Jeannie S. Huang

Efficacy of Probiotic Use in Acute Diarrhea in Children: A Meta-Analysis

Our objective was to determine the efficacy of probiotic use in reducing the duration of increased stool output in children with acute diarrheal illness. Eligible studies were limited to trials of probiotic therapy in otherwise healthy children <5 years old with acute-onset diarrhea. The main outcome variable was difference in diarrhea duration between treatment and control groups. Our meta-analysis of 18 eligible studies suggests that coadministration of probiotics with standard rehydration therapy reduces the duration of acute diarrhea by ∼1 day [random-effects pooled estimate = −0.8 days (−1.1, −0.6), P < 0.001]. Differences in treatment effect between studies was assessed by calculating the Q statistic (Q = 204.1, P < 0.001). In subsequent analyses limited to studies of hospitalized children, to double-blinded trials, and to studies evaluating lactobacilli, the pooled estimates were similar (−0.6 to −1.2 days, P < 0.001). In conclusion, bacterial probiotic therapy shortens the duration of acute diarrheal illness in children by approximately one day.

Bone Disease in HIV Infection: A Practical Review and Recommendations for HIV Care Providers

Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected subjects. Initiation of antiretroviral therapy is associated with a 2%-6% decrease in BMD over the first 2 years, a decrease that is similar in magnitude to that sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review, we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ⩾50 years of age. We also discuss the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of bone disease, while outlining the caveats and gaps in our knowledge.

Reduced bone density in HIV-infected women

Objectives: Although bone density has been previously investigated in HIV-infected men, little is known regarding bone density in HIV-infected women. Methods and design: Bone density was measured by dual-energy X-ray absorptiometry in 84 ambulatory, HIV-infected females and 63 healthy female control subjects similar in age (41 ± 1 versus 41 ± 1 years, P = 0.83), body mass index (26.0 ± 0.6 versus 27.0 ± 0.5 kg/m2, P = 0.44) and racial background (% non-Caucasian, 61 versus 51%; P = 0.24, HIV-infected versus control). Results: Lumbar spine (1.02 ± 0.02 versus 1.07 ± 0.02 g/cm2, P = 0.03) and total hip (0.93 ± 0.01 versus 0.99 ± 0.01 g/cm2, P = 0.004) bone density were reduced in HIV-infected compared with control subjects. Osteopenia was demonstrated in 54 versus 30% (P = 0.004) of HIV-infected versus control subjects and was 2.5 times more likely in a multivariate model accounting for age, race, menstrual function and body mass index. Urinary N-telopeptides of type 1 collagen (NTx) (39.6 ± 3.5 versus 29.9 ± 2.0 nM/mM urine creatinine, P = 0.03) and osteoprotegerin (4.76 ± 0.23 versus 3.39 ± 0.17 pmol/l, P ⩽ 0.0001) were increased in HIV-infected compared with control subjects. Among the HIV-infected women, bone density correlated with weight (r = 0.41, P < 0.001) and inversely with urinary NTx (r = −0.28, P = 0.01). Bone density did not differ by current or past protease inhibitor, nucleoside reverse trancriptase inhibitor, or non-nucleoside reverse transcriptase inhibitor exposure. Conclusions: HIV-infected women demonstrate reduced bone density. Altered nutritional status, hormonal function and body composition may contribute to lower bone density in HIV-infected women. Consideration should be given to testing bone density in HIV-infected women with risk factors for osteopenia.

Current Concepts in the Diagnosis and Management of Metabolic Complications of HIV Infection and Its Therapy

Changes in fat distribution, dyslipidemia, disordered glucose metabolism, and lactic acidosis have emerged as significant challenges to the treatment of human immunodeficiency virus (HIV) infection. Over the past decade, numerous investigations have been conducted to better define these conditions, identify risk factors associated with their development, and test potential therapeutic interventions. The lack of standardized diagnostic criteria, as well as disparate study populations and research methods, have led to conflicting data regarding the diagnosis and treatment of metabolic and body shape disorders associated with HIV infection. On the basis of a review of the medical literature published and/or data presented before April 2006, we have prepared a guide to assist the clinician in the detection and management of these complications.

