Controlled Trial In India Research Articles

Elective induction of labor versus expectant management at 39 weeks among low-risk nulliparous pregnant women: A randomized controlled trial in India (ELITE-39 trial).

The aim of the present open label randomized controlled trial was to compare the rate of cesarean section (CS) after elective induction with that of expectant management in low-risk nulliparous women at 39 weeks. This randomized controlled trial from a tertiary maternity care center enrolled low risk nulliparous pregnant women at 38-38+4 weeks between April 1, 2019 and December 31, 2021. Participants were randomized into either the elective induction group (e-IOL) or the expectant management (EM) group though computer generated block randomization. The primary outcome was cesarean rate and the secondary outcome include adverse maternal and perinatal outcome between e-IOL and EM groups. We performed intention to treat analysis. A total of 360 women were enrolled into the present study. Analysis was performed for 179 women in the e-IOL group and 180 women in the EM group. The baseline demographic characteristics including Bishop score were comparable between the groups. The CS rate in both groups was 17.3% (31/179) and 25% (45/180), which is comparable (P = 0.08). There was one intrapartum stillbirth in the e-IOL group, and two babies succumbed in the neonatal period in the EM group. The maternal and perinatal outcomes between the groups were not found to be significantly different. Elective induction of low-risk nulliparous women at 39 weeks was not associated with increased cesarean section rate. The maternal and perinatal outcomes were comparable. Large, multicentric real time randomized controlled trials are needed to understand the benefit of elective induction in low-risk nulliparous women. This should include centers with large volume of deliveries especially from emerging countries also.

Effectiveness of WhatsApp based debunking reminders on follow-up visit attendance for individuals with hypertension: a randomized controlled trial in India

BackgroundIndividuals with high blood pressure in India often miss essential follow-up visits. Missed visits contribute to gaps across the hypertension care continuum and preventable cardiovascular disease. Widespread misconceptions around hypertension care and treatment may contribute to low follow-up attendance rates, but to date, there is limited evidence of the effect of interventions to debunk such misconceptions on health-seeking behavior. We conducted a randomized controlled trial to measure whether combining information debunking commonly-held misconceptions with a standard reminder reduces missed follow-up visits among individuals with high blood pressure and investigated whether any observed effect was moderated through belief change.MethodsWe recruited 388 patients with uncontrolled blood pressure from the outpatient wards of two public sub-district hospitals in Punjab, India. Participants randomly assigned to the intervention arm received two WhatsApp messages, sent 3 and 1 days before their physician-requested follow-up visit. The WhatsApp message began with a standard reminder, reminding participants of their upcoming follow-up visit and its purpose. Following the standard reminder, we included brief debunking statements aimed at acknowledging and correcting common misconceptions and misbeliefs about hypertension care seeking and treatment. Participants in the control group received usual care and did not receive any messages.ResultsWe did not find evidence that the enhanced WhatsApp reminders improved follow-up visit attendance (Main effect: 2.2 percentage points, p-value = 0.603), which remained low across both treatment (21.8%, 95% CI: 15.7%, 27.9%) and control groups (19.6%, 95% CI: 14.2%, 25.0%). Participants had widespread misconceptions about hypertension care but our debunking messages did not successfully correct these beliefs (p-value = 0.187).ConclusionsThis study re-affirms the challenge of continuity of care for chronic diseases in India and suggests that simple phone-based health communication methods may not suffice for changing prevalent misconceptions and improving health-seeking behavior.Trial registrationThe trial began on July 18th. We registered the trial on July 18th (before recruitment began), including the main outcomes, on the German Clinical Trial Register [Identifier: DRKS00029712] and published a pre-analysis plan in the Open Science Framework [osf.io/67g35].

