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Network meta-analysis is an extension of standard meta-analysis. It allows researchers to build a network of evidence to compare multiple interventions that may have not been compared directly in existing publications. With a Bayesian approach, network meta-analysis can be used to obtain a posterior probability distribution of all the relative treatment effects, which allows for the estimation of relative treatment effects to quantify the uncertainty of parameter estimates, and to rank all the treatments in the network. Ranking treatments using both direct and indirect evidence can provide guidance to policy makers and clinicians for making decisions. The purpose of this paper is to introduce fundamental concepts of Bayesian network meta-analysis (BNMA) to researchers in psychology and social sciences. We discuss several essential concepts of BNMA, including the assumptions of homogeneity and consistency, the fixed and random effects models, prior specification, and model fit evaluation strategies, while pointing out some issues and areas where researchers should use caution in the application of BNMA. Additionally, using an automated R package, we provide a step-by-step demonstration on how to conduct and report the findings of BNMA with a real dataset of psychological interventions extracted from PubMed.

To define metrics of phenotypic aging, it is essential to identify biological and environmental factors that influence the pace of aging. Previous attempts to develop aging metrics were hampered by cross-sectional designs and/or focused on younger populations. In the Baltimore Longitudinal Study of Aging (BLSA), we collected longitudinally across the adult age range a comprehensive list of phenotypes within four domains (body composition, energetics, homeostatic mechanisms and neurodegeneration/neuroplasticity) and functional outcomes. We integrated individual deviations from population trajectories into a global longitudinal phenotypic metric of aging and demonstrate that accelerated longitudinal phenotypic aging is associated with faster physical and cognitive decline, faster accumulation of multimorbidity and shorter survival. These associations are more robust compared with the use of phenotypic and epigenetic measurements at a single time point. Estimation of these metrics required repeated measures of multiple phenotypes over time but may uniquely facilitate the identification of mechanisms driving phenotypic aging and subsequent age-related functional decline.

Older adults experiencing dual decline in memory and gait have greater dementia risk than those with memory or gait decline only, but mechanisms are unknown. Dual decline may indicate specific pathophysiological pathways to dementia which can be reflected by circulating metabolites. We compared longitudinal changes in plasma metabolite biomarkers of older adults with and without dual decline in the Baltimore Longitudinal Study of Aging (BLSA). Participants were grouped into 4 phenotypes based on annual rates of decline in verbal memory and gait speed: no decline in memory or gait, memory decline only, gait decline only, and dual decline. Repeated measures of plasma metabolomics were measured by biocrates p500 kit during the same time of memory and gait assessments. In BLSA, 18 metabolites differed across groups (q-value

Stress, social isolation, and changes in health behaviors during the COVID-19 pandemic period may have a lasting influence on health. Here, the correlation between current or prior demographic, social and health related characteristics, including psychosocial factors with perceived impact of the COVID-19 pandemic assessed by questionnaire during the early pandemic period is evaluated among 770 participants of the Baltimore Longitudinal Study of Aging. In multinomial logistic regression models participants with higher pre-pandemic personal mastery, a construct related to self-efficacy, were more likely to report "both positive and negative" impact of the pandemic than a solely "negative" impact (OR: 2.17, 95% CI: 1.29-3.65). Higher perceived stress and frequent contact with family prior to the pandemic were also associated with pandemic impact. These observations highlight the relevance of psychosocial factors in the COVID-19 pandemic experience and identify characteristics that may inform interventions in future public health crises.

Age-associated DNA methylation in blood cells convey information on health status. However, the mechanisms that drive these changes in circulating cells and their relationships to gene regulation are unknown. We identified age-associated DNA methylation sites in six purified blood borne immune cell types (naïve B, naïve CD4+and CD8+T cells, granulocytes, monocytes and NK cells) collected from healthy individuals interspersed over a wide age range. Of the thousand of age-associated sites, only 350 sites were differentially methylated in the same direction in all cell types and validated in an independent longitudinal cohort. Genes close to age-associated hypomethylated sites were enriched for collagen biosynthesis and complement cascade pathways, while genes close to hypermethylated sites mapped to neuronal pathways. In-silico analyses showed that in most cell types, the age-associated hypo- and hypermethylated sites were enriched for ARNT (HIF1β) and REST transcription factor motifs respectively, which are both master regulators of hypoxia response. To conclude, despite spatial heterogeneity, there is a commonality in the putative regulatory role with respect to transcription factor motifs and histone modifications at and around these sites. These features suggest that DNA methylation changes in healthy aging may be adaptive responses to fluctuations of oxygen availability.

Tongue fungiform papillae contain taste buds crucial for taste and hormone-producing taste receptor cells; therefore, they may be considered as endocrine organs and have important age-associated physiological implications. We examine the cross-sectional and longitudinal trajectories of fungiform papillae density in 1084 participants from the Baltimore Longitudinal Study of Aging using linear regression models and mixed effects models. At baseline, the mean age was 67.86 ± 14.20 years, with a mean follow-up time among those with repeat visits of 4.24 ± 1.70 years. Women (53%) were younger (66.85 ± 13.78 vs. 69.04 ± 14.61 years, p < 0.001) and had a higher fungiform papillae density than men (16.14 ± 9.54 vs. 13.77 ± 8.61 papillae/cm2, p < 0.001). Whites (67%) had a lower fungiform papillae density than non-Whites after adjusting for age and sex. Factors cross-sectionally associated with a lower fungiform papillae density included a higher waist-hip ratio (β = −8.525, p = 0.029), current smoking status (β = −5.133, p = 0.014), and alcohol use within the past 12 months (β = −1.571, p = 0.025). Longitudinally, fungiform papillae density decreased linearly with follow-up time (β = −0.646, p < 0.001). The rate of decline was not affected by sex, race, BMI, waist-hip ratio, smoking, or alcohol use. The longitudinal decline of fungiform papillae density over time needs to be explored further in order to identify other possible age-associated physiological determinants.

Background Human motor function is optimised for energetic efficiency, however, age-related neurodegenerative changes affects neuromotor control of walking. Energy utilisation has been associated with motor performance, but its association with cognitive performance is unknown. Methods The study population included 979 Baltimore Longitudinal Study of Aging participants aged $\ge$50 years (52% female, mean age: 70$\pm$10.2 years) with a median follow-up time of 4.7 years. Energy utilisation for walking was operationalised as a ratio of the energy cost of slow walking to peak walking energy expenditure during standardised tasks (‘cost-ratio’). Cognitive functioning was measured using the Trail Making Tests, California Verbal Learning Test, Wechsler Adult Intelligence Scale (WAIS), letter and category fluency and card rotation tests. Linear mixed models adjusted for demographics, education and co-morbidities assessed the association between baseline cost-ratio and cognitive functioning, cross-sectionally and longitudinally. To investigate the relationship among those with less efficient energy utilisation, subgroup analyses were performed. Results In fully adjusted models, a higher cost-ratio was cross-sectionally associated with poorer performance on all cognitive tests except WAIS (P Conclusions These findings suggest cross-sectional and longitudinal links between energy utilisation and cognitive performance, highlighting an intriguing link between brain function and the energy needed for ambulation. Future research should examine this association earlier in the life course to gauge the potential for interventive mechanisms.

