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.

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.

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.

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.

Self-Reported Dysphagia and Psychosocial Health Among Community-Dwelling Older Adults: Results of a National Study.

BACKGROUND: The risk of dysphagia increases with age, affecting up to 33% of adults over the age of 65. Older adults with dysphagia are at increased risk for negative physical health outcomes such as aspiration pneumonia and death. However, the relationship between dysphagia and psychosocial health is uncertain in this population. OBJECTIVE: We aimed to assess the associations between dysphagia and psychosocial health among older adults (≥ 65) with self-reported dysphagia. DESIGN: We performed a cross-sectional assessment of the National Health and Aging Trends Study (NHATS) conducted in 2019. MAIN MEASURES: Weighted logistic and linear regression models were used to assess the relationship between self-reported dysphagia and psychosocial health using established patient-reported outcome measures including those for depression, anxiety, and social isolation previously used in NHATS analyses, while adjusting for demographics, comorbid conditions, and risk factors for dysphagia identified by purposeful selection. KEY RESULTS: Among the 4041 adults in this cohort, almost half (40%) were between 70 and 74 years old, more than half were female (55%), and a significantly higher proportion were White, non-Hispanic respondents (78.1%, p < 0.01) compared with other races and ethnicities. There were 428 (10.5%) respondents reporting dysphagia symptoms within the previous month. In the multivariable model, dysphagia was associated with significantly increased odds of anxiety (OR 1.33 [1.06, 1.67]) and a significantly decreased sense of well-being (coefficient - 1.10 [- 1.66, - 0.54]), but no association was detected for social isolation. CONCLUSIONS: When accounting for factors associated with underlying physical health status, self-reported dysphagia is independently associated with negative psychosocial health and warrants attention by healthcare providers. Future studies should aim to identify causal factors and the extent to which interventions may mitigate these factors.

COVID-19 Infection Risk Among Previously Uninfected Adults: Development of a Prognostic Model.

Background: Few models exist that incorporate measures from an array of individual characteristics to predict the risk of COVID-19 infection in the general population. The aim was to develop a prognostic model for COVID-19 using readily obtainable clinical variables. Methods: Over 74 weeks surveys were periodically administered to a cohort of 1381 participants previously uninfected with COVID-19 (June 2020 to December 2021). Candidate predictors of incident infection during follow-up included demographics, living situation, financial status, physical activity, health conditions, flu vaccination history, COVID-19 vaccine intention, work/employment status, and use of COVID-19 mitigation behaviors. The final logistic regression model was created using a penalized regression method known as the least absolute shrinkage and selection operator. Model performance was assessed by discrimination and calibration. Internal validation was performed via bootstrapping, and results were adjusted for overoptimism. Results: Of the 1381 participants, 154 (11.2%) had an incident COVID-19 infection during the follow-up period. The final model included six variables: health insurance, race, household size, and the frequency of practicing three mitigation behavior (working at home, avoiding high-risk situations, and using facemasks). The c-statistic of the final model was 0.631 (0.617 after bootstrapped optimism-correction). A calibration plot suggested that with this sample the model shows modest concordance with incident infection at the lowest risk. Conclusion: This prognostic model can help identify which community-dwelling older adults are at the highest risk for incident COVID-19 infection and may inform medical provider counseling of their patients about the risk of incident COVID-19 infection.

Exploration of model misspecification in latent class methods for longitudinal data: Correlation structure matters.

Modeling longitudinal trajectories and identifying latent classes of trajectories is of great interest in biomedical research, and software to identify latent classes of such is readily available for latent class trajectory analysis (LCTA), growth mixture modeling (GMM) and covariance pattern mixture models (CPMM). In biomedical applications, the level of within-person correlation is often non-negligible, which can impact the model choice and interpretation. LCTA does not incorporate this correlation. GMM does so through random effects, while CPMM specifies a model for within-class marginal covariance matrix. Previous work has investigated the impact of constraining covariance structures, both within and across classes, in GMMs-an approach often used to solve convergence problems. Using simulation, we focused specifically on how misspecification of the temporal correlation structure and strength, but correct variances, impacts class enumeration and parameter estimation under LCTA and CPMM. We found (1) even in the presence of weak correlation, LCTA often does not reproduce original classes, (2) CPMM performs well in class enumeration when the correct correlation structure is selected, and (3) regardless of misspecification of the correlation structure, both LCTA and CPMM give unbiased estimates of the class trajectory parameters when the within-individual correlation is weak and the number of classes is correctly specified. However, the bias increases markedly when the correlation is moderate for LCTA and when the incorrect correlation structure is used for CPMM. This work highlights the importance of correlation alone in obtaining appropriate model interpretations and provides insight into model choice.

