Search

This overview of systematic reviews (SRs) aimed to identify dietary and lifestyle interventions in pregnant women that reduce the prevalence of overweight, obesity, and/or risk factors thereof, in their children. Following identification of eligible SRs, a matrix of all included studies identified overlap between SRs. The most recent, comprehensive, high-quality SRs were selected for further dissagregation. We developed a Grading of Recommendations, Assessment, Development and Evaluations (GRADE)-based effectiveness matrix incorporating effect size and study quality to prioritise interventions as (1) beneficial or harmful, (2) possibly beneficial or possibly harmful, (3) no effect, (4) possibly no effect, or (5) uncertain effect. Of the 27 SRs identified, 16 SRs were excluded due to overlap. From 11 remaining SRs, five discrete interventions were ranked "beneficial" or "possibly beneficial" for reducing risk factors for childhood obesity: (1) balanced energy/protein supplements, (2) dietary counseling alone, (3) low glycemic index dietary advice, (4) diet and exercise counseling, (5) diet counseling and supervised exercise. High protein supplementation was ranked "harmful" as it increased the risk of small-for-gestational age (SGA) infants in normal-weight pregnant women. Evidence of the impact of pregnancy-related diet or lifestyle interventions, on childhood obesity was limited. Five dietary interventions, alone or in combination with exercise, showed beneficial effects on the risk factors for childhood obesity.

BACKGROUND: A major challenge in medicine is translation of preclinical model findings to humans, especially therapy duration. One major example is recent shorter-duration therapy regimen failures in tuberculosis. METHODS: We used set theory mapping to develop a computational/modeling framework to map the time it takes to extinguish the Mycobacterium tuberculosis population on chemotherapy from multiple hollow fiber system model of tuberculosis (HFS-TB) experiments to that observed in patients. The predictive accuracy of the derived translation transformations was then tested using data from 108 HFS-TB Rapid Evaluation of Moxifloxacin in Tuberculosis (REMoxTB) units, including 756 colony-forming units (CFU)/mL. Derived transformations, and Latin hypercube sampling–guided simulations were used to predict cure and relapse after 4 and 6 months of therapy. Outcomes were compared to observations, in 1932 patients in the REMoxTB clinical trial. RESULTS: HFS-TB serial bacillary burden and serial sputum data in the derivation dataset formed a structure-preserving map. Bactericidal effect was mapped with a single step transformation, while the sterilizing effect was mapped with a 3-step transformation function. Using the HFS-TB REMoxTB data, we accurately predicted the proportion of patients cured in the 4-month REMoxTB clinical trial. Model-predicted vs clinical trial observations were (i) the ethambutol arm (77.0% [95% confidence interval {CI}, 74.4%–79.6%] vs 77.7% [95% CI, 74.3%–80.9%]) and (ii) the isoniazid arm (76.4% [95% CI, 73.9%–79.0%] vs 79.5% [95% CI, 76.1%–82.5%]). CONCLUSIONS: We developed a method to translate duration of therapy outcomes from preclinical models to tuberculosis patients.

Objectives To identify the pyrazinamide MIC above which standard combination therapy fails. Methods MICs of pyrazinamide were determined for Mycobacterium tuberculosis isolates, cultured from 58 patients in a previous randomized clinical trial in Cape Town, South Africa. The MICs were determined using BACTEC MGIT 960 for isolates that were collected before standard treatment with isoniazid, rifampicin, pyrazinamide and ethambutol commenced. Weekly sputum collections were subsequently made for 8 weeks in order to culture M. tuberculosis in Middlebrook broth medium. Classification and regression tree (CART) analysis was utilized to identify the pyrazinamide MIC predictive of sputum culture results at the end of pyrazinamide therapy. The machine learning-derived susceptibility breakpoints were then confirmed using standard association statistics that took into account confounders of 2 month sputum conversion. Results The pyrazinamide MIC range was 12.5 to >100 mg/L for the isolates prior to therapy. The epidemiological 95% cut-off value was >100 mg/L. The 2 month sputum conversion rate in liquid cultures was 26% by stringent criteria and 48% by less stringent criteria. CART analysis identified an MIC breakpoint of 50 mg/L, above which patients had poor sputum conversion rates. The relative risk of poor sputum conversion was 1.5 (95% CI: 1.2–1.8) for an MIC >50 mg/L compared with an MIC ≤50 mg/L. Conclusions We propose a pyrazinamide susceptibility breakpoint of 50 mg/L for clinical decision making and for development of rapid susceptibility assays. This breakpoint is identical to that identified using computer-aided simulations of hollow fibre system output.

