Older adult participation in cancer clinical trials: A systematic review of barriers and interventions.

Cancer is a disease of aging and, as the world's population ages, the number of older persons with cancer is increasing and will make up a growing share of the oncology population in virtually every country. Despite this, older patients remain vastly underrepresented in research that sets the standards for cancer treatments. Consequently, most of what we know about cancer therapeutics is based on clinical trials conducted in younger, healthier patients, and effective strategies to improve clinical trial participation of older adults with cancer remain sparse. For this systematic review, the authors evaluated published studies regarding barriers to participation and interventions to improve participation of older adults in cancer trials. The quality of the available evidence was low and, despite a literature describing multifaceted barriers, only one intervention study aimed to increase enrollment of older adults in trials. The findings starkly amplify the paucity of evidence-based, effective strategies to improve participation of this underrepresented population in cancer trials. Within these limitations, the authors provide their opinion on how the current cancer research infrastructure must be modified to accommodate the needs of older patients. Several underused solutions are offered to expand clinical trials to include older adults with cancer. However, as currently constructed, these recommendations alone will not solve the evidence gap in geriatric oncology, and efforts are needed to meet older and frail adults where they are by expanding clinical trials designed specifically for this population and leveraging real-world data.

Polypharmacy and Deprescribing in Older Adults.

Older adults commonly end up on many medications. Deprescribing is an important part of individualizing care for older adults. It is an opportunity to discuss treatment options and revisit medications that may not have been reassessed in many years. A large evidence base exists in the field, suggesting that deprescribing is feasible and safe, though questions remain about the potential clinical benefits. Deprescribing research faces a myriad of challenges, such as identifying and employing the optimal outcome measures. Further, there is uncertainty about which deprescribing approaches are likely to be most effective and in what contexts. Evidence on barriers and facilitators to deprescribing has underscored how deprescribing in routine clinical practice can be complex and challenging. Thus, finding practical, sustainable ways to implement deprescribing is a priority for future research in the field.

Precision probiotics supplement strategy in aging population based on gut microbiome composition.

With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.

Lower entorhinal cortex thickness is associated with greater financial exploitation vulnerability in cognitively unimpaired older adults.

Research suggests that increased financial exploitation vulnerability due to declining decision making may be an early behavioral manifestation of brain changes occurring in preclinical Alzheimer's disease. One of the earliest documented brain changes during the preclinical phase is neurodegeneration in the entorhinal cortex. The objective of the current study was to examine the association between a measure of financial exploitation vulnerability and thickness in the entorhinal cortex in 97 cognitively unimpaired older adults. We also investigated financial exploitation vulnerability associations with frontal regions typically associated with decision making (e.g. dorsolateral and ventromedial prefrontal cortices), and additionally examined the interactive effect of age and cortical thickness on financial exploitation vulnerability. Results showed that greater financial exploitation vulnerability was associated with significantly lower entorhinal cortex thickness. There was a significant interaction between age and entorhinal cortex thickness on financial exploitation vulnerability, whereby lower entorhinal cortex thickness was associated with greater financial exploitation vulnerability in older participants. When the group was divided by age using a median split (70+ and <70 years old), lower entorhinal cortex thickness was associated with greater vulnerability only in the older group. Collectively, these findings suggest that financial exploitation vulnerability may serve as a behavioral manifestation of entorhinal cortex thinning, a phenomenon observed in suboptimal brain aging and preclinical Alzheimer's disease.

Perceptual training improves audiovisual integration by enhancing alpha-band oscillations and functional connectivity in older adults.

Numerous studies on perceptual training exist, however, most have focused on the precision of temporal audiovisual perception, while fewer have concentrated on ability promotion for audiovisual integration (AVI). To investigate these issues, continuous 5-day audiovisual perceptual training was applied, during which electroencephalography was performed in response to auditory-only (A), visual-only (V) and audiovisual (AV) stimuli before and after training. The results showed that the perceptual sensitivity was greater for training group than for control group and was greater in the posttest than in the pretest. The response to the AV stimulus was significantly faster in the posttest than in the pretest for the older training group but was significantly greater for A and V stimuli for the younger training group. Electroencephalography analysis found higher P3 AVI amplitudes [AV-(A + V)] in the posttest than in the pretest for training group, which were subsequently reflected by an increased alpha (8-12 Hz) oscillatory response and strengthened global functional connectivity (weighted phase lag index). Furthermore, these facilitations were greater for older training groups than for younger training groups. These results confirm the age-related compensatory mechanism for AVI may be strengthened as audiovisual perceptual training progresses, providing an effective candidate for cognitive intervention in older adults.

