System. Sociodemographic data were gathered from surveys of study participants (community-dwelling veterans with PD). Nurse care manager intervention activities were abstracted from electronic medical records and logbooks. Statistical analysis software was used to provide summary statistics; closed card sorting was used to group some data.ResultsIntervention participants (n = 140) were primarily men, mean age 69.4 years (standard deviation 10.3) and community-dwelling. All received the CHAPS Initial Assessment, which had algorithms designed to identify 31 unique CHAPS standard problems/topics. These were frequently documented (n = 4938), and 98.6% were grouped by assigned domain from the Organizing Framework (Siebens Domain Management Model™). Nurse care managers performed 27 unique activity types to address identified problems, collaborating with participants and PD specialists. The two most frequent unique activities were counseling/emotional support (n = 387) and medication management (n = 349). Both were among 2749 total performed activities in the category Implementing Interventions (coaching). Participants reported unique self-care action types (n = 23) including use of a new notebook self-care tool.ConclusionsCHAPS nurse care managers implemented multiple activities including participant coaching and care coordination per the CHAPS protocol. Participants reported various self-care actions including use of a personalized notebook. These findings indicate good quality and extent of implementation, contribute to ensuring reproducibility, and support CHAPS dissemination as a real-world approach to improve care quality.Trial registrationClinicalTrials.gov as NCT01532986 , registered on January 13, 2012.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.

ObjectiveDuring the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic.MethodsWe conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19.ResultsParticipants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group).ConclusionsImplementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.

BackgroundDespite guidelines recommending not to continue cancer screening for adults > 75 years old, especially those with short life expectancy, primary care providers (PCPs) feel ill-prepared to discuss stopping screening with older adults.ObjectiveTo develop scripts and strategies for PCPs to use to discuss stopping cancer screening with adults > 75.DesignQualitative study using semi-structured interview guides to conduct individual interviews with adults > 75 years old and focus groups and/or individual interviews with PCPs.ParticipantsForty-five PCPs and 30 patients > 75 years old participated from six community or academic Boston-area primary care practices.ApproachParticipants were asked their thoughts on discussions around stopping cancer screening and to provide feedback on scripts that were iteratively revised for PCPs to use when discussing stopping mammography and colorectal cancer (CRC) screening.ResultsTwenty-one (47%) of the 45 PCPs were community based. Nineteen (63%) of the 30 patients were female, and 13 (43%) were non-Hispanic white. PCPs reported using different approaches to discuss stopping cancer screening depending on the clinical scenario. PCPs noted it was easier to discuss stopping screening when the harms of screening clearly outweighed the benefits for a patient. In these cases, PCPs felt more comfortable being more directive. When the balance between the benefits and harms of screening was less clear, PCPs endorsed shared decision-making but found this approach more challenging because it was difficult to explain why to stop screening. While patients were generally enthusiastic about screening, they also reported not wanting to undergo tests of little value and said they would stop screening if their PCP recommended it. By the end of participant interviews, no further edits were recommended to the scripts.ConclusionsTo increase PCP comfort and capability to discuss stopping cancer screening with older adults, we developed scripts and strategies that PCPs may use for discussing stopping cancer screening.

Because powerful people's thinking is impactful, it is critical to understand how power affects cognition. We detail how recent empirical findings reveal that power often improves cognitive functioning. First, power increases controlled processing, in particular intentionality. Second, power improves executive functioning, leading individuals to exhibit better inhibition, working memory, and cognitive flexibility. Third, power increases abstract thinking. Synthesizing these last two points, we propose that high-power individuals' executive functions are enhanced due to their more abstract way of thinking. Both the greater social distance and reduced cognitive vigilance accompanying increased power could explain these effects. Finally, we note remaining questions, such as how much power's cognitive effects are driven by a subjective sense of power versus objective control.

We sought to replicate and expand upon previous work demonstrating antenatal TTC9B and HP1BP3 gene DNA methylation is prospectively predictive of postpartum depression (PPD) with ~80% accuracy. In a preterm birth study from Emory, Illumina MethylEPIC microarray derived 1st but not 3rd trimester biomarker models predicted 3rd trimester Edinburgh Postnatal Depression Scale (EPDS) scores ≥ 13 with an AUC=0.8 (95% CI: 0.63-0.8). Bisulfite pyrosequencing derived biomarker methylation was generated using bisulfite pyrosequencing across all trimesters in a pregnancy cohort at UC Irvine and in 3rd trimester from an independent Johns Hopkins pregnancy cohort. A support vector machine model incorporating 3rd trimester EPDS scores, TTC9B, and HP1BP3 methylation status predicted 4 week to 6 week postpartum EPDS ≥ 13 from 3rd trimester blood in the UC Irvine cohort (AUC=0.78, 95% CI: 0.64-0.78) and from the Johns Hopkins cohort (AUC=0.84, 95% CI: 0.72-0.97), both independent of previous psychiatric diagnosis. Technical replicate predictions in a subset of the Johns Hopkins cohort exhibited strong cross experiment correlation. This study confirms the PPD prediction model has the potential to be developed into a clinical tool enabling the identification of pregnant women at future risk of PPD who may benefit from clinical intervention.