Background: Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell–mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain. Objective: The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear–positive pulmonary tuberculosis. Design: Participants attending a primary care tuberculosis clinic in Cape Town, South Africa, were randomly assigned to receive micronutrients (single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk) or matching placebo. Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media (BACTEC MGIT 960; Becton Dickinson, Sparks, MD). Performance status, chest radiographs, and anthropometric measures were assessed at baseline and again at 8 wk. Results: The participants (n = 154) were randomly assigned to the micronutrient (n = 77) or placebo (n = 77) group. Twenty participants were HIV infected (13%), and 12 participants had an unknown HIV status (8%). No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis (P = 0.15 and P = 0.38, respectively; log-rank test). Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period (P = 0.32). No significant differences in weight gain (2.3 6 3.5 compared with 2.2 6 2.4 kg, P = 0.68) or radiologic resolution were observed between the treatment groups. Conclusion: Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk. This trial was registered at controlled-trials.com as ISRCTN80852505. Am J Clin Nutr 2011;93:93–100.

OBJECTIVE: We wanted to develop and validate a test that assesses the knowledge and practices of health professionals (HPs) with regard to the role of nutrition, physical activity, and smoking cessation (lifestyle modification) in chronic diseases of lifestyle. METHODS: A descriptive cross-sectional validation study was carried out. The validation design consisted of two phases, namely 1) test planning and development and 2) test evaluation. The study sample consisted of five groups of HPs: dietitians, dietetic interns, general practitioners, medical students, and nurses. The overall response rate was 58%, resulting in a sample size of 186 participants. A test was designed to evaluate the knowledge and practices of HPs. The test was first evaluated by an expert group to ensure content, construct, and face validity. Thereafter, the questionnaire was tested on five groups of HPs to test for criterion validity. Internal consistency was evaluated by Cronbach’s. RESULTS: An expert panel ensured content, construct, and face validity of the test. Groups with the most training and exposure to nutrition (dietitians and dietetic interns) had the highest group mean score, ranging from 61% to 88%, whereas those with limited nutrition training (general practitioners, medical students, and nurses) had significantly lower scores, ranging from 26% to 80%. This result demonstrated criterion validity. Internal consistency of the overall test demonstrated a Cronbach’s of 0.99. Most HPs identified the mass media as their main source of information on lifestyle modification. These HPs also identified lack of time, lack of patient compliance, and lack of knowledge as barriers that prevent them from providing counseling on lifestyle modification. CONCLUSIONS: The results of this study showed that this test instrument identifies groups of health professionals with adequate training (knowledge) in lifestyle modification and those who require further training (knowledge). Nutrition 2003;19:760 ‐766. ©Elsevier Inc. 2003

