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Antibodies play a critical role in protection against influenza; yet titers and viral neutralization represent incomplete correlates of immunity. Instead, the ability of antibodies to leverage the antiviral power of the innate immune system has been implicated in protection from and clearance of influenza infection. Here, post-hoc analysis of the humoral immune response to influenza is comprehensively profiled in a cohort of vaccinated older adults (65 +) monitored for influenza infection during the 2012/2013 season in the United States (NCT: 01427309). While robust humoral immune responses arose against the vaccine and circulating strains, influenza-specific antibody effector profiles differed in individuals that later became infected with influenza, who are deficient in NK cell activating antibodies to both hemagglutinin and neuraminidase, compared to individuals who remained uninfected. Furthermore, NK cell activation was strongly associated with the NK cell senescence marker CD57, arguing for the need for selective induction of influenza-specific afucosylated NK activating antibodies in older adults to achieve protection. High dose vaccination, currently used for older adults, was insufficient to generate this NK cell-activating humoral response. Next generation vaccines able to selectively bolster NK cell activating antibodies may be required to achieve protection in the setting of progressively senescent NK cells. Antibodies play a crucial role in protection from influenza virus infection, but functional details, particularly in older adults, are incomplete. Here the authors show that NK cell-activating antibodies are associated with protection from influenza infection in vaccinated older adults. [ABSTRACT FROM AUTHOR]

An introduction is presented concerning an article by Blaum et al and Naik et al concerning the implementing of patient-centered care in the U.S. healthcare system. [ABSTRACT FROM AUTHOR]

Background. Although vitamin D has been mechanistically linked to insulin secretion and sensitivity, it remains unclear whether low 25-hydroxyvitamin D levels confer an increased risk of impaired glucose metabolism. We evaluated the relationship between vitamin D insufficiency (25-hydroxyvitamin D < 20ng/mL) and abnormal hemoglobin A1c (A1c) (>6.5%) in community-dwelling older persons and examined whether this relationship differed according to race. Methods. Participants were 2,193 persons of age 70-79 years at Year 1 (52% women; 37% black) in the Health, Aging, and Body Composition study who had clinic visits at Years 2 and 4. Logistic regression analyses, adjusted for potential confounders, were used to evaluate the association between vitamin D insufficiency and abnormal A1c 2 years later. Interaction of race and vitamin D insufficiency was tested. Results. A total of 665 (30%) and 301 (14%) of the participants had vitamin D insufficiency at Year 2 and abnormal A1c at Year 4, respectively. After controlling for demographics, other potential confounders, and diabetes status at Year 4 (n = 477 diabetics), we found that vitamin D insufficiency was associated with an increased likelihood of having abnormal A1c (odds ratio = 1.56; 95% CI: 1.03-2.37). We also found that this relationship persisted among the 1,765 participants without diabetes in Year 2 (odds ratio = 2.33 ; 95% CI: 1.00-5.40). Findings did not differ by race. Conclusions. Vitamin D insufficiency was associated with abnormal A1c levels among black and white older persons independent of diabetes status. Future studies are needed to establish the temporal relationship between vitamin D and A1c in diverse samples of older persons. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the independent and joint effects of C-reactive protein ( CRP) and 25- OH vitamin D (25( OH) D) levels on mobility disability in older persons. Design U. S. population-based cross-sectional study. Setting National Health and Nutrition Examination Surveys (2001-2002). Participants Individuals aged 50 and older (N = 1,826). Measurements C-reactive protein (mg/dL), with high CRP defined as ≥0.2 mg/dL, and 25( OH) D levels (ng/mL) operationalized as severe deficiency (<10 ng/mL), deficiency (10-19.9 ng/mL), insufficiency (20-29.9 ng/mL), and normal (≥30 ng/mL). Mobility disability was operationalized as gait speed of <0.8 m/s while completing a 20-foot walk (6.1 m). Results High CRP and low 25( OH) D levels were associated with slow gait speed. Individuals with high CRP levels and severe vitamin D deficiency were more likely to have slow gait speed than were those with neither risk factor (odds ratio = 3.54, 95% confidence interval = 1.42-8.84, P = .007). A significant positive association between vitamin D level and gait speed was found only in those with high CRP in stratified analyses. Whites and blacks showed similar findings as the overall population. Conclusion These findings provide evidence of a potential joint effect of vitamin D and CRP on gait speed, suggesting that evaluation and correction of vitamin D levels may be especially important in individuals with high CRP levels. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine whether adjustment of muscle mass for height2 or for body mass represents a more-relevant predictor of physical performance. DESIGN: Cross-sectional study, using baseline data from a trial comparing upper- and lower-body training. SETTING: Women recruited from the community and gynecological practices in Connecticut. PARTICIPANTS: One hundred eighty-nine healthy older (aged 67.5 ± 4.8), active women receiving estrogen for osteoporosis over 2 years. MEASUREMENTS: Total and appendicular skeletal muscle (ASM) and fat mass (AFM) were determined using dual x-ray absorptiometry. Physical performance, muscle strength, and fitness measures were obtained at baseline. RESULTS: Adjusting ASM for height2 identifies lean women who are sarcopenic according to published standards yet fails to identify overweight and obese women whose ASM adjusted for body mass is low. ASM divided by body mass (ASM/body mass) is a stronger physical performance predictor, explaining 32.5%, 13.5%, 11.6%, 6.3%, and 6.8% of the variance in maximum time on treadmill, 6-minute walk, gait speed, 8-foot walk, and single leg stance, respectively, whereas ASM divided by height in m2 (ASM/height2) explained only 2.9%, 0.2%, 2.0%, 0.04%, and 0.1%. Multivariate modeling demonstrated considerable overlap in aspects of ASM/body mass and AFM/body mass associated with performance, with ASM/body mass dominant. In contrast, ASM/height2 is a much stronger predictor of leg press 1 repetition maximum and maximum power. CONCLUSION: The results suggest that relative sarcopenia with ASM adjusted for body mass is a better mobility predictor, with absolute sarcopenia a better indicator of isolated muscle group function in healthy postmenopausal women receiving estrogen replacement. [ABSTRACT FROM AUTHOR]

Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients. • Hip fractures in older women are a major public health problem of increasing magnitude. • Most patients do not reach their pre-fracture mobility status after successful surgical repair of a hip fracture. • Exercise can improve physical function after hip fracture surgery. • Testosterone replacement can augment the effects of exercise but its efficacy is unknown in older women with hip fracture. • Topical testosterone plus high-intensity exercise may improve strength and physical function in women after hip fracture. • RRe Results of the STEP-HI study may help to guide decisions on therapies to improve outcomes after hip fracture in older women. [ABSTRACT FROM AUTHOR]

Background: Dementia, depression, and delirium alone or in combination (3Ds) can threaten independence among older adults, and polypharmacy may further accelerate decline. Clinical pharmacists can play an important role on multidisciplinary home-based care teams by identifying medication therapy problems (MTPs) involving cognition. Within a larger ongoing clinical trial, this paper describes cognition-related MTPs and pharmacist recommendations among older adults with 3Ds followed by a home-based care team., Methods: We conducted a retrospective analysis of medication data among Medicare Advantage members aged ≥ 65 years living at home in Connecticut with International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes related to 3Ds; analyses include the first 105 subjects randomized to the home-based care team from March 2017 to January 2019. Advanced practice registered nurses conducted in-home medication reconciliations along with medical and cognitive assessments. Clinical pharmacists then conducted medication reviews centered on agents treating or exacerbating 3Ds. After review by the study advanced practice registered nurse, geriatrician, and psychiatrist, salient recommendations were forwarded to primary care providers for consideration. Medication therapy problems related to cognition were retrospectively abstracted and classified as: (1) indication: underuse or overuse; (2) effectiveness: ineffective agent or low dose (mainly for antidepressants); and (3) safety: undesirable effect (e.g., impaired cognition, dementia treatment side effects), unsafe medication (e.g., potentially inappropriate medications that can harm cognition), drug interaction, or high dose., Results: Pharmacists identified 166 cognitive MTPs, with a mean (standard deviation) of 1.58 (1.35) [range 0-6] MTPs per subject. Indication MTPs represented 34% of total MTPs, of which 79% involved underuse and 21% overuse; effectiveness represented 13% of total MTPs; and safety represented over half (52%) of all MTPs, with benzodiazepines and anticholinergics frequently implicated. Recommendations commonly included medication reduction (discontinuation 23% and dose reduction 19%). We found MTPs involving cognition among most (79%) patients., Conclusions: Our study findings support the role of pharmacists on multidisciplinary teams to identify cognitively harmful medications, dementia treatment side effects, and untreated cognitive conditions., Clinical Trial Registration: ClinicalTrials.gov NCT02945085.

