Is iron status associated with markers of non-communicable disease in adolescent Indian children?

BACKGROUND: High body iron status has been associated with non-communicable diseases (NCD) like diabetes (high fasting blood glucose, FBG), hypertension (HTN) or dyslipidaemia (high total cholesterol, TC) in adults, but this has not been examined in adolescent children. This is relevant to iron supplementation and food iron fortification programs that are directed at Indian children. METHODS: The association of NCD with Serum Ferritin (SF) was examined using logistic additive models, adjusted for confounders such as age, body mass index, C-Reactive Protein, haemoglobin and sex, in adolescent (10-19 years old) participants of the Indian Comprehensive National Nutrition Survey. The interaction of these associations with wealth and co-existing prediabetes was also examined. A scenario analysis was also done to understand the impact of iron fortification of cereals on the prevalence NCD among adolescents. RESULTS: The odds ratio (OR) of high FBG, HTN and TC were 1.05 (95% CI: 1.01-1.08), 1.02 (95% CI: 1.001-1.03) and 1.04 (95% CI: 1.01-1.06) respectively for every 10 µg/L increase in SF. The odds for high TC increased with co-existing prediabetes. The scenario analysis showed that providing 10 mg of iron/day by fortification could increase the prevalence of high FBG by 2-14% across states of India. Similar increments in HTN and TC can also be expected. CONCLUSIONS: High SF is significantly associated with NCD in adolescents, dependent on wealth and co-existing prediabetes. This should be considered when enhancing iron intake in anaemia prevention programs, and the NCD relationship with body iron stores should be studied.

Effect of participatory women's groups and counselling through home visits on children's linear growth in rural eastern India (CARING trial): a cluster-randomised controlled trial.

BACKGROUND: Around 30% of the world's stunted children live in India. The Government of India has proposed a new cadre of community-based workers to improve nutrition in 200 districts. We aimed to find out the effect of such a worker carrying out home visits and participatory group meetings on children's linear growth. METHODS: We did a cluster-randomised controlled trial in two adjoining districts of Jharkhand and Odisha, India. 120 clusters (around 1000 people each) were randomly allocated to intervention or control using a lottery. Randomisation took place in July, 2013, and was stratified by district and number of hamlets per cluster (0, 1-2, or ≥3), resulting in six strata. In each intervention cluster, a worker carried out one home visit in the third trimester of pregnancy, monthly visits to children younger than 2 years to support feeding, hygiene, care, and stimulation, as well as monthly women's group meetings to promote individual and community action for nutrition. Participants were pregnant women identified and recruited in the study clusters and their children. We excluded stillbirths and neonatal deaths, infants whose mothers died, those with congenital abnormalities, multiple births, and mother and infant pairs who migrated out of the study area permanently during the trial period. Data collectors visited each woman in pregnancy, within 72 h of her baby's birth, and at 3, 6, 9, 12, and 18 months after birth. The primary outcome was children's length-for-age Z score at 18 months of age. Analyses were by intention to treat. Due to the nature of the intervention, participants and the intervention team were not masked to allocation. Data collectors and the data manager were masked to allocation. The trial is registered as ISCRTN (51505201) and with the Clinical Trials Registry of India (number 2014/06/004664). RESULTS: Between Oct 1, 2013, and Dec 31, 2015, we recruited 5781 pregnant women. 3001 infants were born to pregnant women recruited between Oct 1, 2013, and Feb 10, 2015, and were therefore eligible for follow-up (1460 assigned to intervention; 1541 assigned to control). Three groups of children could not be included in the final analysis: 147 migrated out of the study area (67 in intervention clusters; 80 in control clusters), 77 died after the neonatal period and before 18 months (31 in intervention clusters; 46 in control clusters), and seven had implausible length-for-age Z scores (<-5 SD; one in intervention cluster; six in control clusters). We measured 1253 (92%) of 1362 eligible children at 18 months in intervention clusters, and 1308 (92%) of 1415 eligible children in control clusters. Mean length-for-age Z score at 18 months was -2·31 (SD 1·12) in intervention clusters and -2·40 (SD 1·10) in control clusters (adjusted difference 0·107, 95% CI -0·011 to 0·226, p=0·08). The intervention did not significantly affect exclusive breastfeeding, timely introduction of complementary foods, morbidity, appropriate home care or care-seeking during childhood illnesses. In intervention clusters, more pregnant women and children attained minimum dietary diversity (adjusted odds ratio [aOR] for women 1·39, 95% CI 1·03-1·90; for children 1·47, 1·07-2·02), more mothers washed their hands before feeding children (5·23, 2·61-10·5), fewer children were underweight at 18 months (0·81, 0·66-0·99), and fewer infants died (0·63, 0·39-1·00). INTERPRETATION: Introduction of a new worker in areas with a high burden of undernutrition in rural eastern India did not significantly increase children's length. However, certain secondary outcomes such as self-reported dietary diversity and handwashing, as well as infant survival were improved. The interventions tested in this trial can be further optimised for use at scale, but substantial improvements in growth will require investment in nutrition-sensitive interventions, including clean water, sanitation, family planning, girls' education, and social safety nets. FUNDING: UK Medical Research Council, Wellcome Trust, UK Department for International Development (DFID).