A Novel Movement-Evoked Pain Provocation Test for Older Adults With Persistent Low Back Pain: Safety, Feasibility, and Associations With Self-reported Physical Function and Usual Gait Speed.

OBJECTIVES: Low back pain (LBP) is highly prevalent and disabling for older adults. Movement-evoked pain is an emerging measure that may help to predict disability; but is not currently a part of geriatric LBP clinical care. This study tested the safety and feasibility of a new Movement-Evoked Provocation Test for Low Back Pain in Older Adults (MEPLO). We also compared associations between movement-evoked pain via 2 different scoring methods and disability-associated outcomes. MATERIALS AND METHODS: Thirty-nine older adults with persistent LBP provided baseline recalled and resting pain ratings, self-reported physical function, and usual gait speed. Participants then completed MEPLO, involving 4 tasks essential for functional independence: chair rises, trunk rotation, reaching, and walking. Movement-evoked pain was then quantified using the traditional change score (delta) method of pain premovement to postmovement; and also, a new aggregate method that combines pain ratings after the 4 tasks. RESULTS: No safety or feasibility issues were identified. Compared with the delta score, the aggregate score was more strongly associated with self-reported physical function (beta: -0.495 vs. -0.090) and usual gait speed (beta: -0.450 vs. -0.053). Similarly, the aggregate score was more strongly associated with self-reported physical function than recalled and resting pain (beta: -0.470, -0.283, and 0.136, respectively). DISCUSSION: This study shows the safety and feasibility of testing movement-evoked pain in older adults with persistent LBP, and its potential superiority to traditional pain measures. Future studies must validate these findings and test the extent to which MEPLO is implementable to change with geriatric LBP standard of care.

Mitigation behavior prior to COVID-19 vaccination availability is associated with COVID-19 infection and time to vaccination.

BACKGROUND: Mitigation behaviors reduce the incidence of COVID-19 infection. Determining characteristics of groups defined by mitigation behaviors compliance may be useful to inform targeted public health policies and interventions. This study aimed to identify groups of individuals according to self-reported compliance with COVID-19 mitigation behaviors, define compliance class characteristics, and explore associations between compliance classes and important study and public health outcomes. METHODS AND FINDINGS: We studied 1,410 participants in the Cabarrus County COVID-19 Prevalence and Immunity longitudinal cohort study (June 2020 to December 2021) who were asked 10 questions regarding compliance with recommended COVID-19 mitigation behaviors. By Latent Class Analysis, 1,381 participants were categorized into 3 classes (most [49.4%], moderately [45.0%], and least [5.6%] compliant). Compared with the most compliant class, the least and moderately compliant classes were younger (mean = 61.9 v. 59.0 v. 53.8 years), had fewer medical conditions per individual (1.37 v. 1.08 v. 0.77), and differed in Hispanic ethnicity (6.2% v. 2.8% v. 9.1%) and COVID-19 vaccine intention (65.8% v. 59.8% v. 35.1%). Compared to the most compliant class, the least compliant class had fewer women (54.6% v. 76.3%), fewer insured individuals (92.2% v. 97.4%), and more withdrew from study participation early (28.6% v. 16.0%). Relative to the most compliant class, the least compliant class had a higher likelihood of COVID-19 infection (OR = 2.08 [95% CI 1.13, 3.85]), lower rate of COVID-19 vaccination (72.6% v. 95.1%), and longer time to 50% COVID-19 vaccination following eligibility (8-9 vs 16 days). CONCLUSIONS: Classes defined by mitigation behaviors compliance had distinct characteristics, including age, sex, medical history, and ethnicity, and were associated with important study and public health outcomes. Targeted public health policies and interventions according to the compliance group characteristics may be of value in current and future pandemic responses to increase compliance.

