Examining if the relationship between BMI and incident type 2 diabetes among middle-older aged adults varies by race/ethnicity: evidence from the Multi-Ethnic Study of Atherosclerosis (MESA).

AIMS: Disparities persist on the prevalence of undiagnosed type 2 diabetes in racial/ethnic minorities in the USA. This study evaluated the association between BMI and incident type 2 diabetes risk by racial/ethnic group, to determine whether BMI and presence of type 2 diabetes risk factors may help clinicians better target type 2 diabetes screening. METHODS: This prospective cohort analysis included 5659 adults free of type 2 diabetes at baseline from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based cohort (2000-2011). BMI was measured at baseline and time-updated at subsequent visits. Incident type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/l, or use of any diabetes medications. RESULTS: The mean (sd) age was 62 (10) years and 42% of participants were white, 26% African American, 20% Hispanic and 12% Chinese American. During follow-up, 696 (12%) new type 2 diabetes cases were observed. In age- and sex-adjusted models, in the presence of one or more type 2 diabetes risk factors (the most common scenario), a 10% risk of incident type 2 diabetes was observed at a BMI of 21.7 kg/m2 [95% confidence interval (CI) 20.1 to 22.8] in Chinese Americans, 23.8 kg/m2 (22.7 to 24.9) in Hispanics, 24.7 kg/m2 (23.7 to 25.6) in African Americans and 26.2 kg/m2 (25.1 to 26.9) in white participants. CONCLUSIONS: This study supports including BMI and presence of type 2 diabetes risk factors as action points for clinicians to prioritize which adults aged ≥ 45 years should be screened. The application of race/ethnicity-specific BMI thresholds may reduce the disparity of undiagnosed type 2 diabetes observed in minority groups.

Targeted spine strengthening exercise and posture training program to reduce hyperkyphosis in older adults: results from the study of hyperkyphosis, exercise, and function (SHEAF) randomized controlled trial.

A 6-month randomized controlled trial of spine-strengthening exercise and posture training reduced both radiographic and clinical measures of kyphosis. Participants receiving the intervention improved self-image and satisfaction with their appearance. Results suggest that spine-strengthening exercise and postural training may be an effective treatment option for older adults with hyperkyphosis. INTRODUCTION: The purpose of the present study is to determine in a randomized controlled trial whether spine-strengthening exercises improve Cobb angle of kyphosis in community-dwelling older adults. METHODS: We recruited adults ≥60 years with kyphosis ≥40° and enrolled 99 participants (71 women, 28 men), mean age 70.6 ± 0.6 years, range 60-88, with baseline Cobb angle 57.4 ± 12.5°. The intervention included group spine-strengthening exercise and postural training, delivered by a physical therapist, 1-h, three times weekly for 6 months. Controls received four group health education meetings. The primary outcome was change in the gold standard Cobb angle of kyphosis measured from standing lateral spine radiographs. Secondary outcomes included change in kyphometer-measured kyphosis, physical function (modified Physical Performance Test, gait speed, Timed Up and Go, Timed Loaded Standing, 6-Min Walk), and health-related quality of life (HRQoL) (PROMIS global health and physical function indexes, SRS-30 self-image domain). ANCOVA was used to assess treatment effects on change from baseline to 6 months in all outcomes. RESULTS: There was a -3.0° (95% CI -5.2, -0.8) between-group difference in change in Cobb angle, p = 0.009, favoring the intervention and approximating the magnitude of change from an incident vertebral fracture. Kyphometer-measured kyphosis (p = 0.03) and SRS-30 self-esteem (p < 0.001) showed favorable between-group differences in change, with no group differences in physical function or additional HRQoL outcomes, p > 0.05. CONCLUSIONS: Spine-strengthening exercise and posture training over 6 months reduced kyphosis compared to control. Our randomized controlled trial results suggest that a targeted kyphosis-specific exercise program may be an effective treatment option for older adults with hyperkyphosis. TRIAL REGISTRATION NUMBER AND NAME OF TRIAL REGISTER: ClinicalTrials.gov; identifier NCT01751685.

The sixth vital sign: HIV status assessment and severe illness triage in Uganda.