Effectiveness and cost-effectiveness of a community intervention in enhancing access to care and improving clinical outcomes for depression: a protocol for a cluster randomised controlled trial in India

BackgroundAlthough depression is the leading cause of disability worldwide, treatment coverage for the condition is inadequate. Supply-side barriers (e.g. shortage of specialist mental health professionals) and demand-side barriers (e.g. lack of awareness about depression) lead to limited availability of evidence-based interventions, poor demand for care, and low levels of adherence to care. The aim of our study is to examine if the addition of a community intervention delivered by community volunteers enhances the population-level impact of an evidence based psychosocial intervention (Healthy Activity Program [HAP]) in routine primary care by increasing demand for HAP and improving HAP adherence and effectiveness.MethodsA hybrid type 2 effectiveness implementation cluster randomised controlled trial will be implemented in the state of Goa, India. Twenty-eight clusters of villages and their associated public sector health centres will be randomly allocated through restricted randomisation. Clusters will be randomly allocated to the ‘Community Model’ or ‘Facility Model’ arms. All clusters will offer the HAP and clusters in the ‘Community Model’ arm will additionally receive activities delivered by community volunteers (“Sangathis”) to increase awareness about depression and support demand for and adherence to HAP. The primary outcomes are Contact Coverage (Patient Health Questionnaire [PHQ-9] score > 4 as a proportion of those screened) and Effectiveness Coverage (mean PHQ-9 score amongst those who score ≥ 15 at baseline, i.e. those who have moderately severe to severe depression) at 3 months post-recruitment. Additional outcomes at 3 and 6 months will assess sustained effectiveness, remission, response to treatment, depression awareness, social support, treatment completion, and activation levels. Economic and disability outcomes will be assessed to estimate incremental cost-effectiveness ratios. Implementation will be evaluated through process data and qualitative data informed by the RE-AIM framework. A minimum of 79488 primary care attenders will be screened for the Contact Coverage outcome, and 588 individuals with PHQ-9 ≥ 15 will be recruited for the Effectiveness Coverage outcome.DiscussionIf effective, our community intervention will have relevance to India’s Ayushman Bharat universal healthcare programme which is scaling up care for depression in primary care, and also to other low- and middle- income countries.Trial registrationRegistered on ClincalTrials.gov (NCT05890222.) on 12/05/2023.

Digital Twin in Managing Hypertension Among People With Type 2 Diabetes: 1-Year Randomized Controlled Trial

BackgroundDigital twin (DT)-guided lifestyle changes induce type 2 diabetes (T2D) remission but effects on hypertension (HTN) in this population are unknown. ObjectivesThe purpose of this study was to assess effects of DT vs standard of care (SC) on blood pressure (BP), anti-HTN medication, HTN remission, and microalbuminuria in participants with T2D. MethodsThis is a secondary analysis of a randomized controlled trial in India of 319 participants with T2D. Participants were randomized to DT group (N = 233), which used artificial intelligence-enabled DT technology, or SC group (N = 86). A Home Blood Pressure Monitoring system guided anti-HTN medication adjustments. BP, anti-HTN medications, HTN remission rates, and microalbuminuria were compared between groups. ResultsAmong the 319 participants, 44 in DT and 15 in SC group were on anti-HTN medications, totaling 59 (18.4%) participants. DT group achieved significant reductions in systolic blood pressure (−7.6 vs −3.2 mm Hg; P < 0.007) and diastolic blood pressure (−4.3 vs −2.2 mm Hg; P = 0.046) after 1 year compared with SC group. 68.2% of DT group remained off anti-HTN medications compared to none in SC group. Among participants with HTN, DT subgroup achieved higher rates of normotension (40.9% vs 6.7%; P = 0.0009) and HTN remission (50% vs 0%; P < 0.0001) than SC subgroup. DT group had a higher rate of achieving normoalbuminuria (92.4% vs 83.1%; P = 0.018) at 1 year compared with SC group. ConclusionsArtificial intelligence -enabled DT technology is more effective than SC in reducing BP and anti-HTN medications and inducing HTN remission and normoalbuminuria in participants with HTN and T2D. (A Novel WholeBody Digital Twin Enabled Precision Treatment for Reversing Diabetes; CTRI/2020/08/027072)

Why do men with drinking problems change their behavior? A qualitative study nested in a randomized controlled trial in India