BACKGROUND: Micronutrient deficiencies are widespread and compound the effects of HIV disease in children especially in poor communities. Micronutrient supplements may be effective and safe in reducing the burden of HIV disease. This review is an update of an earlier Cochrane review of micronutrient supplementation in children and adults which found that vitamin A and zinc are beneficial and safe in children exposed to HIV and living with HIV infection (Irlam 2010). OBJECTIVES: To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in children with HIV infection. SEARCH METHODS: The CENTRAL EMBASE and PubMed databases were searched for randomized controlled trials of micronutrient supplements (vitamins trace elements and combinations of these) using the search methods of the Cochrane HIV/AIDS Group. SELECTION CRITERIA: Randomized controlled trials were selected that compared the effects of micronutrient supplements with other supplements or placebo or no treatment on the primary outcomes of mortality morbidity and HIV-related hospitalizations. Indicators of HIV disease progession anthropometric measures and any adverse effects of supplementation were secondary outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened and selected trials for inclusion assessed the risk of bias using standardized criteria and extracted data. Review Manager 5.1 was used to calculate the risk ratio (RR) for dichotomous data and the weighted mean difference (WMD) for continuous data and to perform random effects meta-analysis where appropriate. MAIN RESULTS: We included three new studies in addition to the eight studies in the earlier version of the review (Irlam 2010). Eleven studies with a total of 2412 participants were therefore included: five trials of vitamin A one trial of vitamin D two trials of zinc and three trials of multiple micronutrient supplements. All except one trial were conducted in African children.Vitamin A halved all-cause mortality in a meta-analysis of three trials in African children had inconsistent impacts on diarrheal and respiratory morbidity and improved short-term growth in a Tanzanian trial. No significant adverse effects were reported.A single small trial of vitamin D in North American adolescents and children demonstrated safety but no clinical benefits. Zinc supplements reduced diarrheal morbidity and had no adverse effects on disease progression in one small South African trial. Another trial in South African children with and without HIV infection did not show benefit from the the prophylactic use of zinc or multiple supplements versus vitamin A in the small subgroup of children with HIV infection. Multiple micronutrient supplements at twice the RDA did not alter mortality growth or CD4 counts at 12 months in Ugandan children aged one to five years. Short-term supplementation until hospital discharge significantly reduced the duration of all hospital admissions in poorly nourished South African children and supplementation for six months after discharge improved appetite and nutritional indicators. AUTHORS CONCLUSIONS: Vitamin A supplementation is beneficial and safe in children with HIV infection. Zinc is safe and appears to have similar benefits on diarrheal morbidity in children with HIV as in children without HIV infection. Multiple micronutrient supplements have some clinical benefit in poorly nourished children with HIV infection. Further trials of single supplements (vitamin D zinc and selenium) are required to build the evidence base. The long-term effects and optimal composition and dosing of multiple micronutrient supplements require further investigation in children with diverse HIV disease status.

Background Adequate nutrition is important for optimal immune and metabolic function. Dietary support may, therefore, improve clinical outcomes in HIV-infected individuals by reducing the incidence of HIV-associated complications and attenuating progression of HIV disease, improving quality of life and ultimately reducing disease-related mortality. Objectives To evaluate the effectiveness of various macronutrient interventions, given orally, in reducing morbidity and mortality in adults and children living with HIV infection. Search methods We searched CENTRAL (up to August 2011), MEDLINE (1966 to August 2011), EMBASE (1988 to August 2011), LILACS (up to February 2012), and Gateway (March 2006-February 2010). We also scanned reference lists of articles and contacted authors of relevant studies and other researchers. Selection criteria Randomised controlled trials evaluating the effectiveness of macronutrient interventions compared with no nutritional supplements or placebo in the management of adults and children infected with HIV. Data collection and analysis Three reviewers independently applied study selection criteria, assessed study quality, and extracted data. Effects were assessed using mean difference and 95% confidence intervals. Homogenous studies were combined wherever it was clinically meaningful to do so and a meta-analysis using the random effects model was conducted. Main results Fourteen trials (including 1725 HIV positive adults and 271 HIV positive children), were included in this review. Neither supplementary food nor daily supplement of Spirulina significantly altered the risk of death compared with no supplement or placebo in malnourished, ART naive adult participants in the two studies which reported on this outcome. A nutritional supplement enhanced with protein did not significantly alter the risk of death compared to standard nutritional care in children with prolonged diarrhoea. Supplementation with macronutrient formulas given to provide protein and/or energy and fortified with micronutrients, in conjunction with nutrition counselling, significantly improved energy intake (3 trials; n=131; MD 393.57 kcal/day; 95% CI: 224.66 to 562.47;p