OBJECTIVE The concept of frailty has been proposed to capture the vulnerability resulting from aging and has been implemented for the prediction of perioperative outcomes. Carotid artery stenting (CAS) is considered an appropriate minimally invasive procedure for patients considered to high risk to undergo carotid endarterectomy. Recently, the predictive accuracy for perioperative outcomes using the five-item modified frailty index (5mFI) has been reported to be relatively poor for cardiovascular surgery compared with other surgeries. The effects of functional status and the 5mFI on the outcomes after CAS remain unknown. Thus, in the present study, we investigated the relationship between 5mFI, functional status, and perioperative outcomes. METHODS All the patients who had undergone CAS in the Vascular Quality Initiative from November 15, 2016 to December 31, 2018 were included. Good functional status was defined as the ability to perform all predisease activities without restriction using a new variable added to the Vascular Quality Initiative from November 15, 2016 onward. The 5mFI was calculated using functional status and a history of diabetes, chronic obstructive pulmonary disease, congestive heart failure, and hypertension. The perioperative outcomes included in-hospital stroke or death within 30 days after CAS, a prolonged postoperative stay (≥2 days), and nonhome discharge. The associations between functional status, 5mFI, and perioperative outcomes were examined using univariate and multivariable logistic regression, adjusting for sex, age, race, degree of stenosis, symptomatic status, and the usage of preoperative medications. An analysis stratified by functional status was also performed. RESULTS Of the 7836 patients, 188 (2.4%) had experienced perioperative stroke or death, 765 (9.8%) had required a nonhome discharge, and 2584 (33.0%) had required a prolonged postoperative stay. A higher (≥0.6 vs

OBJECTIVES: Acute bronchiolitis commonly causes respiratory failure in children ≤ 2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities. METHODS: Hospital discharge records of children with bronchiolitis aged ≤ 2 years were obtained for 1997–2012 from the Kid’s Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities. RESULTS: There were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n=8,697) was more likely to have OSA [241 (2.77%) vs 1,293 (0.14%), p

Background Physical activity becomes increasingly fragmented with age, which may be an early marker of functional decline. Energetic cost of walking and energy capacity are also linked with functional decline, but their associations with activity fragmentation, and the potential modifying roles of total daily physical activity and age, remains unclear. Method A total of 493 participants (50–93 years) from the Baltimore Longitudinal Study of Aging underwent measures of energetic cost of usual-paced overground walking (mL/kg/m), energy demand during slow walking (mL/kg/min) on a treadmill (0.67 m/s, 0% grade), and average peak walking energy expenditure (mL/kg/min) during a fast-paced 400-m walk. A ratio of slow walking to peak walking energy expenditure (“cost-to-capacity ratio”) was calculated. Activity fragmentation was quantified as an active-to-sedentary transition probability (ASTP) using Actiheart accelerometer data. Linear regression models with ASTP as the dependent variable were used to test whether poorer energy cost and capacity were associated with higher ASTP and whether the associations differed by daily physical activity or age. Results After adjusting for demographics, body composition, comorbidities, and daily physical activity, every 10% higher cost-to-capacity ratio was associated with 0.4% greater ASTP (p = .005). This association was primarily driven by the least active participants (pinteraction = .023). Peak walking energy expenditure was only associated with ASTP among participants aged ≥70 years. Conclusions Higher cost-to-capacity ratio and lower energy capacity may manifest as more fragmented physical activity, especially among those less active or aged ≥70 years. Future studies should examine whether an increasing cost-to-capacity ratio or declining energy capacity predicts subsequent activity fragmentation.

BACKGROUND: Place of death is important to patients and caregivers, and often a surrogate measure of health care disparities. While recent trends in place of death suggest an increased frequency of dying at home, data is largely unknown for older adults with cancer. METHODS: Deidentified death certificate data were obtained via the National Center for Health Statistics. All lung, colon, prostate, breast, and pancreas cancer deaths for older adults (defined as >65 years of age) from 2003 to 2017 were included. Multinomial logistic regression was used to test for differences in place of death associated with sociodemographic variables. RESULTS: From 2003 through 2017, a total of 3,182,707 older adults died from lung, colon, breast, prostate and pancreas cancer. During this time, hospital and nursing home deaths decreased, and the rate of home and hospice facility deaths increased (all p

OBJECTIVE To determine the impact of obstructive sleep apnea (OSA) on asthma exacerbation severity in children hospitalized for asthma exacerbation. HYPOTHESIS OSA is associated with greater use of invasive mechanical ventilation (IMV) and noninvasive mechanical ventilation (NIMV) in children hospitalized for asthma exacerbation. STUDY DESIGN A retrospective cohort study. PATIENT-SUBJECT SELECTION Hospitalization records of children aged 2-18 years admitted for acute asthma exacerbation were obtained for 2000, 2003, 2006, 2009, and 2012 from the Kids' Inpatient Database. METHODOLOGY The primary exposure was OSA, the primary outcome was IMV, and secondary outcomes were NIMV, length of hospital stay (LOS), and inflation-adjusted cost of hospitalization. Multivariable logistic regression, negative binomial, and linear regression were conducted to ascertain the impact of OSA on primary and secondary outcomes. Exploratory analyses investigated the impact of obesity on primary and secondary outcomes. RESULTS Among 564,467 hospitalizations for acute asthma exacerbation, 4209 (0.75%) had OSA. Multivariable regression indicated that OSA was associated with IMV (adjusted odds ratio [OR], 5.33 [95% confidence interval, CI: 4.35-6.54], p

Human aging is a complex multifactorial process associated with a decline of physical and cognitive function and high susceptibility to chronic diseases, influenced by genetic, epigenetic, environmental, and demographic factors. This chapter will provide an overview on the use of epidemiological models with proteomics data as a method that can be used to identify factors that modulate the aging process in humans. This is demonstrated with proteomics data from human plasma and skeletal muscle, where the combination with epidemiological models identified a set of mitochondrial, spliceosome, and senescence proteins as well as the role of energetic pathways such as glycolysis, and electron transport pathways that regulate the aging process.

