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.

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.

Association Between Potentially Inappropriate Medications and 30-Day Post-Hospital Discharge Outcomes in US Veterans.

BACKGROUND: Potentially inappropriate medication (PIMs) use is common in older inpatients and it may lead to increased risk of adverse drug events. OBJECTIVES: To examine prevalence of PIMs at hospital discharge and its contribution to health care utilization and mortality within 30-days of hospital discharge. METHODS: This was a prospective cohort of 117 570 veterans aged ≥65 years and hospitalized in 2013. PIMs at discharge were categorized into central nervous system acting (CNS) and non-CNS. Outcomes within 30-days of hospital discharge were: (1) time to first acute care hospital readmission, and all-cause mortality, (2) an emergency room visit, and (3) ≥3 primary care clinic visits. RESULTS: The cohort's mean age was 74.3 years (SD 8.1), with 51.3% exposed to CNS and 62.8% to non-CNS PIMs. Use of CNS and non-CNS PIMs, respectively, was associated with a reduced risk of readmission, with an adjusted hazard ratio (aHR) of 0.93 (95% CI = 0.89-0.96) for ≥2 (vs 0) CNS PIMs and an aHR of 0.85 (95% CI = 0.82-0.88) for ≥2 (vs 0) non-CNS PIMs. Use of CNS PIMs (≥2 vs 0) was associated with increased risk of mortality (aHR = 1.37 [95% CI = 1.25-1.51]), whereas non-CNS PIMs use was associated with a reduced risk of mortality (aHR = 0.75 [95% CI = 0.69-0.82]). CONCLUSION AND RELEVANCE: PIMs were highly common in this veteran cohort, and the association with outcomes differed by PIMs. Thus, it is important to consider whether PIMs are CNS acting to optimize short-term posthospitalization outcomes.

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS: We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS: There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40- to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40- to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS: Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade.

Racial and Ethnic Differences in Multimorbidity Changes Over Time.

BACKGROUND: Our understanding of how multimorbidity progresses and changes is nascent. OBJECTIVES: Assess multimorbidity changes among racially/ethnically diverse middle-aged and older adults. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study using latent class analysis to identify multimorbidity combinations over 16 years, and multinomial logistic models to assess change relative to baseline class membership. Health and Retirement Study respondents (age 51 y and above) in 1998 and followed through 2014 (N=17,297). MEASURES: Multimorbidity latent classes of: hypertension, heart disease, lung disease, diabetes, cancer, arthritis, stroke, high depressive symptoms. RESULTS: Three latent classes were identified in 1998: minimal disease (45.8% of participants), cardiovascular-musculoskeletal (34.6%), cardiovascular-musculoskeletal-mental (19.6%); and 3 in 2014: cardiovascular-musculoskeletal (13%), cardiovascular-musculoskeletal-metabolic (12%), multisystem multimorbidity (15%). Remaining participants were deceased (48%) or lost to follow-up (12%) by 2014. Compared with minimal disease, individuals in cardiovascular-musculoskeletal in 1998 were more likely to be in multisystem multimorbidity in 2014 [odds ratio (OR)=1.78, P<0.001], and individuals in cardiovascular-musculoskeletal-mental in 1998 were more likely to be deceased (OR=2.45, P<0.001) or lost to follow-up (OR=3.08, P<0.001). Hispanic and Black Americans were more likely than White Americans to be in multisystem multimorbidity in 2014 (OR=1.67, P=0.042; OR=2.60, P<0.001, respectively). Black compared with White Americans were more likely to be deceased (OR=1.62, P=0.01) or lost to follow-up (OR=2.11, P<0.001) by 2014. CONCLUSIONS AND RELEVANCE: Racial/ethnic older adults are more likely to accumulate morbidity and die compared with White peers, and should be the focus of targeted and enhanced efforts to prevent and/or delay progression to more complex multimorbidity patterns.

Comorbid conditions and emergency department treat and release utilization in multimorbid persons with cognitive impairment.

