Abha Aggarwal

Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain

Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.

Clinical Trials Registry - India: Redefining the conduct of clinical trials

Recently, there has been growing concern about the selective publication of clinical trial results[1,2] and its consequences on the practice of “evidence-based medicine.” Selective reporting of clinical trials results leads to bias in published clinical trial literature in favor of positive or promising results. This contention has been convincingly demonstrated by Simes as early as 1986.[3] He reported that a pooled analysis of published clinical trials demonstrates a significant survival advantage for advanced ovarian cancer given combination chemotherapy (versus initial alkylating agent, P = 0.02). However, no significant difference in survival is demonstrated based on a pooled analysis of registered trials (P = 0.25). Similarly, for multiple myeloma patients, whereas pooled analysis of registered trials also shows a survival benefit for patients receiving combination chemotherapy, the estimated magnitude of the benefit is reduced. These data underscore the propensity for misleading information being generated from data analysis of only published clinical trial literature. The most effective antidote to this problem may be through registration of all clinical trials and making their results available publicly. Registration of clinical trials offers other benefits as well, such as safeguarding of patient interests and ensuring greater transparency, accountability and accessibility of clinical trials whereas at the same time also helping to raise the standard of research.

Challenges in Administering a Clinical Trials Registry: Lessons from the Clinical Trials Registry-India

The Clinical Trials Registry - India (CTRI), an online system (www.ctri.nic.in) for the registration of clinical trials being conducted in India, has its secretariat at the National Institute of Medical Statistics of the Indian Council of Medical Research in New Delhi. The primary objective of the CTRI is to ensure that all clinical trials conducted in India are registered in order to bring transparency, accountability and access to clinical trials. Since its launch on 20 July 2007, the CTRI has gone from strength to strength and, as of January 2013, more than 3,300 trials had been registered. Although initiated as a voluntary exercise, registration of trials requiring approval by the drug regulatory authority in India has been made mandatory. Editors from 11 major biomedical journals in India require submission of the clinical trial registration number as a prerequisite for publication. In addition, several ethics committees also insist upon trial registration. The CTRI is a primary registry of the WHO’s International Clinical Trials Registry Platform. This article discusses the challenges encountered during the setting up of the CTRI and the strategies adopted, and also explains the steps to trial registration in the CTRI.

Maternal age at childbirth and perinatal and under-five mortality in a prospective birth cohort from Delhi

ObjectiveTo evaluate the relationship between maternal age at child birth, and perinatal and under-five mortality.DesignProspective birth cohort.SettingUrban community.Participants9169 pregnancies in the New Delhi Birth Cohort resulted in 8181 live births. These children were followed for survival status and anthropometric measurements at birth (+3 days), 3,6,9 and 12 months (7 days), and every 6 months thereafter until 21 years age. Information on maternal age at child birth and socio-demographic profile was also obtained.Outcome measuresOffspring mortality from 28 weeks gestation till 5 years age.ResultsOffspring mortality (stillbirths–5 years; n=328) had a U-shaped association with maternal age (P<0.001). Compared to the reference group (20-24 years), younger (≤19 years) and older (≥ 35 years) maternal ages were associated with a higher risk of offspring mortality (HR: 1.68; 95% CI 1.16, 2.43 and HR 1.48; 95% CI 1.01, 2.16, respectively). In young mothers, the increased risk persisted after adjustment for socio-economic confounders (maternal education, household income and wealth; HR 1.51; 95% CI 1.03, 2.20) and further for additional behavioral (place of delivery) and biological mediators (gestation and birthweight) (HR 2.14; 95% CI 1.25,3.64). Similar associations were documented for post-perinatal deaths but for perinatal mortality the higher risk was not statistically significant (P >0.05). In older mothers, the increased mortality risk was not statistically significant (P >0.05) after adjustment for socio-economic confounders.ConclusionYoung motherhood is associated with an increased risk of post-perinatal mortality and measures to prevent early childbearing should be strengthened.

Reliability of self-collected versus provider-collected vaginal swabs for the diagnosis of bacterial vaginosis

Women reluctant to undergo a per-speculum examination consider self-sampling more acceptable. The aim of this study was to compare self-collected vaginal swabs for detection of bacterial vaginosis (BV), candidiasis and trichomoniasis, with vaginal specimens obtained by the gynaecologist at per-speculum examination. Self-collected and provider-collected vaginal swabs were obtained from 50 women attending the gynaecological outpatients department. The Gram-stained smears and saline wet mounts prepared from the provider-collected vaginal swabs were examined by a microbiologist and a gynaecologist. We determined the validity and the inter-rater reliability of the overall BV score and the morphotype specific score using Kappa statistics. When compared with the provider-collected smear, the ability of the self-collected smear to diagnose BV had a sensitivity of 70% and a specificity of 97%. With specific instructions to help assure the depth of sampling, self-collected swabs can reasonably approximate specimens obtained by clinicians during speculum examination for the diagnosis of BV.