Although a persistent inflammatory state has long been associated with aging and negative health outcomes, the underlying mechanisms remain unclear. Mitochondrial dysfunction has been proposed as a cause of inflammaging, but evidence of an association in humans is lacking. In this study, we analyzed the cross-sectional association between inflammatory biomarkers and mitochondrial oxidative capacity in skeletal muscle, assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy, in a population of 669 adults (mean age 67 years) from the Baltimore Longitudinal Study of Aging. We observed that participants with lower mitochondrial oxidative capacity exhibited hallmarks of inflammation, specifically markedly higher levels of interleukin-6 and C-reactive protein, as well as increased erythrocyte sedimentation rate when compared with participants with better oxidative capacity, independent of age and sex. We speculate that this association reflects the observation that products of damaged mitochondria, such as mitochondrial DNA, activate multiple pathways that lead to inflammation. Furthermore, excess production of oxidative species (ROS) by dysfunctional mitochondria could trigger inflammation either directly via NF-κB or through oxidative damage to proteins, lipids, and nucleic acids. Longitudinal studies are necessary to ascertain whether and through which mechanisms mitochondrial dysfunction activate inflammation or whether both these phenomena derive from a common root.

Carotid artery stenting (CAS) was introduced as an alternative carotid revascularization procedure in patients deemed to be at high risk for carotid endarterectomy. Although techniques and selection criteria for patients have dramatically improved, CAS continues to have higher risk of stroke and death in comparison to carotid endarterectomy. Several risk factors are known to be associated with worse outcomes. Whereas knowledge of these independent factors is helpful, clinical decision-making is further refined when these are considered in aggregate. This study aimed to develop a score to predict the risk of stroke/death after transfemoral CAS (TFCAS).We analyzed the Vascular Quality Initiative CAS data set from 2010 to 2018. Lesions due to trauma, dissection, or transcarotid artery stenting and cases performed without an embolic protection device were excluded. Univariable and multivariable logistic regression methods with bootstrapping (1000 repetitions) were used to identify predictors associated with 30-day stroke/death. Stepwise backward selection for variables was used to achieve model parsimony. A risk score was made by converting regression coefficients for each predictor to integers from which probability was calculated. Scores were grouped into simplified categories.We identified 10,753 patients undergoing TFCAS during the study period with a combined 30-day stroke/death rate of 4.1%. On multivariable adjustment, independent predictors of 30-day stroke/death included age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.06; P .001), nonwhite race (OR, 1.42; 95% CI, 1.16-1.74; P = .001), diabetes (OR,1.34; 95% CI, 1.08-1.67; P = .01), coronary artery disease (OR, 1.40; 95% CI, 1.13-1.73; P = .001), congestive heart failure (OR, 1.41; 95% CI, 1.07-1.85; P = .02), symptomatic status (OR, 2.11; 95% CI, 1.64-2.72; P .001), and contralateral occlusion (OR, 1.64; 95% CI, 1.22-2.19; P = .001). On the other hand, preoperative use of statins (OR, 0.074; 95% CI, 0.59-0.93; P = .02) and dual antiplatelet therapy (P2YIn an analysis of 10,753 patients undergoing TFCAS between 2010 and 2018, significant predictors of perioperative stroke or death included old age, nonwhite race, symptomatic status, diabetes, coronary artery disease, congestive heart failure, and contralateral occlusion in addition to perioperative dual antiplatelet therapy and statin use. These variables were used to develop a risk score calculator that estimates the probability of 30-day stroke/death after TFCAS. External validation of this tool in different populations of patients and data sets is warranted to evaluate its predictive performance.

Objective Although up to 90% of systemic sclerosis (SSc) patients are affected by gastrointestinal (GI) dysmotility, the clinical phenotype of patients with pseudo-obstruction is not well-defined. We sought to identify this phenotype by studying a large cohort of SSc patients with and without pseudo-obstruction. Methods We performed a retrospective analysis of patients seen at the Johns Hopkins Scleroderma Center between February 2003 and September 2017. All SSc patients had clinical data prospectively collected in a longitudinal database. Cross-sectional analyses were performed comparing autoantibody status and clinical and demographic features of patients with and without pseudo-obstruction. Cox proportional hazards regression was used to identify risk factors for pseudo-obstruction. Results 175 patients with SSc had a history of pseudo-obstruction, and 2,637 SSc patients did not. After adjusting for significant variables from the univariate analysis and potential confounders, the Cox proportional hazards multivariable analysis demonstrated that older age (HR 1.02; 95%CI 1.00–1.04), male sex (HR 1.75; 95%CI 1.42–2.43), diffuse cutaneous disease (HR 2.52; 95%CI 1.59–3.99), myopathy (HR 1.83, 95%CI 1.09–3.08), and opioid use (HR 2.38; 95%CI 1.50–3.78) were predictive of pseudo-obstruction. Autoantibodies to RNA polymerase-3 were negatively associated with pseudo-obstruction (HR 0.34; 95%CI 0.17–0.66). Conclusion We identified clinical features associated with pseudo-obstruction in a large US SSc cohort. This study identifies characteristics of patients with SSc who are at a higher risk of developing pseudo-obstruction and suggests that opioids may be a modifiable risk factor. These clinical features may allow for earlier diagnostic evaluation and/or therapeutic intervention for patients at risk for pseudo-obstruction.

Objectives: Age-related hearing loss (ARHL) is highly prevalent among older adults, but the potential mechanisms and predictive markers for ARHL are lacking. Epigenetic age acceleration has been shown to be predictive of many age-associated diseases and mortality. However, the association between epigenetic age acceleration and hearing remains unknown. Our study aims to investigate the relationship between epigenetic age acceleration and audiometric hearing in the Baltimore Longitudinal Study of Aging (BLSA).Methods: Participants with both DNA methylation and audiometric hearing measurements were included. The main independent variables are epigenetic age acceleration measures, including intrinsic epigenetic age acceleration—“IEAA,” Hannum age acceleration—“AgeAccelerationResidualHannum,” PhenoAge acceleration—“AgeAccelPheno,” GrimAge acceleration—“AgeAccelGrim,” and methylation-based pace of aging estimation—“DunedinPoAm.” The main dependent variable is speech-frequency pure tone average. Linear regression was used to assess the association between epigenetic age acceleration and hearing.Results: Among the 236 participants (52.5% female), after adjusting for age, sex, race, time difference between measurements, cardiovascular factors, and smoking history, the effect sizes were 0.11 995% CI: (–0.00, 0.23), p = 0.054] for Hannum’s clock, 0.08 [95% CI: (–0.03, 0.19), p = 0.143] for Horvath’s clock, 0.10 [95% CI: (–0.01, 0.21), p = 0.089] for PhenoAge, 0.20 [95% CI: (0.06, 0.33), p = 0.004] for GrimAge, and 0.21 [95% CI: (0.09, 0.33), p = 0.001] for DunedinPoAm.Discussion: The present study suggests that some epigenetic age acceleration measurements are associated with hearing. Future research is needed to study the potential subclinical cardiovascular causes of hearing and to investigate the longitudinal relationship between DNA methylation and hearing.

