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We recently reported accelerated cognitive decline in Europeans aged > 70 years with low circulating adropin levels. Adropin is a small, secreted peptide that is highly expressed in the human nervous system. Expression profiling indicate relationships between adropin expression in the human brain and pathways that affect dementia risk. Moreover, increased adropin expression or treatment using synthetic adropin improves cognition in mouse models of aging. Here we report that low circulating adropin concentrations associate with poor cognition (worst quintile for a composite score derived from the MMSE and semantic fluency test) in late-middle aged community-dwelling African Americans (OR = 0.775, P < 0.05; age range 45-65 y, n = 352). The binomial logistic regression controlled for sex, age, education, cardiometabolic disease risk indicators, and obesity. Previous studies using cultured cells from the brains of human donors suggest high expression in astrocytes. In snRNA-seq data from the middle temporal gyrus (MTG) of human donors, adropin expression is higher in astrocytes relative to other cell types. Adropin expression in all cell-types declines with advance age, but is not affected by dementia status. In cultured human astrocytes, adropin expression also declines with donor age. Additional analysis indicated positive correlations between adropin and transcriptomic signatures of energy metabolism and protein synthesis that are adversely affected by donor age. Adropin expression is also suppressed by pro-inflammatory factors. Collectively, these data indicate low circulating adropin levels are a potential early risk indicator of cognitive impairment. Declining adropin expression in the brain is a plausible link between aging, neuroinflammation, and risk of cognitive decline., (© 2023. The Author(s).)

Background: Treatments that delay progression of cognitive impairment in older adults are of great public health significance. This manuscript outlines the protocol, recruitment, baseline characteristics, and retention for a randomized controlled trial of cognitive and aerobic physical training to improve cognition in individuals with subjective cognitive dysfunction, the "Cognitive and Aerobic Resilience for the Brain" (CARB) study., Methods: Community-dwelling, older adults with self-reported memory loss were randomly assigned to receive either computer-based cognitive training, aerobic physical training, combined cognitive and physical training, or education control. Treatment was delivered 2- to 3-times per week in 45- to 90-min sessions for 12 weeks by trained facilitators videoconferencing into subject's home. Outcome assessments of were taken at the baseline, immediately following training, and 3-months after training., Results: 191 subjects were randomized into the trial (mean age, 75.5 years; 68% female; 20% non-white; mean education, 15.1 years; 30% with 1+ APOE e4 allele). The sample was generally obese, hypertensive, and many were diabetic, while cognition, self-reported mood, and activities of daily living were in the normal range. There was excellent retention throughout the trial. Interventions were completed at high rates, participants found the treatments acceptable and enjoyable, and outcome assessments were completed at high rates., Conclusions: This study was designed to determine the feasibility of recruiting, intervening, and documenting response to treatment in a population at risk for progressive cognitive decline. Older adults with self-reported memory loss were enrolled in high numbers and were well engaged with the intervention and outcome assessments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Blood biomarkers can offer valuable and easily accessible indicators of normal biological processes, pathogenic conditions, and responses to therapeutic interventions. Recent studies found that levels of neurofilament light chain (NfL) in the blood are associated with mortality in three European cohorts of older adults (median ages 73, 93, and 100 years). Whether similar associations exist in younger adults and in other ethnic groups is currently not known., Methods: We utilized a cohort study that included 294 African Americans (baseline ages 49-65). Serum NfL levels were measured using a Meso Scale Discovery-based assay. Vital status was determined by matching through the National Death Index., Findings: Seventy-two participants (24.5%) died during the 14-15 years of follow up (2000-2014). Baseline serum NfL levels were significantly higher in the decedent group (86.1±65.7 pg/ml vs. 50.1±28.0 pg/ml, p < 0·001). In binomial logistic regression models adjusted for age, gender, education, baseline smoking status, BMI, and total comorbidities (0-11), serum NfL levels remained a strong predictor of all-cause mortality, and sensitivity analyses employing multiple additional covariates did not substantively change the relationship. Further, Kaplan-Meier curves based on serum NfL quartiles showed reduced survival in groups with higher serum NfL levels., Interpretation: This study found a positive association between serum NfL levels and mortality in late middle-aged and older individuals. While our findings support that serum NfL levels may be a useful biomarker for all-cause mortality, further studies are needed to understand the biological mechanisms underlying this association., Funding: National Institute on Aging, Saint Louis University., Competing Interests: Declaration of interests None declared., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: A recent study identified progranulin as a candidate biomarker for frailty, based on gene expression databases. In the present study, we investigated associations between serum progranulin levels and frailty in a population-based sample of late middle-age and older adults., Methods: We utilized a cohort study that included 358 African Americans (baseline ages 49-65). Frailty was assessed by three established methods: the interview-based FRAIL scale, the Cardiovascular Health Study (CHS) frailty scale that includes performance-based measurements, and the Frailty Index (FI) that is based on cumulative deficits. Serum levels of the following proteins and metabolites were measured: progranulin, cystatin C, fructosamine, soluble cytokine receptors (interleukin-2 and -6, tumor necrosis factor α-1 and -2), and C-reactive protein. Sarcopenia was assessed using the SARC-F index. Vital status was determined by matching through the National Death Index (NDI)., Results: Serum progranulin levels were associated with frailty for all indices (FRAIL, CHS, and FI) but not with sarcopenia. Inflammatory markers indicated by soluble cytokine receptors (sIL-2R, sIL-6R, sTNFR1, sTNFR2) were positively associated serum progranulin. Increased serum progranulin levels at baseline predicted poorer outcomes including future frailty as measured by the FRAIL scale and 15-year all-cause mortality independent of age, gender, and frailty., Conclusions: Our findings suggest that serum progranulin levels may be a candidate biomarker for physical frailty, independent of sarcopenia. Further studies are needed to validate this association and assess the utility of serum progranulin levels as a potential biomarker for prevalent frailty, for risk for developing incident frailty, and for mortality risk over and above the effect of baseline frailty., Competing Interests: The authors have declared that no competing interests exist.

Context: Rural communities face unique challenges including fewer healthcare providers and restricted access to nutritious foods, likely leading to poor health outcomes. Community health coalitions are groups of local organizations partnering to address local health needs. Employing such coalitions is one strategy for implementing policy-system-environment changes for improving rural health. However, their success is variable without standardized evaluation. In this review, rural community health coalitions were retrospectively assessed using the W.K. Kellogg Foundation Logic Model. Community health coalition-reported pathways through this model were explored using market basket analysis., Evidence Acquisition: During Spring 2018, PubMed, Web of Science, ScienceDirect, CINAHL, and PsycINFO were searched for (coalition) AND (rural) AND (health) AND (effectiveness OR impact OR outcome OR logic model). Full-text, peer-reviewed, English articles meeting PICOS criteria (Population, rural communities; Intervention, presence of a community health coalition; Comparator, the coalition over time; Outcomes, logic model pathways) were reviewed. During Summer and Fall 2018, coalition-reported pathways were categorized according to logic model inputs and resources; internal and external activities; outputs; short-, medium-, and long-term outcomes; and impact. Market basket analysis was conducted during Winter 2018., Evidence Synthesis: The 10 most frequently reported pathway items were partner diversity; organizational structures; implementing pilot studies, programs, and interventions; funding; community engagement and outreach; university partners; holding regular meetings; having working groups and subcommittees; operating under or partnering with a regional research initiative; and conducting a community health and needs assessment. Half of community health coalitions reported 4 or more of the following: funding; partner diversity; university partners; organizational structures; community engagement and outreach; and implementing pilot studies, programs, and interventions., Conclusions: Many rural community health coalitions reported inputs and capacity building; few impacted health. Recommending common early phase logic model pathways may facilitate downstream success., (Copyright © 2020 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Community health coalitions (CHCs) are a promising approach for addressing disparities in rural health statistics. However, their effectiveness has been variable, and evaluation methods have been insufficient and inconsistent. Thus, we propose a mixed-methods evaluation framework and discuss pilot study findings. CHCs in our pilot study partnered with Purdue Extension. Extension links communities and land grant universities, providing programming and support for community-engaged research. We conducted social network analysis and effectiveness perception surveys in CHCs in 8 rural Indiana counties during summer 2017 and accessed county-level health statistics from 2015-16. We compared calculated variables (i.e., effectiveness survey k-means clusters, network measures, health status/outcomes) using Pearson's correlations. CHC members' positive perceptions of their leadership and functioning correlated with interconnectedness in their partnership networks, while more centralized partnership networks correlated with CHC members reporting problems in their coalitions. CHCs with highly rated leadership and functioning developed in counties with poor infant/maternal health and opioid outcomes. Likewise, CHCs reporting fewer problems for participation developed in counties with poor infant/maternal health, poor opioid outcomes, and more people without healthcare coverage. This pilot study provides a framework for iterative CHC evaluation. As the evidence grows, we will make recommendations for best practices that optimize CHC partnerships to improve local health in rural areas., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The Institute of Medicine has highlighted unequal treatment for African American individuals in health care. We examined the association of underuse of antidepressants in African American individuals with increased mortality., Methods: We conducted a longitudinal cohort study in Metropolitan St Louis, Missouri, in a population-based study of community-dwelling African American individuals, aged 52 to 68 years. Medication evaluations and clinically relevant levels of depressive symptoms (CRLDS) assessments occurred in 2000 and 2004. The analytic sample included 830 (of 853 total, 97%) participants with complete data. CRLDS was defined as ≥9 on the 11-item Center for Epidemiologic Studies Depression scale. Antidepressant use was determined by in-home medication recording and in-center coding. Participants were placed into 4 exposure categories: persistent CRLDS-no antidepressant (n = 69); intermittent CRLDS-no antidepressant (n = 123); antidepressant treatment (n = 110); and no CRLDS-no antidepressant (n = 528). Logistic regression with backwards elimination of the 9 identified potential confounders was used to examine associations of exposures with all-cause mortality over 6 years (2004-2010). Five sensitivity analyses investigated robustness of the primary findings., Results: The antidepressant group was independently associated with reduced mortality compared with the persistent-no antidepressant group (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.08-0.44). Sensitivity analyses showed no substantive differences from the primary model; one indicated that the persistent CRLDS-no antidepressant group experienced significantly increased mortality compared with the no CRLDS-no antidepressant group (OR 2.12, 95% CI 1.10-4.09), whereas the intermittent-no antidepressant group did not (OR 0.83, 95% CI 0.44-1.58)., Conclusions: These results highlight that underuse of antidepressants in African American individuals is associated with increased mortality., (Copyright © 2017. Published by Elsevier Inc.)