Mental health, financial, and social outcomes among older adults with probable COVID-19 infection: A longitudinal cohort study.

We investigated the immediate and longer-term impact (over 4-6 months) of probable COVID-19 infection on mental health, wellbeing, financial hardship, and social interactions among older people living in England. Data were analysed from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). The associations of probable COVID-19 infection (first COVID-19 assessment) with depression, anxiety, poor quality of life (QoL), loneliness, financial hardship, and social contact with family/friends at the first and second COVID-19 assessments were tested using linear/logistic regression and were adjusted for pre-pandemic outcome measures. Participants with probable infection had higher levels of depression and anxiety, poorer QoL, and greater loneliness scores compared with those without probable infection at both the first (ORdepression = 1.62, P-value = 0.005; ORanxiety = 1.59, P-value = 0.049; bpoorQoL = 1.34, P < 0.001; bloneliness = 0.49, P < 0.001) and second (ORdepression = 1.56, P-value = 0.003; ORanxiety = 1.55, P-value = 0.041; bpoorQoL = 1.38, P-value < 0.001; bloneliness = 0.31, P-value = 0.024) COVID-19 assessments. Participants with probable infection also experienced greater financial difficulties than those without infection at the first assessment (OR = 1.50, P-value = 0.011). Probable COVID-19 infection is associated with longer-term deterioration of mental health and wellbeing and short-term increases in financial hardship among older adults. It is important to monitor the mental health of older people affected by COVID-19 and provide additional support to those in need.

Coronary artery disease management in older adults: revascularization and exercise training.

The mean age of patients with coronary artery disease (CAD) is steadily increasing. In older patients, there is a tendency to underutilize invasive approach, coronary revascularization, up-to-date pharmacological therapies, and secondary prevention strategies, including cardiac rehabilitation. Older adults with CAD commonly exhibit atypical symptoms, multi-vessel disease involvement, complex coronary anatomy, and a higher presence of risk factors and comorbidities. Although both invasive procedures and medical treatments are characterized by a higher risk of complications, avoidance may result in a suboptimal outcome. Often, overlooked factors, such as coronary microvascular disease, malnutrition, and poor physical performance, play a key role in determining prognosis, yet they are not routinely assessed or addressed in older patients. Historically, clinicians have relied on sub-analyses or observational findings to make clinical decisions, as older adults were frequently excluded or under-represented in clinical studies. Recently, dedicated evidence through randomized clinical trials has become available for older CAD patients. Nevertheless, the management of older CAD patients still raises several important questions. This review aims to comprehensively summarize and critically evaluate this emerging evidence, focusing on invasive management and coronary revascularization. Furthermore, it seeks to contextualize these interventions within the framework of improved risk stratification tools for older CAD patients, through user-friendly scales along with emphasizing the importance of promoting physical activity and exercise training to enhance the outcomes of invasive and medical treatments. This comprehensive approach may represent the key to improving prognosis in the complex and growing patient population of older CAD patients.

Invasive vs. conservative management of older patients with non-ST-elevation acute coronary syndrome: individual patient data meta-analysis.

BACKGROUND AND AIMS: Older patients with non-ST-elevation acute coronary syndrome (NSTEACS) are less likely to receive guideline-recommended care including coronary angiography and revascularization. Evidence-based recommendations regarding interventional management strategies in this patient cohort are scarce. This meta-analysis aimed to assess the impact of routine invasive vs. conservative management of NSTEACS by using individual patient data (IPD) from all available randomized controlled trials (RCTs) including older patients. METHODS: MEDLINE, Web of Science and Scopus were searched between 1 January 2010 and 11 September 2023. RCTs investigating routine invasive and conservative strategies in persons >70 years old with NSTEACS were included. Observational studies or trials involving populations outside the target range were excluded. The primary endpoint was a composite of all-cause mortality and myocardial infarction (MI) at 1 year. One-stage IPD meta-analyses were adopted by use of random-effects and fixed-effect Cox models. This meta-analysis is registered with PROSPERO (CRD42023379819). RESULTS: Six eligible studies were identified including 1479 participants. The primary endpoint occurred in 181 of 736 (24.5%) participants in the invasive management group compared with 215 of 743 (28.9%) participants in the conservative management group with a hazard ratio (HR) from random-effects model of 0.87 (95% CI 0.63-1.22; P = .43). The hazard for MI at 1 year was significantly lower in the invasive group compared with the conservative group (HR from random-effects model 0.62, 95% CI 0.44-0.87; P = .006). Similar results were seen for urgent revascularization (HR from random-effects model 0.41, 95% CI 0.18-0.95; P = .037). There was no significant difference in mortality. CONCLUSIONS: No evidence was found that routine invasive treatment for NSTEACS in older patients reduces the risk of a composite of all-cause mortality and MI within 1 year compared with conservative management. However, there is convincing evidence that invasive treatment significantly lowers the risk of repeat MI or urgent revascularisation. Further evidence is needed from ongoing larger clinical trials.

