Association of Coprescribing of Gabapentinoid and Other Psychoactive Medications With Altered Mental Status and Falls in Adults Receiving Dialysis.

RATIONALE & OBJECTIVE: Prescribing psychoactive medications for patients with kidney disease is common, but for patients receiving dialysis, some medications may be inappropriate. We evaluated the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (PPIMs) (e.g., sedatives, opioids) with altered mental status (AMS) and falls, and whether the associations are modified by frailty. STUDY DESIGN: Observational cohort study. SETTING: & Participants: Adults receiving dialysis represented in the United States Renal Data System who had an active gabapentinoid prescription and no other PPIM prescriptions in the prior 6 months. EXPOSURE: PPIM coprescribing, or the presence of overlapping prescriptions of a gabapentinoid and ≥1 additional PPIM. OUTCOMES: Acute care visits for AMS and injurious falls. ANALYTICAL APPROACH: Prentice-Williams-Petersen Gap Time models estimated the association between PPIM coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty (assessed by a validated frailty index (FI)). Each model tested for interaction between PPIM coprescribing and frailty. RESULTS: Overall, PPIM coprescribing was associated with increased hazard of AMS (HR: 1.66 [95% CI 1.44, 1.92]) and falls (HR: 1.55 [95% CI 1.36, 1.77]). Frailty significantly modified the effect of PPIM coprescribing on the hazard of AMS (interaction p=0.01), but not falls. Among individuals with low frailty (FI=0.15), the hazard ratio for AMS with PPIM co-prescribing was 2.14 (95% CI: 1.69, 2.71); while for individuals with severe frailty (FI=0.34), the hazard ratio for AMS with PPIM coprescribing was 1.64 (95% CI: 1.42, 1.89). Individuals with PPIM coprescribing and severe frailty (FI =0.34) had the highest hazard of AMS [HR 4.04 (95% CI: 3.20, 5.10)] and falls [HR 2.77 (95% CI: 2.27, 3.38)] compared to non-frail individuals without PPIM coprescribing. LIMITATIONS: Outcome ascertainment bias; residual confounding. CONCLUSIONS: Compared to gabapentinoid prescriptions alone, PPIM coprescribing was associated with an increased risk of AMS and falls. Clinicians should consider these risks when coprescribing PPIMs to patients receiving dialysis.

Sustained caloric restriction potentiates insulin action by activating prostacyclin synthase.

OBJECTIVE: Caloric restriction (CR) is known to enhance insulin sensitivity and reduce the risk of metabolic disorders; however, its molecular mechanisms are not fully understood. This study aims to elucidate specific proteins and pathways responsible for these benefits. METHODS: We examined adipose tissue from participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy Phase 2 (CALERIE 2) study, comparing proteomic profiles from individuals after 12 and 24 months of CR with baseline and an ad libitum group. Biochemical and cell-specific physiological approaches complemented these analyses. RESULTS: Our data revealed that CR upregulates prostacyclin synthase (PTGIS) in adipose tissue, an enzyme crucial for producing prostacyclin (PGI2). PGI2 improves the ability of insulin to stimulate the tether-containing UBX domain for GLUT4 (TUG) cleavage pathway, which is essential for glucose uptake regulation. Additionally, iloprost, a PGI2 analog, was shown to increase insulin receptor density on cell membranes, increasing glucose uptake in human adipocytes. CR also reduces carbonylation of GLUT4, a modification that is detrimental to GLUT4 function. CONCLUSIONS: CR enhances insulin sensitivity by promoting PTGIS expression and stimulating the TUG cleavage pathway, leading to increased GLUT4 translocation to the cell surface and decreased GLUT4 carbonylation. These findings shed light on the complex molecular mechanisms through which CR favorably impacts insulin sensitivity and metabolic health.

Prediction of individual weight loss using supervised learning: findings from the CALERIETM 2 study.