Aging baby-boomers present significant challenges to accessible, affordable emergency care in America for patients of all ages. St. Louis physicians served as early innovators in the field of geriatric emergency medicine. This manuscript summarizes a multi-institutional November 2016 symposium reviewing the Missouri history of geriatric emergency care. In addition, this manuscript describes multispecialty organizations' guidelines, healthcare outcomes research, contemporary medical education paradigms, and evolving efforts to disseminate guideline-based geriatric emergency care using a "Boot Camp" approach and implementation science. This manuscript also reviews local adaptations to emergency medical services and palliative care, as well as the perspectives of emergency department leaders exploring the balance between infrastructure and personnel required to promote guideline-based geriatric emergency care with the anticipated benefits. This discussion is framed within the context of the American College of Emergency Physician's planned geriatric emergency department accreditation process scheduled to begin in 2018.

Background: Healthy diet and physical activity (PA) have been associated with reduced depressive symptoms, but few studies have examined them simultaneously in African Americans., Aims: To investigate fruit and vegetable intake (FVI) and PA as predictors of clinically-relevant levels of depressive symptoms (CRLDS) in African Americans., Methods: African American Health (AAH) is a population-based longitudinal study of African Americans in St. Louis, MO, who were born in 1936-1950 (inclusive) and empaneled in 2000-01 (wave 1). At wave 8, participants self-reported fruit and vegetable intake (FVI) and completed the Yale Physical Activity Scale. At both waves 8 and 10, the CES-D 11-item scale was used to identify those who met criteria for CRLDS. Sequential logistic regression modeling was used to examine the associations of components of FVI/PA with CRLDS, both cross-sectionally (n = 680, including imputed values) and longitudinally (n = 582, including imputed values). Modeling employed gender, age, perceived income adequacy, and education as potential confounders., Results: Cross-sectionally, vigorous PA, and leisurely walking PA, were independently associated with lower odds of CRLDS in all but the fifth model and green vegetables in all models. Longitudinally, green vegetables and interactions between the FVI summary score, the PA summary score, and other factors at wave 8 were most consistently associated with CRLDS at wave 10. In both cross-sectional and longitudinal models, the socioeconomic variables showed the strongest association as risk factors for CRLDS., Limitations: Both FVI and PA were self-reported rather than observed, our cohort had limited geographic- and age-ranges, and confidence intervals for some results were broad., Conclusions: Green vegetables, total FVI, and various aspects of PA showed protective effects regarding CRLDS. Therefore, the promotion of such lifestyles is likely to help prevent CRLDS in this population., (Copyright © 2017. Published by Elsevier B.V.)

The Indiana Clinical and Translational Sciences Institute's Community Engagement Partners-Purdue Extension collaborative model demonstrates tremendous potential for creating state-wide programmatic efforts and improvements in both the health culture and status of Indiana residents across the state. It can serve as a prototype not only for others interested in pursuing wide geographic health improvements through Clinical and Translational Sciences Award-Cooperative Extension partnerships but also for broader collaborations among United States Department of Agriculture, National Institutes of Health, Centers for Disease Control and Prevention, state and local health departments, and health foundation efforts to improve population health.

Purpose of the study The study objective was to understand providers' perceptions regarding identifying and treating older adults with delirium, a common complication of acute illness in persons with dementia, in the pre-hospital and emergency department environments. Design and methods The authors conducted structured focus group interviews with separate groups of emergency medical services staff, emergency nurses, and emergency physicians. Recordings of each session were transcribed, coded, and analyzed for themes with representative supporting quotations identified. Results Providers shared that the busy emergency department environment was the largest challenge to delirium recognition and treatment. When describing delirium, participants frequently detailed hyperactive features of delirium, rather than hypoactive features. Participants shared that they employed no clear diagnostic strategy for identifying the condition and that they used heterogeneous approaches to treat the condition. To improve care for older adults with delirium, emergency nurses identified the need for more training around the management of the condition. Emergency medical services providers identified the need for more support in managing agitated patients when in transport to the hospital and more guidance from emergency physicians on what information to collect from the patient's home environment. Emergency physicians felt that delirium care would be improved if they could have baseline mental status data on their patients and if they had access to a simple, accurate diagnostic tool for the condition. Implications Emergency medical services providers, emergency nurses, and emergency physicians frequently encounter delirious patients, but do not employ clear diagnostic strategies for identifying the condition and have varying levels of comfort in managing the condition. Clear steps should be taken to improve delirium care in the emergency department including the development of mechanisms to communicate patients' baseline mental status, the adoption of a systematized approach to recognizing delirium, and the institution of a standardized method to treat the condition when identified.

Objective: We examined associations between observed neighborhood conditions (good/adverse) and psychosocial outcomes (stress, depressive symptoms, resilience, and sense of control) among middle-aged and older African Americans., Methods: The sample included 455 middle-aged and older African Americans examined in Wave 10 of the African American Health (AAH) study. Linear regression was adjusted for attrition, self-selection into neighborhoods, and potential confounders, and stratified by the duration at current address (<5 vs ≥5 years) because of its hypothesized role as an effect modifier., Results: Among individuals who lived at their current address for ≥5 years, residing in neighborhoods with adverse versus good conditions was associated with significantly less stress (standardized β = -0.18; P = .002) and depressive symptoms (standardized β = -0.12; P = .048). Among those who lived at their current address for <5 years, residing in neighborhoods with adverse versus good conditions was not significantly associated with stress (standardized β = 0.18; P = .305) or depressive symptoms (standardized β = 0.36; P = .080)., Conclusion: Neighborhood conditions appear to have significant, complex associations with psychosocial factors among middle-aged and older African Americans. This holds important policy implications, especially since adverse neighborhood conditions may still result in adverse physical health outcomes in individuals with >5 years at current residence despite being associated with better psychosocial outcomes.