Screening programs for lung cancer aim to allow diagnosis at the early stage, and therefore the decline in mortality rates. Thus, the aim of this retrospective cohort study was to the comparison of screened and non-screened lung cancer in terms of lung cancer characteristics, overdiagnosis and survival rate. A retrospective study in which 2883 patients with 2883 lung cancer diagnosed according to the hospital-based lung cancer register database between 2007 and 2017. A comparison was performed in term of clinical characteristics and outcomes of lung cancer between the screened and non-screening patient groups. 2883 subjects were identified (93 screened and 2790 non-screened). Screened group patients were younger (59.91 ± 8.14 versus 67.58 ± 12.95; p 0.0001), and were more likely to be female than non-screened group (61.3% versus 36.8%; p 0.0001). The screened group showed significantly better outcomes in overall mortality than the non-screened group (10.75% versus 79.06%; 0.0001). In a Cox proportional hazard model, lung cancer in the screened group proved to be an independent prognostic factor in lung cancer subjects. Our findings point to the improved survival outcome in the screened group and might underline the benefit of low-dose computed tomography (LDCT) screening program in Asian populations with the high prevalence of non-smoking-related lung cancer. Further study aimed at the LDCT mass screening program targeting at light smokers and non-smoker outside of existing screening criteria is warranted.

187 Background: Place of death (PoD) is a surrogate determinant of health care inequity in patients with cancer. Aggregation of Asian Americans, a diverse group, may mask significant health disparities in end-of-life care. Methods: De-identified death certificate data were obtained via the National Center for Health Statistics. All adult (> 18 years of age) prostate cancer deaths from 2018 to 2019 were included. Multinomial logistic regression was used to test for differences in place of death associated with sociodemographic variables. Results: From 2018 through 2019, 81,292 adults died from prostate cancer. Overall, most Asians were less likely to die at home (p < 0.05) or nursing facility (p < 0.05) compared to White patients. Significant differences in nursing facility use was noted in disaggregated analysis, with Samoan patients 12.44 times more likely to die in a hospice facility compared to hospital (CI 2.89, 53.6; p < 0.001) and Chinese patients 100 times less likely to die in a hospice facility (CI 0.01, 0.02; p < 0.001) to give two notable examples. Chinese (OR 0.26), Guamanian (OR 0.2), and Vietnamese race (OR 0.05) had the lowest likelihood of dying at home, with odds ratio lower than Black race (OR 0.3) (Table). Conclusions: Increased attention to PoD over recent years has highlighted issues around equity in end-of-life care. Overall, our data underscore important differences among Asian subpopulations and possible barriers to quality end of life care that would otherwise be masked with data aggregation. It is well known that resources are needed to allow death at home or at a nursing facility. Further qualitative work is planned to investigate culture differences contributing to PoD differences for patients with cancer through the lens of the social determinants of health.

Objective: To investigate whether APOE ε4 genotype—an established risk factor for dementia—is associated with earlier age at diagnosis in addition to increased risk overall and in secondary analysis by race and sex. Methods: We followed up 13,782 dementia-free individuals (n = 10,137 White, n = 3,645 Black, baseline age 60–66 years) in the Atherosclerosis Risk in Communities study for up to 30 years. Dementia was operationalized using standardized algorithms incorporating longitudinal cognitive change, proxy report, and hospital or death certificate dementia codes. We used a mixture of generalized gamma distributions to simultaneously estimate time to dementia, time to dementia-free death, and the proportion of individuals with dementia, by APOE ε4 status (≥1 vs. no alleles). Results: Median age of dementia onset among APOE ε4 carriers was 81.7 (Blacks) and 83.3 years (Whites) compared with 82.6 (Blacks) and 85.7 years (Whites) in non-APOE ε4 carriers (p > 0.05 Blacks; p < 0.01 Whites). Age of dementia diagnosis did not differ by sex in ε4 carriers, but among non-carriers, average age was earlier in males than females regardless of race. APOE ε4 carriers had on average a higher proportion of diagnoses; results did not differ by race or sex. Conclusions: APOE ε4 carrier status is associated with earlier age of dementia diagnosis with differences across race and sex. These findings clarify the causal role of APOE in dementia etiology, which could help better identify at-risk subgroups and may help facilitate better research trial recruitment and design.

Importance Hearing impairment, a common treatable condition, may contribute to poorer physical function with aging. Objective To assess whether hearing impairment is associated with poorer physical function, reduced walking endurance, and faster decline in physical function. Design, Setting, and Participants In this cohort study, cross-sectional and longitudinal analyses were performed using data from the 2011 to 2019 period of the Atherosclerosis Risk in Communities study, a population-based study of community-dwelling adults at 4 sites in the US. Exposures Hearing thresholds (per 10 dB) assessed with pure tone audiometry and categorized as normal hearing or mild, moderate, or severe hearing impairment. Main Outcomes and Measures Physical function was assessed using the short physical performance battery (SPPB), with composite scores ranging from 0 to 12. A composite score of 6 or less and a score for each component (balance, gait speed, and chair stands) of 2 or less indicated poor performance. Walking endurance was assessed using a 2-minute fast-paced walk test. Tobit regression models adjusted for sociodemographic factors and medical history were used to calculate the mean differences in SPPB composite scores; logistic regression models, to estimate the odds ratios (ORs) of low SPPB composite and component scores; and linear mixed-effects models, to estimate the mean rate of change in SPPB composite scores over time. Results Of the 2956 participants (mean [SD] age, 79 [4.6] years) who attended study visit 6 between 2016 and 2017, 1722 (58.3%) were women, and 2356 (79.7%) were White. As determined by pure tone audiometry, 973 (33%) participants had normal hearing, 1170 (40%) had mild hearing impairment, 692 (23%) had moderate hearing impairment, and 121 (4%) had severe hearing impairment. In the Tobit regression model, severe hearing impairment was associated with a lower mean SPPB score (β, –0.82; 95% CI, –0.34 to –1.30) compared with normal hearing. In fully adjusted logistic regression models, hearing impairment was associated with higher odds of low physical performance scores (severe impairment vs normal hearing: OR for composite physical performance, 2.51 [95% CI, 1.47-4.27]; OR for balance, 2.58 [95% CI, 1.62-4.12]; OR for gait speed, 2.11 [95% CI, 1.03-4.33]). Over time (2 to 3 visits; maximum, 8.9 years), participants with hearing impairment had faster declines in SPPB compared with those with normal hearing (moderate hearing impairment × time interaction, –0.34 [–0.52 to –0.16]). In adjusted models for walking endurance, participants with moderate or severe hearing impairment walked a mean distance of –2.81 m (95% CI, –5.45 to –0.17 m) and –5.31 m (95% CI, –10.20 to –0.36 m) than those with normal hearing, respectively, during the 2-minute walk test. Conclusions and Relevance In this cohort study, hearing impairment was associated with poorer performance, faster decline in physical function, and reduced walking endurance. The results of the longitudinal analysis suggest that hearing impairment may be associated with poorer physical function with aging. Whether management of hearing impairment could delay decline in physical function requires further investigation.