The aim of this qualitative study, nested in a randomized controlled trial, was to assess the mechanisms of the effects in both arms through examining perceptions of the participants about changes in their drinking behavior and their attributions for any perceived changes. We conducted semi-structured interviews with a sub-sample of trial participants. We used thematic analysis to analyze the data. Self-perceived change, mostly positive, was reported regardless of the objectively measured remission status. Participating in the trial itself was a major catalyst for change. Participants in both arms used a variety of similar strategies to make these changes; additionally, for those who received the intervention, both the style of the counselor (for example, the non-judgmental stance) as well as specific elements of the intervention were seen to influence change in drinking behavior. Absence of self-reported change was relatively uncommon and primarily related to the felt need for alcohol (e.g., drinking was perceived to be necessary to maintain good health), or the belief that one did not need to or want to change. Experiences of participating in a trial, the counselor style, and specific elements of a brief psychological treatment, play a role in influencing change in harmful drinking behaviors.

Evidence from the first Shared Medical Appointments (SMAs) randomised controlled trial in India: SMAs increase the satisfaction, knowledge, and medication compliance of patients with glaucoma.

In Shared Medical Appointments (SMAs), patients with similar conditions meet the physician together and each receives one-on-one attention. SMAs can improve outcomes and physician productivity. Yet privacy concerns have stymied adoption. In physician-deprived nations, patients' utility from improved access may outweigh their disutility from loss of privacy. Ours is to our knowledge the first SMA trial for any disease, in India, where doctors are scarce. In a 1,000-patient, single-site, randomized controlled trial at Aravind Eye Hospital, Pondicherry, we compared SMAs and one-on-one appointments, over four successive visits, for patients with glaucoma. We examined patients' satisfaction, knowledge, intention-to-follow-up, follow-up rates, and medication compliance rates (primary outcomes) using intention-to-treat analysis. Of 1,034 patients invited between July 12, 2016 -July 19, 2018, 1,000 (96.7%) consented to participate, and were randomly assigned to either SMAs (NSMA = 500) or one-on-one appointments (N1-1 = 500). Patients who received SMAs showed higher satisfaction (MeanSMA = 4.955 (SD 0.241), Mean1-1 = 4.920 (SD 0.326); difference in means 0.035; 95% CI, 0.017-0.054, p = 0.0002) and knowledge (MeanSMA = 3.416 (SD 1.340), Mean1-1 = 3.267 (SD 1.492); difference in means 0.149; 95% CI, 0.057-0.241, p = 0.002) than patients who received one-on-one appointments. Across conditions, there was no difference in patients' intention-to-follow-up (MeanSMA = 4.989 (SD 0.118), Mean1-1 = 4.986 (SD 0.149); difference in means 0.003; 95% CI, -0.006-0.012, p = 0.481) and actual follow-up rates (MeanSMA = 87.5% (SD 0.372), Mean1-1 = 88.7% (SD 0.338); difference in means -0.012; 95% CI, -0.039-0.015, p = 0.377). Patients who received SMAs exhibited higher medication compliance rates (MeanSMA = 97.0% (SD 0.180), Mean1-1 = 94.9% (SD 0.238); difference in means 0.020; 95% CI, 0.004-0.036, p = 0.013). SMAs improved satisfaction, learning, and medication compliance, without compromising follow-up rates or measured clinical outcomes. Peer interruptions were negatively correlated with patient satisfaction in early-trial SMAs and positively correlated with patient satisfaction in later-trial SMAs. Trial registration: The trial was registered with Clinical Trials Registry of India (https://ctri.nic.in/) with reference no. REF/2016/11/012659 and registration no. CTRI/2018/02/011998.

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

EBNEO Commentary: Safety and efficacy of erythropoietin in neonates with hypoxic-ischaemic encephalopathy.

Milk-cereal mix supplementation during infancy and impact on neurodevelopmental outcomes at 12 and 24 months of age: a randomized controlled trial in India.