Setting: Four in-patient health facilities in western Uganda. Objective: To determine the impact of an innovative multi-modal quality improvement program on human immunodeficiency virus (HIV) status assessment and the impact of HIV status on severe illness conditions and mortality. Design: This was a staggered, pre-post quasi-experimental study designed to assess a multi-modal intervention (collaborative improvement meetings, audit and feedback, clinical mentoring) for improving quality of care following formal training in the management of severe illness in low-income settings. Results: From August 2014 to May 2015, 5759 patients were hospitalized, of whom 2451 (42.6%) had their HIV status assessed; 395 (16.1%) were HIV-infected. HIV-infected patients were significantly more likely to meet criteria for shock (27.5% vs. 15.1%, risk ratio [RR] 1.8, 95% confidence interval [CI] 1.7-1.9, P < 0.001) and severe respiratory distress (6.7% vs. 4.3%, RR 1.5, 95%CI 1.2-2.0, P < 0.001), and were significantly more likely to die in hospital (12.0% vs. 2.9%, RR 4.1, 95%CI 3.2-5.4, P < 0.001). There was no evidence of improved HIV status assessment during the intervention period (36.5% vs. 44.8%, +8.3%, 95%CI -8.3 to 24.8, P = 0.33). Conclusions: Hospitalized HIV-infected patients in western Uganda are at high risk for severe illness and death. Novel quality improvement strategies are needed to enhance hospital-based HIV testing in high-burden settings.

Contexte : Quatre structures de santé hospitalières dans l'ouest de l'Ouganda.Objectif : Déterminer l'impact d'un programme innovant multimodal d'amélioration de la qualité sur l'évaluation du statut du virus de l'immunodéficience humaine (VIH) et l'impact du statut VIH sur les états de maladie grave et la mortalité.Schéma : Une étude échelonnée, pré-post et quasi-expérimentale conçue pour évaluer une intervention multimodale (réunions d'amélioration concertée, audit et rétro-information, tutorat clinique) pour améliorer la qualité des soins après la formation initiale sur la prise en charge de maladies graves dans un contexte de faibles ressources.Résultats : Entre août 2014 et mai 2015, 5759 patients ont été hospitalisés : 2451 (42,6%) ont eu une évaluation de leur statut VIH et 395 (16,1%) se sont avérés infectés par le VIH. Ces derniers ont été significativement plus susceptibles de répondre à des critères de choc (27,5% contre 15,1% ; rapport de risque [RR] 1,8 ; intervalle de confiance [IC] 95% 1,7­1,9 ; P < 0,001) et de détresse respiratoire grave (6,7% contre 4,3 ; RR 1,5 ; IC95% 1,2­2,0 ; P < 0,001), et ont été significativement plus susceptibles de décéder à l'hôpital (12,0% contre 2,9% ; RR 4,1 ; IC95% 3,2­5,4 ; P < 0,001). Il n'y a pas eu d'éléments en faveur d'une amélioration de l'évaluation du statut VIH pendant la période d'intervention (36,5% contre 44,8% ; +8,3% ; IC95% −8,3 à 24,8 ; P = 0,33).Conclusions : Les patients infectés par le VIH hospitalisés dans l'ouest de l'Ouganda ont un risque élevé de maladie grave et de décès. De nouvelles stratégies d'amélioration de qualité sont requises afin d'augmenter les tests VIH en hôpital dans les contextes à fardeau élevé de maladie.