BACKGROUND: Predicting individual weight loss (WL) responses to lifestyle interventions is challenging but might help practitioners and clinicians select the most promising approach for each individual. OBJECTIVE: The primary aim of this study was to develop machine learning (ML) models to predict individual WL responses using only variables known before starting the intervention. In addition, we used ML to identify pre-intervention variables influencing the individual WL response. METHODS: We used 12-mo data from the comprehensive assessment of long-term effects of reducing intake of energy (CALERIETM) phase 2 study, which aimed to analyze the long-term effects of caloric restriction on human longevity. On the basis of the data from 130 subjects in the intervention group, we developed classification models to predict binary ("Success" and "No/low success") or multiclass ("High success," "Medium success," and "Low/no success") WL outcomes. Additionally, regression models were developed to predict individual weight change (percent). Models were evaluated on the basis of accuracy, sensitivity, specificity (classification models), and root mean squared error (RMSE; regression models). RESULTS: Best classification models used 20-40 predictors and achieved 89%-97% accuracy, 91%-100% sensitivity, and 56%-86% specificity for binary classification. For multiclass classification, accuracy (69%) and sensitivity (50%) tended to be lower. The best regression performance was obtained with 36 variables with an RMSE of 2.84%. Among the 21 variables predicting individual weight change most consistently, we identified 2 novel predictors, namely orgasm satisfaction and sexual behavior/experience. Other common predictors have previously been associated with WL (16) or are already used in traditional prediction models (3). CONCLUSIONS: The prediction models could be implemented by practitioners and clinicians to support the decision of whether lifestyle interventions are sufficient or more aggressive interventions are needed for a given individual, thereby supporting better, faster, data-driven, and unbiased decisions. The CALERIETM phase 2 study was registered at clinicaltrials.gov as NCT00427193.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

CONTEXT: Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. OBJECTIVE: To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. DESIGN: Post-hoc analyses of prospective cohort studies. SETTING: Clinical research center. PATIENTS: Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). INTERVENTIONS: C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. MAIN OUTCOME MEASURES: C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. RESULTS: C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. CONCLUSION: Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.

Psychiatry Resident Physicians Experience Personal and Professional Grief, Burnout and Depression: Results From a National Survey.

BACKGROUND: Resident physicians experience personal and professional stressors throughout training. These experiences may increase levels of burnout, depression, and grief. Understanding how these stressors impact trainees is essential for improving wellbeing during residency. OBJECTIVE: We examined the prevalence and associations between burnout, depression, and grief among a national sample of psychiatry resident physicians. METHODS: A survey including validated scales for burnout (Modified Maslach Burnout Inventory-Health Services Survey [MBI]), depression (Patient Health Questionnaire-9 [PHQ-9]), and grief (Traumatic Grief Inventory Self Report [TGSIR]) was distributed to 296 psychiatry program directors in January 2023 for dispersal to their respective residents. RESULTS: Fifty-seven participants completed the survey out of 245 participants who opened and started the survey (23.3%). All participants were current psychiatry residents. MBI scores averaged 21.2 (SD 6.5, range 11-40); 11 participants reported high levels of burnout (scores >27; 19.3%). PHQ-9 scores averaged 3.42 (SD 3.0, range 0-14), with 8 responses meeting the criteria for moderate depressive symptoms (scores >10-14; 14.0%). Suicidal ideation was reported by 5 of 57 participants (8.7%). TGISR scores averaged 12.2 (SD 11, range 0-43); no participants met the criteria for pathologic grief. TGISR scores were correlated with MBI (r = .30; P = .02) and PHQ-9 scores (r = .53; P < .0001). MBI scores were also correlated with PHQ-9 scores (r = .54; P < .0001). CONCLUSIONS: Non-pathological grief was correlated with burnout and depression. 14% to 20% of psychiatry residents reported clinically significant levels of burnout and depression. Future studies should aim to further characterize burnout, depression, and grief in larger samples of trainees.

