Multimorbidity and associated informal care receiving characteristics for US older adults: a latent class analysis.

BACKGROUND: Older adults with varying patterns of multimorbidity may require distinct types of care and rely on informal caregiving to meet their care needs. This study aims to identify groups of older adults with distinct, empirically-determined multimorbidity patterns and compare characteristics of informal care received among estimated classes. METHODS: Data are from the 2011 National Health and Aging Trends Study (NHATS). Ten chronic conditions were included to estimate multimorbidity patterns among 7532 individuals using latent class analysis. Multinomial logistic regression model was estimated to examine the association between sociodemographic characteristics, health status and lifestyle variables, care-receiving characteristics and latent class membership. RESULTS: A four-class solution identified the following multimorbidity groups: some somatic conditions with moderate cognitive impairment (30%), cardiometabolic (25%), musculoskeletal (24%), and multisystem (21%). Compared with those who reported receiving no help, care recipients who received help with household activities only (OR = 1.44, 95% CI 1.05-1.98), mobility but not self-care (OR = 1.63, 95% CI 1.05-2.53), or self-care but not mobility (OR = 2.07, 95% CI 1.29-3.31) had greater likelihood of being in the multisystem group versus the some-somatic group. Having more caregivers was associated with higher odds of being in the multisystem group compared with the some-somatic group (OR = 1.09, 95% CI 1.00-1.18), whereas receiving help from paid helpers was associated with lower odds of being in the multisystem group (OR = 0.36, 95% CI 0.19-0.77). CONCLUSIONS: Results highlighted different care needs among persons with distinct combinations of multimorbidity, in particular the wide range of informal needs among older adults with multisystem multimorbidity. Policies and interventions should recognize the differential care needs associated with multimorbidity patterns to better provide person-centered care.

Mental-somatic multimorbidity in trajectories of cognitive function for middle-aged and older adults.

INTRODUCTION: Multimorbidity may confer higher risk for cognitive decline than any single constituent disease. This study aims to identify distinct trajectories of cognitive impairment probability among middle-aged and older adults, and to assess the effect of changes in mental-somatic multimorbidity on these distinct trajectories. METHODS: Data from the Health and Retirement Study (1998-2016) were employed to estimate group-based trajectory models identifying distinct trajectories of cognitive impairment probability. Four time-varying mental-somatic multimorbidity combinations (somatic, stroke, depressive, stroke and depressive) were examined for their association with observed trajectories of cognitive impairment probability with age. Multinomial logistic regression analysis was conducted to quantify the association of sociodemographic and health-related factors with trajectory group membership. RESULTS: Respondents (N = 20,070) had a mean age of 61.0 years (SD = 8.7) at baseline. Three distinct cognitive trajectories were identified using group-based trajectory modelling: (1) Low risk with late-life increase (62.6%), (2) Low initial risk with rapid increase (25.7%), and (3) High risk (11.7%). For adults following along Low risk with late-life increase, the odds of cognitive impairment for stroke and depressive multimorbidity (OR:3.92, 95%CI:2.91,5.28) were nearly two times higher than either stroke multimorbidity (OR:2.06, 95%CI:1.75,2.43) or depressive multimorbidity (OR:2.03, 95%CI:1.71,2.41). The odds of cognitive impairment for stroke and depressive multimorbidity in Low initial risk with rapid increase or High risk (OR:4.31, 95%CI:3.50,5.31; OR:3.43, 95%CI:2.07,5.66, respectively) were moderately higher than stroke multimorbidity (OR:2.71, 95%CI:2.35, 3.13; OR: 3.23, 95%CI:2.16, 4.81, respectively). In the multinomial logistic regression model, non-Hispanic Black and Hispanic respondents had higher odds of being in Low initial risk with rapid increase and High risk relative to non-Hispanic White adults. CONCLUSIONS: These findings show that depressive and stroke multimorbidity combinations have the greatest association with rapid cognitive declines and their prevention may postpone these declines, especially in socially disadvantaged and minoritized groups.

Recommendations on Methods for Assessing Multimorbidity Changes Over Time: Aligning the Method to the Purpose.