Marco de referencia: Cuatro establecimientos hospitalarios en la zona occidental de Uganda.Objetivo: Determinar la repercusión de un programa innovador multimodal de mejora de la calidad sobre la evaluación de la situación frente al virus de la inmunodeficiencia humana (VIH) y la repercusión del estado frente al VIH en materia de enfermedades graves y mortalidad.Método: Se realizó un estudio semi-experimental escalonado pre y post con el fin de evaluar una intervención multimodal (reuniones de colaboración para mejorar de la calidad, auditorías y retroalimentación, tutoría clínica) encaminada a mejorar la calidad de la atención, tras una capacitación formal sobre el manejo de las enfermedades graves en entornos con bajos ingresos.Resultados: De agosto del 2014 a mayo del 2015 se hospitalizaron 5759 pacientes; en 2451 se examinó su situación frente al VIH (42,6%) y 395 presentaban infección por el VIH (16,1%). Los pacientes afectados por el VIH exhibieron una probabilidad significativamente mayor de cumplir con los criterios diagnósticos de choque (27,5% contra 15,1%; cociente de riesgos [RR] 1,8; intervalo de confianza [IC] del 95% 1,7­1,9; P < 0,001) y de insuficiencia respiratoria grave (6,7% contra 4,3%, RR 1,5; IC95% 1,2­2,0; P < 0,001) y la probabilidad de morir en el hospital fue significativamente más alta en estos pacientes (12,0% contra 2,9%, RR 4,1; IC95% 3,2­5,4; P < 0,001). No se encontraron pruebas en favor de una mejor evaluación de la situación frente al VIH durante el período de la intervención (36,5% contra 44,8%; +8,3%; IC95% −8,3 hasta 24,8; P = 0,33).Conclusión: Los pacientes hospitalizados aquejados de infección por el VIH en Uganda occidental son muy susceptibles de sufrir una enfermedad grave o la muerte. Se precisan nuevas estrategias de mejora de la calidad que refuercen la práctica de las pruebas diagnósticas de infección por el VIH en los entornos con alta carga de morbilidad.

Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial.

SUMMARY: Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture. INTRODUCTION: Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture. METHODS: We used data from the Fracture Intervention Trial among 3038 women 55-81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD. RESULTS: Mean baseline kyphosis was 48° (SD = 12) (range 7-83). At baseline, 962 (32%) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95% CI 2.8-4.6, p < 0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22% increase (95% CI 8-38%, p = 0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8% per 10° kyphosis (95% CI -4 to 22%, p = 0.18). CONCLUSIONS: While greater kyphosis increased the rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture.

Serum biomarkers of treatment response within a randomized clinical trial for pulmonary tuberculosis.

RATIONALE: Biomarkers for monitoring response to anti-tuberculosis treatment are needed. We explored immune markers previously published as having predictive capability for 8 week culture status in 39 adults enrolled in a clinical trial in Kampala, Uganda. METHODS: We consecutively selected 20 HIV-negative pulmonary TB subjects with positive cultures, and 19 subjects with negative cultures at the end of intensive phase therapy. At baseline and after 8 weeks, serum was assayed for nine cytokines and soluble cytokine receptors using multiplexed platforms or ELISA. We evaluated their association with week 8 culture status first using single-variable logistic models, then using cross-validated estimates of the C-statistic, a measure of discrimination, of candidate models including 2 or 3 analytes in addition to age. RESULTS: All but one analyte decreased from baseline to week 8 (all p < 0.01). Individual biomarkers were not associated with 8 week culture status. Logistic models including increasing age, higher baseline soluble tumor necrosis factor receptor alpha 1 (sTNF-R1), and higher week 8 C-reactive protein (CRP) concentration classified subjects by culture status with up to 85% accuracy and acceptable discrimination (cross-validated C-statistic 0.76) and calibration (Hosmer-Lemeshow P > 0.2). CONCLUSION: Exploratory post-hoc models including sTNF-R1, CRP, and age, classified 8 week culture status with promising accuracy.

Acculturation and Subclinical Atherosclerosis among U.S. South Asians: Findings from the MASALA study.

OBJECTIVE: Longer duration of residence among immigrants to the United States, a proxy measure of acculturation, has been associated with higher subclinical atherosclerosis. South Asian immigrants are the second fastest growing immigrant group in the U.S. but little is known about the effects of acculturation with atherosclerosis in this high cardiovascular risk population. METHODS: We conducted a cross-sectional analysis using data from a community-based cohort called the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Participants (n=900) were between ages of 40-84 years and had no existing cardiovascular disease. We developed a multi-dimensional measure of acculturation in South Asians, called traditional cultural beliefs, and measured other proxy measures of acculturation to determine whether they were associated with higher levels of subclinical atherosclerosis after controlling for socioeconomic, behavior/lifestyle, and cardiovascular risk factors. RESULTS: Mean duration of residence in the U.S. was 27±11 years and tertiles of strength of traditional cultural beliefs were examined. Longer duration of U.S. residence was associated with higher levels of coronary artery calcium even after adjustment for covariates and lifestyle mediators. The novel measure of strength of traditional cultural beliefs was associated with lower common carotid intima media thickness among those with moderate traditional beliefs only. CONCLUSIONS: These findings support the need for better conceptualization and measurement of how migration influences cultural beliefs and practices, and their subsequent influence on health behaviors and cardiovascular disease risk.