ObjectivesTo identify participants living at home and to estimate the risk of their transition into an institutional setting.DesignProspective cohort study from the National Health and Aging Trends Study (NHATS), a nationally representative survey of US adults aged 65 and older.SettingUS national sample.ParticipantsA total of 4712 NHATS participants were living at home in 2011. Residential transitions were described every year through 2017.MeasurementsThe primary outcome was transition time into an institutional setting. Primary predictors were social support factors (living spouse, lives with others, presence of social network, and participation in social activities). Covariates included age, sex, race, cognitive status, functional disability, multimorbidity, and Medicaid enrollment. A Fine and Gray hazards model estimated the risk of transition into an institutional setting, with death before institutionalization considered a competing risk.ResultsIn 2011, 4712 NHATS participants were living at home (78 ± 8 y; 57% female; 80% white; 10% probable dementia; 7% with three or more activities of daily living disabilities). By 2017, 58% remained at home, 17% had either transitioned to an institution or died in an institution, and 25% died before institutionalization. In multivariable analyses that adjusted for age, sex, race, cognitive status, functional disability, multimorbidity, and Medicaid enrollment, participants were more likely to move out of the home into an institution if they had no social network (0 vs three or more people; subhazard ratio [sHR] = 1.8; 95% confidence interval [CI] = 1.2-2.5; P = .003) or lived alone (sHR = 1.9; 95% CI = 1.6-2.2; P < .0001). Older adults who enjoyed going to the movies, dinner, or the casino and visiting family or friends had a lower probability of institutionalization compared with participants who did not enjoy these activities or did not visit family or friends (adjusted sHR = .7; 95% CI = .6-.9; adjusted sHR = .7; 95% CI = .6-.9, respectively).ConclusionPolicy initiatives should target older adults with limited social support to reduce the risk of moving from home into an institution. J Am Geriatr Soc 67:2622-2627, 2019.

ObjectivesLittle population-level evidence exists to guide the development of interventions for people with dementia in non-nursing home settings. We hypothesized people living at home with moderately severe dementia would differ in social, functional, and medical characteristics from those in either residential care or nursing home settings.DesignRetrospective cohort study using pooled data from the National Health and Aging Trends Study, an annual survey of a nationally representative sample of Medicare beneficiaries.SettingUS national sample.ParticipantsRespondents newly meeting criteria for incident moderately severe dementia, defined as probable dementia with functional impairment: 728 older adults met our definition between 2012 and 2016.MeasurementsSocial characteristics examined included age, sex, race/ethnicity, country of origin, income, educational attainment, partnership status, and household size. Functional characteristics included help with daily activities, falls, mobility device use, and limitation to home or bed. Medical characteristics included comorbid conditions, self-rated health, hospital stay, symptoms, and dementia behaviors.ResultsExtrapolated to the population, an estimated 3.3 million older adults developed incident moderately severe dementia between 2012 and 2016. Within this cohort, 64% received care at home, 19% in residential care, and 17% in a nursing facility. social, functional, and medical characteristics differed across care settings. Older adults living at home were 2 to 5 times more likely to be members of disadvantaged populations and had more medical needs: 71% reported bothersome pain compared with 60% in residential care or 59% in nursing homes.ConclusionOver a 5-year period, 2.1 million people lived at home with incident moderately severe dementia. People living at home had a higher prevalence of demographic characteristics associated with systematic patterns of disadvantage, more social support, less functional impairment, worse health, and more symptoms compared with people living in residential care or nursing facilities. This novel study provides insight into setting-specific differences among people with dementia. J Am Geriatr Soc 67:1907-1912, 2019.

The decision-making process on behalf of unrepresented adults (ie, those who lack capacity to make medical decisions and have no identifiable surrogate) is at risk for not incorporating their interests, raising ethical concerns. We performed semistructured interviews with key stakeholders across multiple sectors in an urban county who participate in the care of or decision-making process for unrepresented adults. This included a safety net healthcare system, social services, and legal services. Participants were healthcare, social service, and legal professionals who worked with unrepresented adults (n = 25). Our interview questions explored the current process for proxy decision making in cases of unrepresented adults and potential alternatives. We recorded, transcribed, and analyzed interviews using the constant comparative method to identify major themes related to ethical challenges if they were raised. Participants grappled with multiple ethical challenges around the care of unrepresented adults. Themes described by participants were: (1) prioritizing autonomy; (2) varying safety thresholds; (3) distributing resources fairly; and (4) taking a moral toll on stakeholders. In conclusion, all stakeholders identified ethical challenges in caring for unrepresented adults. An applied ethical framework that takes these dilemmas into account could improve ethical practice for unrepresented adults and lessen the emotional toll on stakeholders. J Am Geriatr Soc 67:1724-1729, 2019.