BACKGROUND: There is an increasing focus in the emergency department (ED) on addressing the needs of persons with cognitive impairment, most of whom have multiple chronic conditions. We investigated which common comorbidities among multimorbid persons with cognitive impairment conferred increased risk for ED treat and release utilization. METHODS: We examined the association of 16 chronic conditions on use of ED treat and release visit utilization among 1006 adults with cognitive impairment and ≥ 2 comorbidities using the nationally-representative National Health and Aging Trends Study merged with Fee-For-Service Medicare claims data, 2011-2015. RESULTS: At baseline, 28.5% had ≥6 conditions and 35.4% were ≥ 85 years old. After controlling for sex, age, race, education, urban-living, number of disabled activities of daily living, and sampling strata, we found significantly increased adjusted risk ratios (aRR) of ED treat and release visits for persons with depression (aRR 1.38 95% CI 1.15-1.65) representing 78/100 person-years, and osteoarthritis or rheumatoid arthritis (aRR 1.32 95% CI 1.12-1.57) representing 71/100 person-years. At baseline 93.9% had ≥1 informal caregiver and 69.7% had a caregiver that helped with medications or attended physician visits. CONCLUSION: These results show that multimorbid cognitively impaired older adults with depression or osteoarthritis or rheumatoid arthritis are at higher risk of ED treat and release visits. Future ED research with multimorbid cognitively impaired persons may explore behavioral aspects of depression and/or pain and flairs associated with osteoarthritis or rheumatoid arthritis, as well as the role of informal caregivers in the care of these conditions.

Health-care use and cost for multimorbid persons with dementia in the National Health and Aging Trends Study.

BACKGROUND: Most persons with dementia have multiple chronic conditions; however, it is unclear whether co-existing chronic conditions contribute to health-care use and cost. METHODS: Persons with dementia and ≥2 chronic conditions using the National Health and Aging Trends Study and Medicare claims data, 2011 to 2014. RESULTS: Chronic kidney disease and ischemic heart disease were significantly associated with increased adjusted risk ratios of annual hospitalizations, hospitalization costs, and direct medical costs. Depression, hypertension, and stroke or transient ischemic attack were associated with direct medical and societal costs, while atrial fibrillation was associated with increased hospital and direct medical costs. No chronic condition was associated with informal care costs. CONCLUSIONS: Among older adults with dementia, proactive and ambulatory care that includes informal caregivers along with primary and specialty providers, may offer promise to decrease use and costs for chronic kidney disease, ischemic heart disease, atrial fibrillation, depression, and hypertension.

Are China's oldest-old living longer with less disability? A longitudinal modeling analysis of birth cohorts born 10 years apart.

BACKGROUND: China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group-they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old-that is, whether successive generations are living longer and with less disability-is of great importance for policy and planning purposes. METHODS: We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment. RESULTS: More recently born Chinese octogenarians (born 1919-1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909-1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenarians. Subgroup analyses revealed that gains in partial LE and DFLE primarily occurred among the urban resident population. CONCLUSIONS: Successive generations of China's oldest-old are living with less disability as a whole, and LE is expanding among octogenarians. However, we found a widening urban-rural disparity in longevity and disability, highlighting the need to improve policies to alleviate health inequality throughout the population.

Functional Trajectories Before and After Major Surgery in Older Adults.

OBJECTIVES: We hypothesized that distinct sets of functional trajectories can be identified in the year before and after major surgery, with unique transition probabilities from pre to postsurgical functional trajectories, and that outcomes would be better among participants undergoing elective versus nonelective surgery. BACKGROUND: Major surgery is common and can be highly morbid in older persons. The relationship between the course of disability (ie, functional trajectory) before and after surgery in older adults has not been well-studied for most operations. METHODS: Prospective cohort study of 754 community-living persons 70 years or older. The analytic sample included 250 participants who underwent their first major surgery during the study period. RESULTS: Before surgery, 4 functional trajectories were identified: no disability (n = 60, 24.0%), and mild (n = 84, 33.6%), moderate (n = 73, 29.2%), and severe (n = 33, 13.2%) disability. After surgery, 4 functional trajectories were identified: rapid (n = 39, 15.6%), gradual (n = 76, 30.4%), partial (n = 70, 28.0%), and little (n = 57, 22.8%) improvement. Rapid improvement was seen for n = 31 (51.7%) participants with no disability before surgery, but was uncommon among those with mild disability (n = 8, 9.5%) and was not observed in the moderate and severe trajectory groups. For participants with mild to moderate disability before surgery, gradual improvement (n = 46, 54.8%) and partial improvement (n = 36, 49.3%) were most common. Most participants with severe disability (n = 27, 81.8%) before surgery exhibited little improvement. Outcomes were better for participants undergoing elective versus nonelective surgery. CONCLUSIONS: Functional prognosis in the year after major surgery is highly dependent on premorbid function.

Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project.

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40-80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.

The effect of intervening hospitalizations on the benefit of structured physical activity in promoting independent mobility among community-living older persons: secondary analysis of a randomized controlled trial.