Housing instability and incident hypertension in the CARDIA cohort.

Housing instability, a growing public health problem, may be an independent environmental risk factor for hypertension, but limited prospective data exist. We sought to determine the independent association of housing instability in early adulthood (year 5, 1990-1991) and incident hypertension over the subsequent 15 years of follow-up (years 7, 10, 15, and 20) in the Coronary Artery Risk Development in Young Adults (CARDIA) study (N = 5,115). Because causes of inadequate housing and its effects on health are thought to vary by race and sex, we hypothesized that housing instability would exert a differential effect on incident hypertension by race and sex. At year 5, all CARDIA participants were asked about housing and those free of hypertension were analyzed (N = 4,342). We defined housing instability as living in overcrowded housing, moving frequently, or living doubled up. Of the 4,342 participants, 8.5 % were living in unstable housing. Across all participants, housing instability was not associated with incident hypertension (incidence rate ratio (IRR), 1.1; 95 % CI, 0.9-1.5) after adjusting for demographics, socioeconomic status, substance use, social factors, body mass index, and study site. However, the association varied by race and sex (p value for interaction, <0.001). Unstably housed white women had a hypertension incidence rate 4.7 times (IRR, 4.7; 95 % CI, 2.4-9.2) that of stably housed white women in adjusted analysis. There was no association among white men, black women, or black men. These findings suggest that housing instability may be a more important risk factor among white women, and may act independently or as a marker for other psychosocial stressors (e.g., stress from intimate partner violence) leading to development of hypertension. Studies that examine the role of these psychosocial stressors in development of hypertension risk among unstably housed white women are needed.

Patient, center and geographic characteristics of nationally placed livers.

Once a liver offer has been refused locally and regionally, it is offered nationally. We characterized nationally (n = 1567) versus locally (n = 19 893) placed grafts from adult, nonfulminant, deceased donor liver transplants (LT) from 2/1/05 to 1/31/10. Donors of nationally versus locally placed livers differed by age (50 vs. 42 years), positive HCV antibody (11 vs. 2%) and death from stroke (51 vs. 42%) (p < 0.001 for all). Recipients of nationally versus locally placed livers differed by LT-MELD (20 vs. 24), rates of ascites (35 vs. 37%), encephalopathy (12 vs. 15%), hepatocellular (17 vs. 24%) and nonhepatocellular exceptions (6 vs. 11%) (p ≤ 0.03 for all). Six (5%) centers utilized 64% of the nationally placed grafts while 43 (38%) centers accepted zero during the 5-year period; all high volume centers used ≥1. Compared to local distribution, transplantation with a nationally placed liver was associated with a similar adjusted risk of graft (HR, 0.99; 95% CI, 0.86-1.14) and patient (HR, 0.98; 95% CI, 0.84-1.14; p = 0.77) survival. In conclusion, utilization of nationally placed livers is highly concentrated in very few centers, with no increased adjusted risk of graft loss. These findings provide the foundation for a more informed discussion about changing our current liver allocation and distribution policies.

Advanced glycation end product level, diabetes, and accelerated cognitive aging.

OBJECTIVE: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. METHODS: We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of >1.0 SD on each test) was analyzed with logistic regression. RESULTS: Older adults with high pentosidine level had worse baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. CONCLUSION: High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes.

Age-related hyperkyphosis, independent of spinal osteoporosis, is associated with impaired mobility in older community-dwelling women.