Increased abdominal visceral fat is associated with reduced bone density in Hiv-infected men with lipodystrophy

ObjectiveTo examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. DesignCross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. SettingTertiary care academic medical institution. PatientsA total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). MethodsBone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. ResultsMen with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men [mean ± SD, 132 ± 29 versus 154 ± 30 mg/cm3;P = 0.02] and HIV-negative controls [mean ± SD 132 ± 29 versus 148 ± 18) mg/cm3;P = 0.04]. Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, −0.47;P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. ConclusionsLumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density.

A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis.

Objective:To evaluate the efficacy of a single dose of intravenous zoledronate for the treatment of HIV-associated osteopenia and osteoporosis. Design:A double-blinded, randomized, placebo-controlled, 12-month trial of 5 mg intravenous zoledronate dose to treat 30 HIV-infected men and women with osteopenia and osteoporosis. Methods:Following zoledronate or placebo infusions, participants were followed for 12 months on daily calcium and vitamin D supplements. Lumbar spine and hip bone density was assessed at baseline, 6 and 12 months. Biomarkers of bone metabolism were measured at baseline, 2 weeks, 3, 6, 9, and 12 months. Students t-test and repeated measure analyses were used to evaluate bone density and bone marker changes over time. Results:In the 30 HIV-infected individuals [men (27) and women (3)] in the trial, median T-scores at entry were −1.7 for the lumbar spine and −1.4 for the hip. Median CD4 cell count was 461 cells/μl, 93% had HIV-RNA viral loads less than 400 copies/ml, and 97% were taking antiretroviral medications. Bone density measured either absolutely or as sex-adjusted T-scores significantly improved in zoledronate recipients as compared with minimal changes in those receiving placebo. Bone resorption markers significantly decreased over the study period in the zoledronate recipients as compared with placebo controls. No acute infusion reactions were detected, but one patient developed uveitis, a recognized complication of zoledronate, which responded to therapy. Conclusion:In this small study, annual zoledronate appears to be a well tolerated and effective therapy for HIV-associated bone loss.

Preparing Adolescents With Chronic Disease for Transition to Adult Care: A Technology Program

BACKGROUND: Adolescents with chronic disease (ACD) must develop independent disease self-management and learn to communicate effectively with their health care team to transition from pediatric to adult-oriented health care systems. Disease-specific interventions have been implemented to aid specific ACD groups through transition. A generic approach might be effective and cost-saving. METHODS: Eighty-one ACD, aged 12 to 20 years, were recruited for a randomized clinical trial evaluating an 8-month transition intervention (MD2Me). MD2Me recipients received a 2-month intensive Web-based and text-delivered disease management and skill-based intervention followed by a 6-month review period. MD2Me recipients also had access to a texting algorithm for disease assessment and health care team contact. The intervention was applicable to adolescents with diverse chronic illnesses. Controls received mailed materials on general health topics. Disease management, health-related self-efficacy, and health assessments were performed at baseline and at 2 and 8 months. Frequency of patient-initiated communications was recorded over the study period. Outcomes were analyzed according to assigned treatment group over time. RESULTS: MD2Me recipients demonstrated significant improvements in performance of disease management tasks, health-related self-efficacy, and patient-initiated communications compared with controls. CONCLUSIONS: Outcomes in ACD improved significantly among recipients of a generic, technology-based intervention. Technology can deliver transition interventions to adolescents with diverse chronic illnesses, and a generic approach offers a cost-effective means of positively influencing transition outcomes. Further research is needed to determine whether improved short-term outcomes translate into an improved transition for ACD.