BACKGROUND Childhood pneumonia is a leading cause of mortality worldwide. Growing evidence suggests that lung ultrasound (LUS) may be a reliable diagnostic alternative to chest x-ray for childhood pneumonia. However, it is unclear whether sonographer experience affects the diagnostic accuracy of LUS. We summarize the diagnostic accuracy of LUS for pneumonia and compare the performance between novice and advanced sonographers with a systematic review and meta-analysis. METHODS We searched PubMed and EMBASE from inception to February 2018 for eligible studies that evaluated the utility of LUS in children suspected of having pneumonia against the reference standard of either imaging results alone or a combination of clinical, laboratory, and imaging results. We reported the study using the Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies. We used QUADAS-2 to appraise the included studies' methodologic quality. We employed a random-effect bivariate model and a hierarchical summary receiver operating characteristic curve to evaluate LUS's performance characteristics. We conducted subgroup analyses and meta-regression based on level of sonographer training to summarize and compare LUS's diagnostic accuracy for pneumonia between novice (training ≤ 7 days) and advanced sonographers. RESULTS Twenty-five studies (n = 3,353) were included in the meta-analysis. For diagnosing pneumonia, LUS demonstrated an overall sensitivity of 0.94 (95% confidence interval [CI] = 0.89 to 0.97), specificity of 0.92 (95% CI = 0.78 to 0.98), positive likelihood ratio of 12.40 (95% CI = 4.00 to 38.10), and negative likelihood ratio of 0.07 (95% CI = 0.04 to 0.12), with an area under ROC curve of 0.97 (95% CI = 0.95 to 0.98). Meta-regression revealed a significant difference in the diagnostic accuracy for pneumonia for LUS between novice and advanced sonographers (p

Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data. Unfortunately, measurements for individual CpGs can be surprisingly unreliable due to technical noise, and this may limit the utility of epigenetic clocks. We report that noise produces deviations up to 3 to 9 years between technical replicates for six major epigenetic clocks. The elimination of low-reliability CpGs does not ameliorate this issue. Here, we present a novel computational multi-step solution to address this noise, involving performing principal component analysis on the CpG-level data followed by biological age prediction using principal components as input. This method extracts shared systematic variation in DNAm while minimizing random noise from individual CpGs. Our novel principal-component versions of six clocks show agreement between most technical replicates within 0 to 1.5 years, equivalent or improved prediction of outcomes, and more stable trajectories in longitudinal studies and cell culture. This method entails only one additional step compared to traditional clocks, does not require prior knowledge of CpG reliabilities, and can improve the reliability of any existing or future epigenetic biomarker. The high reliability of principal component-based epigenetic clocks will make them particularly useful for applications in personalized medicine and clinical trials evaluating novel aging interventions.

Background Although hearing impairment (HI) is linked to poorer physical functioning, the longitudinal associations between HI and higher-level functional measures are unclear. Method Data are from the Baltimore Longitudinal Study of Aging (2012–2019). Using pure-tone audiometry, we categorized hearing into normal, mild, and moderate or greater HI. Physical function was assessed with the expanded Short Physical Performance Battery (eSPPB) and walking endurance with time to walk 400 m. Multivariable and mixed-effects linear models tested the hypotheses that participants with HI, at baseline, have poorer physical performance and walking endurance, and faster decline over time (up to 6 measurements). In a subset (n = 526), we further adjusted for vestibular function. Among participants with HI, we evaluated the differences in eSPPB scores and walking endurance between hearing aid users and nonusers. Results Of 831 participants, 26% had mild, and 17% moderate or greater HI. After adjustment for demographics and medical history, moderate or greater impairment versus normal hearing was associated with poorer function (0.17 [95% CI: 0.09, 0.26] lower eSPPB score, and 13.3 [95% CI: 3.31, 23.4] seconds slower 400-m walk time) and faster decline in these parameters over 6 years. Adjustment for vestibular function did not attenuate these associations. Hearing aid users walked 400 m 24 seconds faster than nonusers (p = .001). Conclusion Moderate or greater HI is associated with poorer initial and greater decline in higher-level physical performance. The observation that hearing aid users had better walking endurance suggests that screening for and treatment of HI may delay or slow progression of hearing-related functional decline.

Key Points Question What is the prevalence of functional dual sensory impairment and is it associated with dementia risk among community-dwelling older adults in the US? Findings In this cohort study of adults over the age of 65 years, 14.9% of adults aged 90 years or older reported functional dual sensory impairment. Functional dual sensory impairment was associated with a higher 7-year risk of dementia compared with no sensory impairment. Meaning The results of this study suggest that functional sensory impairments are prevalent among older adults, and interventions to address multiple sensory impairments may be a potential target to reduce dementia risk., This cohort study of community-dwelling older adults in the US examined the age-specific prevalence of functional dual sensory impairment and assessed cross-sectional and longitudinal associations between functional dual impairment and dementia., Importance Impairments in vision or hearing are common and have been independently linked to higher risk of dementia in older adults. There is a limited understanding of the prevalence of concurrent functional vision and hearing impairment (dual sensory impairment) and its contribution to dementia risk. Objective To examine the age-specific prevalence of functional dual sensory impairment among older adults, and to investigate the cross-sectional and 7-year longitudinal associations between functional dual sensory impairment and dementia. Design, Setting, and Participants This cohort study of 7562 older adults used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community-dwelling, Medicare beneficiaries aged 65 years and older in the US. Participants in the study with complete data on hearing, vision, and dementia were included in analysis. Data were collected between 2011 and 2018, and between March 2018 and May 2020. Exposures Self-reported functional sensory impairments (ie, no sensory impairment, functional vision impairment only, functional hearing impairment only, and functional dual sensory impairment). Main Outcomes and Measures Age-specific prevalence of functional sensory impairments was calculated. Generalized linear regression with a complementary log-log link and a discrete time proportional hazards model with a complementary log-log link were used to assess the cross-sectional and 7-year longitudinal hazard of dementia. Results Of 7562 participants, 3073 (40.7%) were ages 80 years or older and 4411 (58.3%) were women. Overall, 5.4% (95% CI, 4.7%-6.1%) of participants reported functional vision impairment only, 18.9% (95% CI, 18.9%-17.8%) reported functional hearing impairment only, and 3.1% (95% CI, 2.7%-3.5%) reported functional dual sensory impairment (prevalence estimates are weighted). Participants reporting sensory impairments were older (no impairment: age ≥90 years, 2.12% [95% CI, 1.79%-2.46%] vs functional dual sensory impairment: age ≥90 years, 20.06% [95% CI, 16.02%-24.10%]), had lower education (no impairment