BACKGROUND: The rapidly growing field of multimorbidity research demonstrates that changes in multimorbidity in mid- and late-life have far reaching effects on important person-centered outcomes, such as health-related quality of life. However, there are few organizing frameworks and comparatively little work weighing the merits and limitations of various quantitative methods applied to the longitudinal study of multimorbidity. METHODS: We identify and discuss methods aligned to specific research objectives with the goals of (i) establishing a common language for assessing longitudinal changes in multimorbidity, (ii) illuminating gaps in our knowledge regarding multimorbidity progression and critical periods of change, and (iii) informing research to identify groups that experience different rates and divergent etiological pathways of disease progression linked to deterioration in important health-related outcomes. RESULTS: We review practical issues in the measurement of multimorbidity, longitudinal analysis of health-related data, operationalizing change over time, and discuss methods that align with 4 general typologies for research objectives in the longitudinal study of multimorbidity: (i) examine individual change in multimorbidity, (ii) identify subgroups that follow similar trajectories of multimorbidity progression, (iii) understand when, how, and why individuals or groups shift to more advanced stages of multimorbidity, and (iv) examine the coprogression of multimorbidity with key health domains. CONCLUSIONS: This work encourages a systematic approach to the quantitative study of change in multimorbidity and provides a valuable resource for researchers working to measure and minimize the deleterious effects of multimorbidity on aging populations.

Profile of Caregiving Activities and Association With Physical Health Among Dementia Spousal Caregivers.

Background and Objectives: This study aims to identify patterns of caregiving intensity and assess associations between caregiving intensity and multidimensional physical health indicators and health behaviors among spousal caregivers of persons with Alzheimer's disease and related dementia. Research Design and Methods: Using data from 152 spousal caregivers aged 65 and older, the intensity of their caregiving experience was measured as the number and frequency of health- and medical-related helping activities for their care recipient. Multidimensional health indicators included self-reported fatigue, sleep disturbance, physical functioning, pain interference, general health, and the number of chronic conditions from the electronic health records. Self-reported health promotion behaviors were assessed as health responsibility, physical activity, nutrition, interpersonal relations, and stress management. Results: Two distinct caregiving intensity patterns, high-intensity (37.5%) and low-intensity (62.5%) caregiving, were identified with cluster analysis. Caregivers in the high-intensity caregiving cluster reported feeling more tired (t = 2.25, p < .05), experiencing more sleep disturbance (t = 3.06, p < .01), and performing less physical activity (t = 2.05, p < .05) compared with caregivers in the low-intensity group. Discussion and Implications: Future studies are needed to develop effective interventions to address caregiving intensity and its consequences on the health of spousal caregivers of persons with dementia.

Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

Seasonal infection rates of individual viruses are influenced by synergistic or inhibitory interactions between coincident viruses. Endemic patterns of SARS-CoV-2 and influenza infection overlap seasonally in the Northern hemisphere and may be similarly influenced. We explored the immunopathologic basis of SARS-CoV-2 and influenza A (H1N1pdm09) interactions in Syrian hamsters. H1N1 given 48 h prior to SARS-CoV-2 profoundly mitigated weight loss and lung pathology compared to SARS-CoV-2 infection alone. This was accompanied by the normalization of granulocyte dynamics and accelerated antigen-presenting populations in bronchoalveolar lavage and blood. Using nasal transcriptomics, we identified a rapid upregulation of innate and antiviral pathways induced by H1N1 by the time of SARS-CoV-2 inoculation in 48 h dual-infected animals. The animals that were infected with both viruses also showed a notable and temporary downregulation of mitochondrial and viral replication pathways. Quantitative RT-PCR confirmed a decrease in the SARS-CoV-2 viral load and lower cytokine levels in the lungs of animals infected with both viruses throughout the course of the disease. Our data confirm that H1N1 infection induces rapid and transient gene expression that is associated with the mitigation of SARS-CoV-2 pulmonary disease. These protective responses are likely to begin in the upper respiratory tract shortly after infection. On a population level, interaction between these two viruses may influence their relative seasonal infection rates.