Immunogenicity and Safety Following 1 Dose of AS01E-Adjuvanted Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults: A Phase 3 Trial.

BACKGROUND: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds. METHODS: This ongoing phase 3 study in ≥60-year-olds evaluates immune persistence until 3 years after RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until 1 year post-dose 1. RESULTS: In total, 1653 participants were vaccinated. One month post-dose 1, neutralization titers increased 10.5-fold (RSV-A) and 7.8-fold (RSV-B) vs pre-dose 1. Titers then declined to levels 4.4-fold (RSV-A) and 3.5-fold (RSV-B) above pre-dose 1 at month 6 and remained 3.1-fold (RSV-A) and 2.3-fold (RSV-B) above pre-dose 1 levels after 1 year. RSVPreF3-binding immunoglobulin G levels and CD4+ T-cell frequencies showed similar kinetics. Solicited administration-site and systemic adverse events (mostly mild to moderate and transient) were reported by 62.2% and 49.5% of participants. Serious adverse events were reported by 3.9% of participants within 6 months post-dose 1; 1 case was considered vaccine related. CONCLUSIONS: One RSVPreF3 OA dose elicited cell-mediated and RSV-A- and RSV-B-specific humoral immune responses that declined over time but remained above pre-dose 1 levels for at least 1 year. The vaccine was well tolerated with an acceptable safety profile. Clinical Trials Registration. NCT04732871 (ClinicalTrials.gov).

Respiratory syncytial virus (RSV) is a major cause of illness and hospitalization in older adults. An RSV vaccine for older adults developed by GSK was recently approved. The vaccine was well tolerated and provided protection against RSV disease in adults aged ≥60 years during at least 1 RSV season. In this ongoing study, we are evaluating the magnitude and durability of the immune response, as well as vaccine safety, until 3 years after vaccination of adults aged ≥60 years from 5 countries. Here, we report the results of an interim analysis until 1 year after vaccination with 1 dose. In total, 1653 participants were vaccinated. We found that the vaccine induced a strong immune response that was evident 1 month after vaccination, after which it declined but persisted for at least 1 year. Study participants most often reported pain at the injection site, muscle pain, tiredness, and headache as adverse reactions, which were mostly mild to moderate and of short duration. One serious adverse reaction was considered related to the vaccine. The long-term immune response that was observed in this study is consistent with the vaccine providing protection during at least 1 RSV season.

Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach.

AIMS/HYPOTHESIS: Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis. METHODS: Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument. RESULTS: Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA1c reduction was similar between SGLT2i and DPP4i (-0.3 mmol/mol [-1.6, 1.1], -0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (-4 mmol/mol [4.8, -3.1], -0.4% [-0.4, -0.3]). CONCLUSIONS/INTERPRETATION: Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.

Exercise-induced cortical disinhibition mediates the relationship between fitness and memory in older adults.

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations.

Sarcopenia and Cardiovascular Diseases.

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be particularly important among those with chronic disease states. Early recognition of sarcopenia is important because it can provide an opportunity for interventions to reverse or delay the progression of muscle disorder, which may ultimately impact cardiovascular outcomes. Relying on body mass index is not useful for screening because many patients will have sarcopenic obesity, a particularly important phenotype among older cardiac patients. In this review, we aimed to: (1) provide a definition of sarcopenia within the context of muscle wasting disorders; (2) summarize the associations between sarcopenia and different cardiovascular diseases; (3) highlight an approach for a diagnostic evaluation; (4) discuss management strategies for sarcopenia; and (5) outline key gaps in knowledge with implications for the future of the field.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons.

BACKGROUND: The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1. METHODS: In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). RESULTS: The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. CONCLUSIONS: One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.

Ballet practice improves neuromuscular and biomechanical responses to an unexpected standing-slip in older adults.