Background: Alzheimer disease results in progressive functional decline, leading to loss of independence., Objective: To determine whether collaborative care plus 2 years of home-based occupational therapy delays functional decline., Design: Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950)., Setting: Urban public health system., Patients: 180 community-dwelling participants with Alzheimer disease and their informal caregivers., Intervention: All participants received collaborative care for dementia. Patients in the intervention group also received in-home occupational therapy delivered in 24 sessions over 2 years., Measurements: The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL); performance-based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM)., Results: At baseline, clinical characteristics did not differ significantly between groups; the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The intervention group received a median of 18 home visits from the study occupational therapists. In both groups, ADCS ADL scores declined over 24 months. At the primary end point of 24 months, ADCS ADL scores did not differ between groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not definitively demonstrate between-group differences in mean SPPB or SPSM values., Limitation: The results of this trial are indeterminate and do not rule out potential clinically important effects of the intervention., Conclusion: The authors could not definitively demonstrate whether the addition of 2 years of in-home occupational therapy to a collaborative care management model slowed the rate of functional decline among persons with Alzheimer disease. This trial underscores the burden undertaken by caregivers as they provide care for family members with Alzheimer disease and the difficulty in slowing functional decline., Primary Funding Source: National Institute on Aging.

The objectives of this report are to determine the association between performance-based measures of physical function with caregiver reports of physical function in older adults with Alzheimer disease (AD) and to examine whether those associations vary by the level of patients' cognitive functioning. Subjects included 180 patient-caregiver dyads who are enrolled in a clinical trial testing the impact of an occupational therapy intervention plus guideline-level care to delay functional decline among older adults with AD. The primary caregiver-reported measure is the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory (ADCS-ADL). Performance-based measures include the Short Physical Performance Battery and the Short Portable Sarcopenia Measure. Analysis of covariance (ANCOVA) models were used to determine the associations of each physical performance measure with ADCS-ADL, adjusting for cognition function and other covariates. We found significant correlations between caregiver reports and observed performance-based measures across all levels of cognitive function, with patients in the lowest cognitive group showing the highest correlation. These findings support the use of proxy reports to assess physical function among older adults with AD.

Background: A brief, inexpensive screening test for sarcopenia would be helpful for clinicians and their patients. To screen for persons with sarcopenia, we developed a simple five-item questionnaire (SARC-F) based on cardinal features or consequences of sarcopenia., Methods: We investigated the utility of SARC-F in the African American Health (AAH) study, Baltimore Longitudinal Study of Aging (BLSA), and National Health and Nutrition Examination Survey (NHANES). Internal consistency reliability for SARC-F was determined using Cronbach's alpha. We evaluated SARC-F factorial validity using principal components analysis and criterion validity by examining its association with exam-based indicators of sarcopenia. Construct validity was examined using cross-sectional and longitudinal differences among those with high (≥4) vs. low (<4) SARC-F scores for mortality and health outcomes., Results: SARC-F exhibited good internal consistency reliability and factorial, criterion, and construct validity. AAH participants with SARC-F scores ≥ 4 had more Instrumental Activity of Daily Living (IADL) deficits, slower chair stand times, lower grip strength, lower short physical performance battery scores, and a higher likelihood of recent hospitalization and of having a gait speed of <0.8 m/s. SARC-F scores ≥ 4 in AAH also were associated with 6 year IADL deficits, slower chair stand times, lower short physical performance battery scores, having a gait speed of <0.8 m/s, being hospitalized recently, and mortality. SARC-F scores ≥ 4 in the BLSA cohort were associated with having more IADL deficits and lower grip strength (both hands) in cross-sectional comparisons and with IADL deficits, lower grip strength (both hands), and mortality at follow-up. NHANES participants with SARC-F scores ≥ 4 had slower 20 ft walk times, had lower peak force knee extensor strength, and were more likely to have been hospitalized recently in cross-sectional analyses., Conclusions: The SARC-F proved internally consistent and valid for detecting persons at risk for adverse outcomes from sarcopenia in AAH, BLSA, and NHANES.

Although persons with dementia are frequently hospitalized, relatively little is known about the health profile, patterns of health care use, and mortality rates for patients with dementia who access care in the emergency department (ED). We linked data from our hospital system with Medicare and Medicaid claims, Minimum Data Set, and Outcome and Assessment Information Set data to evaluate 175,652 ED visits made by 10,354 individuals with dementia and 15,020 individuals without dementia over 11 years. Survival rates after ED visits and associated charges were examined. Patients with dementia visited the ED more frequently, were hospitalized more often than patients without dementia, and had an increased odds of returning to the ED within 30 days of an index ED visit compared with persons who never had a dementia diagnosis (odds ratio, 2.29; P<0.001). Survival rates differed significantly between patients by dementia status (P<0.001). Mean Medicare payments for ED services were significantly higher among patients with dementia. These results show that older adults with dementia are frequent ED visitors who have greater comorbidity, incur higher charges, are admitted to hospitals at higher rates, return to EDs at higher rates, and have higher mortality after an ED visit than patients without dementia.

Objectives: Efforts to prevent activity of daily living (ADL) dependency may be improved through models that assess older adults' dependency risk. We evaluated whether cognition and gait speed measures improve the predictive validity of interview-based models., Method: Participants were 8,095 self-respondents in the 2006 Health and Retirement Survey who were aged 65 years or over and independent in five ADLs. Incident ADL dependency was determined from the 2008 interview. Models were developed using random 2/3rd cohorts and validated in the remaining 1/3rd., Results: Compared to a c-statistic of 0.79 in the best interview model, the model including cognitive measures had c-statistics of 0.82 and 0.80 while the best fitting gait speed model had c-statistics of 0.83 and 0.79 in the development and validation cohorts, respectively., Conclusion: Two relatively brief models, one that requires an in-person assessment and one that does not, had excellent validity for predicting incident ADL dependency but did not significantly improve the predictive validity of the best fitting interview-based models., (© The Author(s) 2013.)

Objective: Depression may be a predictor and consequence of obesity. However, available evidence for racial minorities has been inconsistent, and more prospective studies are needed. Thus, this study's objective was to examine whether depressive symptom severity is a predictor and/or consequence of total adiposity over a 9-year period in a representative sample of late middle-aged African-Americans., Methods: A total of 410 participants (aged 49-65 years; baseline) in the prospective cohort African American Health study were examined. Depressive symptom severity was assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). Total body fat percent (BF%) and body mass index (BMI; kg/m(2) ) were assessed. Structural equation models were tested., Results: All model fit statistics, other than χ(2) , indicated good fit (RMSEA ≤ 0.058, SRMR ≤ 0.052, CFI ≥ 0.95). Baseline CES-D did not predict 9-year changes in BF% (β = -0.01, P = 0.78) or BMI (β = -0.01, P = 0.77). Baseline BF% (β = 0.05, P = 0.39) and BMI (β = 0.08, P = 0.095) did not predict 9-year change in CES-D., Conclusions: Depressive symptom severity was not a predictor or consequence of excess total adiposity in late middle-aged African-American adults. Including a depression module in obesity prevention and treatment programs specifically designed for late middle-aged African-Americans may not have a beneficial effect on obesity outcomes., (© 2014 The Obesity Society.)

Asthmatic smokers have poor symptom control and accelerated decline in lung function. A reduced ratio of matrix metalloproteinase (MMP)-9/tissue inhibitors of metalloproteinases (TIMPs) in nonsmokers with asthma has been implicated in airway remodelling. We tested the hypothesis that sputum MMP-9 activity/TIMPs ratios are reduced in smokers compared with never-smokers with asthma and are associated with reduced lung function and altered computed tomography (CT) measures of airway wall dimensions. Lung function, airway dimensions by CT, and induced sputum concentrations (and activity) of MMP-9 and TIMP-1 and -2 were measured in 81 asthmatics and 43 healthy subjects (smokers and never-smokers). Respiratory epithelial MMP9 and TIMP mRNA was quantified in 31 severe asthmatics and 32 healthy controls. Sputum MMP-9 activity/TIMP-1 and TIMP-2 ratios, and nasal epithelial MMP9/TIMP1 and MMP9/TIMP2 expression ratios were reduced in smokers with asthma compared with never-smokers with asthma. Low sputum ratios in asthmatic smokers were associated with reduced post-bronchodilator forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity ratio and segmental airway lumen area. The association of a low sputum MMP-9 activity/TIMP-1 ratio with persistent airflow obstruction and reduced CT airway lumen area in smokers with asthma may indicate that an imbalance of MMP-9 and TIMPs contributes to structural changes to the airways in this group., (©ERS 2014.)