Study ObjectivesObstructive sleep apnea (OSA) is associated with cardiovascular and cerebrovascular morbidity. Patients with sickle cell disease (SCD) are at increased risk for both neurologic complications (NC) and OSA. However, the relationship between OSA and SCD complications is unclear. We hypothesized that there would be an association between OSA diagnosis and SCD complications.MethodsHospital discharge records of patients with SCD aged < 19 years were obtained for the years 1997, 2000, 2003, 2006, 2009, and 2012 from the Kid’s Inpatient Database. The primary outcome, NC, a composite of stroke, transient ischemic attack, and seizures. Secondary outcomes included acute chest syndrome (ACS), vaso-occlusive crisis, length of hospital stay, and inflation-adjusted cost of hospitalization. Multivariable regression was conducted to ascertain the association of OSA with primary and secondary outcomes. Analyses were adjusted for the use of noninvasive mechanical ventilation (NIMV) to determine its role as NC risk modifier.ResultsThere were 203,705 SCD discharges included in the analysis, of which 2,820 (1.4%) and 4,447 (2.2%) also included OSA and NC diagnoses. Multivariable logistic regression indicated that OSA was associated with NC (adjusted odds ratio [OR], 1.50 [95% CI 1.02–2.21], p = 0.039) and ACS (OR, 1.34 [95% CI 1.08–1.67], p = 0.009) in children with SCD. In the multivariable analysis adjusted for NIMV, the significant association between OSA and NC was no longer observed (OR, 1.39 [95% CI 0.94–2.05], p = 0.100).ConclusionsOSA is associated with a 50% increase of odds of NC in children with SCD in this nationwide dataset. The use of NIMV to treat OSA may modify the risk of OSA-associated NC.

Biological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic architecture underlying epigenetic ageing and its shared genetic contributions with lifestyle factors and longevity.

Over the past three decades, considerable effort has been dedicated to quantifying the pace of ageing yet identifying the most essential metrics of ageing remains challenging due to lack of comprehensive measurements and heterogeneity of the ageing processes. Most of the previously proposed metrics of ageing have been emerged from cross-sectional associations with chronological age and predictive accuracy of mortality, thus lacking a conceptual model of functional or phenotypic domains. Further, such models may be biased by selective attrition and are unable to address underlying biological constructs contributing to functional markers of age-related decline. Using longitudinal data from the Baltimore Longitudinal Study of Aging (BLSA), we propose a conceptual framework to identify metrics of ageing that may capture the hierarchical and temporal relationships between functional ageing, phenotypic ageing and biological ageing based on four hypothesized domains: body composition, energy regulation, homeostatic mechanisms and neurodegeneration/neuroplasticity. We explored the longitudinal trajectories of key variables within these phenotypes using linear mixed-effects models and more than 10 years of data. Understanding the longitudinal trajectories across these domains in the BLSA provides a reference for researchers, informs future refinement of the phenotypic ageing framework and establishes a solid foundation for future models of biological ageing.

The study of aging relates to changes in physical and functional dimensions that occur over time in living organisms. Yet, a model that establishes the hierarchical relationship and interlaced time courses of molecular, phenotypic, and functional hierarchical domains of aging in humans has not been established. We propose that studying the mechanisms and consequences of aging through the lens of these hierarchical domains and their connections will provide clarity in semantics and enhance a translational perspective. The study of human aging would be most informative from a life course, longitudinal perspective, given that manifestations of aging are already detectable early in life at the molecular level, yet the phenotypic responses remain masked by compensatory/resiliency mechanisms. Understanding the nature of these mechanisms is paramount for developing interventions that reduce the burden of disease and disability in older persons.

The longitudinal associations between hearing impairment and higher-level functional measures and the potential confounding role of vestibular function have not been assessed. We investigated these associations in 831 participants of the Baltimore Longitudinal Study of Aging (2012–2019). Hearing was measured using pure-tone audiometry and categorized using WHO standards. Physical function was assessed with the Health Aging and Body Composition Physical Performance Battery (HABCPPB, higher=better) and walking endurance with time to walk 400 meters. Multivariable regression models tested the hypotheses that participants with hearing impairment have poorer physical outomes. In a subset, we further adjusted for vestibular function. Hearing impairment was associated with decrements in higher-level physical performance and walking endurance, and faster decline over time, regardless of vestibular function. Among participants with any hearing impairment, hearing aid users were faster in the 400-m walk. Early screening for higher-level functional loss among older adults with hearing loss is warranted.

Key Points Question Can assessment of activity fragmentation (the degree to which an individual alternates bouts of activity and periods of rest) identify older individuals in whom slow gait indicates neurological impairment and risk of developing Alzheimer disease? Findings This cohort study of 520 initially cognitively normal patients evaluated whether slow gait and low activity fragmentation could help identify a subgroup of older adults who are at high risk of developing mild cognitive impairment or Alzheimer disease (MCI/AD). At low activity fragmentation, each 0.05-m/s slower gait was associated with a 19% increase in the hazard of developing MCI/AD; at high activity fragmentation, slower gait was not associated with risk of developing MCI/AD. Meaning These findings suggest that activity patterns may help to identify individuals in whom slow gait indicates an increased risk of developing MCI/AD., This cohort study assesses whether mobility behavioral compensation in older adults could help identify subgroups of individuals in whom slow gait speed may indicate subclinical neurological impairment and future risk of developing mild cognitive impairment and Alzheimer disease., Importance Among older people, slow walking is an early indicator of risk for Alzheimer disease (AD). However, studies that have assessed this association have not considered that slow walking may have different causes, some of which are not necessarily associated with higher AD risk. Objective To evaluate whether low activity fragmentation among older adults with slow gait speed indicates neurological causes of slow walking that put these individuals at higher risk of AD. Design, Setting, and Participants This prospective cohort study performed survival analyses using data from the Baltimore Longitudinal Study of Aging. Participants included 520 initially cognitively normal persons aged 60 years or older. New diagnoses of mild cognitive impairment (MCI) or AD were adjudicated during a mean (SD) follow-up of 7.3 (2.7) years. Initial assessment of gait speed and activity fragmentation occurred from January 3, 2007, to May 11, 2015, with follow-up completed on December 31, 2020. Data were analyzed from February 1 to May 15, 2021. Exposures Gait speed for 6 m and activity fragmentation assessed by accelerometry. Main Outcomes and Measures Associations of gait speed, activity fragmentation, and their interaction with incident MCI/AD were evaluated using Cox proportional hazards models, adjusted for covariates. Results Among the 520 participants (265 women [51.0%]; 125 Black participants [24.0%]; 367 White participants [70.6%]; mean [SD] age, 73 [8] years), MCI/AD developed in 64 participants. Each 0.05-m/s slower gait was associated with a 7% increase in risk of developing MCI/AD (hazard ratio [HR], 1.07 [95% CI, 1.00-1.15]; P = .04). Activity fragmentation alone was not associated with MCI/AD risk (HR, 0.83 [95% CI, 0.56-1.23]; P = .35), but there was a significant interaction between gait speed and activity fragmentation (HR, 0.92 [95% CI, 0.87-0.98]; P = .01). At low activity fragmentation (−1 SD), each 0.05-m/s slower gait speed was associated with a 19% increase in hazard of developing MCI/AD (HR, 1.19 [95% CI, 1.07-1.32]), whereas at higher activity fragmentation (+1 SD), gait speed was not associated with MCI/AD (HR, 1.01 [95% CI, 0.93-1.10]). Among participants with slow gait, higher activity fragmentation was associated with higher odds of having lower extremity osteoarthritis (odds ratio, 1.31 [95% CI, 1.01-1.69]) and less decline in pegboard dominant hand performance (β = 0.026 [SE, 0.009]; P > .05). Conclusions and Relevance These findings suggest that frequent rests among older adults with slow gait speed are associated with lower risk of future MCI/AD and that this behavioral strategy is associated with a lower likelihood of subclinical neurological impairment.