Falls and fall-induced injuries are common and consequential in older adults. Ballet emphasizes full-body coordination, leg strength, and postural control. However, it remains unknown whether ballet can indeed reduce falls in older adults. This study examined biomechanical and neuromuscular responses of older recreational ballet dancers to an unexpected standing-slip. Twenty older ballet dancers (17 females, 3 males) and 23 age- and sex-matched nondancers (19 females, 4 males) were exposed to an unexpected slip during treadmill standing. The slip-faller rate was the primary outcome. The secondary outcomes were kinematic measurements, including dynamic gait stability, slip distance, and recovery stepping performance (step latency, duration, length, and speed). The tertiary outcome was the electromyography latency of leg muscles (bilateral tibialis anterior, medial gastrocnemius, rectus femoris, and biceps femoris). Fewer dancers fell than nondancers after the standing-slip (45% vs. 83%, P = 0.005, d = 0.970). Dancers displayed better stability at recovery foot liftoff (P = 0.006) and touchdown (P = 0.012), a shorter step latency (P = 0.020), shorter step duration (P = 0.011), faster step speed (P = 0.032), and shorter slip distance (P = 0.015) than nondancers. They also exhibited shorter latencies than nondancers for the standing leg rectus femoris (P = 0.028) and tibialis anterior (P = 0.002), and the stepping leg biceps femoris (P = 0.031), tibialis anterior (P = 0.017), and medial gastrocnemius (P = 0.030). The results suggest that older ballet dancers experience a lower fall risk and are more stable than nondancers following an unexpected standing-slip. The greater stability among dancers could be attributed to more biomechanically effective recovery stepping, possibly associated with the ballet-induced neuromuscular benefit-an earlier leg muscle activation.NEW & NOTEWORTHY This is the first study to examine how older ballet dancers respond to an unexpected external slip perturbation while standing. The results suggest that older ballet dancers experience a reduced fall risk after the slip than their nondancer counterparts. The lower fall risk can be accounted for by dancers' quicker neuromuscular reactions to the slip that result in a more effective recovery step and thus higher stability against backward falls due to the slip.

Exercise to socialize? Bidirectional relationships between physical activity and loneliness in middle-aged and older American adults.

Physical inactivity and loneliness are both associated with health risks and can affect each other through various social and behavioral mechanisms. However, current evidence on this relationship is equivocal and mostly based on cross-sectional data. This longitudinal study aimed to determine whether current levels of physical activity (moderate and vigorous intensity) and loneliness are associated with future respective states of themselves and each other. We used data from waves 6-14 (2002-2018) of the Health and Retirement Study (n = 20 134) in a mixed-effects and random-intercept cross-lagged panel model. Analysis showed that current loneliness and physical activity were associated with each future respective state. Additionally, weekly participation in moderate-intensity, but not vigorous-intensity, physical activity was associated with a lower likelihood of becoming lonely in the future (relative risk [RR] = 0.94; 95% CI, 0.90-0.99). However, changes in physical activity were not associated with deviation from a person's typical level of loneliness (for vigorous intensity, mean deviation [MD] = 0.00; 95% CI: -0.04 to 0.03; for moderate-intensity, MD = 0.01; 95% CI: -0.03 to 0.04). Loneliness was not associated with moderate- or vigorous-intensity physical activity in subsequent waves. This suggests that while lower physical activity levels can be associated with future loneliness, changing levels of physical activity has little impact on loneliness at the individual level.

Modeling Risk Factors for Intraindividual Variability: A Mixed-Effects Beta-Binomial Model Applied to Cognitive Function in Older People in the English Longitudinal Study of Ageing.

Cognitive functioning in older age profoundly impacts quality of life and health. While most research on cognition in older age has focused on mean levels, intraindividual variability (IIV) around this may have risk factors and outcomes independent of the mean value. Investigating risk factors associated with IIV has typically involved deriving a summary statistic for each person from residual error around a fitted mean. However, this ignores uncertainty in the estimates, prohibits exploring associations with time-varying factors, and is biased by floor/ceiling effects. To address this, we propose a mixed-effects location scale beta-binomial model for estimating average probability and IIV in a word recall test in the English Longitudinal Study of Ageing. After adjusting for mean performance, an analysis of 9,873 individuals across 7 (mean = 3.4) waves (2002-2015) found IIV to be greater at older ages, with lower education, in females, with more difficulties in activities of daily living, in later birth cohorts, and when interviewers recorded issues potentially affecting test performance. Our study introduces a novel method for identifying groups with greater IIV in bounded discrete outcomes. Our findings have implications for daily functioning and care, and further work is needed to identify the impact for future health outcomes.

A Systematic Approach to Evaluating Instrumental Variable Assumptions: Applied Example of Glucose-lowering Medications and Risk for Hospitalized Heart Failure in Older Adults.