Longitudinal Care Network Changes and Associated Healthcare Utilization Among Care Recipients.

This study examines caregiver networks, including size, composition, and stability, and their associations with the likelihood of hospitalization and skilled-nursing facility (SNF) admissions. Data from the National Health and Aging Trends Study linked to Center for Medicare and Medicaid Services data were analyzed for 3855 older adults across five survey waves. Generalized estimating equation models assessed the associations. The findings indicate each additional paid caregiver was associated with higher adjusted risk ratios (aRR) for hospitalization (aRR = 1.24, 95% CI 1.10-1.41) and SNF admission (aRR = 1.28, 95% CI 1.06-1.54) among care recipients, a pattern that is also observed with the addition of unpaid caregivers (hospitalization: aRR = 1.13, 95% CI 1.06-1.20; SNF: aRR = 1.12, 95% CI 1.02-1.23). These results suggest that policies and approaches to enhance the quality and coordination of caregivers may be warranted to support improved outcomes for care recipients.

A Joint Model for Disability, Self-Rated Health, and Mortality Among Medicare Beneficiaries-Differences by Chronic Disease and Race/Ethnicity.

OBJECTIVES: Quantifying interdependence in multiple patient-centered outcomes is important for understanding health declines among older adults. METHODS: Medicare-linked National Health and Aging Trends Study data (2011-2015) were used to estimate a joint longitudinal logistic regression model of disability in activities of daily living (ADL), fair/poor self-rated health (SRH), and mortality. We calculated personalized concurrent risk (PCR) and typical concurrent risk (TCR) using regression coefficients. RESULTS: For fair/poor SRH, highest odds were associated with COPD. For mortality, highest odds were associated with dementia, hip fracture, and kidney disease. Dementia and hip fracture were associated with highest odds of ADL disability. Hispanic respondents had highest odds of ADL disability. Hispanic and NH Black respondents had higher odds of fair/poor SRH, ADL disability, and mortality. PCRs/TCRs demonstrated wide variability for respondents with similar sociodemographic-multimorbidity profiles. DISCUSSION: These findings highlight the variability of personalized risk in examining interdependent outcomes among older adults.

Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.

Dectin-1 is an innate immune receptor that recognizes and binds ß-1, 3/1, 6 glucans on fungi. We evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. Stimulation of monocytes with ß-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). Overall, our study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging.

Racial, ethnic, and socioeconomic disparities in trajectories of morbidity accumulation among older Americans.

Introduction: Multimorbidity, the presence of multiple chronic health conditions, generally starts in middle and older age but there is considerable heterogeneity in the trajectory of morbidity accumulation. This study aimed to clarify the number of distinct trajectories and the potential associations between race/ethnicity and socioeconomic status and these trajectories. Methods: Data from 13,699 respondents (age ≥51) in the Health and Retirement Study between 1998 and 2016 were analyzed with growth mixture models. Nine prevalent self-reported morbidities (arthritis, cancer, cognitive impairment, depressive symptoms, diabetes, heart disease, hypertension, lung disease, stroke) were summed for the morbidity count. Results: Three trajectories of morbidity accumulation were identified: low [starting with few morbidities and accumulating them slowly (i.e., low intercept and low slope); 80% of sample], increasing (i.e., low intercept and high slope; 9%), and high (i.e., high intercept and low slope; 11%). Compared to non-Hispanic (NH) White adults in covariate-adjusted models, NH Black adults had disadvantages while Hispanic adults had advantages. Our results suggest a protective effect of education for NH Black adults (i.e., racial health disparities observed at low education were ameliorated and then eliminated at increasing levels of education) and a reverse pattern for Hispanic adults (i.e., increasing levels of education was found to dampen the advantages Hispanic adults had at low education). Compared with NH White adults, higher levels of wealth were protective for both NH Black adults (i.e., reducing or reversing racial health disparities observed at low wealth) and Hispanic adults (i.e., increasing the initial health advantages observed at low wealth). Conclusion: These findings have implications for addressing health disparities through more precise targeting of public health interventions. This work highlights the imperative to address socioeconomic inequalities that interact with race/ethnicity in complex ways to erode health.