Chronic low-grade inflammation often occurs with aging and has been associated with negative health outcomes. Despite extensive research on the origins of “inflammaging”, the causative mechanisms remain unclear. However, a connection between poor mitochondrial health and chronic inflammation has been hypothesized, with decreasing mitochondrial function occurring with age and precipitating an increase in reactive oxygen species and other pro-inflammatory macromolecules such as mitochondrial DNA. We tested this hypothesis on a population of 619 subjects from the Baltimore Longitudinal Study of Aging, measuring muscle mitochondrial oxidative capacity in vivo by phosphorus magnetic resonance spectroscopy (P-MRS), and plasma interleukin (IL)-6, the most widely used biomarker of inflammaging. The P-MRS-derived post-exercise phosphocreatine recovery time constant tau-PCr, a measure of oxidative capacity, was expressed as a categorical variable through assignment to quintiles. Participants in the first quintile of tau-PCr (best mitochondrial function) were taken as reference and compared to the others using linear regression analysis adjusted for sex, age, lean and fat body mass, and physical activity. Those participants with the lowest oxidative capacity had significantly higher log(IL-6) levels as compared to the reference group. However, data from the other quintiles was not significantly different from the reference values. In conclusion, severe impairment of oxidative capacity is associated with increased inflammation. This study design does not provide conclusive evidence of whether increased inflammation and impaired bioenergetic recovery are both caused by underlying poor health status, or whether mitochondrial deficits lead directly to the observed inflammation; we anticipate addressing this important question with longitudinal studies.

Objective Fear of falling (FoF) may alter mobility in older adults, especially among those with visual impairment. Using a longitudinal prospective cohort of older glaucoma patients, we investigated whether and how FoF is associated with future falls and physical activity. Design Prospective observational cohort study. Setting Hospital-based single-center recruitment. Participants Individuals with glaucoma or suspected glaucoma. Measurements FoF was measured annually over a 3-year period using the University of Illinois at Chicago FoF Questionnaire, with lower Rasch-analyzed FoF scores (in logit units) indicating less fear. Participants recorded falls prospectively over the 3-year period using monthly mail-in calendars. Daily steps were collected annually over 7 days using an accelerometer. Visual field (VF) sensitivity was derived by combining sensitivities from monocular VF results. Participants completed questionnaires to determine other demographic/health characteristics. Multivariate random effects models evaluated within-participant changes in fall rates and physical activity across study years. Results At lower FoF levels (FoF≤0), each one-unit worsening in FoF score across study years was associated with 2.73 times higher odds of reporting at least one fall in the next year (95% confidence interval [CI] = 1.55-4.81) but was not associated with average daily steps (P = .44). Similar results were seen when fall rates were normalized by number of steps taken (P = .97). At higher FoF levels (FoF > 0), inter-year changes in FoF scores were not significantly associated with reporting a fall in the following year (P = .78) but were associated with 407 fewer average daily steps per one-unit change in FoF (95% CI = -743 to -71). Conclusion FoF is an important psychological factor associated with mobility in glaucoma patients, although specific aspects of mobility (fall rates vs activity levels) affected vary by the degree of FoF. Our findings suggest that customizing behavioral interventions for older adults based on their levels of FoF may be an important strategy for fall prevention and activity promotion. J Am Geriatr Soc 68:1847-1851, 2020.

Key Points Question Is the manner in which older adults accumulate physical activity throughout the day, beyond the total amount of physical activity, associated with their mortality risk? Findings In this cohort study of 548 well-functioning adults aged 65 years and older, more fragmentated physical activity, but not total daily activity, was associated with increased mortality risk. Meaning Fragmented physical activity of bouts lasting less than 5 minutes may reveal compensatory changes resulting from impaired physical function and may be associated with increased mortality risk., This cohort study of adults aged 65 years and older examines whether more fragmentated physical activity, rather than total daily activity, is associated with increased mortality risk., Importance Fragmented daily physical activity may be a sign of physiological decline that provides more powerful insight into impending mortality than total daily activity. Objective To compare and contrast the association between total daily activity and activity fragmentation, which encompasses activity bouts and duration, and mortality risk. Design, Setting, and Participants In this cohort study, accelerometer data from 2007 through 2015 and mortality data from 2007 through 2017 were collected from 548 adults aged 65 years and older participating in the Baltimore Longitudinal Study of Aging. The dates of analysis were November 2016 to June 2019, with data collected through December 31, 2017. Using Cox proportional hazards regression, the association between accelerometer-derived patterns of physical activity and mortality was estimated after adjusting for demographic characteristics, lifestyle factors, and comorbidities. Exposures Minute-by-minute physical activity data were collected over a 24-hour, 7-day period (excluding times between 11:00 pm and 4:59 am) using an accelerometer. Each minute was labeled either active or sedentary, and 5 features of accelerometer data were extracted: total daily activity (defined as any activity performed throughout the day), activity fragmentation (defined as an active-to-sedentary transition probability), and 3 measures of activity bouts (

Background Using objectively collected physical activity (PA) data from the Baltimore Longitudinal Study of Aging, the authors tested whether patterns of daily activity and sedentary time differed by cancer survivorship in older adults. Methods In total, 659 participants (mean age ± standard deviation, 71 ± 10 years; 51% women) who had self-reported information on cancer history were instructed to wear an accelerometer for 7 consecutive days. Accelerometer data were summarized into: 1) PA volume and 2) activity fragmentation (interrupted activity), expressed as both continuous and as dichotomized (low and high) variables. Participants were categorized into 4 groups by cross-classification of dichotomous PA volume and fragmentation. Multiple regression models were used to estimate differences in PA patterns by cancer history. Results Cancer survivors averaged 0.12 fewer log-transformed activity counts per day (standard error, 0.05; P = .02) than individuals who reported no history of cancer after adjusting for demographics, behavioral factors, and comorbidities. Although fragmentation did not differ by cancer survivorship in the continuous model (P = .13), cancer survivorship was associated with 77% greater odds (odds ratio, 1.77; 95% confidence interval, 1.11-2.82) of having high (vs low) fragmentation and 94% greater odds (odds ratio, 1.94; 95% confidence interval, 1.13-3.33) of having combined low PA/high fragmentation (vs high PA/low fragmentation) relative to those with no cancer history. Conclusions The current findings suggest that cancer survivors engage in lower total daily PA and that they perform this activity in a more fragmented manner compared with adults without a history of cancer. These results may reflect the onset and progression of a low-activity phenotype that is more vulnerable to heightened levels of fatigue and functional decline with aging.