Remotely Supervised Weight Loss and Exercise Training to Improve Rheumatoid Arthritis Cardiovascular Risk: Rationale and Design of the Supervised Weight Loss Plus Exercise Training-Rheumatoid Arthritis Trial.

Patients with rheumatoid arthritis (RA) remain at an increased risk for cardiovascular disease (CVD) and mortality. RA CVD results from a combination of traditional risk factors and RA-related systemic inflammation. One hypothetical means of improving overall RA CVD risk is through reduction of excess body weight and increased physical activity. Together, weight loss and physical activity can improve traditional cardiometabolic health through fat mass loss, while also improving skeletal muscle health. Additionally, disease-related CVD risk may improve as both fat mass loss and exercise reduce systemic inflammation. To explore this hypothesis, 26 older persons with RA and overweight/obesity will be randomized to 16 weeks of a usual care control arm or to a remotely Supervised Weight Loss Plus Exercise Training (SWET) program. A caloric restriction diet (targeting 7% weight loss) will occur via a dietitian-led intervention, with weekly weigh-ins and group support sessions. Exercise training will consist of both aerobic training (150 minutes/week moderate-to-vigorous exercise) and resistance training (twice weekly). The SWET remote program will be delivered via a combination of video conference, the study YouTube channel, and study mobile applications. The primary cardiometabolic outcome is the metabolic syndrome Z score, calculated from blood pressure, waist circumference, high-density lipoprotein cholesterol, triglycerides, and glucose. RA-specific CVD risk will be assessed with measures of systemic inflammation, disease activity, patient-reported outcomes, and immune cell function. The SWET-RA trial will be the first to assess whether a remotely supervised, combined lifestyle intervention improves cardiometabolic health in an at-risk population of older individuals with RA and overweight/obesity.

Prospective Association of Daily Steps With Cardiovascular Disease: A Harmonized Meta-Analysis.

BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD.

Tryptophan Metabolism and Neurodegeneration: Longitudinal Associations of Kynurenine Pathway Metabolites with Cognitive Performance and Plasma Alzheimer's Disease and Related Dementias Biomarkers in the Duke Physical Performance Across the LifeSpan Study.

BACKGROUND: The kynurenine pathway (KP) comprises a family of tryptophan-derived metabolites that some studies have reported are associated with poorer cognitive performance and an increased risk of Alzheimer's disease and related dementias (ADRD). OBJECTIVE: The objective of this study was to determine the associations of plasma KP metabolites (kynurenine [KYN], kynurenic acid [KA], and tryptophan [TRP]) with a panel of plasma ADRD biomarkers (Aß42/ ß40 ratio, pTau-181, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]) and cognitive performance in a subset of older adults drawn from the Duke Physical Performance Across the LifeSpan (PALS) study. METHODS: The Montreal Cognitive Assessment (MoCA) was used to assess cognitive performance. We used multivariate multiple regression to evaluate associations of the KYN/TRP and KA/KYN ratios with MoCA score and plasma ADRD biomarkers at baseline and over two years (n = 301; Age = 74.8±8.7). RESULTS: Over two years, an increasing KYN/TRP ratio was associated with increasing plasma concentrations of plasma p-Tau181 (ß= 6.151; 95% CI [0.29, 12.01]; p = 0.040), GFAP (ß= 11.12; 95% CI [1.73, 20.51]; p = 0.020), and NfL (ß= 11.13; 95% CI [2.745, 19.52]; p = 0.009), but not MoCA score or the Aß42/Aß40 ratio. There were no significant associations of KA/KYN with MoCA score or plasma ADRD biomarkers. CONCLUSION: Our findings provide evidence that greater concentrations of KP metabolites are associated longitudinally over two years with greater biomarker evidence of neurofibrillary tau pathology (pTau-181), neuroinflammation (GFAP), and neurodegeneration (NfL), suggesting that dysregulated KP metabolism may play a role in ADRD pathogenesis.