A multivariate joint model to adjust for random measurement error while handling skewness and correlation in dietary data in an epidemiologic study of mortality.

PURPOSE: A substantial proportion of global deaths is attributed to unhealthy diets, which can be assessed at baseline or longitudinally. We demonstrated how to simultaneously correct for random measurement error, correlations, and skewness in the estimation of associations between dietary intake and all-cause mortality. METHODS: We applied a multivariate joint model (MJM) that simultaneously corrected for random measurement error, skewness, and correlation among longitudinally measured intake levels of cholesterol, total fat, dietary fiber, and energy with all-cause mortality using US National Health and Nutrition Examination Survey linked to the National Death Index mortality data. We compared MJM with the mean method that assessed intake levels as the mean of a person's intake. RESULTS: The estimates from MJM were larger than those from the mean method. For instance, the logarithm of hazard ratio for dietary fiber intake increased by 14 times (from -0.04 to -0.60) with the MJM method. This translated into a relative hazard of death of 0.55 (95% credible interval: 0.45, 0.65) with the MJM and 0.96 (95% credible interval: 0.95, 0.97) with the mean method. CONCLUSIONS: MJM adjusts for random measurement error and flexibly addresses correlations and skewness among longitudinal measures of dietary intake when estimating their associations with death.

Platelet response to influenza vaccination reflects effects of aging.

Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21-35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age-associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age-associated differences were also identified in post-vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)-resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community-dwelling older adults at the protein level, compared to young individuals both prior to and post-vaccination; whereas SNF residents showed decreased platelet activation compared to community-dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age-associated chronic inflammation and the increased incidence of thrombotic and pro-inflammatory diseases in older adults.

Depressive Multimorbidity and Trajectories of Functional Status among Older Americans: Differences by Racial/Ethnic Group.

OBJECTIVE: This study aims to evaluate the impact of depressive multimorbidity (ie, including depressive symptoms) on the long-term development of activities of daily living (ADL) and instrumental activities of daily living (IADL) limitations according to racial/ethnic group in a representative sample of US older adults. DESIGN: Prospective, observational, population-based 16-year follow-up study of nationally representative sample. SETTING AND PARTICIPANTS: Sample of older non-Hispanic Black, Hispanic, and nonHispanic White Americans from the Health and Retirement Study (2000‒2016, N = 16,364, community-dwelling adults ≥65 years of age). METHODS: Data from 9 biennial assessments were used to evaluate the accumulation of ADL-IADL limitations (range 0‒11) among participants with depressive (8-item Center for Epidemiologic Studies Depression score≥4) vs somatic (ie, physical conditions only) multimorbidity vs those without multimorbidity (no or 1 condition). Generalized estimating equations included race/ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White), baseline age, sex, body mass index, education, partnered, and net worth. RESULTS: Depressive and somatic multimorbidity were associated with 5.18 and 2.95 times greater accumulation of functional limitations, respectively, relative to no disease [incidence rate ratio (IRR) = 5.18, 95% confidence interval, CI (4.38,6.13), IRR = 2.95, 95% CI (2.51,3.48)]. Hispanic and Black respondents experienced greater accumulation of ADL-IADL limitations than White respondents [IRR = 1.27, 95% CI (1.14, 1.41), IRR = 1.31, 95% CI (1.20, 1.43), respectively]. CONCLUSIONS AND IMPLICATIONS: Combinations of somatic diseases and high depressive symptoms are associated with greatest accumulation of functional limitations over time in adults ages 65 and older. There is a more rapid growth in functional limitations among individuals from racial/ethnic minority groups. Given the high prevalence of multimorbidity and depressive symptomatology among older adults and the availability of treatment options for depression, these results highlight the importance of screening/treatment for depression, particularly among older adults with socioeconomic vulnerabilities, to slow the progression of functional decline in later life.

Multidimensional trajectories of multimorbidity, functional status, cognitive performance, and depressive symptoms among diverse groups of older adults.