Background & aimsCrohn's disease is a relapsing and remitting inflammatory disorder with a variable clinical course. Although most patients present with an inflammatory phenotype (B1), approximately 20% of patients rapidly progress to complicated disease, which includes stricturing (B2), within 5 years. We analyzed DNA methylation patterns in blood samples of pediatric patients with Crohn's disease at diagnosis and later time points to identify changes that associate with and might contribute to disease development and progression.MethodsWe obtained blood samples from 164 pediatric patients (1-17 years old) with Crohn's disease (B1 or B2) who participated in a North American study and were followed for 5 years. Participants without intestinal inflammation or symptoms served as controls (n = 74). DNA methylation patterns were analyzed in samples collected at time of diagnosis and 1-3 years later at approximately 850,000 sites. We used genetic association and the concept of Mendelian randomization to identify changes in DNA methylation patterns that might contribute to the development of or result from Crohn's disease.ResultsWe identified 1189 5'-cytosine-phosphate-guanosine-3' (CpG) sites that were differentially methylated between patients with Crohn's disease (at diagnosis) and controls. Methylation changes at these sites correlated with plasma levels of C-reactive protein. A comparison of methylation profiles of DNA collected at diagnosis of Crohn's disease vs during the follow-up period showed that, during treatment, alterations identified in methylation profiles at the time of diagnosis of Crohn's disease more closely resembled patterns observed in controls, irrespective of disease progression to B2. We identified methylation changes at 3 CpG sites that might contribute to the development of Crohn's disease. Most CpG methylation changes associated with Crohn's disease disappeared with treatment of inflammation and might be a result of Crohn's disease.ConclusionsMethylation patterns observed in blood samples from patients with Crohn's disease accompany acute inflammation; with treatment, these change to resemble methylation patterns observed in patients without intestinal inflammation. These findings indicate that Crohn's disease-associated patterns of DNA methylation observed in blood samples are a result of the inflammatory features of the disease and are less likely to contribute to disease development or progression.

BackgroundDespite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery.MethodsParticipants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently.ResultsOf 3,105 participants, 1,921 (62%) underwent catheterization and 1,184 (38%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95% confidence interval: -0.046 to 0.005 memory units, p = 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26% or 0.19% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95% confidence interval: 0.74 to 1.18).ConclusionsIn this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.

BackgroundPhysical frailty is a powerful tool for identifying nondisabled individuals at high risk of adverse outcomes. The extent to which cognitive impairment in those without dementia adds value to physical frailty in detecting high-risk individuals remains unclear.ObjectivesTo estimate the effects of combining physical frailty and cognitive impairment without dementia (CIND) on the risk of basic activities of daily living (ADL) dependence and death over 8 years.DesignProspective cohort study.SettingThe Health and Retirement Study (HRS).ParticipantsA total of 7338 community-dwelling people, 65 years or older, without dementia and ADL dependence at baseline (2006-2008). Follow-up assessments occurred every 2 years until 2014.MeasurementsThe five components of the Cardiovascular Health Study defined physical frailty. A well-validated HRS method, including verbal recall, series of subtractions, and backward count task, assessed cognition. Primary outcomes were time to ADL dependence and death. Hazard models, considering death as a competing risk, associated physical frailty and CIND with outcomes after adjusting for sociodemographics, comorbidities, depression, and smoking status.ResultsThe prevalence of physical frailty was 15%; CIND, 19%; and both deficits, 5%. In unadjusted and adjusted analyses, combining these factors identified older adults at an escalating risk for ADL dependence (no deficit = 14% [reference group]; only CIND = 26%, sub-hazard ratio [sHR] = 1.5, 95% confidence interval [CI] = 1.3-1.8; only frail = 33%, sHR = 1.7, 95% CI = 1.4-2.0; both deficits = 46%, sHR = 2.0, 95%CI = 1.6-2.6) and death (no deficit = 21%; only CIND = 41%, HR = 1.6, 95% CI = 1.4-1.9; only frail = 56%, HR = 2.2, 95% CI = 1.7-2.7; both deficits = 66%, HR = 2.6, 95% CI = 2.0-3.3) over 8-year follow-up. Adding the cognitive measure to models that already included physical frailty alone increased accuracy in identifying those at higher risk of ADL dependence (Harrell's concordance [C], 0.74 vs 0.71; P < .001) and death (Harrell's C, 0.70 vs 0.67; P < .001).ConclusionPhysical frailty and CIND are independent predictors of incident disability and death. Because together physical frailty and CIND identify vulnerable older adults better, optimal risk assessment should supplement measures of physical frailty with measures of cognitive function. J Am Geriatr Soc 67:477-483, 2019.