Central nervous system medication use around hospitalization.

BACKGROUND: Central nervous system (CNS) medication use is common among older adults, yet the impact of hospitalizations on use remains unclear. This study details CNS medication use, discontinuations, and user profiles during hospitalization periods. METHODS: Retrospective cohort study using electronic health records on patients ≥65 years, from three hospitals (2018-2020), and prescribed a CNS medication around hospitalization (90 days prior to 90 days after). Latent class transitions analysis (LCTA) examined profiles of CNS medication class users across four time points (90 days prior, admission, discharge, 90 days after hospitalization). RESULTS: Among 4666 patients (mean age 74.3 ± 9.3 years; 63% female; 70% White; mean length of stay 4.6 ± 5.6 days (median 3.0 [2.0, 6.0]), the most commonly prescribed CNS medications were antidepressants (56%) and opioids (49%). Overall, 74% (n = 3446) of patients were persistent users of a CNS medication across all four time points; 7% (n = 388) had discontinuations during hospitalization, but of these, 64% (216/388) had new starts or restarts within 90 days after hospitalization. LCTA identified three profile groups: (1) low CNS medication users, 54%-60% of patients; (2) mental health medication users, 30%-36%; and (3) acute/chronic pain medication users, 9%-10%. Probability of staying in same group across the four time points was high (0.88-1.00). Transitioning to the low CNS medication use group was highest from admission to discharge (probability of 9% for pain medication users, 5% for mental health medication users). Female gender increased (OR 2.4, 95% CI 1.3-4.3), while chronic kidney disease lowered (OR 0.5, 0.2-0.9) the odds of transitioning to the low CNS medication use profile between admission and discharge. CONCLUSIONS: CNS medication use stays consistent around hospitalization, with discontinuation more likely between admission and discharge, especially among pain medication users. Further research on patient outcomes is needed to understand the benefits and harms of hospital deprescribing, particularly for medications requiring gradual tapering.

Multimorbidity trajectories in early adulthood and middle age: Findings from the CARDIA prospective cohort study.

Background: Multimorbidity research has focused on the prevalence and consequences of multimorbidity in older populations. Less is known about the accumulation of chronic conditions earlier in the life course. Methods: We identified patterns of longitudinal multimorbidity accumulation using 30 years of data from in-person exams, annual follow-ups, and adjudicated end-points among 4,945 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Chronic conditions included arthritis, asthma, atrial fibrillation, cancer, end stage renal disease, chronic obstructive pulmonary disease, coronary heart disease, diabetes, heart failure, hyperlipidemia, hypertension, and stroke. Trajectory patterns were identified using latent class growth curve models. Results: Mean age (SD) at baseline (1985-6) was 24.9 (3.6), 55% were female, and 51% were Black. The median follow-up was 30 years (interquartile range 25-30). We identified six trajectory classes characterized by when conditions began to accumulate and the rapidity of accumulation: (1) early-fifties, slow, (2) mid-forties, fast, (3) mid-thirties, fast, (4) late-twenties, slow, (5) mid-twenties, slow, and (6) mid-twenties, fast. Compared with participants in the early-fifties, slow trajectory class, participants in mid-twenties, fast were more likely to be female, Black, and currently smoking and had a higher baseline mean waist circumference (83.6 vs. 75.6 cm) and BMI (27.0 vs. 23.4 kg/m2) and lower baseline physical activity (414.1 vs. 442.4 exercise units). Conclusions: A life course approach that recognizes the heterogeneity in patterns of accumulation of chronic conditions from early adulthood into middle age could be helpful for identifying high risk subgroups and developing approaches to delay multimorbidity progression.

Grief Training in Palliative Care Fellowships.

