Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.

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.

Improving Emergency Department Care for Aging Missourians: Guidelines, Accreditation, and Collaboration.

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.

Emergency Department Use Among Older Adults With Dementia.

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.

Correlation Between Caregiver Reports of Physical Function and Performance-based Measures in a Cohort of Older Adults With Alzheimer Disease.

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.

Low sputum MMP-9/TIMP ratio is associated with airway narrowing in smokers with asthma.

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.

Screening for delirium in the emergency department: a systematic review.

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.

Using Google Street View to audit the built environment: inter-rater reliability results.

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.

Hospital and nursing home use from 2002 to 2008 among U.S. older adults with cognitive impairment, not dementia in 2002.

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.

The St. Louis African American health-heart study: methodology for the study of cardiovascular disease and depression in young-old African Americans.

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.

Observer ratings of neighborhoods: comparison of two methods.

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.

Sputum matrix metalloproteinase-12 in patients with chronic obstructive pulmonary disease and asthma: relationship to disease severity.

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.

Low circulating adropin levels in late-middle aged African Americans with poor cognitive performance.

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.

Design and baseline characteristics of the Cognitive and Aerobic Resilience for the Brain (CARB) study.

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.

A comparison and cross-validation of models to predict basic activity of daily living dependency in older adults.

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.

Childhood school segregation and later life sense of control and physical performance in the African American Health cohort.

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.

Serum neurofilament light levels are predictive of all-cause mortality in late middle-aged individuals.

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.

Testosterone is not associated with mortality in older African-American males.

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  ±â€Š 6.4, range 68-102) from Saint Louis, Missouri that includes 190 males (age 79.38  ±â€Š 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  ±â€Š 24.4 (n above 70 ng/dl = 5) and mean total testosterone levels (ng/dl) were 246.63  ±â€Š 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.

Matrix metalloproteinase-12 is a therapeutic target for asthma in children and young adults.

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.

Off-season physiological profiles of elite National Collegiate Athletic Association Division III male soccer players.

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.

Computerized decision support for medication dosing in renal insufficiency: a randomized, controlled trial.

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.