ObjectivesTo characterize the goals and approaches of clinicians with experience discussing long-term prognostic information with older adults.DesignWe used a semistructured interview guide containing 2 domains of perceived benefits and strategies to explore why and how clinicians choose to discuss long-term prognosis, defined as life expectancy on the scale of years, with patients.SettingClinicians from home-based primary care practices, community-based clinics, and academic medical centers across San Francisco.ParticipantsFourteen physicians, including 11 geriatricians and 1 geriatric nurse practitioner, with a mean age of 40 and a mean 9 years in practice.MeasurementsClinician responses were analyzed qualitatively using the constant comparisons approach.ResultsPerceived benefits of discussing long-term prognosis included establishing realistic expectations for patients, encouraging conversations about future planning, and promoting shared decision-making through understanding of patient goals of care. Communication strategies included adapting discussions to individual patient preferences and engaging in multiple conversations over time. Clinicians preferred to communicate prognosis in words and with a visual aid, although most did not know of a suitable visual aid.ConclusionEngaging in customized longitudinal discussions of long-term prognosis aids clinicians in anchoring conversations about future planning and preparing patients for the end of life. J Am Geriatr Soc 66:2367-2371, 2018.

ContextPain may be a potentially modifiable risk factor for expensive and burdensome emergency department (ED) visits near the end of life for older adults with dementia.ObjectivesThe objective of this study was to assess the effect of pain and unmet need for pain management on ED visits in the last month of life in older adults with dementia.MethodsThis is a mortality follow-back study of older adults with dementia in the National Health and Aging Trends Study who died between 2012 and 2014, linked to Medicare claims.ResultsTwo hundred eighty-one National Health and Aging Trends Study decedents with dementia met criteria (mean age 86 years, 61% female, 81% white). Fifty-seven percent had at least one ED visit in the last month of life, and 46.5% had an ED visit that resulted in a hospital admission. Almost three out of four (73%) of decedents experienced pain in the last month of life, and 10% had an unmet need for pain management. After adjustment for age, gender, race, educational attainment, income, comorbidities, and impairment in activities of daily living, pain was not associated with increased ED use in the last month of life (adjusted incident rate ratio 0.87, 95% CI 0.64-1.17). However, decedents with unmet need for pain management had an almost 50% higher rate of ED visits in the last month of life than those without unmet needs (adjusted incident rate ratio 1.46, 95% CI 1.07-1.99).ConclusionAmong older adults with dementia, unmet need for pain management was associated with more frequent ED visits in the last month of life.

Evaluation is central to human experience, and multiple literatures have studied it. This article pulls from research on attitudes, human and nonhuman mating preferences, consumer behavior, and beyond to build a more comprehensive framework for studying evaluation. First, we distinguish between evaluations of objects (persons, places, things) and evaluations of attributes (dimensions, traits, characteristics). Then, we further distinguish between summarized attribute preferences (a valenced response to a direction on a dimension, such as liking sweetness in desserts) and functional attribute preferences (a valenced response to increasing levels of a dimension in a set of targets, such as the extent to which sweetness predicts liking for desserts). We situate these constructs with respect to existing distinctions in the attitude literature (e.g., specific/general, indirect/direct). Finally, new models address how people translate functional into summarized preferences, as well as how attribute preferences affect (a) subsequent evaluations of objects and (b) situation selection.

BackgroundOlder black and Latino Americans are more likely than white Americans to die in the hospital. Whether ethnic differences in expectation of death account for this disparity is unknown.ObjectivesTo determine whether surviving family members' expectation of death has a differential association with site of death according to race or ethnicity.MethodsWe conducted an analysis of decedents from the Health and Retirement Study, a nationally representative study of US older adults. Telephone surveys were conducted with family members for 5979 decedents (decedents were 55% were women, 85% white, 9% black, and 6% Latino). The outcome of interest was death in the hospital; the predictor variable was race/ethnicity, and the intervening variable was expectation of death. Covariates included sociodemographics (gender, age, household net worth, educational attainment level, religion) and health factors (chronic conditions, symptoms, health-care utilization).ResultsDecedents' race/ethnicity was statistically related to the expectation of death and death in the hospital. When death was not expected, whites and Latinos were more likely to die in the hospital than when death was expected (49% vs 29% for whites and 55% vs 37% for Latinos; P < .001). There was no difference in site of death according to family's expectation of death among blacks.ConclusionExpectation of death did not fully account for site of death and played a greater role among whites and Latinos than among black Americans. Discussing prognosis by itself is unlikely to address ethnic disparities. Other factors appear to play an important role as well.