INTRODUCTION: No prior study has assessed grief and bereavement curriculum in Hospice and Palliative Medicine (HPM) fellowship programs in the United States. METHODS: A 14-item survey was created and distributed to Accreditation Council for Graduate Medical Education (ACGME)-accredited HPM fellowship Program Directors to assess program demographics, curriculum emphasis, grief and bereavement programming, and attitudes toward grief and bereavement training for HPM fellows. RESULTS: The overall survey response rate was 63%. Most palliative care programs were academic (74%) and had four or fewer fellows (85%). 90% devoted a minority (0%-10%) of their curriculum to grief and bereavement training. Most programs reported at least some program-led grief and bereavement programming (69%); however, 53% endorsed that fellows are not very or not at all involved in this programming. Almost half of programs only have a small amount of programming related to supporting families after loss (49%). The majority endorsed having a great deal of programming for debriefing or supporting fellows through professional grief (55%), and the most common modalities were debriefing sessions (62%) and ensuring access to mental health resources (41%). The most common ways of teaching grief and bereavement were through bedside/anecdotal teaching and lectures/case conferences. Most program directors felt that palliative care fellowships should provide grief and bereavement training (81%) and consider it important or very important for fellows to learn how to process grief and bereavement (92%). DISCUSSION: It was widely reported by program directors that grief and bereavement training are important curricular components for HPM fellows. Acknowledging professional grief remains an underrecognized need in palliative care training and practice. Our study suggests that for grief and bereavement curricula in HPM fellowships, the time dedicated, specific types, and amount of fellow involvement was highly variable. It will be critical for programs to disseminate best practices to help move toward a more uniform approach for ensuring basic competency in grief and bereavement training in HPM fellowship programs in the United States.

A Pragmatic Clinical Trial of Hearing Screening in Primary Care Clinics: Effect of Setting and Provider Encouragement.

OBJECTIVES: The prevalence of hearing loss increases with age. Untreated hearing loss is associated with poorer communication abilities and negative health consequences, such as increased risk of dementia, increased odds of falling, and depression. Nonetheless, evidence is insufficient to support the benefits of universal hearing screening in asymptomatic older adults. The primary goal of the present study was to compare three hearing screening protocols that differed in their level of support by the primary care (PC) clinic and provider. The protocols varied in setting (in-clinic versus at-home screening) and in primary care provider (PCP) encouragement for hearing screening (yes versus no). DESIGN: We conducted a multisite, pragmatic clinical trial. A total of 660 adults aged 65 to 75 years; 64.1% female; 35.3% African American/Black completed the trial. Three hearing screening protocols were studied, with 220 patients enrolled in each protocol. All protocols included written educational materials about hearing loss and instructions on how to complete the self-administered telephone-based hearing screening but varied in the level of support provided in the clinic setting and by the provider. The protocols were as follows: (1) no provider encouragement to complete the hearing screening at home, (2) provider encouragement to complete the hearing screening at home, and (3) provider encouragement and clinical support to complete the hearing screening after the provider visit while in the clinic. Our primary outcome was the percentage of patients who completed the hearing screening within 60 days of a routine PC visit. Secondary outcomes following patient access of hearing healthcare were also considered and consisted of the percentage of patients who completed and failed the screening and who (1) scheduled, and (2) completed a diagnostic evaluation. For patients who completed the diagnostic evaluation, we also examined the percentage of those who received a hearing loss intervention plan by a hearing healthcare provider. RESULTS: All patients who had provider encouragement and support to complete the screening in the clinic completed the screening (100%) versus 26.8% with encouragement to complete the screening at home. For patients who were offered hearing screening at home, completion rates were similar regardless of provider encouragement (26.8% with encouragement versus 22.7% without encouragement); adjusted odds ratio of 1.25 (95% confidence interval 0.80-1.94). Regarding the secondary outcomes, roughly half (38.9-57.1% depending on group) of all patients who failed the hearing screening scheduled and completed a formal diagnostic evaluation. The percentage of patients who completed a diagnostic evaluation and received a hearing loss intervention plan was 35.0% to 50.0% depending on the group. Rates of a hearing loss intervention plan by audiologists ranged from 28.6% to 47.5% and were higher compared with those by otolaryngology providers, which ranged from 15.0% to 20.8% among the groups. CONCLUSIONS: The results of the pragmatic clinical trial showed that offering provider encouragement and screening facilities in the PC clinic led to a significantly higher rate of adherence with hearing screening associated with a single encounter. However, provider encouragement did not improve the significantly lower rate of adherence with home-based hearing screening.

Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient-reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. METHODS: Twenty older (60-80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate-to-vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check-ins. The primary outcome was a composite metabolic syndrome z-score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein-cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient-reported outcomes. RESULTS: Both groups improved MSSc (absolute change -1.67 ± 0.64 in SWET; -1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between-group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score-28 C-reactive protein, and patient-reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between-group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component-specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score-28 C-reactive protein. CONCLUSION: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient-reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at-risk RA population.

A Detailed Analysis of Cardiac Rehabilitation on 180-Day All-Cause Hospital Readmission and Mortality.

PURPOSE: Cardiac rehabilitation (CR) is endorsed for coronary artery disease (CAD), but studies report inconsistent findings regarding efficacy. The objective of this study was to determine whether confounding factors, potentially contributing to these heterogeneous findings, impact the effect of CR on all-cause readmission and mortality. METHODS: Patients (n = 2641) with CAD, CR eligible, and physically able were identified. Electronic medical records were inspected individually for each patient to extract demographic, clinical characteristic, readmission, and mortality information. Patients (n = 214) attended ≥1 CR session (CR group). Survival was considered free from: all-cause readmission; or composite outcome of all-cause readmission or death. Cox proportional hazards models, adjusting for demographics, comorbidities, and discharge criteria, were used to determine HR with 95% CI and to compare 180-d survival rates between the CR and no-CR groups. RESULTS: During 180 d of follow-up, 12.1% and 18.7% of the CR and non-CR patients were readmitted to the hospital. There was one death (0.5%) in the CR group, while 98 deaths (4.0%) occurred in the non-CR group. After adjustment for age, sex, race, depression, anxiety, dyslipidemia, hypertension, obesity, smoking, type 2 diabetes, and discharge criteria, the final model revealed a significant 42.7% reduction in readmission or mortality risk for patients who attended CR (HR = 0.57: 95% CI, 0.33-0.98; P = .043). CONCLUSIONS: Regardless of demographic characteristics, comorbidities, and cardiovascular discharge criteria, the risk of 180-d all-cause readmission or death was markedly decreased in patients who attended CR compared with those who did not.

Clinical readiness for essential maternal and child health services in Kenya: A cross-sectional survey.

High rates of maternal and neonatal morbidity and mortality in Kenya may be influenced by provider training and knowledge in emergency obstetric and neonatal care in addition to availability of supplies necessary for this care. While post-abortion care is a key aspect of life-saving maternal health care, no validated questionnaires have been published on provider clinical knowledge in this arena. Our aim was to determine provider knowledge of maternal-child health (MCH) emergencies (post-abortion care, pre-eclampsia, postpartum hemorrhage, neonatal resuscitation) and determine factors associated with clinical knowledge. Our secondary aim was to pilot a case-based questionnaire on post-abortion care. We conducted a cross-sectional survey of providers at health facilities in western Kenya providing maternity services. Providers estimated facility capacity through perceived availability of both general and specialized supplies. Providers reported training on the MCH topics and completed case-based questions to assess clinical knowledge. Knowledge was compared between topics using a linear mixed model. Multivariable models identified variables associated with scores by topic. 132 providers at 37 facilities were interviewed. All facilities had access to general supplies at least sometime while specialized supplies were available less frequently. While only 56.8% of providers reported training on post-abortion care, more than 80% reported training on pre-eclampsia, postpartum hemorrhage, and neonatal resuscitation. Providers' clinical knowledge across all topics was low (mean score of 63.3%), with significant differences in scores by topic area. Despite less formal training in the subject area, providers answered 71.6% (SD 16.7%) questions correctly on post-abortion care. Gaps in supply availability, training, and clinical knowledge on MCH emergencies exist. Increasing training on MCH topics may decrease pregnancy and postpartum complications. Further, validated tools to assess knowledge in post-abortion care should be created, particularly in sub-Saharan Africa where legal restrictions on abortion services exist and many abortions are performed in unsafe settings.