UNLABELLED: While many assume hyperkyphosis reflects underlying spinal osteoporosis and vertebral fractures, our results suggest hyperkyphosis is independently associated with decreased mobility. Hyperyphosis is associated with slower Timed Up and Go performance times and may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk. INTRODUCTION: While multiple studies have demonstrated negative effects of hyperkyphosis on physical function, none have disentangled the relationship between hyperkyphosis, impaired function, and underlying spinal osteoporosis. The purpose of this study is to determine whether kyphosis, independent of spinal osteoporosis, is associated with mobility on the Timed Up and Go, and to quantify effects of other factors contributing to impaired mobility. METHODS: We used data for 3,108 community-dwelling women aged 55-80 years in the Fracture Intervention Trial. All participants had measurements of kyphosis, mobility time on the Timed Up and Go test, height, weight, total hip bone mineral density (BMD), grip strength, and vertebral fractures at baseline visits in 1993. Demographic characteristics included age and smoking status. We calculated mean Timed Up and Go time by quartile of kyphosis. Using multivariate linear regression, we estimated the independent association of kyphosis with mobility time, and quantified effects of other covariates on mobility. RESULTS: Mean mobility time increased from 9.3 s in the lowest to 10.1 s in the highest quartile of kyphosis. In a multivariate-adjusted model, mobility time increased 0.11 s (p = 0.02) for each standard deviation (11.9°) increase in kyphosis. Longer performance times were significantly associated with increasing age, decreasing grip strength, vertebral fractures, body mass index ≥25, and total hip BMD in the osteoporotic range. CONCLUSIONS: Kyphosis angle is independently associated with decreased mobility on the Timed Up and Go, which is in turn correlated with increased fall risk. Hyperkyphosis may be a useful clinical marker signaling the need for evaluation of vertebral fracture and falling risk.

Height contributes to the gender difference in wait-list mortality under the MELD-based liver allocation system.

This study examined factors associated with the gender disparity in wait-list mortality in the MELD era. Adult patients listed for liver transplantation from 2002 to 2008 were included. Females [12 585(36%)] and males [22 126(64%)] differed clinically by age (54 vs. 52 years), height (1.6 vs. 1.8 m), listing estimated glomerular filtration rate [(eGFR); 70 vs. 83 mL/min] and cirrhosis etiology. Holding MELD constant, females were at 19% (95% CI, 1.13-1.25, p < 0.001) higher risk of wait-list mortality than males under the current allocation system. The relative hazard increased with worsening renal function, whether measured by serum creatinine or eGFR. Adjustment for MELD, age, African-American race, cirrhosis etiology, region and ABO group attenuated this relative hazard (HR 1.16; 95% CI, 1.10-1.22; p < 0.001) but additional adjustment for height completely explained this gender disparity in wait-list mortality (HR 1.05; 95% CI, 0.98-1.12; p = 0.2). Transplantation rates, however, remained lower among females, even after adjustment for height (HR 0.88; 95% CI, 0.82-0.92; p < 0.001). In conclusion, under the current liver allocation system, women have a 19% increased risk of wait-list mortality compared to men with the same MELD scores. Height contributes to this gender disparity, possibly reflecting differences in transplantation rates for shorter individuals.

Optimal brain perfusion CT coverage in patients with acute middle cerebral artery stroke.

BACKGROUND AND PURPOSE: PCT has emerged as an alternative to MR imaging for the assessment of patients with suspected acute stroke. However, 1 disadvantage of PCT is its limited anatomic coverage, which may impact the characterization of hemispheric ischemic strokes. The purpose of this study was to determine the optimal brain CT coverage required to accurately estimate the size of the infarct core relative to the MCA territory and the infarct-penumbra mismatch, by using a criterion standard of these parameters measured on PCT with 80-mm z-axis coverage. MATERIALS AND METHODS: Fifty-one patients with acute ischemic hemispheric stroke underwent PCT scanning (2 boluses, total coverage of 80 mm, 16 x 5 mm sections) within the first 24 hours of symptom onset and a follow-up NCCT of the brain between 3 days and 3 months after the initial stroke CT study. The volumes of PCT infarct and penumbra for each possible extent of z-axis coverage derived from the individual PCT sections were recorded (beginning with 5 mm of z-axis coverage above the orbits and then increasing the coverage in 5-mm increments in the z-axis up to 80 mm above the orbits). The infarct-penumbra mismatch and the size of the infarction relative to the MCA territory were calculated for each extent of z-axis coverage. Using the 80-mm z-axis coverage as the criterion standard, we calculated the accuracy of the values of the relative PCT infarct size and mismatch that were obtained by using more limited z-axis coverage. The impact of different levels of PCT z-axis coverage on the eligibility for reperfusion treatment was assessed. RESULTS: On the admission PCT, by using 80-mm of z-axis coverage, the mean perfusion infarct core volume was 45.9 +/- 44.0 cm(3) (range, 0-170 cm(3)) and the mean penumbra volume was 64.5 +/- 64.4 cm(3) (range, 0-226 cm(3)). The mean perfusion infarct core/MCA territory ratio was 19.6% +/- 16.2% (range, 0.1%-56%). The penumbra / (infarct + penumbra) ratio was 68.6% +/- 23.6% (range, 16.4%-100%). The final infarct volume on follow-up NCCT was 115.4 +/- 157.3 cm(3) (range, 1.79-647.4 cm(3)). The minimal z-axis PCT coverage required to obtain values similar to those obtained with 80-mm z-axis coverage was 75 mm for a mismatch of 0.5, fifty millimeters for a mismatch of 0.2, and 55 mm for a size of PCT infarct relative to the MCA territory. CONCLUSIONS: Seventy-five millimeters is the minimal PCT coverage required to use PCT as a tool to select patients with acute stroke for reperfusion therapy by using a mismatch of 0.5. A z-axis coverage of 50 mm was sufficient for a mismatch of 0.2; and 55 mm, for the size of PCT infarct relative to MCA territory (one-third or more).

