Intermittent versus daily therapy for treating tuberculosis in children.

BACKGROUND: Childhood tuberculosis (TB) is a neglected global public health problem. Short treatment courses with rifampicin-containing anti-TB drugs given daily for six-months cure over 90% of infected children, but poor adherence reduces treatment success. Intermittent, short-course anti-TB regimens, given two or three times a week under direct observation, are associated with higher adherence in observational studies; but how they compare with daily treatment in relation to cure is unclear. Current international and national recommendations differ on use of intermittent regimens to treat TB in children. OBJECTIVES: To compare the efficacy and safety of intermittent, short-course anti-TB regimens (twice- or thrice-weekly) with daily short-course anti-TB regimens in treating childhood TB. SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, clinical trials registries, regional databases, conference proceedings, and references without language restrictions up to 30 May 2013; and contacted experts for relevant published, unpublished, and on-going trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs of children aged 15 years or younger, diagnosed with TB (according to the World Health Organization diagnostic categories 1, 2, or 3), who were treated with intermittent twice-weekly or thrice-weekly, short-course anti-TB regimens compared to daily short-course anti-TB treatment regimens. All regimens had to contain rifampicin for at least the first two months. DATA COLLECTION AND ANALYSIS: The review authors independently screened and selected trials, assessed risk of bias, and extracted data. We sought clarifications from trial authors. We pooled relative risks with their 95% confidence intervals and used a random-effects model where there was significant heterogeneity. We assessed overall evidence-quality using the GRADE approach. MAIN RESULTS: We included four trials published between 1996 to 2000 that randomized 563 children (465 evaluable) aged five months to 15 years to intermittent twice-weekly versus daily anti-TB treatment. Two trials were from India, one from South Africa, and one from Turkey. All trials used rifampicin and isoniazid, three trials used pyrazinamide, and one trial used streptomycin. The drug combination, and the duration of intermittent and daily treatments differed between trials, and no trials used drug combinations and schedules currently recommended for childhood TB. No trial reported if any child was HIV-positive.In comparisons of twice-weekly versus daily anti-TB treatment regimens, the trials did not detect differences in the number of patients cured, but trials were small, and the comparator regimens were not standard (four trials, 465 children; very low quality evidence). Trials were underpowered to provide estimates for death (two trials, 213 participants, very low quality evidence), relapse (one trial, 214 participants,very low quality evidence), and treatment limiting adverse events (four trials, 441 participants, very low quality evidence)Reported adherence to treatment was similar (87% versus 84%; four trials, 458 children, very low quality evidence)We did not find trials comparing the commonly used thrice-weekly anti-TB short-course regimen with the daily treatment regimen. AUTHORS' CONCLUSIONS: Trials conducted to date are insufficient to support or refute the use of intermittent twice- or thrice-weekly, short-course treatment regimens over daily short-course treatment in children with TB. Further randomized trials conducted in high TB-transmission settings will help inform policy and practice.

Hyperinsulinemia: an early biomarker of metabolic dysfunction.

Introduction: Hyperinsulinemia in the absence of impaired glucose tolerance and normal HbA1c is considered indicative of pre-diabetes. Very few Indian studies have focused on hyperinsulinemia particularly in young adults. The present study aimed to determine whether hyperinsulinemia may be present despite HbA1c being normal. Methods: This was a cross-sectional study conducted on adolescents and young adults aged 16-25 years living in Mumbai, India. The participants attended various academic institutions and were those who underwent screening as the first step of a clinical trial for studying the efficacy of almond intake in prediabetes. Results: Among this young population (n=1313), 4.2% (n=55) of the participants were found to be prediabetic (ADA criteria) and 19.7% of them had HbA1c levels between 5.7%-6.4%. However, almost, 30.5% had hyperinsulinemia inspite of normal blood glucose levels and normal HbA1c. Among those with HbA1c<5.7 (n=533), 10.5% (n=56) participants had fasting insulin>15 mIU/L and a higher percentage (39.4%, n=260) had stimulated insulin above 80 mIU/L. These participants had higher mean anthropometric markers than those with normal fasting and/or stimulated insulin. Conclusion: Hyperinsulinaemia in the absence of impaired glucose tolerance and normal HbA1c may provide a much earlier indicator of detection for risk of metabolic disease and progression to metabolic syndrome and diabetes mellitus.

Effect of Almond Consumption on Metabolic Risk Factors-Glucose Metabolism, Hyperinsulinemia, Selected Markers of Inflammation: A Randomized Controlled Trial in Adolescents and Young Adults.