Nightshift imposes irregular lifestyle behaviors in police academy trainees.

Study Objective: Shiftwork increases risk for numerous chronic diseases, which is hypothesized to be linked to disruption of circadian timing of lifestyle behaviors. However, empirical data on timing of lifestyle behaviors in real-world shift workers are lacking. To address this, we characterized the regularity of timing of lifestyle behaviors in shift-working police trainees. Methods: Using a two-group observational study design (N = 18), we compared lifestyle behavior timing during 6 weeks of in-class training during dayshift, followed by 6 weeks of field-based training during either dayshift or nightshift. Lifestyle behavior timing, including sleep-wake patterns, physical activity, and meals, was captured using wearable activity trackers and mobile devices. The regularity of lifestyle behavior timing was quantified as an index score, which reflects day-to-day stability on a 24-hour time scale: Sleep Regularity Index, Physical Activity Regularity Index, and Mealtime Regularity Index. Logistic regression was applied to these indices to develop a composite score, termed the Behavior Regularity Index (BRI). Results: Transitioning from dayshift to nightshift significantly worsened the BRI, relative to maintaining a dayshift schedule. Specifically, nightshift led to more irregular sleep-wake timing and meal timing; physical activity timing was not impacted. In contrast, maintaining a dayshift schedule did not impact regularity indices. Conclusions: Nightshift imposed irregular timing of lifestyle behaviors, which is consistent with the hypothesis that circadian disruption contributes to chronic disease risk in shift workers. How to mitigate the negative impact of shiftwork on human health as mediated by irregular timing of sleep-wake patterns and meals deserves exploration.

Factors Associated with COVID-19 Vaccination Promptness after Eligibility in a North Carolina Longitudinal Cohort Study.

Many studies identified factors associated with vaccination intention and hesitancy, but factors associated with vaccination promptness and the effect of vaccination intention on vaccination promptness are unknown. This study identified factors associated with COVID-19 vaccination promptness and evaluated the role of vaccination intention on vaccination promptness in 1223 participants in a community-based longitudinal cohort study (June 2020 to December 2021). Participants answered questions regarding COVID-19 vaccination intention, vaccination status, and reasons for not receiving a vaccine. The association of baseline vaccine hesitancy with vaccination was assessed by the Kaplan-Meier survival analysis. Follow-up analyses tested the importance of other variables predicting vaccination using the Cox proportional hazards model. Older age was associated with shorter time to vaccination (HR = 1.76 [1.37-2.25] 85-year-old versus 65-year-old). Lower education levels (HR = 0.80 [0.69-0.92]), household incomes (HR = 0.84 [0.72-0.98]), and baseline vaccination intention of 'No' (HR = 0.16 [0.11-0.23]) were associated with longer times to vaccination. The most common reasons for not being vaccinated (N = 58) were vaccine safety concerns (n = 33), side effects (n = 28), and vaccine effectiveness (n = 25). Vaccination campaigns that target populations prone to hesitancy and address vaccine safety and effectiveness could be helpful in future vaccination rollouts.

Associations Between Traumatic Brain Injury and Cognitive Decline Among Older Male Veterans: A Twin Study.