Laboratory reproducibility of biochemical markers of bone turnover in clinical practice.

SUMMARY: To determine the laboratory reproducibility of urine N-telopeptide and serum bone-specific alkaline phosphatase measurements, we sent identical specimens to six US commercial labs over an 8-month period. Longitudinal and within-run laboratory reproducibility varied substantially. Efforts to improve the reproducibility of these tests are needed. INTRODUCTION: We assessed the laboratory reproducibility of urine N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP). METHODS: Serum and urine were collected from five postmenopausal women, pooled, divided into identical aliquots, and frozen. To evaluate longitudinal reproducibility, identical specimens were sent to six US commercial labs on five dates over an 8-month period. To evaluate within-run reproducibility, on the fifth date, each lab was sent five identical specimens. Labs were unaware of the investigation. RESULTS: Longitudinal coefficients of variation (CVs) ranged from 5.4% to 37.6% for NTX and from 3.1% to 23.6% for BAP. Within-run CVs ranged from 1.5% to 17.2% for NTX. Compared to the Osteomark NTX assay, the Vitros ECi NTX assay had significantly higher longitudinal reproducibility (mean CV 7.2% vs. 30.3%, p < 0.0005) and within-run reproducibility (mean CV 3.5% vs. 12.7%, p < 0.0005). CONCLUSIONS: Reproducibility of urine NTX and serum BAP varies substantially across US labs.

Ascites improves upon [corrected] serum sodium plus [corrected] model for end-stage liver disease (MELD) for predicting mortality in patients with advanced liver disease.

BACKGROUND: The clinical impact of ascites has historically been well recognized; however, its value is unclear in the context of current prognostic models. AIM: To determine whether ascites can improve risk discrimination beyond model for end-stage liver disease (MELD) and serum sodium (MELDNa). METHODS: Consecutive cirrhotic patients were evaluated for ascites on the basis of an outpatient CT along with concurrent MELD and Na values. Cox models were used to determine the added value of ascites for predicting 1-year mortality. Increases in the C-index, integrated discrimination improvement (IDI) and the net reclassification index (NRI) were used to assess improvements in discrimination after the addition of ascites. RESULTS: A total of 1003 patients had Na and MELD scores available within 30 days of the CT scan. A total of 60 deaths occurred within 1 year, with mortality higher in patients with ascites (21.4% vs. 4.0%, HR 6.08, 95% CI 3.62-10.19, P < 0.0005). In the presence of ascites, the MELD and MELDNa scores underestimated mortality risk when the scores were less than 21. The addition of ascites to the MELDNa model substantially improved discrimination by the C-index (0.804 vs. 0.770, increase of 3.4%, 95% CI 0.2-9.9%), IDI (1.8%, P = 0.016) and NRI (15.8%, P = 0.0006). CONCLUSION: The incorporation of radiographic ascites significantly improves upon MELDNa for predicting 1-year mortality. The presence of ascites may help identify patients at increased risk for mortality, not otherwise captured by either MELD or MELDNa.

Predictors of maintaining cognitive function in older adults: the Health ABC study.