Protocol for the economic evaluation of a community-based intervention to improve growth among children under two in rural India (CARING trial).

INTRODUCTION: Undernutrition affects ∼165 million children globally and contributes up to 45% of all child deaths. India has the highest proportion of global undernutrition-related morbidity and mortality. This protocol describes the planned economic evaluation of a community-based intervention to improve growth in children under 2 years of age in two rural districts of eastern India. The intervention is being evaluated through a cluster-randomised controlled trial (cRCT, the CARING trial). METHODS AND ANALYSIS: A cost-effectiveness and cost-utility analysis nested within a cRCT will be conducted from a societal perspective, measuring programme, provider, household and societal costs. Programme costs will be collected prospectively from project accounts using a standardised tool. These will be supplemented with time sheets and key informant interviews to inform the allocation of joint costs. Direct and indirect costs incurred by providers will be collected using key informant interviews and time use surveys. Direct and indirect household costs will be collected prospectively, using time use and consumption surveys. Incremental cost-effectiveness ratios (ICERs) will be calculated for the primary outcome measure, that is, cases of stunting prevented, and other outcomes such as cases of wasting prevented, cases of infant mortality averted, life years saved and disability-adjusted life years (DALYs) averted. Sensitivity analyses will be conducted to assess the robustness of results. ETHICS AND DISSEMINATION: There is a shortage of robust evidence regarding the cost-effectiveness of strategies to improve early child growth. As this economic evaluation is nested within a large scale, cRCT, it will contribute to understanding the fiscal space for investment in early child growth, and the relative (in)efficiency of prioritising resources to this intervention over others to prevent stunting in this and other comparable contexts. The protocol has all necessary ethical approvals and the findings will be disseminated within academia and the wider policy sphere. TRIAL REGISTRATION NUMBER: ISRCTN51505201; pre-results.

Efficacy of IV tissue plasminogen activator in acute stroke: does stroke subtype really matter?

BACKGROUND: The National Institute of Neurological Disorders and Stroke (NINDS) trial reported that stroke subtype (e.g., large-artery atherothrombosis, cardioembolism, and lacunae) does not affect response to IV thrombolytic treatment. However, these conclusions were based upon stroke subtypes determined prior to extensive diagnostic evaluation. Because such initial diagnoses are frequently inaccurate, the efficacy of IV recombinant tissue plasminogen activator (rt-PA) based upon verified specific stroke subtypes remains uncertain. METHODS: The records of consecutive acute stroke patients treated with IV rt-PA at two regional stroke centers were retrospectively reviewed. The final stroke subtype after complete diagnostic evaluation was determined. The relationship between final stroke subtype and response to thrombolytic therapy was then investigated and compared with the results reported in the NINDS trial. RESULTS: Ninety consecutive patients were studied. After adjusting for baseline NIH Stroke Scale scores, no significant difference in final outcome based on confirmed stroke mechanism was identified. CONCLUSIONS: These data are consistent with those of the NINDS trial that reported that the efficacy of IV thrombolysis within the 3-hour time window is similar between different stroke subtypes. Based upon these data, allocating treatment of stroke patients with IV rt-PA based upon presumed stroke mechanism may be unnecessary. Such testing may result in time delays that could compromise the efficacy of treatment.

Joseph disease: a multisystem degenerative disorder of the nervous system.

We studied Joseph disease clinically and pathologically in two patients of Portuguese ancestry, but from different families. We found involvement of spinocerebellar tracts, Clarke's column, anterior horn cells, motor cranial nerve nuclei, and substantia nigra. One patient also had pallidosubthalamic and pontocerebellar degeneration with normal inferior olives. The second patient, a Joseph family member, had nerve cell loss in the subthalamic nucleus. The neostriatum appeared normal in both cases. The pigmented nuclei contained a few Lewy bodies. The almost identical pathology in two families support the hypothesis that Joseph disease is a genetic entity.

Frequency of hypergraphia in temporal lobe epilepsy: an index of interictal behaviour syndrome.

Frequency and degree of hypergraphia were studied in order to assess interictal behaviour change in temporal lobe epilepsy. Patients with temporal lobe epilepsy tended to reply more frequently to a standard questionnaire, and wrote extensively (mean: 1301 words) as compared to others (mean: 106 words). The incidence of temporal lobe epilepsy was 73% in patients exhibiting hypergraphia compared to 17% in patients without this trait. These findings suggest that hypergraphia may be a quantitative index of behaviour change in temporal lobe epilepsy.