Homoeopathic Genus Epidemicus 'Bryonia alba' as a prophylactic during an outbreak of Chikungunya in India: A cluster -randomised, double -blind, placebo- controlled trial

Objective: The objective was to assess the usefulness of homoeopathic genus epidemicus (Bryonia alba 30C) for the prevention of chikungunya during its epidemic outbreak in the state of Kerala, India. Materials and Methods: A cluster- randomised, double- blind, placebo -controlled trial was conducted in Kerala for prevention of chikungunya during the epidemic outbreak in August-September 2007 in three panchayats of two districts. Bryonia alba 30C/placebo was randomly administered to 167 clusters (Bryonia alba 30C = 84 clusters; placebo = 83 clusters) out of which data of 158 clusters was analyzed (Bryonia alba 30C = 82 clusters; placebo = 76 clusters) . Healthy participants (absence of fever and arthralgia) were eligible for the study (Bryonia alba 30 C n = 19750; placebo n = 18479). Weekly follow-up was done for 35 days. Infection rate in the study groups was analysed and compared by use of cluster analysis. Results: The findings showed that 2525 out of 19750 persons of Bryonia alba 30 C group suffered from chikungunya, compared to 2919 out of 18479 in placebo group. Cluster analysis showed significant difference between the two groups [rate ratio = 0.76 (95% CI 0.14 - 5.57), P value = 0.03]. The result reflects a 19.76% relative risk reduction by Bryonia alba 30C as compared to placebo. Conclusion: Bryonia alba 30C as genus epidemicus was better than placebo in decreasing the incidence of chikungunya in Kerala. The efficacy of genus epidemicus needs to be replicated in different epidemic settings.

Intergenerational change in anthropometric indices and their predictors among children in New Delhi birth cohort

ObjectiveTo evaluate intergenerational change in anthropometric indices of children and their predictors.DesignProspective cohort.ParticipantsNew Delhi Birth Cohort participants (F1), born between 1969 and 1972, were followed-up for anthropometry at birth and 6-monthly intervals until 21 years. Their children (F2) below 10 years were evaluated anthropometrically.Outcome measureIntergenerational change (F2-F1) in height, weight and body mass index (BMI) of children in comparison to their parents at corresponding ages.Results432 F2-F1 pairs were analyzed in age-groups of 0-5 (26.9%) and 5-10 (73.1%) years. Children were considerably taller (0-5 years 0.99 SD; 5-10 years 1.17 SD) and heavier (0-5 years 0.77 SD; 5-10 years 1.52 SD) while only those aged 5-10 years were broader (had a higher BMI; 1.03 SD), than their parents. These increases for 0-5 and 5-10 years, respectively corresponded to 3.9 and 6.4 cm for height, 1.3 and 5.4 kg for weight and 0.2 and 1.9 kg/m2 for BMI. Lower parents’ anthropometric indices and poor water supply and sanitation facilities; higher age of parents at child birth and of children when measured (for height and weight); and more parental education (for weight and BMI), were associated with greater intergenerational gains in children.ConclusionOver one generation in an urban middle-class population, whose general living conditions had improved, underfive children have become considerably taller and heavier, and 5- 10 year old children have additionally become broader, than their parents at corresponding ages. Child populations probably ‘grow up’ before ‘growing out’.

National sample survey to assess the new case disease burden of leprosy in India

A national sample survey of leprosy was undertaken in partnership with Indian Council of Medical Research (ICMR) institutions, National Leprosy Eradication Programme (NLEP), Panchayati Raj members, and treated leprosy patients to detect new cases of leprosy in India. The objectives of the survey were to estimate the new leprosy case load; record both Grade 1 and Grade 2 disabilities in the new cases; and to assess the magnitude of stigma and discrimination prevalent in the society. A cluster based, cross-sectional survey involving all States was used for the door-to-door survey using inverse sampling methodology. Rural and urban clusters were sampled separately. The population screened for detecting 28 new cases in rural and 30 in urban clusters was enumerated, recorded and analyzed. Data capture and analysis in different schedules were the main tools used. For quality control three tiers of experts were utilized for the confirmation of cases and disabilities. Self-stigma was assessed in more than half of the total new patients detected with disabilities by the approved questionnaire. A different questionnaire was used to assess the stigma in the community. A population of 14,725,525 (10,302,443 rural; 4,423,082 urban) was screened and 2161 new cases - 1300 paucibacillary (PB) and 861 multibacillary (MB) were detected. New case estimates for leprosy was 330,346 (95% Confidence limits, 287,445-380,851). Disabilities observed in these cases were 2.05/100,000 population and 13.9 per cent (302/2161) in new cases. Self-stigma in patients with disabilities was reduced, and the patients were well accepted by the spouse, neighbour, at workplace and in social functions.

Testing of Hypothesis in Equivalence and Non Inferiority Trials-A Concept.

Establishing the appropriate hypothesis is one of the important steps for carrying out the statistical tests/analysis. Its understanding is important for interpreting the results of statistical analysis. The current communication attempts to provide the concept of testing of hypothesis in non inferiority and equivalence trials, where the null hypothesis is just reverse of what is set up for conventional superiority trials. It is similarly looked for rejection for establishing the fact the researcher is intending to prove. It is important to mention that equivalence or non inferiority cannot be proved by accepting the null hypothesis of no difference. Hence, establishing the appropriate statistical hypothesis is extremely important to arrive at meaningful conclusion for the set objectives in research.