BACKGROUND: Although several risk factors for cognitive decline have been identified, much less is known about factors that predict maintenance of cognitive function in advanced age. METHODS: We studied 2,509 well-functioning black and white elders enrolled in a prospective study. Cognitive function was measured using the Modified Mini-Mental State Examination at baseline and years 3, 5, and 8. Random effects models were used to classify participants as cognitive maintainers (cognitive change slope > or = 0), minor decliners (slope < 0 and > 1 SD below mean), or major decliners (slope < or = 1 SD below mean). Logistic regression was used to identify domain-specific factors associated with being a maintainer vs a minor decliner. RESULTS: Over 8 years, 30% of the participants maintained cognitive function, 53% showed minor decline, and 16% had major cognitive decline. In the multivariate model, baseline variables significantly associated with being a maintainer vs a minor decliner were age (odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.55-0.77 per 5 years), white race (OR = 1.72, 95% CI 1.30-2.28), high school education level or greater (OR = 2.75, 95% CI 1.78-4.26), ninth grade literacy level or greater (OR = 4.85, 95% CI 3.00-7.87), weekly moderate/vigorous exercise (OR = 1.31, 95% CI 1.06-1.62), and not smoking (OR = 1.84, 95% CI 1.14-2.97). Variables associated with major cognitive decline compared to minor cognitive decline are reported. CONCLUSION: Elders who maintain cognitive function have a unique profile that differentiates them from those with minor decline. Importantly, some of these factors are modifiable and thus may be implemented in prevention programs to promote successful cognitive aging. Further, factors associated with maintenance may differ from factors associated with major cognitive decline, which may impact prevention vs treatment strategies.

Statin use is associated with lower risk of atrial fibrillation in women with coronary disease: the HERS trial.

OBJECTIVE: To determine the efficacy of statin treatment in atrial fibrillation (AF) prevention in women. DESIGN: Cohort study using data obtained in the Heart and Estrogen/Progestin Replacement Study (HERS). SETTING: Secondary analysis of a multicentre, randomised controlled clinical trial. PATIENTS: 2673 Postmenopausal women with coronary disease. MAIN OUTCOME MEASURES: AF prevalence at baseline and incident AF over a mean follow-up of 4.1 years. RESULTS: 88 Women with AF were identified: 29 at baseline and 59 during follow-up. Women with AF were significantly less likely to be taking a statin at study enrollment than those without AF (22% vs 37%, p = 0.003). Baseline statin use was associated with a 65% lower odds of having AF at baseline after controlling for age, race, history of myocardial infarction or revascularisation and history of heart failure (odds ratio 0.35, 95% confidence interval (CI) 0.13 to 0.93, p = 0.04). The risk of developing AF during the study among those free from AF at baseline, adjusted for the same covariates, was 55% less for those receiving statin treatment (hazard ratio 0.45, 95% CI 0.26 to 0.78, p = 0.004). CONCLUSIONS: Statin treatment is associated with a lower prevalence and incidence of AF after adjustment for potential confounders in postmenopausal women with coronary disease.

Sample size calculations for evaluating mediation.

This paper presents sample size calculations for testing the mediation of the effect of a primary predictor by an intermediate variable. This problem is related to validating surrogate markers and to testing the effect of a primary predictor in the presence of confounders. For those problems, proposals for sample size calculation exist in the literature and can be adapted to the problem of mediation. Methods based on the variance inflation factor in linear regression provide exact sample size calculations for the linear model and approximations for the logistic, Poisson, and Cox models. We propose another procedure based on simulation of the underlying data structure, with applications to the logistic and Cox models. For the Poisson model, a new analytic method is also proposed. The behavior of the different proposals is investigated by means of simulation studies.

Vitamin D insufficiency does not affect response of bone mineral density to alendronate.