Background: We addressed two understudied issues in estimating lower extremity functional trajectories in older adults-incorporating the effect of mortality and evaluating heterogeneity among African Americans., Methods: Data were taken from the 998 participants in the African American Health cohort. A highly reliable and valid 8-item lower extremity function scale was used at baseline and at the 1-, 2-, 3-, 4-, 7-, and 9-year follow-up interviews. Semiparametric (ie, discrete) group-based mixture modeling identified the trajectories, and multinomial logistic regression identified risk factors for differential trajectory groups., Results: When treating mortality as informative censoring, six discrete trajectories were observed with 45% of the participants belonging to three stable trajectories (good, fair, or poor function), and the remainder belonging to three declining trajectories (very high function with minimal improvement then minimal decline, very good function with a slow and modest decline, and very good function with a large and quick decline)., Conclusion: Substantial heterogeneity in lower extremity function trajectories exists in the African American Health cohort, after appropriately treating mortality as informative censoring., (© The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In order to improve our understanding of the relationship between the built environment and physical activity, it is important to identify associations between specific geographic characteristics and physical activity behaviors., Purpose: Examine relationships between observed physical activity behavior and measures of the built environment collected on 291 street segments in Indianapolis and St. Louis., Methods: Street segments were selected using a stratified geographic sampling design to ensure representation of neighborhoods with different land use and socioeconomic characteristics. Characteristics of the built environment on-street segments were audited using two methods: in-person field audits and audits based on interpretation of Google Street View imagery with each method blinded to results from the other. Segments were dichotomized as having a particular characteristic (e.g., sidewalk present or not) based on the two auditing methods separately. Counts of individuals engaged in different forms of physical activity on each segment were assessed using direct observation. Non-parametric statistics were used to compare counts of physically active individuals on each segment with built environment characteristic., Results: Counts of individuals engaged in physical activity were significantly higher on segments with mixed land use or all non-residential land use, and on segments with pedestrian infrastructure (e.g., crosswalks and sidewalks) and public transit., Conclusion: Several micro-level built environment characteristics were associated with physical activity. These data provide support for theories that suggest changing the built environment and related policies may encourage more physical activity.

Older adults who visit emergency departments (EDs) often experience delirium, but it is infrequently recognized. A systematic review was therefore conducted to identify what delirium screening tools have been used in ED-based epidemiologic studies of delirium, whether there is a validated set of screening instruments to identify delirium among older adults in the ED or prehospital environments, and an ideal schedule during an older adult's visit to perform a delirium evaluation. MEDLINE/EMBASE, Cochrane, PsycINFO, and CINAHL databases were searched from inception through February 2013 for original, English-language research articles reporting on the assessment of older adults' mental status for delirium. Twenty-two articles met all study inclusion criteria. Overall, 7 screening instruments were identified, though only 1 has undergone initial validation for use in the ED environment and a second instrument is currently undergoing such validation. Minimal information was identified to suggest the ideal scheduling of a delirium assessment process to maximize the recognition of this condition in the ED. Study results indicate that several delirium screening tools have been used in investigations in the ED, though validation of these instruments for this particular environment has been minimal to date. The ideal interval(s) during which a delirium screening process should take place has yet to be determined. Research will be needed both to validate delirium screening instruments to be used for investigation and clinical care in the ED and to define the ideal timing and form of the delirium assessment process for older adults., (Copyright © 2013 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Background: An accurate physical fitness survey could be useful in research and clinical care., Purpose: To estimate the validity and reliability of a Self-Reported Fitness (SRFit) survey; an instrument that estimates muscular fitness, flexibility, cardiovascular endurance, BMI, and body composition (BC) in adults ≥ 40 years of age., Methods: 201 participants completed the SF-36 Physical Function Subscale, International Physical Activity Questionnaire (IPAQ), Older Adults' Desire for Physical Competence Scale (Rejeski), the SRFit survey, and the Rikli and Jones Senior Fitness Test. BC, height and weight were measured. SRFit survey items described BC, BMI, and Senior Fitness Test movements. Correlations between the Senior Fitness Test and the SRFit survey assessed concurrent validity. Cronbach's Alpha measured internal consistency within each SRFit domain. SRFit domain scores were compared with SF-36, IPAQ, and Rejeski survey scores to assess construct validity. Intraclass correlations evaluated test-retest reliability., Results: Correlations between SRFit and the Senior Fitness Test domains ranged from 0.35 to 0.79. Cronbach's Alpha scores were .75 to .85. Correlations between SRFit and other survey scores were -0.23 to 0.72 and in the expected direction. Intraclass correlation coefficients were 0.79 to 0.93. All P-values were 0.001., Conclusion: Initial evaluation supports the SRFit survey's validity and reliability.

Objectives: To determine how well the interview-based, clinic-friendly International Academy of Nutrition and Aging (FRAIL) frailty scale predicts future disability and mortality in the African American Health (AAH) cohort compared with the clinic-friendly Study of Osteoporotic Fractures (SOF) frailty scale, the phenotype-based Cardiovascular Health Study (CHS) frailty scale, and the comprehensive Frailty Index (FI)., Design: Longitudinal cohort study., Setting: Metropolitan St. Louis, Missouri., Participants: African American Health is a population-based panel study of African Americans (baseline age 49-65) from St. Louis, Missouri. Participants completed in-home assessments at baseline (N = 998) and 3- (n = 853) and 9- (n = 582) year follow-up., Measurements: Outcomes included activity of daily living (ADL) and instrumental ADL difficulties at 3 and 9 years and 9-year mortality. Frailty measures included the FRAIL, SOF, and CHS scales and the FI., Results: The FRAIL, SOF, CHS, and FI measures predicted new 3- and 9-year disability, and the FRAIL and FI scales predicted 9-year mortality. Receiver operating characteristic (ROC) contrasts showed that the FRAIL scale performed as well as (9-year disability and mortality) or better than (3-year disability) the CHS and SOF scales and the FI better than the FRAIL, CHS, and SOF scales for all outcomes except the FRAIL and CHS scales for 9-year ADL difficulties. The CHS and SOF scales were equivalent for all outcomes in ROC contrasts., Conclusion: Overall the FI and the FRAIL scale exhibited the strongest predictive validity for disability and mortality in AAH. The best prediction tool to identify frail individuals at risk of disability and mortality may be one that includes a comorbidity measure. The FRAIL scale includes a comorbidity item and is a brief interview-based measure that is easy to administer, score, and interpret. The FRAIL scale has demonstrated validity and may prove to be a valuable scale for use by clinicians., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Background: Currently, there are no valid and reliable biomarkers to identify delirious patients predisposed to longer delirium duration. We investigated the hypothesis that elevated S100 calcium binding protein B (S100β) levels will be associated with longer delirium duration in critically ill patients., Methods: A prospective observational cohort study was performed in the medical, surgical, and progressive intensive care units (ICUs) of a tertiary care, university affiliated, and urban hospital. Sixty-three delirious patients were selected for the analysis, with two samples of S100β collected on days 1 and 8 of enrollment. The main outcome measure was delirium duration. Using the cutoff of <0.1 ng/mL and ≥0.1 ng/mL as normal and abnormal levels of S100β, respectively, on day 1 and day 8, four exposure groups were created: Group A, normal S100β levels on day 1 and day 8; Group B, normal S100β level on day 1 and abnormal S100β level on day 8; Group C, abnormal S100β level on day 1 and normal on day 8; and Group D, abnormal S100β levels on both day 1 and day 8., Results: Patients with abnormal levels of S100β showed a trend towards higher delirium duration (P=0.076); Group B (standard deviation) (7.0 [3.2] days), Group C (5.5 [6.3] days), and Group D (5.3 [6.0] days), compared to patients in Group A (3.5 [5.4] days)., Conclusion: This preliminary investigation identified a potentially novel role for S100β as a biomarker for delirium duration in critically ill patients. This finding may have important implications for refining future delirium management strategies in ICU patients.

Background: Matrix-metalloproteinase (MMP)-9 has been implicated in the pathogenesis of COPD, although its link to disease severity is unclear. The purpose of the study was to examine the relationship between disease severity assessed by lung function and computed tomography (CT) and sputum MMP-9 expression, concentration and activity in patients with COPD., Findings: In 53 COPD subjects, smokers and ex-smokers; 46 healthy controls, smokers and never smokers, we measured sputum MMP-9 concentrations (ELISA) and enzyme activity (FRET), sputum MMP-9 mRNA expression, spirometry, diffusing capacity for carbon monoxide (DLco) and CT assessment of emphysema (% low attenuation areas below-950 Hounsfield units). Sputum MMP-9 concentrations and mRNA expression in COPD subjects were significantly greater than in healthy never-smokers (p = 0.007 and p = 0.001 respectively) and similar to those in healthy smokers. Disease severity when assessed by the extent of emphysema measured by CT, but not by spirometry or DLco values, was directly associated with sputum MMP-9 concentrations [r = 0.442 (0.171, 0.634), p = 0.020], and MMP-9 activity [r = 0.447 (0.219, 0.643), p = 0.010]. In moderate to severe COPD, increased MMP-9 mRNA expression levels were associated with reduced post-bronchodilator FEV1 [r = -0.530 (-0.686, -0.327), p < 0.001], FEV1/FVC ratio [r = -0.551 (-0.701, -0.354), p < 0.001] and reduced DLco [r = -0.399 (-539, -0.102), p = 0.048]., Conclusions: Sputum MMP-9 concentrations in COPD are directly associated with the extent of emphysema measured by CT and MMP-9 expression levels are inversely associated with DLco. These findings support a role for MMP-9 in the pathogenesis of COPD.