One obstacle to adopting instrumental variable (IV) methods in pharmacoepidemiology is their reliance on strong, unverifiable assumptions. We can falsify IV assumptions by leveraging the causal structure, which can strengthen or refute their plausibility and increase the validity of effect estimates. We illustrate a systematic approach to evaluate calendar time IV assumptions in estimating the known effect of thiazolidinediones on hospitalized heart failure. Using cohort entry time before and after 09/2010, when the U.S. Food and Drug Administration issued a safety communication as a proposed IV, we estimated IV and propensity score-weighted 2-year risk differences (RDs) using Medicare data (2008-2014). We (i) performed inequality tests, (ii) identified the negative control IV/outcome using causal assumptions, (iii) estimated RDs after narrowing the calendar time range and excluding patients likely associated with unmeasured confounding, (iv) derived bounds for RDs, and (v) estimated the proportion of compliers and their characteristics. The findings revealed that IV assumptions were violated and RDs were extreme, but the assumptions became more plausible upon narrowing the calendar time range and restricting the cohort by excluding prevalent heart failure (the strongest measured predictor of outcome). Systematically evaluating IV assumptions could help detect bias in IV estimators and increase their validity.

Translation and validation of a lifestyle questionnaire related to prostate cancer.

BACKGROUND: Valid and reliable instruments are needed to measure prostate cancer-related lifestyle changes, plan evidence-based interventions to modify lifestyle, and improve treatment outcomes. Due to the lack of appropriate instruments, this study was conducted to translate the Effects of Prostate Cancer upon Lifestyle Questionnaire (EPCLQ) into Persian and examine its psychometric properties in a sample of Iranian older adults with prostate cancer. METHODS: This methodological study was carried out between 2021 and 2022. Initially, the EPCLQ, comprising 36 items, was translated into Persian through a meticulous translation and back-translation procedure. Subsequent steps involved the assessment of face validity, qualitative content validity, content validity index, content validity ratio, construct validity via confirmatory factor analysis, and reliability testing of the Persian version of the EPCLQ. RESULTS: The psychometric evaluation led to the exclusion of 4 items from the EPCLQ. The refined model demonstrated satisfactory fit indices (PCFI = 0.732, PNFI = 0.696, CMIN/DF = 2.29, RMSEA = 0.072, IFI = 0.920, CFI = 0.919, and GFI = 0.971), indicating an appropriate fit of the final model. The internal consistency, as measured by Cronbach's alpha, was 0.67, and the intraclass correlation coefficient for the questionnaire was 0.938, reflecting high reliability. CONCLUSIONS: The Persian version of the EPCLQ, now consisting of 32 items, has been validated and is reliable for assessing the impact of prostate cancer on lifestyle among older adults. Its simplicity and the clarity of the items make it suitable for use in clinical settings or during home visits for follow-up assessments.

The association between food access and frailty among older adults with gastrointestinal malignancies-The CARE Registry.

BACKGROUND: Food access is associated with higher gastrointestinal (GI) cancer mortality; however, its association with frailty, which is a predictor of premature mortality among older adults with cancer, is less understood. METHODS: The authors included 880 adults aged 60 years and older who were recently diagnosed with GI cancers and were undergoing self-reported geriatric assessment at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. Food access was measured using the 2019 US Department of Agriculture Economic Research Service designation low-income, low-access (LILA), classifying census tracts based on income and/or access to food stores at various distances. The primary outcome was frailty on the CARE (Cancer and Aging Resilience Evaluation) Frailty Index, a composite of the proportion of impaired geriatric assessment measures. The authors examined the LILA-frailty association with modified Poisson regression accounting for census-tract clustering. RESULTS: The median patient age was 69 years, 58.1% were men, 22.5% were non-Hispanic Black, 29.2% had colorectal cancer, 28.0% had pancreatic cancer, 70.1% presented with stage III/IV disease, and 34.9% were frail. A higher proportion in LILA areas were non-Hispanic Black (44.1% vs. 10.8%; p < .001) and had less education (high school or less: 48.1% vs. 37.9%; p = .020). Adjusting for age, race and ethnicity, sex, cancer type and stage, and education, an LILA designation was associated with 58% greater odds of worsening frailty status (95% confidence interval, 1.18-2.12). An analysis of LILA subcategories revealed that associations were maintained across all LILA measures. CONCLUSIONS: Poor food access was associated with a greater risk of frailty among newly diagnosed older adults with GI cancers before they received systemic treatment. Intervening on local food access, particularly in LILA areas, may be a target for improving rates of frailty and promoting health equity in this population.