BACKGROUND: Among older persons, disability is often precipitated by intervening illnesses and injuries leading to hospitalization. In the Lifestyle Interventions and Independence for Elders (LIFE) Study, a structured moderate-intensity physical activity program, compared with a health education program, was shown to significantly reduce the amount of time spent with major mobility disability (MMD) over the course of 3.5 years. We aimed to determine whether the benefit of the physical activity program in promoting independent mobility was diminished in the setting of intervening hospitalizations. METHODS: We analyzed data from a single-blinded, parallel group randomized trial (ClinicalTrials.gov: NCT01072500). In this trial, 1635 sedentary persons, aged 70-89 years, who had functional limitations but were able to walk 400 m, were randomized from eight US centers between February 2010 and December 2013: 818 to physical activity (800 received intervention) and 817 to health education (805 received intervention). Intervening hospitalizations and MMD, defined as the inability to walk 400 m, were assessed every 6 months for up to 3.5 years. RESULTS: For both the physical activity and health education groups, intervening hospitalizations were strongly associated with the initial onset of MMD and inversely associated with recovery from MMD, defined as a transition from initial MMD onset to no MMD. The benefit of the physical activity intervention did not differ significantly based on hospital exposure. For onset of MMD, the hazard ratios (HR) were 0.79 (95% confidence interval [CI] 0.58-1.1) and 0.77 (0.62-0.95) in the presence and absence of intervening hospitalizations, respectively (P-interaction, 0.903). For recovery of MMD, the magnitude of effect was modestly greater among participants who were hospitalized (HR 1.5, 95% CI 0.71-3.0) than in those who were not hospitalized (HR 1.2, 95% CI 0.88-1.7), but this difference did not achieve statistical significance (P-interaction, 0.670). CONCLUSIONS: Intervening hospitalizations had strong deleterious effects on the onset of MMD and recovery from MMD, but did not diminish the beneficial effect of the LIFE physical activity intervention in promoting independent mobility. To achieve sustained benefits over time, structured physical activity programs should be designed to accommodate acute illnesses and injuries leading to hospitalizations given their high frequency in older persons with functional limitations. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01072500 .

Polypharmacy in older adults: Association Rule and Frequent-Set Analysis to evaluate concomitant medication use.

The aim of this study was to apply Association Rule and Frequent-Set analysis, and novel means of data visualisation to ascertain patterns of medication use and medication combinations contributing to medication group clusters according to geriatric syndrome status in older adults. Participants were community-dwelling men (aged ≥70 years, n=1686), Sydney, Australia. Medication exposure was categorised at medication class level and data were analysed according to geriatric syndrome status (presence of at least one syndrome including frailty, falls, cognitive impairment and urinary incontinence). Association Rule and Frequent-Set analysis were performed to identify "interesting" patterns of medication combinations that occur together. This analysis involves advanced computer algorithms that investigated all possible combinations of medications in the dataset in order to identify those which are observed more or much less frequently than expected. Frequent-Set Analysis demonstrated one unexpected medication combination, antiulcer and antidiabetic medications (3.5% of participants) in the overall population (n=1687). Frequency of medication combinations was similar in participants with (n=666) and without (n=1020) geriatric syndromes. Among participants with geriatric syndromes, the most frequent combinations included antigout with lipid-lowering agents (5.7%) followed by angiotensin II and diuretics combination (22%). This novel methodology can be used to detect common medication combinations overall by data visualisation, and against specific adverse drug reactions such as geriatric syndromes. This methodology may be a valuable pharmacovigilance approach to monitor large databases for the safety of medications.

Emergency Department Visits Without Hospitalization Are Associated With Functional Decline in Older Persons.

STUDY OBJECTIVE: Among older persons, disability and functional decline are associated with increased mortality, institutionalization, and costs. The aim of the study was to determine whether illnesses and injuries leading to an emergency department (ED) visit but not hospitalization are associated with functional decline among community-living older persons. METHODS: From a cohort of 754 community-living older persons who have been followed with monthly interviews for up to 14 years, we matched 813 ED visits without hospitalization (ED only) to 813 observations without an ED visit or hospitalization (control). We compared the course of disability during the following 6 months between the 2 matched groups. To establish a frame of reference, we also compared the ED-only group with an unmatched group who were hospitalized after an ED visit (ED-hospitalized). Disability scores (range 0 [lowest] to 13 [highest]) were compared using generalized linear models adjusted for relevant covariates. Admission to a nursing home and mortality were evaluated as secondary outcomes. RESULTS: The ED-only and control groups were well matched. For both groups, the mean age was 84 years, and 69% were women. The baseline disability scores were 3.4 and 3.6 in the ED-only and control groups, respectively. During the 6-month follow-up period, the ED-only group had significantly higher disability scores than the control group, with an adjusted risk ratio of 1.14 (95% confidence interval [CI] 1.09 to 1.19). Compared with participants in the ED-only group, those who were hospitalized after an ED visit had disability scores that were significantly higher (risk ratio 1.17; 95% CI 1.12 to 1.22). Both nursing home admissions (hazard ratio 3.11; 95% CI 2.05 to 4.72) and mortality (hazard ratio 1.93; 95% CI 1.07 to 3.49) were higher in the ED-only group versus control group during the 6-month follow-up period. CONCLUSION: Although not as debilitating as an acute hospitalization, illnesses and injuries leading to an ED visit without hospitalization were associated with a clinically meaningful decline in functional status during the following 6 months, suggesting that the period after an ED visit represents a vulnerable time for community-living older persons.