Background: Inter-relationships between multimorbidity and geriatric syndromes are poorly understood. This study assesses heterogeneity in joint trajectories of somatic disease, functional status, cognitive performance, and depressive symptomatology. Methods: We analyzed 16 years of longitudinal data from the Health and Retirement Study (HRS, 1998-2016) for n = 11,565 older adults (≥65 years) in the United States. Group-based mixture modeling identified latent clusters of older adults following similar joint trajectories across domains. Results: We identified four distinct multidimensional trajectory groups: (1) Minimal Impairment with Low Multimorbidity (32.7% of the sample; mean = 0.60 conditions at age 65, 2.1 conditions at age 90) had limited deterioration; (2) Minimal Impairment with High Multimorbidity (32.9%; mean = 2.3 conditions at age 65, 4.0 at age 90) had minimal deterioration; (3) Multidomain Impairment with Intermediate Multimorbidity (19.9%; mean = 1.3 conditions at age 65, 2.7 at age 90) had moderate depressive symptomatology and functional impariments with worsening cognitive performance; (4) Multidomain Impairment with High Multimorbidity (14.1%; mean = 3.3 conditions at age 65; 4.7 at age 90) had substantial functional limitation and high depressive symptomatology with worsening cognitive performance. Black and Hispanic race/ethnicity, lower wealth, lower education, male sex, and smoking history were significantly associated with membership in the two Multidomain Impairment classes. Conclusions: There is substantial heterogeneity in combined trajectories of interrelated health domains in late life. Membership in the two most impaired classes was more likely for minoritized older adults.

Digital phenotyping by wearable-driven artificial intelligence in older adults and people with Parkinson's disease: Protocol of the mixed method, cyclic ActiveAgeing study.

BACKGROUND: Active ageing is described as the process of optimizing health, empowerment, and security to enhance the quality of life in the rapidly growing population of older adults. Meanwhile, multimorbidity and neurological disorders, such as Parkinson's disease (PD), lead to global public health and resource limitations. We introduce a novel user-centered paradigm of ageing based on wearable-driven artificial intelligence (AI) that may harness the autonomy and independence that accompany functional limitation or disability, and possibly elevate life expectancy in older adults and people with PD. METHODS: ActiveAgeing is a 4-year, multicentre, mixed method, cyclic study that combines digital phenotyping via commercial devices (Empatica E4, Fitbit Sense, and Oura Ring) with traditional evaluation (clinical assessment scales, in-depth interviews, and clinical consultations) and includes four types of participants: (1) people with PD and (2) their informal caregiver; (3) healthy older adults from the Helgetun living environment in Norway, and (4) people on the Helgetun waiting list. For the first study, each group will be represented by N = 15 participants to test the data acquisition and to determine the sample size for the second study. To suggest lifestyle changes, modules for human expert-based advice, machine-generated advice, and self-generated advice from accessible data visualization will be designed. Quantitative analysis of physiological data will rely on digital signal processing (DSP) and AI techniques. The clinical assessment scales are the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS), Geriatric Anxiety Inventory (GAI), Apathy Evaluation Scale (AES), and the REM Sleep Behaviour Disorder Screening Questionnaire (RBDSQ). A qualitative inquiry will be carried out with individual and focus group interviews and analysed using a hermeneutic approach including narrative and thematic analysis techniques. DISCUSSION: We hypothesise that digital phenotyping is feasible to explore the ageing process from clinical and lifestyle perspectives including older adults and people with PD. Data is used for clinical decision-making by symptom tracking, predicting symptom evolution, and discovering new outcome measures for clinical trials.

Perceptions of generic medicines and medication adherence after percutaneous coronary intervention: a prospective multicentre cohort study.