Objective: Cross-sectional associations between childhood school segregation and adult sense of control and physical performance have been established in the African American Health (AAH) cohort. Here we extend that work by estimating the association between childhood school segregation and 2-year changes in adult sense of control. Method. Complete data on 541 older AAH men and women were used to estimate the association between childhood school segregation and changes in the sense of control. Exposure to segregation was self-reported in 2004, and the sense of control was measured in 2008 and 2010 using Blom rank transformations of Mirowsky and Ross' 8-item scale. Declining subjective income and experiencing major life stressors between 2008 and 2010, as well as traditional covariates (demographic factors, socioeconomic status, self-rated health, racial attitudes and beliefs, and religiosity) were included for statistical adjustment. Multiple linear regression analysis with propensity score reweighting was used., Results: Receiving the majority of one's primary and secondary education in segregated schools had a significant net positive association (d = 0.179; p = .029) with 2-year changes in adult sense of control., Conclusion: AAH participants receiving the majority of their primary and secondary educations in segregated schools appeared to have been protected, in part, from age-related declines in the sense of control.

Background: Although neighborhood characteristics have important relationships with health outcomes, direct observation involves imperfect measurement. The African American Health (AAH) study included two observer neighborhood rating systems (5-item Krause and 18-item AAH Neighborhood Assessment Scale [NAS]), initially fielded at two different waves. Good measurement characteristics were previously shown for both, but there was more rater variability than desired. In 2010 both measures were re-fielded together, with enhanced training and field methods implemented to decrease rater variability while maintaining psychometric properties., Methods: AAH included a poor inner city and more heterogeneous suburban areas. Four interviewers rated 483 blocks, with 120 randomly-selected blocks rated by two interviewers. We conducted confirmatory factor analysis of scales and tested the Krause (5-20 points), AAH 18-item NAS (0-28 points), and a previous 7-item and new 5-item versions of the NAS (0-17 points, 0-11 points). Retest reliability for items (kappa) and scales (Intraclass Correlation Coefficient [ICC]) were calculated overall and among pre-specified subgroups. Linear regression assessed interviewer effects on total scale scores and assessed concurrent validity on lung and lower body functions. Mismeasurement effects on self-rated health were also assessed., Results: Scale scores were better in the suburbs than in the inner city. ICC was poor for the Krause scale (ICC=0.19), but improved if the retests occurred within 10 days (ICC=0.49). The 7- and 5-item NAS scales had better ICCs (0.56 and 0.62, respectively), and were higher (0.71 and 0.73) within 10 days. Rater variability for the Kraus and 5- and 7-item NAS scales was 1-3 points (compared to the supervising rater). Concurrent validity was modest, with residents living in worse neighborhood conditions having worse function. Unadjusted estimates were biased towards the null compared with measurement-error corrected estimates., Conclusions: Enhanced field protocols and rater training did not improve measurement quality. Specifically, retest reliability and interviewer variability remained problematic. Measurement error partially reduced, but did not eliminate concurrent validity, suggesting there are robust associations between neighborhood characteristics and health outcomes. We conclude that the 5-item AAH NAS has sufficient reliability and validity for further use. Additional research on the measurement properties of environmental rating methods is encouraged.

Little is known about health care use in the cognitive impairment, not dementia (CIND) subpopulation. Using a cohort of 7130 persons aged 71 years or over from the Health and Retirement Survey, we compared mean and total health care use from 2002 to 2008 for those with no cognitive impairment, CIND, or dementia in 2002. Cognitive status was determined using a validated method based on self or proxy interview measures. Health care use was also based on self or proxy reports. On the basis of the Health and Retirement Survey, the CIND subpopulation in 2002 was 5.3 million or 23% of the total population 71 years of age or over. Mean hospital nights was similar and mean nursing home nights was less in persons with CIND compared with persons with dementia. The CIND subpopulation, however, had more total hospital and nursing home nights--71,000 total hospital nights and 223,000 total nursing home nights versus 32,000 hospital nights and 138,000 nursing home nights in the dementia subpopulation. A relatively large population and high health care use result in a large health care impact of the CIND subpopulation.

Background: Coronary artery disease (CAD) is a major cause of death and disability worldwide. Depression has complex bidirectional adverse associations with CAD, although the mechanisms mediating these relationships remain unclear. Compared to European Americans, African Americans (AAs) have higher rates of morbidity and mortality from CAD. Although depression is common in AAs, its role in the development and features of CAD in this group has not been well examined. This project hypothesizes that the relationships between depression and CAD can be explained by common physiological pathways and gene-environment interactions. Thus, the primary aims of this ongoing project are to: a) determine the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling older AAs; b) examine the relationships between CAD and depression phenotypes in this population; and c) evaluate genetic variants from serotoninP and inflammatory pathways to discover potential gene-depression interactions that contribute significantly to the presence of CAD in AAs., Methods/design: The St. Louis African American Health (AAH) cohort is a population-based panel study of community-dwelling AAs born in 1936-1950 (inclusive) who have been followed from 2000/2001 through 2010. The AAH-Heart study group is a subset of AAH participants recruited in 2009-11 to examine the inter-relationships between depression and CAD in this population. State-of-the-art CAD phenotyping is based on cardiovascular characterizations (coronary artery calcium, carotid intima-media thickness, cardiac structure and function, and autonomic function). Depression phenotyping is based on standardized questionnaires and detailed interviews. Single nucleotide polymorphisms of selected genes in inflammatory and serotonin-signaling pathways are being examined to provide information for investigating potential gene-depression interactions as modifiers of CAD traits. Information from the parent AAH study is being used to provide population-based prevalence estimates. Inflammatory and other biomarkers provide information about potential pathways., Discussion: This population-based investigation will provide valuable information on the prevalence of both depression and CAD phenotypes in this population. The study will examine interactions between depression and genetic variants as modulators of CAD, with the intent of detecting mechanistic pathways linking these diseases to identify potential therapeutic targets. Analytic results will be reported as they become available.

Background: Recent efforts to provide a consensus definition propose that sarcopenia be considered a clinical syndrome associated with the loss of both skeletal muscle mass and muscle function that occurs with aging. Validation of sarcopenia definitions that include both low muscle mass and poor muscle function is needed., Methods: In the population-based African American Health (AAH) study (N = 998 at baseline/wave 1), muscle mass and mobility were evaluated in a clinical testing center in a subsample of N = 319 persons (ages 52-68) at wave 4 (2004). Muscle mass was measured using dual energy x-ray absorptiometry and mobility by a 6-min walk test and 4-m gait walk test. Height corrected appendicular skeletal mass (ASM; 9.0 ± 1.5 in n = 124 males, 8.3 ± 2.2 in n = 195 females) was computed as total lean muscle mass in arms and legs (kilograms) divided by the square of height (meters). Cross-sectional and longitudinal (6-year) associations of low ASM (bottom 25 % AAH sample; <7.96 males and <7.06 females) and low ASM with limited mobility (4-m gait walk ≤1 m/s or 6-min walk <400 m) were examined for basic activities of daily living (ADL) difficulties, instrumental activities of daily living (IADL) difficulties, frailty, falls, and mortality (longitudinal only)., Results: Low ASM with limited mobility was associated with IADL difficulties (p = .008) and frailty (p = .040) but not with ADL difficulties or falls in cross-sectional analyses; and with ADL difficulties (p = .022), IADL difficulties (p = .006), frailty (p = .039), and mortality (p = .003) but not with falls in longitudinal analyses adjusted for age and gender. Low ASM alone was marginally associated with mortality (p = .085) but not with other outcomes in cross-sectional or longitudinal analyses., Conclusion: Low ASM with limited mobility is associated with poor health outcomes among late middle-aged African Americans.

