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.

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.

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.

PTPRC (CD45) is not associated with the development of multiple sclerosis in U.S. patients.

A C-->G nucleotide transition in exon 4 of PTPRC (encoding protein-tyrosine phosphatase receptor-type C, also known as CD45) was recently reported to be genetically associated with the development of multiple sclerosis (MS). We performed an extensive evaluation of this polymorphism using large family-based and case-control comparisons. Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course.

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.

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.

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.

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.

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Contrasting genetic influence of CCR2 and CCR5 variants on HIV-1 infection and disease progression. Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC), ALIVE Study.

The critical role of chemokine receptors (CCR5 and CXCR4) in human immunodeficiency virus-type 1 (HIV-1) infection and pathogenesis prompted a search for polymorphisms in other chemokine receptor genes that mediate HIV-1 disease progression. A mutation (CCR2-64I) within the first transmembrane region of the CCR2 chemokine and HIV-1 receptor gene is described that occurred at an allele frequency of 10 to 15 percent among Caucasians and African Americans. Genetic association analysis of five acquired immunodeficiency syndrome (AIDS) cohorts (3003 patients) revealed that although CCR2-64I exerts no influence on the incidence of HIV-1 infection, HIV-1-infected individuals carrying the CCR2-64I allele progressed to AIDS 2 to 4 years later than individuals homozygous for the common allele. Because CCR2-64I occurs invariably on a CCR5-+-bearing chromosomal haplotype, the independent effects of CCR5-Delta32 (which also delays AIDS onset) and CCR2-64I were determined. An estimated 38 to 45 percent of AIDS patients whose disease progresses rapidly (less than 3 years until onset of AIDS symptoms after HIV-1 exposure) can be attributed to their CCR2-+/+ or CCR5-+/+ genotype, whereas the survival of 28 to 29 percent of long-term survivors, who avoid AIDS for 16 years or more, can be explained by a mutant genotype for CCR2 or CCR5.

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

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.

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.

Depressive affect and survival among gay and bisexual men infected with HIV.

BACKGROUND: Although depression has been related to chronic disease processes and outcomes, studies examining the relationship between depression and disease progression in persons with human immunodeficiency virus (HIV) infection have produced inconsistent results. OBJECTIVE: To investigate whether depressive affect is associated with HIV mortality. METHODS: This was a prospective cohort study (San Francisco Men's Health Study) using a population based probability sample of single men living in areas of San Francisco, Calif, with high case rates of acquired immunodeficiency syndrome. Data collection was at 6-month intervals with up to 15 waves of follow-up. Subjects included all 402 homosexual or bisexual men who in July 1984 had serologic evidence of HIV infection and who survived a minimum of 1 wave after baseline. Depressive affect was measured at each wave with the affective subscale of the Center for Epidemiologic Studies-Depression Scale. Laboratory markers, World Health Organization staging, antiretroviral use, and hospitalizations were also used as predictor variables. The primary outcome measure was survival. RESULTS: In a Cox proportional hazards model, a time-dependent measure of depressive affect was associated with greater mortality (adjusted risk ratio, 1.67; 95% confidence interval, 1.01-2.78). CONCLUSIONS: Depressive affect was associated with mortality risk, highlighting the importance of diagnosis and treatment of depression among HIV-infected gay and bisexual men. Replication of this effect in incident cohorts with well-characterized dates of HIV infection is needed and, if replicated, an exploration of mediating pathways suggested.

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.

The characterization of non-progressors: long-term HIV-1 infection with stable CD4+ T-cell levels.