OBJECTIVE: To determine patient perceptions of generic medicines 2 and 6 months after percutaneous coronary intervention (PCI), and to determine whether these perceptions moderate medication adherence. DESIGN: Prospective multicentre cohort study with repeated measures of perceptions of generic medicines and medication adherence. SETTING: The CONCARDPCI study conducted at seven large referral PCI centres in Norway and Denmark between June 2017 and May 2020. PARTICIPANTS: A total of 3417 adults (78% men), using both generic and brand name medicines, with a mean age of 66 years (SD 11) who underwent PCI were followed up 2 and 6 months after discharge from hospital. MAIN OUTCOME MEASURES: Perceptions of generic medicines were the main outcome. The secondary outcome was medication adherence. RESULTS: Perceptions of generic medicines were significantly more negative at 2 than at 6 months (1.10, 95% CI 0.41 to 1.79, p=0.002). Female sex (-4.21, 95% CI -6.75 to -1.71, p=0.001), older age (-0.12, 95% CI -0.23 to -0.02, p=0.020), lower education level (overall p<0.001), ethnicity (overall p=0.002), Norwegian nationality (10.27, 95% CI 8.19 to 12.40, p<0.001) and reduced self-reported health status (0.19, 95% CI 0.09 to 0.41, p=0.003) were significantly associated with negative perceptions of generic medicines. There was no evidence to suggest that perceptions of generic medicines moderate the association between sociodemographic and clinical variables and medication adherence (p≥0.077 for all covariates). Moreover, self-reported medication adherence was high, with 99% scoring at or above the Medication Adherence Report Scale midpoint at both time points. There were no substantial correlations between negative perceptions of generic medicines and medication non-adherence at 2 months (r=0.041, 95% CI 0.002 to 0.081, p=0.037) or 6 months (r=0.038, 95% CI -0.005 to 0.081, p=0.057). CONCLUSIONS: Mistrust and uncertainty about the safety and efficacy of generic medicines remains in a sizeable proportion of patients after PCI. This applies especially to those of lower socioeconomic status, older age, female sex, immigrants and those with poorer mental health. However, this study demonstrated a shift towards more positive perceptions of generic medicines in the longer term.

The Contribution of Chronic Conditions to Hospitalization, Skilled Nursing Facility Admission, and Death: Variation by Race.

Multimorbidity (≥2 chronic conditions) is a common and important marker of aging. To better understand racial differences in multimorbidity burden and associations with important health-related outcomes, we assessed differences in the contribution of chronic conditions to hospitalization, skilled nursing facility admission, and mortality among non-Hispanic Black and non-Hispanic White older adults in the United States. We used data from a nationally representative study, the National Health and Aging Trends Study, linked to Medicare claims from 2011-2015 (n = 4,871 respondents). This analysis improved upon prior research by identifying the absolute contributions of chronic conditions using a longitudinal extension of the average attributable fraction for Black and White Medicare beneficiaries. We found that cardiovascular conditions were the greatest contributors to outcomes among White respondents, while the greatest contributor to outcomes for Black respondents was renal morbidity. This study provides important insights into racial differences in the contributions of chronic conditions to costly health-care utilization and mortality, and it prompts policy-makers to champion delivery reforms that will expand access to preventive and ongoing care for diverse Medicare beneficiaries.

Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data.

The contours of endemic coronaviral disease in humans and other animals are shaped by the tendency of coronaviruses to generate new variants superimposed upon nonsterilizing immunity. Consequently, patterns of coronaviral reinfection in animals can inform the emerging endemic state of the SARS-CoV-2 pandemic. We generated controlled reinfection data after high and low risk natural exposure or heterologous vaccination to sialodacryoadenitis virus (SDAV) in rats. Using deterministic compartmental models, we utilized in vivo estimates from these experiments to model the combined effects of variable transmission rates, variable duration of immunity, successive waves of variants, and vaccination on patterns of viral transmission. Using rat experiment-derived estimates, an endemic state achieved by natural infection alone occurred after a median of 724 days with approximately 41.3% of the population susceptible to reinfection. After accounting for translationally altered parameters between rat-derived data and human SARS-CoV-2 transmission, and after introducing vaccination, we arrived at a median time to endemic stability of 1437 (IQR = 749.25) days with a median 15.4% of the population remaining susceptible. We extended the models to introduce successive variants with increasing transmissibility and included the effect of varying duration of immunity. As seen with endemic coronaviral infections in other animals, transmission states are altered by introduction of new variants, even with vaccination. However, vaccination combined with natural immunity maintains a lower prevalence of infection than natural infection alone and provides greater resilience against the effects of transmissible variants.