Design and implementation of a randomized controlled social and mobile weight loss trial for young adults (project SMART)

PURPOSE To describe the theoretical rationale, intervention design, and clinical trial of a two-year weight control intervention for young adults deployed via social and mobile media. METHODS A total of 404 overweight or obese college students from three Southern California universities (M(age) = 22( ± 4) years; M(BMI) = 29( ± 2.8); 70% female) were randomized to participate in the intervention or to receive an informational web-based weight loss program. The intervention is based on behavioral theory and integrates intervention elements across multiple touch points, including Facebook, text messaging, smartphone applications, blogs, and e-mail. Participants are encouraged to seek social support among their friends, self-monitor their weight weekly, post their health behaviors on Facebook, and e-mail their weight loss questions/concerns to a health coach. The intervention is adaptive because new theory-driven and iteratively tailored intervention elements are developed and released over the course of the two-year intervention in response to patterns of use and user feedback. Measures of body mass index, waist circumference, diet, physical activity, sedentary behavior, weight management practices, smoking, alcohol, sleep, body image, self-esteem, and depression occur at 6, 12, 18, and 24 months. Currently, all participants have been recruited, and all are in the final year of the trial. CONCLUSION Theory-driven, evidence-based strategies for physical activity, sedentary behavior, and dietary intake can be embedded in an intervention using social and mobile technologies to promote healthy weight-related behaviors in young adults.

Low Baseline CD4+ Count Is Associated With Greater Bone Mineral Density Loss After Antiretroviral Therapy Initiation

BACKGROUND Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss. METHODS We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed. We used linear regression to evaluate effects of baseline CD4(+) and 16-week CD4(+) change (both absolute and relative) on 96-week total BMD change from baseline. We performed multivariable linear regression to assess associations between baseline variables of age, sex, race/ethnicity, body mass index (BMI), hepatitis C status, parent study, human immunodeficiency virus type 1 (HIV-1) RNA level, and assignment to a protease inhibitor (PI)- or tenofovir-containing regimen on 96-week total BMD change. RESULTS The included 796 subjects had mean 96-week total BMD loss of 2.0%. In multivariable analysis, baseline CD4(+) cell count was significantly associated with 96-week BMD loss; individuals with baseline CD4(+) <50 cells/µL lost significantly more BMD compared to those with CD4(+) ≥500 cells/µL. A greater relative, but not absolute, 16-week increase in CD4(+) count was significantly associated with greater declines in BMD, but not after controlling for baseline CD4(+) count. In multivariable analysis, older age, female sex, lower BMI, higher HIV-1 RNA levels, and PI and tenofovir assignment were also associated with greater BMD decline. CONCLUSIONS Low pretreatment CD4(+) count, but not greater CD4(+) count increase, is a strong and independent risk factor for bone loss after ART initiation. ART initiation at higher CD4(+) counts may reduce the burden of osteoporosis and fragility fractures.

Fractures after antiretroviral initiation.

Background:Bone mineral density declines by 2–6% within 1–2 years after initiation of antiretroviral therapy (ART); however, it is uncertain whether this results in an immediate or cumulative increase in fracture rates. Methods:We evaluated the incidence and predictors of fracture in 4640 HIV-positive participants from 26 randomized ART studies followed in the AIDS Clinical Trials Group (ACTG) Longitudinal-Linked Randomized Trial study for a median of 5 years. Fragility and nonfragility fractures were recorded prospectively at semiannual visits. Incidence was calculated as fractures/total person-years. Cox proportional hazards models evaluated effects of traditional fracture risks, HIV disease characteristics, and ART exposure on fracture incidence. Results:Median (interquartile range) age was 39 (33, 45) years; 83% were men, 48% white, and median nadir CD4 cell count was 187 (65, 308) cells/&mgr;l. Overall, 116 fractures were reported in 106 participants with median time-to-first fracture of 2.3 years. Fracture incidence was 0.40 of 100 person-years among all participants and 0.38 of 100 person-years among 3398 participants who were ART naive at enrollment into ACTG parent studies. Among ART-naive participants, fracture rates were higher within the first 2 years after ART initiation (0.53/100 person-years) than subsequent years (0.30/100 person-years). In a multivariate analysis of ART-naive participants, increased hazard of fracture was associated with current smoking and glucocorticoid use but not with exposure to specific antiretrovirals. Conclusion:Fracture rates were higher within the first 2 years after ART initiation, relative to subsequent years. However, continuation of ART was not associated with increasing fracture rates in these relatively young HIV-positive individuals.