Background: Observational field audits are recommended for public health research to collect data on built environment characteristics. A reliable, standardized alternative to field audits that uses publicly available information could provide the ability to efficiently compare results across different study sites and time., Purpose: This study aimed to assess inter-rater reliability of built environment audits conducted using Google Street View imagery., Methods: In 2011, street segments from St. Louis and Indianapolis were geographically stratified to ensure representation of neighborhoods with different land use and socioeconomic characteristics in both cities. Inter-rater reliability was assessed using observed agreement and the prevalence-adjusted bias-adjusted kappa statistic (PABAK)., Results: The mean PABAK for all items was 0.84. Ninety-five percent of the items had substantial (PABAK ≥ 0.60) or nearly perfect (PABAK ≥ 0.80) agreement., Conclusions: Using Google Street View imagery to audit the built environment is a reliable method for assessing characteristics of the built environment.

Background: The association between childhood school desegregation and later life sense of control and physical performance among African Americans is not clear. We hypothesized that childhood school desegregation adversely affected the sense of control of in later life, and that this reduced sense of control accounts in part for reduced physical performance., Methods: In-home follow-up assessments were completed in 2010 with 582 of the 58-74 year old men and women participating in the on-going African American Health cohort. We used these data to examine the relationship between (a) retrospective self-reports of attending segregated schools during one's 1st-to-12th grade education and one's current sense of control, as well as (b) the association between current sense of control and physical performance. Multiple linear regression analysis with propensity score re-weighting was used., Results: Attending segregated schools for at least half of one's 1st-to-12th grade education was significantly associated with higher scores on the sense of control. Adjusting for all covariates and potential confounders, those receiving half or more of their 1st-to-12th grade education in segregated schools had sense of control scores that were .886 points higher (p ≤ .01; standardized effect size = .22). Sense of control scores were independently (all p < .01) associated with better systolic blood pressure, grip strength, peak expiratory flow, chair stands, balance tests, and the Short Portable Physical Battery even after adjusting for all covariates and potential confounders. Moreover, sense of control scores either partially or fully mediated the statistically significant beneficial associations between childhood school segregation and physical performance., Conclusions: Childhood school desegregation was adversely associated with the sense of control of African Americans in later life, and this reduced sense of control appears, in part, to account for their poorer physical performance. The etiologic mechanism through which childhood school segregation at the time that this cohort experienced it improved the sense of control in later life, which subsequently led to better physical performance, has not been identified. We suspect, however, that the pathway involves greater exposure to racial solidarity, same-race students as peer role models and same-race teachers and principals as authority role models, the reduced likelihood of exposure to race-based discrimination or antagonism during their formative early lives, and greater exposure to encouragement and support for academic and life success.

Purpose: We hypothesize that lower street connectivity increases the risk of incident lower-body functional limitations (LBFLs) among urban African Americans aged 49-65 years., Methods: This population-based cohort was interviewed in home visits. Five items measuring LBFL were obtained at baseline and after 3 years. Participants were considered to have LBFL if they reported difficulty on at least two of the five tasks. Census-tract street connectivity was measured as the ratio of the number of street intersections to the maximum possible number of intersections., Results: Of 563 subjects with zero or one LBFL at baseline, 109 (19.4%) experienced two or more LBFLs at the 3-year follow-up. Adjusted logistic regression showed that persons who lived in census tracts with the lowest quartile of street connectivity were 3.45 times (95% confidence interval, 1.21-9.78) more likely to develop two or more LBFLs than those who lived in census tracts with the highest quartile of street connectivity independent of other important environmental factors., Conclusions: Areas with low street connectivity appear to be an independent contributor to the risk of incident LBFL in middle-aged African Americans., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Given the current lack of disease-modifying therapies, it is important to explore new models of longitudinal care for older adults with dementia that focus on improving quality of life and delaying functional decline. In a previous clinical trial, we demonstrated that collaborative care for Alzheimer's disease reduces patients' neuropsychiatric symptoms as well as caregiver stress. However, these improvements in quality of life were not associated with delays in subjects' functional decline., Trial Design: Parallel randomized controlled clinical trial with 1:1 allocation., Participants: A total of 180 community-dwelling patients aged ≥45 years who are diagnosed with possible or probable Alzheimer's disease; subjects must also have a caregiver willing to participate in the study and be willing to accept home visits. Subjects and their caregivers are enrolled from the primary care and geriatric medicine practices of an urban public health system serving Indianapolis, Indiana, USA., Interventions: All patients receive best practices primary care including collaborative care by a dementia care manager over two years; this best practices primary care program represents the local adaptation and implementation of our prior collaborative care intervention in the urban public health system. Intervention patients also receive in-home occupational therapy delivered in twenty-four sessions over two years in addition to best practices primary care. The focus of the occupational therapy intervention is delaying functional decline and helping both subjects and caregivers adapt to functional impairments. The in-home sessions are tailored to the specific needs and goals of each patient-caregiver dyad; these needs are expected to change over the course of the study., Objective: To determine whether best practices primary care plus home-based occupational therapy delays functional decline among patients with Alzheimer's disease compared to subjects treated in the control group., Outcomes: The primary outcome is the Alzheimer's Disease Cooperative Studies Group Activities of Daily Living Scale; secondary outcome measures are two performance-based measures including the Short Physical Performance Battery and Short Portable Sarcopenia Measure. Outcome assessments for both the caregiver-reported scale and subjects' physical performance scales are completed in the subject's home., Randomization: Eligible patient-care giver dyads will be stratified by clinic type and block randomized with a computer developed randomization scheme using a 1:1 allocation ratio., Blinding: Single blinded. Research assistants completing the outcome assessments were blinded to the subjects' treatment group., Trial Status: Ongoing CLINICALTRIAL.GOV IDENTIFIER: NCT01314950; date of completed registration 10 March 2011; date first patient randomized 9 March 2011.

Background: A simple method of identifying elders at high risk for activity of daily living (ADL) dependence could facilitate essential research and implementation of cost-effective clinical care programs., Objective: We used a nationally representative sample of 9446 older adults free from ADL dependence in 2006 to develop simple models for predicting ADL dependence at 2008 follow-up and to compare the models to the most predictive published model. Candidate predictor variables were those of published models that could be obtained from interview or medical record data., Methods: Variable selection was performed using logistic regression with backward elimination in a two-third random sample (n = 6233) and validated in a one-third random sample (n = 3213). Model fit was determined using the c-statistic and evaluated vis-a-vis our replication of a published model., Results: At 2-year follow-up, 8.0% and 7.3% of initially independent persons were ADL dependent in the development and validation samples, respectively. The best fitting, simple model consisted of age and number of hospitalizations in past 2 years, plus diagnoses of diabetes, chronic lung disease, congestive heart failure, stroke, and arthritis. This model had a c-statistic of 0.74 in the validation sample. A model of just age and number of hospitalizations achieved a c-statistic of 0.71. These compared with a c-statistic of 0.79 for the published model. Sensitivity analyses demonstrated model robustness., Conclusions: Models based on a widely available data achieve very good validity for predicting ADL dependence. Future work will assess the validity of these models using medical record data.