OBJECTIVE: To identify and characterize individuals with long-term HIV-1 infection who have experienced little or no progressive CD4+ T-cell loss during follow-up. PATIENTS AND METHODS: The rate of CD4+ T-cell loss (CD4 slope) was determined for each of the 290 participants in the San Francisco Men's Health Study who were seropositive at study entry in 1984. The study population was stratified, by CD4 slope, into 10 groups of 29 individuals and each group was characterized using a variety of cross-sectional and longitudinal laboratory measurements. RESULTS: Approximately 10% of the HIV-1-infected men experienced no net CD4+ T-cell loss during 78 months of follow-up. Compared with all other seropositive subjects, these 'non-progressors' were the extreme cases in a relatively continuous distribution of CD4 slopes, rather than a discrete subpopulation. Although they had no net cell loss, their mean CD4+ cell count was approximately 400 x 10(6)/l lower and their mean CD8+ cell count approximately 250 x 10(6)/l higher than seronegative subjects, suggesting early changes followed by stabilization. The CD4 slope was associated with the levels of beta 2-microglobulin, neopterin, p24 antibody, erythrocyte sedimentation rate, viral burden, and the proportion of HIV-1 isolates with tropism for the MT-2 T-cell line. Multivariate cluster analysis of these laboratory markers did not distinguish the non-progressors as a distinct subgroup. CONCLUSIONS: These findings support both a biphasic natural history and the suggestion that the broad range in HIV disease progression rates may be the result of several independent factors interacting in a variety of combinations. Recent changes in laboratory markers, known to predict both CD4+ cell loss and AIDS, suggest that non-progressors are undergoing slow HIV disease progression.

The efficacy of brief group counseling in HIV risk reduction among homosexual Asian and Pacific Islander men.

OBJECTIVES: The incidence of AIDS is increasing at a higher rate among homosexual Asian and Pacific Islanders (API) than white homosexual men in the United States. The number of homosexual API men engaging in unsafe sex is increasing at an alarming rate. HIV risk reduction is urgently needed in this population. SUBJECTS AND METHODS: We developed and evaluated culturally appropriate brief group counseling with 329 self-identified homosexual API recruited in San Francisco between 1992 and 1994. Participants were randomized into a single, 3-h skills training group or a wait-list control group. The intervention consisted of four components: (1) development of positive self-identity and social support, (2) safer sex education, (3) eroticizing safer sex, and (4) negotiating safer sex. Data were collected at baseline and 3 months after the intervention. RESULTS: Significant reductions in number of sexual partners were observed among all treatment subjects, regardless of ethnicity (P = 0.003). Treatment decreased the number of partners reported at 3-month follow-up by 46% [95% confidence interval (CI), 28-77]. Chinese and Filipino men further benefited from the intervention: treatment subjects from these two ethnic groups reduced unprotected anal intercourse at follow-up by more than half when compared to their counterparts (odds ratio = 0.41; 95% CI, 0.19-0.89; P = 0.024). CONCLUSIONS: We demonstrated the efficacy of brief group counseling in reducing HIV risk among homosexual API. Cities with significant API populations should adopt culturally tailored skills training as part of HIV prevention strategies for this group of homosexual men.

Home collection for frequent HIV testing: acceptability of oral fluids, dried blood spots and telephone results. HIV Early Detection Study Group.

OBJECTIVE: To assess the feasibility and acceptability of bimonthly home oral fluid (OF) and dried blood spot (DBS) collection for HIV testing among high-risk individuals. DESIGN: A total of 241 participants [including men who have sex with men (MSM), injecting drug users (IDU), and women at heterosexual risk] were recruited from a randomly selected subset of study participants enrolled at four sites in the HIV Network for Prevention Trials (HIVNET) cohort, and assigned at random to bimonthly home collection of OF or DBS specimens over a 6 month interval. Participants could select telephone calls or clinic visits to receive HIV test results. METHODS: Bimonthly specimens were tracked for adherence to the schedule, were evaluated for adequacy for testing, and tested using antibody assays and polymerase chain reaction (PCR) for DBS. The acceptability of bimonthly home OF and DBS collection and telephone counseling was assessed in an end-of-study questionnaire. RESULTS: The laboratory received 96 and 90% of expected OF and DBS specimens, respectively; 99% of each specimen type was adequate for testing. Almost all (95%) participants chose results disclosure by telephone. The majority of participants (85%) reported that bimonthly testing did not make them worry more about HIV, and almost all (98%) judged that with bimonthly testing their risk behavior remained the same (77%) or became less risky (21%). CONCLUSION: Bimonthly home specimen collection of both OF and DBS with telephone counseling is acceptable and feasible among study participants at high risk. These methods will be useful for the early detection of HIV infection and remote follow-up of research cohort participants in HIV vaccine and prevention trials.