Background Micronutrient deficiencies are widespread and compound the effects of HIV disease; micronutrient supplements may be effective and safe in reducing this burden. Objectives To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in pregnant and lactating women with HIV infection and their infants. Search methods The review has been updated three times since publication in 2005. In reviews prior to this update (2011), we searched the CENTRAL, EMBASE, PubMed, and GATEWAY databases to identify randomised controlled trials of micronutrient supplements using the search methods of the Cochrane HIV/AIDS Group. In the 2011 review the PubMed, EMBASE, and CENTRAL databases were searched in July 2011. As the GATEWAY database does not include conference abstracts after 2006, we also searched the AIDS-specific conference database, www.aegis.org, and contacted researchers and organisations active in the field of research to identify additional unpublished trials. Selection criteria Randomised controlled trials were selected that compared the effects of micronutrient supplements (vitamins, trace elements, and combinations of these) with other supplements, placebo or no treatment on mortality, morbidity, pregnancy outcomes, immunologic indicators, and anthropometric measures in HIV-positive pregnant and lactating women. Any adverse effects of supplementation were recorded. Data collection and analysis Two reviewer authors independently selected trials, appraised trial quality for risk of bias using standardised criteria, and extracted data using standardised forms. Where disagreements arose, a third author, acted as arbiter. Main results One additional trial is included in this update in addition to the three trials included in the 2010 update of the initial Cochrane review. Four relatively large, well-conducted randomised controlled trials of the benefits of micronutrient supplementation have been conducted in pregnant and lactating women infected with HIV. Each of the trials evaluated a different micronutrient supplement and no direct comparisons or analyses can be made across the four trials. The four trials were conducted between 1995 and 2006. The trials have all been conducted by the same research team in Dar es Salaam in Tanzania, in an urban setting in hospital-based antenatal clinics. Pregnant women were recruited with gestational age ranging from 12 to 27 weeks in each of the trials. Sample sizes range from 400 to 1129 with a median of 1000 participants. Three of the trials were placebo-controlled. Different interventions have been evaluated in each trial, viz.:Vitamin A versus Vitamin A and multivitamins versus Multivitamins versus placebo; Selenium versus placebo; Zinc versus placebo; and Multiple RDA multivitamins versus Single RDA multivitamins. None of the women were receiving antiretrovrial therapy (ART). Multiple micronutrient supplements conferred multiple clinical benefits to pregnant women and their offspring. No significant adverse effects were reported. No significant clinical benefits were found from zinc supplementation of pregnant Tanzanian women. Selenium supplements given during and after pregnancy did not delay maternal HIV disease progression or improve pregnancy outcomes, but may improve child survival and decrease maternal diarrhoeal morbidity. There were no differences in maternal and infant outcomes when women received single RDA multivitamins or multiple RDA multivitamin supplementation. The evidence is lacking for the effects of micronutrient supplementation given concomitantly to pregnant women already initiated on antiretroviral therapy for treatment purposes. GRADE assessments were conducted on outcomes for each trial and included reviewing the data and the potential biases in each trial before grading the level of evidence. None of the trials were graded as providing high quality evidence primarily because there was no replication of results in other trials in other settings. Authors' conclusions In keeping with previous World Health Organization (WHO) recommendations everything possible should be done to promote and support adequate dietary intake of micronutrients, while recognising that this may not be sufficient to correct specific micronutrient deficiencies in all HIV-infected individuals. Specific recommendations for pregnant and lactating women infected with HIV would be to include the provision of multivitamin supplements in single RDA formulations during the antenatal period and at least for 6 weeks post-partum, especially for women who are breast-feeding. There is no conclusive evidence to provide stand-alone zinc or selenium supplementation to HIV-infected pregnant and lactating women. Micronutrient supplementation should not be used as a substitute for provision of recommended antiretroviral medication for preventing mother-to-child transmission of HIV and treating maternal HIV infection when this is recommended. Further trials of single supplements are required to build the evidence base. The long-term clinical benefits, adverse effects, and optimal formulation of multiple micronutrient supplements require further investigation in pregnant women at different stages of HIV infection.

BackgroundTime to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.AimTo assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.DesignBetween May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable.Results113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype.ConclusionWe found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.

A cross-sectional study of 132 adults attending an HIV clinic in Cape Town, South Africa, was conducted to determine predictors of low plasma vitamin A and Zn levels. No patients were on antiretroviral therapy. The possible confounding effect of the acute-phase response was controlled by including C-reactive protein levels in multivariate analysis and by excluding active opportunistic infections. Retinol levels were low (Pv.36 and 45 % with stage III and IV disease respectively (Pr0·27; 95 % CI 0·1, 0·43) and Zn (r0·31; 95 % CI 0·25, 0·46). Multivariate analysis showed the following independent predictors of low retinol levels: WHO stage IV (odds ratio 3·4; 95 % CI 2·1, 5·7) and body weight (odds ratio per 5 kg decrease 1·15; 95 % CI, 1·08, 1·25), while only body weight was significantly associated with low Zn levels (OR per 5 kg decrease 1·19; 95 % CI 1·09, 1·30). CD4+ lymphocyte count