Effects of high-intensity interval training on health-related quality of life in chronic lymphocytic leukemia: A pilot study.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common incurable leukemia/lymphoma in the United States. Individuals with CLL are at risk for disability, frailty, and cancer-specific complications that negatively affect health-related quality of life (HRQOL). High-intensity interval training (HIIT) and resistance training (RT) are safe and feasible for individuals with chronic diseases and when combined, they may be beneficial for reducing cancer-related fatigue, symptom burden, and global quality of life. However, no studies have examined the impact of HIIT or RT on HRQOL in CLL. The purpose of this study was to investigate the effects of a 12-week HIIT and RT (HIIT+RT) intervention on HRQOL in adults with treatment naïve CLL. MATERIALS AND METHODS: Changes in HRQOL was a secondary outcome in this pilot study. Individuals with CLL (63.9 ± 8.5 yrs) were non-randomly assigned to 12 weeks of HIIT+RT or a control group. The HIIT+RT protocol consisted of three 30-min sessions/week of HIIT and two sessions/week of RT. The control group maintained usual daily activities. We assessed pre and post HRQOL using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire with domains of physical (PWB), social (SWB), emotional (EWB), functional (FWB), and general (FACT-G) well-being as well as a lymphoma-specific subscale (LymS). We used a two-way mixed analysis of variance to assess changes in HRQOL. We calculated effect size (ES) using Cohen's d. RESULTS: Fifteen participants (HIIT+RT: n = 9; Control: n = 6) completed the study and questionnaire. Scores for FWB improved following HIIT+RT (21.7 ± 3.4 to 23.9 ± 3.2; ES = 1.38) compared to controls (25.7 ± 2.2 to 25.7 ± 2.3). The HIIT+RT group experienced clinically meaningful improvements in total FACT-Lym, FWB, FACT-G, and LymS. The control group had clinically meaningful changes only in LymS. DISCUSSION: The large effect sizes and clinically meaningful improvements associated with 12 weeks of HIIT+RT support the potential benefits of this type of exercise program for FWB, lymphoma-specific symptoms, and general well-being in CLL. A future randomized trial with an adequately powered sample size is needed to evaluate these findings. TRIAL REGISTRATION: NCT04950452.

Parenthood and Medical Training: Challenges and Experiences of Physician Moms in the US.

Phenomenon: Balancing the demands of medical training and parenthood is challenging. We explored perceptions of programmatic support, parental leave, breastfeeding, and self-reported biggest challenges among a large cohort of physician mothers in a variety of medical specialties and across the stage of training when they had their first child. Our goal was to inform strategies to help improve the physician parent experience. Approach: This cross-sectional, observational survey study was performed using a convenience sample from an online physician-mom support group from January to February 2018. Descriptive statistics and bivariate analyses were used to report results and examine relationships between career stage at first child and outcome variables. Responses to the open-ended question, "What is your biggest challenge as a physician mom?" were qualitatively analyzed. Findings: The survey received 896 complete responses. The most common specialties were obstetrics and gynecology (25.3%), pediatrics (19.9%), internal medicine or medicine/pediatrics (17.1%), and family medicine (10.2%). The majority of participants (63.9%) had their first child during medical training, including medical school (14.3%), residency (35.8%) or fellowship (13.6%). Medical students were less likely to perceive programmatic support than residents or fellows (44.1% vs. 63.1% vs. 62.3%, respectively), and only 19.9% of participants who became parents during medical training reported having a clear and adequate parental leave policy. Nearly 70% of participants breastfed for six months or more, with no statistical differences across career stage. Most participants (57.6%) delayed child-bearing for one or more reasons, with 32.3% delaying to complete training. The most common codes applied to responses for 'biggest challenges as a physician mom' were insufficient time, lack of work-life balance, missing out, and over-expectation. Insights: Physician mothers, particularly those who had their first child during training, continue to struggle with support from training programs, finding work-life balance, and feelings of inadequacy. Interventions such as clear and adequate leave policies, program-sponsored or onsite childcare and improved programmatic support of breastfeeding and pumping may help to ameliorate the challenges described by our participants.