Background: Matrix metalloproteinase (MMP)-12 has been implicated in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and asthma. The influence of disease severity on sputum MMP-12 concentrations and activity is not known., Objectives: We sought to examine the relationship between disease severity assessed by means of lung function and computed tomography (CT) and induced sputum MMP-12 concentrations and activity in patients with asthma and COPD., Methods: In 208 subjects (109 asthmatic patients, smokers and never smokers, mild, moderate, and severe; 53 patients with COPD, smokers and exsmokers, mild, moderate, and severe; and 46 healthy control subjects, smokers and never smokers), we measured induced sputum MMP-12 concentrations (ELISA) and enzyme activity (fluorescence resonance energy transfer), sputum cell MMP12 mRNA expression (quantitative PCR [qPCR]), diffusing capacity for carbon monoxide (Dlco), and CT assessment of emphysema (percentage of low-attenuation areas at less -950 Hounsfield units)., Results: Sputum MMP-12 concentrations are greater in patients with COPD and smokers with asthma than in healthy nonsmokers (P = .003 and P = .035, respectively) but similar to those seen in healthy smokers. In patients with COPD, disease severity, when measured by means of CT-assessed emphysema, but not by means of spirometry or Dlco values, is directly associated with sputum MMP-12 concentrations and activity. In the asthma groups there is no significant association between disease severity and sputum MMP-12 concentrations or activity., Conclusions: Sputum MMP-12 concentrations and activity in patients with COPD are directly associated with the extent of emphysema measured by means of CT. This finding supports a role for MMP-12 in the pathogenesis of COPD and might suggest that blocking MMP-12 activity in patients with COPD could prevent the further development of emphysema., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Observational audits commonly are used in public health research to collect data on built environment characteristics that affect health-related behaviors and outcomes, including physical activity and weight status. However, implementing in-person field audits can be expensive if observations are needed over large or geographically dispersed areas or at multiple points in time. A reliable and more efficient method for observational audits could facilitate extendibility (i.e., expanded geographic and temporal scope) and lead to more standardized assessment that strengthens the ability to compare results across different regions and studies. The purpose of the current study was to evaluate the degree of agreement between field audits and audits derived from interpretation of three types of omnidirectional imagery. Street segments from St. Louis MO and Indianapolis IN were stratified geographically to ensure representation of neighborhoods with different socioeconomic characteristics in both cities. Audits were conducted in 2008 and 2009 using four methods: field audits, and interpretation of archived imagery, new imagery, and Google Street View™ imagery. Agreement between field audits and image-based audits was assessed using observed agreement and the prevalence-adjusted bias-adjusted kappa statistic (PABAK). Data analysis was conducted in 2010. When measuring the agreement between field audits and audits from the different sources of imagery, the mean PABAK statistic for all items on the instrument was 0.78 (archived); 0.80 (new); and 0.81 (Street View imagery), indicating substantial to nearly perfect agreement among methods. It was determined that image-based audits represent a reliable method that can be used in place of field audits to measure several key characteristics of the built environment important to public health research., (Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Self-rated health taps health holistically and dynamically blends prior health histories with current illness burdens and expectations for future health. While consistently found as an independent predictor of functional decline, sentinel health events, physician visits, hospital episodes, and mortality, much less is known about intra-individual changes in self-rated health across the life course, especially for African Americans., Materials/methods: Data on 998 African American men and women aged 50-64 years old were taken from a probability-based community sample that was first assessed in 2000-2001 and re-assessed 1, 2, 3, 4, 7, and 9 years later. Using an innovative approach for including decedents in the analysis, semi-parametric group-based mixture models were used to identify person-centered group trajectories of self-rated health over time. Multivariable multinomial logistic regression analysis was then used to differentiate the characteristics of AAH participants classified into the different group trajectories., Results: Four self-rated health group trajectories were identified: persistently good health, good but declining health, persistently fair health, and fair but declining health. The main characteristics that differentiated the self-rated health trajectory groups from each other were age, education, smoking, morbidity (angina, congestive heart failure, diabetes, and kidney disease), having been hospitalized in the year prior to baseline, depressive symptoms, mobility limitations, and initial self-rated health., Conclusions: This is the first study to examine self-rated health trajectories separately among African Americans. Four qualitatively distinct self-rated health group trajectories were identified that call into question the accuracy of prior reports that a single, average self-rated health trajectory for African Americans adequately captures their within-group heterogeneity.

Objective: To identify testable solutions that may improve the quality and safety of care transitions between nursing homes (NHs) and emergency departments (EDs)., Design: Structured focus group interviews., Setting: Group interviews took place in Indianapolis, Indiana., Participants: NH administrators, nurses, and physicians; emergency medical services directors, paramedics, and emergency medicine technicians; ED nurses and physicians; and a representative from the Indiana State Department of Health., Measurements: Opinions, perceptions, and insights of participants., Results: Eighteen participants were included. The central theme was the need for additional structure to support care transitions between NHs and EDs. Participants agreed that the structure afforded by hospital-to-hospital transfers would benefit patients and providers during transitions between NHs and EDs. Because transfer forms currently vary from NH to NH, participants recommended that the entire state use the same form. They recommended that the transfer form be useful in both directions by including a section for the ED provider to complete to support the ED-to-NH transition. Participants suggested that systems use a transfer checklist to help ensure that all processes occur as expected. They strongly recommended verbal communication across care settings to complement written communication and to improve on deficiencies that occur with transfer form-only strategies. Notably, participants suggested that the different care sites engage in relationship-building efforts to improve compliance with recommendations (eg, form completion) and collaborative problem solving., Conclusion: Participants advised additional structure to NH-ED care transitions, similar to hospital-to-hospital transfers, that includes a 2-way, statewide transfer form; a checklist; and verbal communication., (Copyright © 2011 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

Emergency services constitute crucial and frequently used safety nets for older persons, an emergency visit by a senior very often indicates high vulnerability for functional decline and death, and interventions via the emergency system have significant opportunities to change the clinical course of older patients who require its services. However, the evidence base for widespread employment of emergency system-based interventions is lacking. In this article, we review the evidence and offer crucial research questions to capitalize on the opportunity to optimize health trajectories of older persons seeking emergency care in four areas: prehospital care, delirium, adverse drug events, and falls.

INTRODUCTION. Although testosterone and its association with disease progression and mortality is a widely studied topic, no studies have evaluated mortality risks related to testosterone levels in an older African-American population. The mechanisms for known racial differences in mortality risk for certain cancers and cardiovascular risk factors are largely unknown. Elucidating a mortality risk associated with testosterone levels may give insight into the elevated risk for certain diseases in African-Americans. METHODS AND RESULTS. Study data were derived from a cohort 622 African-Americans (age 80.05  ±  6.4, range 68-102) from Saint Louis, Missouri that includes 190 males (age 79.38  ±  6.2, range 70-102). The eligible sample for this report includes 56 of the 190 males (age 78.89  ±  6.9, range 70-102) who donated blood at baseline in 1992-1994 and subsequently tested for total testosterone and bioavailable testosterone. Covariates for adjusted analyses were lower body functional limitations, physician visits and comorbidities, also collected at baseline. Males' mean bioavailable testosterone levels (ng/dl) were 33.33  ±  24.4 (n above 70 ng/dl = 5) and mean total testosterone levels (ng/dl) were 246.63  ±  118.7 (n above 300 ng/dl = 20). Vital status was determined through 2002; 41 males (73%) were deceased and 15 were alive. Mortality did not differ among males with testosterone levels <300 versus 300+ (p = 0.42) or with bioavailable testosterone levels <70 versus > 70 (p  =  0.34). Total testosterone levels did not predict mortality when adjusted for age (Adjusted Hazard Ratio [AHR] = 0.998; 95% confidence interval [CI] 0.995-1.001; p = 0.28) or adjusted for age and other covariates (AHR  =  0.099; 95% CI 0.996, 1.002; p  =  0.35). Bioavailable testosterone levels did not predict mortality when adjusted for age (AHR  =  0.992; 95% CI .977-1.007; p  =  0.30) or when adjusted for age and other covariates (AHR 0.991; 95% CI .976-1.006; p  =  0.261). CONCLUSION. In older African-American males, total and bioavailable testosterone levels, with and without adjustment for covariates, are not independently associated with mortality risk.

Background: Geriatric adults represent an increasing proportion of emergency department (ED) users and can be particularly vulnerable to acute illnesses. Health care providers have recently begun to focus on the development of quality indicators (QIs) to define a minimal standard of care., Objectives: The original objective of this project was to develop additional ED-specific QIs for older patients within the domains of medication management, screening and prevention, and functional assessment, but the quantity and quality of evidence were insufficient to justify unequivocal minimal standards of care for these three domains. Accordingly, the authors modified the project objectives to identify key research opportunities within these three domains that can be used to develop QIs in the future., Methods: Each domain was assigned one or two content experts who created potential QIs based on a systematic review of the literature, supplemented by expert opinion. Candidate QIs were then reviewed by four groups: the Society for Academic Emergency Medicine (SAEM) Geriatric Task Force, the SAEM Geriatric Interest Group, and audiences at the 2008 SAEM Annual Meeting and the 2009 American Geriatrics Society Annual Meeting, using anonymous audience response system technology as well as verbal and written feedback., Results: High-quality evidence based on patient-oriented outcomes was insufficient or nonexistent for all three domains. The participatory audiences did not reach a consensus on any of the proposed QIs. Key research questions for medication management (three), screening and prevention (two), and functional assessment (three) are presented based on proposed QIs that the majority of participants accepted., Conclusions: In assessing a minimal standard of care by which to systematically derive geriatric QIs for medication management, screening and prevention, and functional assessment, compelling clinical research evidence is lacking. Patient-oriented research questions that are essential to justify and characterize future QIs within these domains are described., (© 2011 by the Society for Academic Emergency Medicine.)