The geriatrics research instrument library: A resource for guiding instrument selection for researchers studying older adults with multiple chronic conditions.

Background: After the passage of the 21st Century Cures Act in the U.S., the Inclusion Across the Lifespan policy eliminates upper-age limits for research participation unless risk justified. Broader inclusion will necessitate the use of reliable instruments in research that characterize the health status and function of older adults with multiple chronic conditions. As there is a plethora of such instruments, the Geriatrics Research Instrument Library (GRIL) was developed as freely available online resource of data collection instruments commonly used in gerontological research. GRIL has been revised and updated by the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative, a joint endeavor of the Health Care Systems Research Network (HCSRN) and the Older Americans Independence Centers (OAICs). Methods: Extensive PubMed literature searches and domain expert feedback were utilized to inventory and update GRIL through the addition of instruments and compiling of instrument metadata. GRIL is hosted on the National Institute on Aging OAIC Coordinating Center website with a platform utilizing Microsoft Structured Query Language (SQL) and an Adobe ColdFusion application server. Tracking statistics are collected using Google Analytics. Results: Presently, GRIL includes 175 instruments across 18 domains, including instrument metadata such as instrument description, copyright information, completion time estimates, keywords, available translations, and a link and reference to the original manuscript describing the instrument. The GRIL website includes user-friendly features such as mobile platforming and resource links. Conclusions: GRIL provides a user-friendly public resource that facilitates clinical researchers in efficiently selecting appropriate instruments to measure clinical outcomes relevant to older adults across a full range of domains.

Trajectories of cognitive functioning in later life: Disparities by race/ethnicity, educational attainment, sex, and multimorbidity combinations.

Evaluating multimorbidity combinations, racial/ethnic background, educational attainment, and sex associations with age-related cognitive changes is critical to clarifying the health, sociodemographic, and socioeconomic mechanisms associated with cognitive function in later life. Data from the 2011-2018 National Health and Aging Trends Study for respondents aged 65 years and older (N = 10,548, mean age = 77.5) were analyzed using linear mixed effect models. Racial/ethnic differences (mutually-exclusive groups: non-Latino White, non-Latino Black, and Latino) in cognitive trajectories and significant interactions with sex and education (

Multimorbidity Accumulation Among Middle-Aged Americans: Differences by Race/Ethnicity and Body Mass Index.

BACKGROUND: Obesity and multimorbidity are more prevalent among U.S. racial/ethnic minority groups. Evaluating racial/ethnic disparities in disease accumulation according to body mass index (BMI) may guide interventions to reduce multimorbidity burden in vulnerable racial/ethnic groups. METHOD: We used data from the 1998-2016 Health and Retirement Study on 8 106 participants aged 51-55 at baseline. Disease burden and multimorbidity (≥2 co-occurring diseases) were assessed using 7 chronic diseases: arthritis, cancer, heart disease, diabetes, hypertension, lung disease, and stroke. Four BMI categories were defined per convention: normal, overweight, obese class 1, and obese class 2/3. Generalized estimating equations models with inverse probability weights estimated the accumulation of chronic diseases. RESULTS: Overweight and obesity were more prevalent in non-Hispanic Black (82.3%) and Hispanic (78.9%) than non-Hispanic White (70.9 %) participants at baseline. The baseline burden of disease was similar across BMI categories, but disease accumulation was faster in the obese class 2/3 and marginally in the obese class 1 categories compared with normal BMI. Black participants across BMI categories had a higher initial burden and faster accumulation of disease over time, while Hispanics had a lower initial burden and similar rate of accumulation, compared with Whites. Black participants, including those with normal BMI, reach the multimorbidity threshold 5-6 years earlier compared with White participants. CONCLUSIONS: Controlling weight and reducing obesity early in the lifecourse may slow the progression of multimorbidity in later life. Further investigations are needed to identify the factors responsible for the early and progressing nature of multimorbidity in Blacks of nonobese weight.