SUMMARY: We investigated whether osteoporosis therapy with alendronate in postmenopausal patients is equally effective in patients who are vitamin D insufficient as in those who are vitamin D sufficient. We found that vitamin D insufficiency is common among patients with low bone density but that vitamin D insufficiency did not impair response to alendronate. INTRODUCTION: Treatment of vitamin D deficiency leads to significant improvements in bone mineral density (BMD); however, whether insufficiency affects BMD's response to bisphosphonate therapy is unknown. METHODS: To determine whether vitamin D insufficiency at initiation of alendronate therapy for low BMD affects treatment efficacy, we used data from 1,000 postmenopausal women randomly selected from the vertebral fracture arm (n = 2,027) of the placebo-controlled Fracture Intervention Trial of alendronate. Participants were randomly assigned to placebo (50%) or alendronate therapy and most (83%) to calcium (500 mg/day) and cholecalciferol (250 IU/day). We measured serum 25-hydroxy vitamin D (25OHD) at enrollment, then categorized baseline vitamin D status according to 25OHD concentration (10 but 30 ng/ml = sufficient) and used linear regression to compare the effects of alendronate treatment among these categories. RESULTS AND CONCLUSION: At baseline, participants were vitamin D sufficient (14%), insufficient (83%), and deficient (2%). We found that BMD response to therapy at total hip or spine did not vary by vitamin D status at baseline (p for heterogeneity = 0.6). We determined that vitamin D insufficiency is common among participants with low BMD. However, vitamin D status at initiation of therapy does not affect BMD's response to alendronate, when it is coadministered with cholecalciferol and calcium.

Perfusion CT Imaging Follows Clinical Severity in Left Hemispheric Strokes.

OBJECTIVE: The purpose of this study was to assess how imaging findings on admission perfusion CT (PCT) and follow-up noncontrast CT (NCT), and their changes over time, correlate with clinical scores of stroke severity measured on admission, at discharge and at 6-month follow-up. METHODS: Fifty-two patients with suspected hemispheric acute ischemic stroke underwent a PCT within the first 24 h of symptom onset and a follow-up NCT of the brain between 24 h and 3 months after the initial stroke CT study. NIH Stroke Scale (NIHSS) scores were recorded for each patient at admission, discharge and 6 months; modified Rankin scores were determined at discharge and 6 months. Baseline PCT and follow-up NCT were analyzed quantitatively (volume of ischemic/infarcted tissue) and semiquantitatively (anatomical grading score derived from the Alberta Stroke Program Early CT Score). The correlation between imaging volumes/scores and clinical scores was assessed. Analysis was performed for all patients considered together and separately for those with right and left hemispheric strokes. RESULTS: Significant correlations were found between clinical scores and both quantitative and semiquantitative imaging. The volume of the acute PCT mean transit time lesion showed best correlation with admission NIHSS scores (R2 = 0.61, p < 0.001). This association was significantly better for left hemispheric strokes (R(2) = 0.80, p < 0.001) than for right hemispheric strokes (R2 = 0.39, p = 0.131). Correlation between imaging and NIHSS scores was better than correlation between imaging and modified Rankin scores (p = 0.047). The correlation with discharge clinical scores was better than that with 6-month clinical scores (p = 0.012). CONCLUSIONS: Baseline PCT and follow-up NCT volumes predict stroke severity at baseline, discharge and, to a lesser extent, 6 months. The correlation is stronger for left-sided infarctions. This finding supports the use of PCT as a surrogate stroke outcome measure.

Communication of HIV viral load to guide sexual risk decisions with serodiscordant partners among San Francisco men who have sex with men.

The objective of this study was to estimate frequency and correlates of discussing HIV viral load (VL) with serodiscordant sex partners to guide decisions about sexual activities among men who have sex with men (MSM). We conducted a cross-sectional survey of 573 San Francisco MSM. Among 507 who knew their HIV status, 397 (78%) were familiar with the term 'viral load', and half (n=199) had a serodiscordant partner in the prior year. These 199 respondents (n=130 [65%] HIV-positive; n=69 [35%] HIV-negative) were the focus of this analysis. A majority (n=111, 56%) discussed VL in the prior year with serodiscordant partners specifically to guide decisions about sexual risk behaviour. Discussion was more common among HIV-positive than HIV-negative participants (adjusted odds ratio [AOR], 3.5; 95% confidence interval [CI], 1.6-7.6), and African Americans compared to whites (AOR, 3.7; 95% CI, 1.5-9.5). HIV-negative men who discussed VL were more concerned about becoming infected, but also more willing to engage in risky behaviour with a partner whose VL is undetectable, than men not discussing VL. Some HIV-negative men may be discussing VL to engage in higher risk behaviour upon learning of an HIV-positive partner's undetectable VL. Interventions targeting MSM should explain that while risk of transmission is likely reduced with a low blood plasma VL, it is not necessarily eliminated.