A large percentage of the Indian population has diabetes or is at risk of pre-diabetes. Almond consumption has shown benefits on cardiometabolic risk factors in adults. This study explored the effect of almond consumption on determinants of metabolic dysfunction-blood glucose, lipids, insulin and selected inflammatory markers in adolescents and young adults aged 16-25 years from Mumbai city. This randomized controlled trial was conducted for a period of 90 days on individuals with impaired levels of fasting glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) and 2-h post-glucose value 140-199 mg/dL (7.8-11.0 mmol/L) and/or fasting insulin (≥15 mIU/ml)/stimulated insulin (≥80 mIU/ml). Of 1,313 individuals screened, 421 met the inclusion criteria, of which 275 consented to participate and 219 completed the trial. The trial was registered with Clinical Trials Registry India (CTRI) CTRI/2018/02/011927. The almonds group (n = 107) consumed 56 g almonds daily, the control group (n = 112) was provided an iso-caloric cereal-pulse based snack. At baseline and endline, blood glucose, insulin, HbA1c, LDL-c, HDL-c, total and ox-cholesterol, triglycerides, hs-CRP, IL-6, TNF-α, adiponectin, leptin were measured and HOMA-IR and FG:FI ratios were calculated. Dietary intakes were assessed. The anthropometric measurements, biochemical markers as well as macronutrient intakes did not differ significantly between the two groups at baseline. Almond consumption significantly decreased HbA1c, total cholesterol and LDL-c. Stimulated insulin decreased post-intervention in both groups, but the decrease was greater in the almonds group. Fasting glucose was reduced post intervention in the controls with no change in the almonds group. FG:FI ratio decreased in the almonds group. TNF-α and IL-6 decreased in the almonds group, while it increased in the control group. Our results showed that almonds reduced HbA1c, LDL-c and total cholesterol levels in just 12 weeks of consumption in these adolescents and young adults who were at risk for developing diabetes. Almonds can be considered as part of food-based strategies for preventing pre-diabetes. Clinical Trial Registration: ClinicalTrials.gov, identifier: CTRI/2018/02/011927.

Almonds and Cardiovascular Health: A Review.

Several preventive strategies to reduce dyslipidemia have been suggested, of which dietary modification features as an important one. Dyslipidemia is a major risk factor for coronary heart disease and strategies to manage dyslipidemia have been shown to reduce the incidence of cardiovascular disease (CVD). Although there are proven pharmacological therapies to help manage this condition, nutritional interventions are a safer option to help prevent and manage dyslipidemia. Addition of almonds in the daily diet has been proposed to beneficially impact the lipid profile. This review critically examines the available evidence assessing the effect of almonds on dyslipidemia in the South Asian (particularly Indian) context. An extensive review comprised of epidemiological studies, clinical trials, meta-analyses, and systematic reviews was conducted from published literature from across the world. Studies examining the effect of almonds on different aspects of dyslipidemia viz. high low-density lipoprotein-cholesterol (LDL-C), low high-density lipoprotein-cholesterol (HDL-C), triglyceridaemia, and high total cholesterol levels have been included. In several studies, almonds have been shown to reduce LDL-C-which is a known risk factor for CHD-and the effect of almonds has been well documented in systematic reviews and meta-analysis of clinical trials. Addition of almonds in the diet has been shown to not only to reduce LDL-C levels, but also to maintain HDL-C levels. This review provides information about the use of this simple nutritional strategy which may help manage known major risk factors for heart disease, such as high LDL-C and low HDL-C levels especially in the context of South Asians.

A Randomized, Double-Blind Study Assessing Changes in Cognitive Function in Indian School Children Receiving a Combination of Bacopa monnieri and Micronutrient Supplementation vs. Placebo.

Several studies have indicated a chronic cognitive enhancing effect of Bacopa monnieri across different ages and cognitive impairment associated with vitamin and mineral deficiencies in children. Therefore, we investigated the effects of 4-month supplementation with a combination of B. monnieri extract and multiple micronutrients on cognitive functions in Indian school children aged 7-12 years. This was a randomized, double-blind, parallel design, single-center study in which 300 children were randomized to receive a beverage either fortified with B. monnieri and multiple micronutrients ("fortified") or a non-fortified isocaloric equivalent ("control") twice-daily for 4 months. Cognitive function was assessed by the Cambridge Neuropsychological Automated Test Battery (CANTAB) administered at baseline, Day 60 and Day 121. The primary endpoint was change in short-term memory (working memory) from baseline in subjects receiving "fortified" vs. "control" beverages after 4 months. Secondary endpoints included sustained attention, episodic memory, and executive function. The "fortified" beverage did not significantly improve short-term memory or any of the secondary outcomes tested relative to the "control" beverage. However, the spatial working memory "strategy" score showed significant improvement on Day 60 (difference between groups in change from baseline: -0.55; p < 0.05), but not on Day 121 due to the active intervention. Study products were well-tolerated. Reasons for these unexpected findings are discussed.