The purpose of this study was to develop a profile of soccer-related fitness parameters on elite National Collegiate Athletic Association (NCAA) Division III male soccer players during the off-season. Sixteen underclassmen from a recent NCAA Division III national championship soccer team completed a series of tests across 3 separate occasions over a 15-day period, with adequate recovery time between sessions to eliminate any carryover effect. Physiological parameters measured included aerobic endurance, anaerobic power and capacity, jumping power, agility, hamstring flexibility, and body composition. Descriptive statistics such as the mean (±SD) and range were calculated for each test. Two-tailed Pearson correlations were run to determine significant relationships that existed between variables. Test results were T-Tests (9.9 ± 0.4), Active Knee Extension degrees (-34.2 ± 11.9 right, -34.0 ± 13.9 left), vertical jump (61.8 ± 7.2 cm), percent fat (5.6 ± 1.6), Progressive Aerobic Cardiovascular Endurance Run (PACER) laps (113.2 ± 12.3), estimated VO2max (53.6 ± 2.9 ml · kg(-1) · min(-1)), Wingate peak (802.7 ± 155.6 W), Wingate peak (10.9 ± 1.2 W · kg(-1)), Wingate mean (651.2 ± 101.6 W), Wingate mean (8.9 ± 0.6 W · kg), and Wingate fatigue rate (35.9 ± 8.4%). Strong correlations existed between PACER laps and percent fat, between peak W and peak W · kg(-1), and between peak W and fatigue rate. These results suggest that elite Division III soccer players maintain relatively high fitness levels during the off-season. Additionally, they provide coaches with preliminary norms that can be used to determine off-season training expectations and adjust programs accordingly for their athletes.

Background: Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations., Methodology/principal Findings: Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations., Conclusions/significance: This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs.

Study Objective: Emergency physicians prescribe several discharge medications that require dosage adjustment for patients with renal disease. The hypothesis for this research was that decision support in a computerized physician order entry system would reduce the rate of excessive medication dosing for patients with renal impairment., Methods: This was a randomized, controlled trial in an academic emergency department (ED), in which computerized physician order entry was used to write all prescriptions for patients being discharged from the ED. The sample included 42 physicians who were randomized to the intervention (21 physicians) or control (21 physicians) group. The intervention was decision support that provided dosing recommendations for targeted medications for patients aged 18 years and older when the patient's estimated creatinine clearance level was below the threshold for dosage adjustment. The primary outcome was the proportion of targeted medications that were excessively dosed., Results: For 2,783 (46%) of the 6,015 patient visits, the decision support had sufficient information to estimate the patient's creatinine clearance level. The average age of these patients was 46 years, 1,768 (64%) were women, and 1,523 (55%) were black. Decision support was provided 73 times to physicians in the intervention group, who excessively dosed 31 (43%) prescriptions. In comparison, control physicians excessively dosed a significantly larger proportion of medications: 34 of 46, 74% (effect size=31%; 95% confidence interval 14% to 49%; P=.001)., Conclusion: Emergency physicians often prescribed excessive doses of medications that require dosage adjustment for renal impairment. Computerized physician order entry with decision support significantly reduced excessive dosing of targeted medications., (Copyright © 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

New models of health care delivery are inevitable. There is likely to be increasing emphasis on patient self-monitoring, health care delivery at patient homes, interdisciplinary treatment plans, a greater percentage of medical care delivered by non-physician health professionals, targeted health educational materials, and greater involvement and training of informal caregivers. The Information Technologies (IT) infrastructure of health systems will need to adapt. We have begun sorting out the implications of this future within a County public hospital system: defining the desirable features, relevant technologies, necessary modifications to the network, and additional data elements to be captured. We seek to build an infrastructure that will support new patient-focused technologies designed to more efficiently and effectively support older individuals. We hypothesize utility to further exploring the impact that new health care delivery models will have on health systems' IT infrastructures.

Objectives: To investigate associations between quality of life (QoL) and incontinence in a population-based African-American sample., Design: Cross-sectional survey., Setting: Metropolitan St. Louis, Missouri., Participants: Eight hundred fifty-three non-institutionalized African Americans aged 52 to 68 in the African American Health study., Measurements: Respondents who reported having involuntarily lost urine over the previous month were classified as having urinary incontinence (UI), and respondents who reported having lost control of their bowels or stool over the past year were classified as having fecal incontinence (FI). QoL was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the 11-item Center for Epidemiologic Studies Depression Scale (CES-D)., Results: Prevalences of UI and FI were 12.1% (weighted n=102/841) and 5.0% (weighted n=42/841). Participants with UI and those with FI had worse SF-36 scores than their referent groups (physical function -15.5 and -38.1 points, respectively; role physical -13.2 and -26.5 points; bodily pain -15.7 and -24.5 points; general health perceptions -15.5 and -27.6 points; vitality -15.0 and -16.5 points; social functioning -18.4 and -25.6 points; role emotional -13.2 and -22.1 points; mental health -12.2 and -17.5 points; all Ps<.001), adjusting for age, sex, body mass index, and chronic conditions. Proportions with clinically relevant levels of depressive symptoms were also higher in both groups (UI+17.9%; P<.001) and FI (+37.2%; P<.001) than in their referent groups., Conclusion: UI and FI were strongly associated with worse health-related QoL as well as symptoms of depression in this population-based sample of African Americans., (© 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.)

Background: Matrix metalloproteinase (MMP)-12-mediated pathologic degradation of the extracellular matrix and the subsequent repair cycles influence the airway changes in patients with asthma and chronic obstructive pulmonary disease (COPD). The common serine variant at codon 357 of the MMP12 gene (rs652438) is associated with clinical manifestations consistent with more aggressive matrix degradation in other tissues., Objective: We sought to explore the hypothesis that MMP12 represents a novel therapeutic target in asthma., Methods: The role of the rs652438 variant on clinical phenotype was explored in young asthmatic patients and patients with COPD. Candidate MMP-12 inhibitors were identified on the basis of potency and selectivity against a panel of other MMPs. The role of MMP-12-specific inhibition was tested in vitro, as well as in animal models of allergic airway inflammation., Results: The odds ratio for having greater asthma severity was 2.00 (95% CI, 1.24-3.24; P = .004) when comparing asthmatic patients with at least 1 copy of the serine variant with those with none. The carrier frequency for the variant increased in line with asthma treatment step (P = .000). The presence of the variant nearly doubled the odds in favor of asthmatic exacerbations (odds ratio, 1.90; 95% CI, 1.19-3.04; P = .008) over the previous 6 months. The serine variant was also associated with increased disease severity in patients with COPD (P = .016). Prior administration of an MMP-12-specific inhibitor attenuated the early airway response and completely blocked the late airway response with subsequent Ascaris suum challenge in sheep., Conclusion: Studies on human participants with asthma and COPD show that the risk MMP12 gene variant is associated with disease severity. In allergen-sensitized sheep pharmacologic inhibition of MMP12 downregulates both early and late airway responses in response to allergic stimuli., (Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Objectives: Among patients who arrive at an emergency department (ED) with pain, over half remain in moderate or severe pain at ED discharge. Our objectives were to identify ED physicians' prescribing patterns when discharging patients with common musculoskeletal conditions and to determine if disparities in opioid prescribing exist., Design: Five-year retrospective investigation., Setting: An urban, academic ED with approximately 100,000 annual visits, where physicians write discharge prescriptions, including over-the-counter medications, using a computerized order entry system., Patients: Adult patients who were discharged home from an ED with fractures (clavicle or long bone fractures) or non-fracture musculoskeletal diagnoses (sprains, strains, sciatica, or back pain)., Outcome Measures: Patient demographics and pain medications prescribed for use at home., Results: The study sample included 13,335 patients with a mean age of 39 years. Half were female; 52% were white; 39% were black; and 7% were Hispanic. Among fracture patients, 77% received an opioid prescription, 2% received a non-opioid prescription, and 21% received no analgesic prescription. The percentages for patients with non-fracture diagnoses were 65% (opioids), 18% (non-opioid analgesics), and 17% (no analgesic). Patients aged 80 years and older were significantly less likely to receive opioid prescriptions. Although prescribing by race for fractures was similar, significantly fewer black and Hispanic patients with non-fracture diagnoses received opioid prescriptions, compared with white patients., Conclusions: Approximately one fifth of patients in the fracture and non-fracture groups did not receive an analgesic prescription. Age greater than 80 years and minority race/ethnic status were associated with lower rates of opioid prescribing.