BACKGROUND: With aging, daily physical activity (PA) becomes less frequent and more fragmented. Accumulation patterns of daily PA—including transitions from active-to-sedentary behaviors—may provide important insights into functional status in older, less active populations. METHODS: Participants of the Baltimore Longitudinal Study of Aging (n = 680, 50% male, aged 27–94 years) completed a clinical assessment and wore an Actiheart accelerometer. Transitions between active and sedentary states were modeled as a probability (Active-to-Sedentary Transition Probability [ASTP]) defined as the reciprocal of the average PA bout duration. Cross-sectional associations between ASTP and gait speed (m/s), fatigability (rating-of-perceived-exertion [RPE]), 400 m time (seconds), and expanded short physical performance battery score were modeled using linear and logistic regression, adjusted for chronic conditions. Further analyses explored the utility of ASTP over-and-above total daily PA. RESULTS: In continuous models, each 0.10-unit higher ASTP was associated slower gait (β = −0.06 m/s, SE = 0.01), higher fatigability (β = 0.60 RPE, SE = 0.12), slower 400 m time (β = 16.31 s, SE = 2.70), and lower functioning (β = −0.13 expanded short physical performance battery score, SE = 0.03; p < .001). In categorical analyses, those in the highest tertile of ASTP were >2 times more likely to have high fatigability (rating of perceived exertion ≥10), slow 400 m time (>300 seconds) and reduced functional performance (expanded short physical performance battery score < 3.07) than those in the lowest tertile (p < .01). Further analyses demonstrated ASTP provided additional insight into functional outcomes beyond total daily PA. CONCLUSION: Fragmented daily PA—as measured by ASTP—is strongly linked with measures of health and functional status and may identify those at risk of high fatigability and reduced functional performance over and above traditional PA metrics.

The timing of carotid revascularization in symptomatic patients is a matter of ongoing debate. Current evidence indicates that carotid endarterectomy (CEA) within 2 weeks of symptoms is superior to delayed treatment. However, there is little evidence on the outcomes of emergent CEA (eCEA). The purpose of this study was to compare outcomes of emergency eCEA vs nonemergent CEA (non-eCEA), stratified by type of presenting symptoms.We analyzed the Vascular Targeted-National Surgical Quality Improvement Program dataset from 2011 to 2016. Symptomatic patients were divided into two groups: eCEA and non-eCEA. Univariable and multivariable methods were used to compare patient characteristics and to evaluate stroke, death, myocardial infarction (MI), stroke/death, and stroke/death/MI within 30 days of surgery adjusting for all potential confounders. A further subgroup analysis was done to compare the outcomes of eCEA vs non-eCEA stratified by the type of presenting symptoms (amaurosis, transient ischemic attack [TIA], and stroke).A total of 9271 patients were identified, of which 10.7% were eCEA vs 89.3% non-eCEA. Comparing eCEA vs non-eCEA, the two groups were similar in age (70.8 vs 70.5), female gender (36.3% vs 36.9%), diabetes (26.2% vs 28.9%), and smoking status (31.9% vs 28.7%; all P.05). Patients undergoing eCEA were less likely to be hypertensive (76.2% vs 80.2%; P = .025), but more likely to belong to non-white race (51.5% vs 20.5%; P .001). The eCEA patients were less likely to be on preprocedural medication vs non-eCEA (antiplatelets, 76.8% vs 89.2%; statins, 74.2% vs 79.9%; beta-blockers, 44.6% vs 50.4%; all P .05). The 30-day outcomes comparing eCEA vs non-eCEA were: stroke, 6.2% vs 3.1%; death, 2% vs 1%; and stroke/death, 6.9% vs 3.7% (all P .05). After risk adjustment, perioperative stroke (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.36-3.0), stroke/death (OR, 1.66; 95% CI, 1.13-2.45), and stroke/death/MI (OR, 1.58; 95% CI, 1.18-2.23) were higher after eCEA (all P .01). When stratified by the type of presenting symptom, eCEA vs non-eCEA stroke outcomes were similar in patients who presented with stroke or amaurosis fugax. However, in the subset of patients presenting with TIA, eCEA had much worse outcomes compared with non-eCEA (stroke, 8.3% vs 2.5%; stroke/death, 8.3% vs 3.2%) and had significantly higher odds of stroke (OR, 3.12; 95% CI, 1.71-5.68) and stroke/death (OR, 2.24; 95% CI, 1.25-4.03) in the adjusted analysis (all P .05).In patients presenting with stroke, eCEA does not seem to add significant risk compared with non-eCEA. However, patients presenting with TIA might be better served with non-emergent surgery as their risk of stroke is tripled when CEA is performed emergently.

Energy utilization, which becomes more inefficient with age and is measured by a ratio of energy-cost-to-energy-capacity (“cost-ratio”), has been associated with functional decline. However, the interplay between longitudinal changes in energy efficiency and physical/cognitive functioning remains unclear. We investigated this relationship in 1020 participants of the Baltimore Longitudinal Study of Aging (baseline age: 68.9 (IQR: 59.8, 80.5), male: 44.7%). In linear mixed effects models adjusted for baseline age, sex, and height, an increasing cost-ratio was associated with faster decline in usual gait speed among those aged 50-64 years (beta = -0.20 m/s, p = 0.003), and >=65 years (beta = -0.16 m/s, p less than 0.001), but not those less than 50 years (beta = -0.22 m/s, p = 0.178). In models adjusted for baseline age, sex, race, and years of education, higher cost-ratio was associated with faster declines in executive function, as measured by time to finish Trail B, among those aged >=65 years (beta = 22.96 seconds, p = 0.020), but not

Delineating trajectories of aging phenotypes is essential to understanding mechanisms of clinical disease and disability. We investigated longitudinal changes in measures of body composition, energy expenditure, and brain volumes in >900 participants (age 67.0 (IQR: 57-77) years, 48.1% male) of the Baltimore Longitudinal Study of Aging using mixed effects regression models. Computed tomography-derived thigh muscle cross-sectional area declined 754.2 cm2 per decade at age 60 years (p

[This corrects the article DOI: 10.1371/journal.pmed.1002718.].

There are limited studies regarding childhood and adolescent psoriasis in Taiwan. A total of 86 pathologically confirmed cases diagnosed from 1989 to 2017 were retrospectively reviewed. Mean disease onset age was 10.51 years, and plaque psoriasis was the most common type. Compared to studies on Caucasian and other Asian populations, we found a lower estimated prevalence, higher rate of psoriasis limited to the nail at presentation, and higher prevalence of psoriatic arthritis. The most common comorbidities were related to atopy and metabolic syndrome. Positive family history of psoriasis and psoriasis preceded by infection were significantly associated with moderate-to-severe disease.

Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database. This was a nationwide, propensity score-matched case–control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI). Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08–2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status. Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status.