Effect of Structured Physical Activity on Overall Burden and Transitions Between States of Major Mobility Disability in Older Persons: Secondary Analysis of a Randomized Trial.

Background: The total time a patient is disabled likely has a greater influence on his or her quality of life than the initial occurrence of disability alone. Objective: To compare the effect of a long-term, structured physical activity program with that of a health education intervention on the proportion of patient assessments indicating major mobility disability (MMD) (that is, MMD burden) and on the risk for transitions into and out of MMD. Design: Single-blinded, parallel-group, randomized trial. (ClinicalTrials.gov: NCT01072500). Setting: 8 U.S. centers between February 2010 and December 2013. Participants: 1635 sedentary persons, aged 70 to 89 years, who had functional limitations but could walk 400 m. Intervention: Physical activity (n = 818) and health education (n = 817). Measurements: MMD, defined as the inability to walk 400 m, was assessed every 6 months for up to 3.5 years. Results: During a median follow-up of 2.7 years, the proportion of assessments showing MMD was substantially lower in the physical activity (0.13 [95% CI, 0.11 to 0.15]) than the health education (0.17 [CI, 0.15 to 0.19]) group, yielding a risk ratio of 0.75 (CI, 0.64 to 0.89). In a multistate model, the hazard ratios for comparisons of physical activity with health education were 0.87 (CI, 0.73 to 1.03) for the transition from no MMD to MMD; 0.52 (CI, 0.10 to 2.67) for no MMD to death; 1.33 (CI, 0.99 to 1.77) for MMD to no MMD; and 1.92 (CI, 1.15 to 3.20) for MMD to death. Limitation: The intention-to-treat principle was maintained for MMD burden and first transition out of no MMD, but not for subsequent transitions. Conclusion: A structured physical activity program reduced the MMD burden for an extended period, in part through enhanced recovery after the onset of disability and diminished risk for subsequent disability episodes. Primary Funding Source: National Institute on Aging, National Institutes of Health.

Improving the quality of survivorship for older adults with cancer.

In May 2015, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging through a U13 grant, convened a conference to identify research priorities to help design and implement intervention studies to improve the quality of life and survivorship of older, frailer adults with cancer. Conference attendees included researchers with multidisciplinary expertise and advocates. It was concluded that future intervention trials for older adults with cancer should: 1) rigorously test interventions to prevent the decline of or improve health status, especially interventions focused on optimizing physical performance, nutritional status, and cognition while undergoing cancer treatment; 2) use standardized care plans based on geriatric assessment findings to guide targeted interventions; and 3) incorporate the principles of geriatrics into survivorship care plans. Also highlighted was the need to integrate the expertise of interdisciplinary team members into geriatric oncology research, improve funding mechanisms to support geriatric oncology research, and disseminate high-impact results to the research and clinical community. In conjunction with the 2 prior U13 meetings, this conference provided the framework for future research to improve the evidence base for the clinical care of older adults with cancer. Cancer 2016;122:2459-68. © 2016 American Cancer Society.

Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults.

We evaluated in vivo innate immune responses in monocyte populations from 67 young (aged 21-30 years) and older (aged ≥65 years) adults before and after influenza vaccination. CD14(+)CD16(+) inflammatory monocytes were induced after vaccination in both young and older adults. In classical CD14(+)CD16(-) and inflammatory monocytes, production of tumor necrosis factor α and interleukin 6, as measured by intracellular staining, was strongly induced after vaccination. Cytokine production was strongly associated with influenza vaccine antibody response; the highest levels were found as late as day 28 after vaccination in young subjects and were substantially diminished in older subjects. Notably, levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were markedly elevated in monocytes from older subjects before and after vaccination. In purified monocytes, we found age-associated elevation in phosphorylated signal transducer and activator of transcription-3, and decreased serine 359 phosphorylation of the negative IL-10 regulator dual-specificity phosphatase 1. These findings for the first time implicate dysregulated IL-10 production in impaired vaccine responses in older adults.