Care management approaches are being widely tested in the Medicare-eligible population to manage chronic conditions, but few have focused on cognitive vulnerability as the pathway to optimizing independence in the community-dwelling older population. Cognitive vulnerability refers to living with dementia, depression, and/or a history of delirium. Many studies have shown that cognitive vulnerability is associated with poor health-related outcomes in community-dwelling older adults, raising the health policy importance of finding evidence-based approaches to improve outcomes for this target population. Moreover, very little is known about effects of care management approaches in the rapidly growing Medicare Advantage population. In response to these knowledge gaps, we are testing the efficacy of an in-home, nurse practitioner-led care management team for adults age ≥ 65 with cognitive vulnerability in a Medicare Advantage population. Older adults and family caregivers randomized either to this multidisciplinary care management team, or to a telephonic care management program routinely offered by our Medicare Advantage partner. The intervention period is 12 months and the primary outcome is any emergency department visit or hospitalization over the 12-month period. In this paper, we report on the rationale for testing a multidisciplinary care management intervention for this target population, and explain how a university-based research team collaborated with a Medicare Advantage insurer to conceptualize and implement the clinical trial. We also provide details on study design, and on components of the in-home and telephonic care management interventions. We conclude with a synopsis of recruitment progress along with selected baseline characteristics of the study cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To examine the prevalence of adverse childhood experiences (ACEs) and the associations of ACEs with psychiatric and substance use disorders among older adults in the United States., Design: Cross-sectional analysis of the 2012-2013 National Epidemiological Survey on Alcohol and Related Conditions Wave III (NESARC-III)., Setting: Nationally representative drug-related health interview survey in the United States., Participants: Survey respondents aged 65 or older (n = 5806 unweighted)., Measurements: ACEs, the key independent variable, were assessed using validated measures. Outcome variables consisted of past-year psychiatric disorders (eg, major depressive disorder and generalized anxiety disorder) and substance use disorders (eg, alcohol use disorder) using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. We estimated the national prevalence of ACEs in older adults and used multivariable-adjusted logistic regression analyses to assess the association between ACEs and the outcomes after adjusting for sociodemographics and clinical comorbidities., Results: Overall, 35.9% of older adults, representative of 14.8 million older adults nationwide, reported some form of ACEs. The most common types were parental psychopathology (20.3%), other traumatic events (14.0%), and physical/psychological abuse (8.4%). Having experienced any ACEs was associated with higher odds of having a past-year psychiatric disorder (adjusted odds ratio = 2.11; 95% confidence interval = 1.74-2.56). Similar results were found for substance use disorders (P < .01)., Conclusion: ACEs are linked to an increased risk for past-year psychiatric and substance use disorders in older adults. ACEs may have long-term effects on older adults' mental well-being. Although further research is needed, preventing ACEs may lead to large improvements in public mental health that persist well into older age. J Am Geriatr Soc 67:2085-2093, 2019., (© 2019 The American Geriatrics Society.)

Advances in understanding fundamental processes of aging have led to a variety of investigational therapies to delay or prevent age-related diseases and conditions. These geroscience therapeutics hold the promise of revolutionizing medical care of older adults by treating the complex syndromes of aging and preserving health and independence. A crucial bottleneck is the study of geroscience therapeutics in early-stage, first-in-human, or proof-of-concept clinical trials. There is a limited pool of clinical investigators with the combination of knowledge and skills at the interface of clinical research, care of older adults, and aging biology needed to successfully design, fund, and implement geroscience trials. Current training pipelines are insufficient to meet the need. The sixth retreat of the National Institute on Aging R24 Geroscience Network brought together basic scientists, gerontologists, clinicians, and clinical researchers from the United States and Europe to discuss how to identify, recruit, and train investigators who can perform early-stage clinical trials in geroscience. We present herein the group's consensus on necessary subject domains and competencies, identification of candidate learners, credentialing learners, and the efficient and rapid implementation of training programs. Foundations and funding agencies have crucial roles to play in catalyzing the development of these programs. Geriatrician investigators are indispensable but cannot meet the need alone. Translational geroscience training programs can create a cadre of groundbreaking investigators from a variety of backgrounds and foster institutional cultures supportive of multidisciplinary translational aging research to turn innovative ideas into transformative therapeutics that can improve the health and independence of older adults. J Am Geriatr Soc 67:1934-1939, 2019., (© 2019 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

The American Geriatrics Society, with support from the National Institute on Aging and other funders, held its ninth Bedside-to-Bench research conference, entitled "Urinary Incontinence in the Older Adult: A Translational Research Agenda for a Complex Geriatric Syndrome," October 16 to 18, 2016, in Bethesda, Maryland. As part of a conference series addressing three common geriatric syndromes-delirium, sleep and circadian rhythm disturbance, and urinary incontinence-the series highlighted relationships and pertinent clinical and pathophysiological commonalities between these conditions. The conference provided a forum for discussing current epidemiology, basic science, and clinical and translational research on urinary incontinence in older adults; for identifying gaps in knowledge; and for developing a research agenda to inform future investigative efforts. The conference also promoted networking involving emerging researchers and thought leaders in the field of incontinence, aging, and other fields of research, as well as National Institutes of Health program personnel., (© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.)

Geriatricians have embraced the term "geriatric syndrome," using it extensively to highlight the unique features of common health conditions in older people. Geriatric syndromes, such as delirium, falls, incontinence, and frailty, are highly prevalent, multifactorial, and associated with substantial morbidity and poor outcomes. Nevertheless, this central geriatric concept has remained poorly defined. This article reviews criteria for defining geriatric syndromes and proposes a balanced approach of developing preliminary criteria based on peer-reviewed evidence. Based on a review of the literature, four shared risk factors-older age, baseline cognitive impairment, baseline functional impairment, and impaired mobility-were identified across five common geriatric syndromes (pressure ulcers, incontinence, falls, functional decline, and delirium). Understanding basic mechanisms involved in geriatric syndromes will be critical to advancing research and developing targeted therapeutic options, although given the complexity of these multifactorial conditions, attempts to define relevant mechanisms will need to incorporate more-complex models, including a focus on synergistic interactions between different risk factors. Finally, major barriers have been identified in translating research advances, such as preventive strategies of proven effectiveness for delirium and falls, into clinical practice and policy initiatives. National strategic initiatives are required to overcome barriers and to achieve clinical, research, and policy advances that will improve quality of life for older persons.