BACKGROUND AND OBJECTIVES: Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because twins share many genes and environmental factors, we capitalize on the twin study design to examine the association between lifetime TBI and cognitive decline. METHODS: Participants were members of the National Academy of Sciences-National Research Council's Twin Registry of male veterans of World War II with self or proxy-reported history of TBI and with up to 4 observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random-effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included number of TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [older age TBI]). Models were adjusted for age (centered at 70 years), age-squared, education, wave, twin pair, lifestyle behaviors, and medical conditions. RESULTS: Of 8,662 participants, 25% reported TBI. History of any TBI (ß = -0.56, 95% CI -0.73 to -0.39), TBI with LOC (ß = -0.51, 95% CI -0.71 to -0.31), and older age TBI (ß = -0.66, 95% CI -0.90 to -0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (ß = -0.03, 95% CI -0.05 to -0.001), more than one TBI (ß = -0.05, 95% CI -0.09 to -0.002,), and older age TBI (ß = -0.06, 95% CI -0.09 to -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (ß = -0.55, 95% CI -0.91 to -0.19) and older age TBI (ß = -0.74, 95% CI -1.22 to -0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (ß = -0.13, 95% CI -0.23 to -0.03) and older age TBI (ß = -0.07, 95% CI -0.13 to -0.002) showed greater cognitive decline compared with their co-twin without TBI. DISCUSSION: These findings support an association of the effect of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures, particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late-life cognitive outcomes.

A prospective randomized study examining the impact of intravenous versus inhalational anesthesia on postoperative cognitive decline and delirium.

The present prospective randomized study was designed to investigate whether the development of Post Operative Cognitive Decline (POCD) is related to anesthesia type in older adults. All patients were screened for delirium and mental status, received baseline neuropsychological assessment, and evaluation of activities of daily living (ADLs). Follow-up assessments were performed at 3-6 months and 12-18 months. Patients were randomized to receive either inhalation anesthesia (ISO) with isoflurane or total intravenous anesthesia (TIVA) with propofol for maintenance anesthesia. ISO (n = 99) and TIVA (n = 100) groups were similar in demographics, preoperative cognition, and incidence of post-operative delirium. Groups did not differ in terms of mean change in memory or executive function from baseline to follow-up. Pre-surgical cognitive function is the only variable predictive of the development of POCD. Anesthetic type was not predictive of POCD. However, ADLs were predictive of post-operative delirium development. Overall, this pilot study represents a prospective, randomized study demonstrating that when examining ISO versus TIVA for maintenance of general anesthesia, there is no significant difference in cognition between anesthetic types. There is also no difference in the occurrence of postoperative delirium. Postoperative cognitive decline was best predicted by lower baseline cognition and functional status.

Nightshift Imposes Irregular Lifestyle Behaviors in Police Academy Trainees.

Study Objective: Shiftwork increases risk for numerous chronic diseases, which is hypothesized to be linked to disruption of circadian timing of lifestyle behaviors. However, empirical data on timing of lifestyle behaviors in real-world shift workers are lacking. To address this, we characterized the regularity of timing of lifestyle behaviors in shift-working police trainees. Methods: Using a two-group observational study design (N=18), we compared lifestyle behavior timing during 6 weeks of in-class training during dayshift, followed by 6 weeks of field-based training during either dayshift or nightshift. Lifestyle behavior timing, including sleep/wake patterns, physical activity, and meals, was captured using wearable activity trackers and mobile devices. The regularity of lifestyle behavior timing was quantified as an index score, which reflects day-to-day stability on a 24h time scale: Sleep Regularity Index (SRI), Physical Activity Regularity Index (PARI) and Mealtime Regularity Index (MRI). Logistic regression was applied to these indices to develop a composite score, termed the Behavior Regularity Index (BRI). Results: Transitioning from dayshift to nightshift significantly worsened the BRI, relative to maintaining a dayshift schedule. Specifically, nightshift led to more irregular sleep/wake timing and meal timing; physical activity timing was not impacted. In contrast, maintaining a dayshift schedule did not impact regularity indices. Conclusion: Nightshift imposed irregular timing of lifestyle behaviors, which is consistent with the hypothesis that circadian disruption contributes to chronic disease risk in shift workers. How to mitigate the negative impact of shiftwork on human health as mediated by irregular timing of sleep/wake patterns and meals deserves exploration.