Functional trajectories in the year before hospice.

PURPOSE: We undertook a study to identify distinct functional trajectories in the year before hospice, to determine how patients with these trajectories differ according to demographic characteristics and hospice diagnosis, and to evaluate the association between these trajectories and subsequent outcomes. METHODS: From an ongoing cohort study of 754 community-living persons aged 70 years or older, we evaluated data on 213 persons who were subsequently enrolled in hospice from March 1998 to December 2011. Disability in 13 basic, instrumental, and mobility activities was assessed during monthly telephone interviews through June 2012. RESULTS: In the year before hospice, we identified 5 clinically distinct functional trajectories, representing worsening cumulative burden of disability: late decline (10.8%), accelerated (10.8%), moderate (21.1%), progressively severe (24.9%), and persistently severe (32.4%). Participants with a cancer diagnosis (34.7%) had the most favorable functional trajectories (ie, lowest burden of disability), whereas those with neurodegenerative disease (21.1%) had the worst. Median survival in hospice was only 14 days and did not differ significantly by functional trajectory. Compared with participants in the persistently severe trajectory, those in the moderate trajectory had the highest likelihood of surviving and being independent in at least 1 activity in the month after hospice admission (adjusted odds ratio = 5.5; 95% CI, 1.9-35.9). CONCLUSIONS: The course of disability in the year before hospice differs greatly among older persons but is particularly poor among those with neurodegenerative disease. Late admission to hospice (as shown by the short survival), coupled with high levels of severe disability before hospice, highlight potential unmet palliative care needs for many older persons at the end of life.

A longitudinal, observational study with many repeated measures demonstrated improved precision of individual survival curves using Bayesian joint modeling of disability and survival.

UNLABELLED: BACKGROUND/STUDY CONTEXT: It has not been previously demonstrated whether Bayesian joint modeling (BJM) of disability and survival can, under certain conditions, improve precision of individual survival curves. METHODS: A longitudinal, observational study wherein 754 initially nondisabled community-dwelling adults in greater New Haven, Connecticut, were observed on a monthly basis for over 10 years. RESULTS: In this study, BJM exploited many monthly observations to demonstrate, relative to a separate survival model with adjustment, improved precision of individual survival curves, permitting detection of significant differences between survival curves of two similar individuals. The gain in precision was lost when using only those observations from intervals of 6, 9, or 12 months. CONCLUSION: When there are many repeated measures, BJM of longitudinal functional disability and interval-censored survival can potentially increase the precision of individual survival curves relative to those from a separate survival model. This may facilitate the identification of significant differences between individual survival curves, a useful result usually precluded by the large variability inherent to individual-level estimates from stand-alone survival models.

Baseline cluster membership demonstrates positive associations with first occurrence of multiple gerontologic outcomes over 10 years.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The potential of cluster analysis (CA) as a baseline predictor of multivariate gerontologic outcomes over a long period of time has not been previously demonstrated. METHODS: Restricting candidate variables to a small group of established predictors of deleterious gerontologic outcomes, various CA methods were applied to baseline values from 754 nondisabled, community-living persons, aged 70 years or older. The best cluster solution yielded at baseline was subsequently used as a fixed explanatory variable in time-to-event models of the first occurrence of the following outcomes: any disability in four activities of daily living, any disability in four mobility measures, and death. Each outcome was recorded through a maximum of 129 months or death. Associations between baseline ordinal cluster level and first occurrence of all three outcomes were modeled over a 10-year period with proportional hazards regression and compared with the associations yielded by the analogous latent class analysis (LCA) solution. RESULTS: The final cluster-defining variables were continuous measures of cognitive status and depressive symptoms, and dichotomous indicators of slow gait and exhaustion. The best solution yielded by baseline values of these variables was obtained with a K-means algorithm and cosine similarity and consisted of three clusters representing increasing levels of impairment. After adjustment for age, sex, ethnic group, and number of chronic conditions, baseline ordinal cluster level demonstrated significantly positive associations with all three outcomes over a 10-year period that were equivalent to those from the corresponding LCA solution. CONCLUSION: These findings suggest that baseline clusters based on previously established explanatory variables have potential to predict multivariate gerontologic outcomes over a long period of time.