Demographically-adjusted normative data among Latinos for the version 3 of the Alzheimer's Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

INTRODUCTION: We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). METHODS: Healthy Latino adults (N = 437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). RESULTS: Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. DISCUSSION: These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. HIGHLIGHTS: We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.

Use of Quantile Treatment Effects Analysis to Describe Antidepressant Response in Randomized Clinical Trials Submitted to the US Food and Drug Administration: A Secondary Analysis of Pooled Trial Data.

Importance: Major depressive disorder (MDD) is a leading cause of global distress and disability. Earlier studies have indicated that antidepressant therapy confers a modest reduction in depressive symptoms on average, but the distribution of this reduction requires more research. Objective: To estimate the distribution of antidepressant response by depression severity. Design, Setting, and Participants: In this secondary analysis of pooled trial data, quantile treatment effect (QTE) analysis was conducted from the US Food and Drug Administration (FDA) database of antidepressant monotherapy for patients with MDD, encompassing 232 positive and negative trials submitted to the FDA between 1979 and 2016. Analysis was restricted to participants with severe MDD (17-item Hamilton Rating Scale for Depression [HAMD-17] score ≥20). Data analysis was conducted from August 16, 2022, to April 16, 2023. Intervention: Antidepressant monotherapy compared with placebo. Main Outcomes and Measures: The distribution of percentage depression response was compared between the pooled treatment arm and pooled placebo arm. Percentage depression response was defined as 1 minus the ratio of final depression severity to baseline depression severity, expressed as a percentage. Depression severity was reported in HAMD-17-equivalent units. Results: A total of 57 313 participants with severe depression were included in the analysis. There was no significant imbalance in baseline depression severity between the pooled treatment arm and pooled placebo arm, with a mean HAMD-17 difference of 0.037 points (P = .11 by Wilcoxon rank sum test). An interaction term test for rank similarity did not reject the rank similarity governing percentage depression response (P > .99). The entire distribution of depression response was more favorable in the pooled treatment arm than in the pooled placebo arm. The maximum separation between treatment and placebo occurred at the 55th quantile and corresponded to an absolute improvement in depression due to active drug of 13.5% (95% CI, 12.4%-14.4%). The separation between treatment and placebo diminished near the tails of the distribution. Conclusions and Relevance: In this QTE analysis of pooled clinical trial data from the FDA, antidepressants were found to confer a small reduction in depression severity that was broadly distributed across participants with severe depression. Alternatively, if the assumptions behind the QTE analysis are not met, then the data are also compatible with antidepressants eliciting more complete response in a smaller subset of participants than is suggested by this QTE analysis.

Dysphagia in Older Adults is Associated With Food Insecurity and Being Homebound.

Objective: Our aim was to evaluate relationships between swallowing difficulty (dysphagia) and social determinants of health (SDOH) in older adults ≥65 years. Method: Cross-sectional analyses were performed in community-dwelling Medicare beneficiaries from the National Health & Aging Trends Study (NHATS). The primary exposure was self-reported difficulty chewing/swallowing in the prior month. Dependent measures included a variety of SDOH outcomes (e.g., food insecurity [FI]). Weighted logistic regression models were estimated to determine associations between dysphagia and SDOH outcomes. Results: Of 4041 participants, 428 (10.6%) self-reported dysphagia. In the adjusted model, dysphagia was associated with significantly increased odds for FI (odds ratio [OR] = 1.48, 95% confidence interval [CI] = 1.06, 2.07, p = .023) and being homebound (OR = 1.32, 95% CI = 1.13, 1.55, p= < .001). Discussion: Older adults with dysphagia had increased odds of FI and being homebound. These associations have implications for health-promoting interventions at the individual and policy levels in older adults.