Inadequate protein intake and lack of micronutrients may affect neurodevelopment in infants. This randomized controlled trial was conducted to measure the effect of two milk-cereal mixes with modest and high amounts of protein and enriched with multiple micronutrients (MMN), given between 6-12 months, on cognitive, language, motor and behavioural scores at 12 and 24 months of age, compared to no-supplementation. The two supplements were also compared with each other. The study was conducted in urban Delhi, India and the infants were randomized in a 1:1:1 ratio to the three study groups. At 12 and 24 months of age, 1134 and 1214 children were available, respectively. At 12 months of age, compared to no supplement group, an increase in the motor scores (mean difference, MD 1.52, 95% CI: 0.28, 2.75) and a decrease in the infant temperament scores (mean difference, MD -2.76, 95% CI: -4.23, -1.29) in the modest protein group was observed. Those in the high protein group had lower socio-emotional scores (MD -1.40, 95% CI: -2.43, -0.37) and higher scores on infant temperament scale (MD 2.05, 95% CI: 0.62, 3.48) when compared to modest protein group. At 24 months, no significant differences in any of the neurodevelopment scores between the three study groups was found. In conclusion, supplementation with modest amount of protein and MMN may lead to short term small improvements in motor function and infant temperament. There appears no advantage of supplementing with high protein, rather negative effects on infant behaviour were observed.

Videoconferencing-delivered psychological intervention for the treatment of COVID-19 related psychological distress in University students: study protocol for a randomised controlled trial in India

BackgroundThe mental health impacts of the COVID-19 pandemic have been profound. This paper outlines the study protocol for a trial that tests the efficacy of a brief group-based psychological intervention (Coping with COVID; CWC), relative to Supportive Counselling, to reduce distress associated with COVID-19 in a young adult population in Bangalore, India.MethodsA single-blind, parallel, randomized controlled trial will be carried out via video conferencing in a small group format. Following informed consent, adults that screen positive for levels of psychological distress (Kessler 10 (K-10 score ≥ 20) and have access to a videoconferencing platform will be randomised to an adapted version of CWC (n = 90) or Supportive Counselling (SC) (n = 90). The primary outcome will be reduction in psychological distress including anxiety and depression at 2-months post treatment. Secondary outcomes include worry, positive wellbeing, and stress in relation to COVID-19.DiscussionThis treatment trial will assess whether CWC will result in reduced distress relative to Supportive Counselling in a young adult population in Bangalore, India. This study will yield important insights into the role of nonspecific factors versus the intervention’s components in impacting COVID-19 related distress.Trial registrationThis trial was prospectively registered on the Australian New Zealand Clinical Trials Registry (ACTRN12621001064897).Ethics and disseminationEthics approval has been obtained from the participating institution, CHRIST University in Bangalore. Results of the trial will be submitted for publication in peer reviewed journals and findings presented at scientific conferences and to key service providers and policy makers.

Methodological adaptations to a theory of change model: Experiences from the ARTEMIS cluster randomized trial in India

This article discusses methodological adaptations that were made to the Theory of Change (ToC) process by incorporating imagery during a ToC workshop organized as part of a cluster randomize control trial in India, entitled ARTEMIS. The objective of this adaptation was to make the ToC interesting and interactive for adolescents who are the primary stakeholders in the project. This in turn led to a demystification of the concepts of ToC making it easier for participants of the workshop to contribute more effectively. An added advantage of such adaptations was that it allowed for engaging with specific groups using non-traditional strategies and adapting methods to local needs to make them more effective. Such an exercise will contribute to strengthening of the evidence base on the usefulness of adapting and simplifying methods as well as add to the body of participatory or collaborative visual research by promoting the use of visual material.

Learning from Unincentivized and Incentivized Communication: A Randomized Controlled Trial in India

Interactions among peers of the same social network play significant roles in facilitating the adoption and diffusion of modern technologies in poor communities. We conduct a large-scale randomized controlled trial in rural India to identify the impact of information from friends on willingness to pay (WTP) for high-quality and multipurpose solar lanterns. We offered solar lanterns to seed households from 200 nonelectrified villages and randomly assigned three of their friends to two communication treatments (unincentivized and incentivized) that led to different exposures to their seed friend. We also introduce a second treatment to investigate whether the seed’s gender impacts the magnitude of peer effects. We show that unincentivized communication increases WTP for solar lanterns by 90% and incentivized communication by 145%, but gender does not seem to matter. We also show that learning from others is the mechanism that drives the increase in WTP. Our findings have significant implications for policies that aim at promoting the diffusion of new technologies in developing countries.

State of use of Electronic Data Capture (EDC) tools in randomized controlled trials in India

ObjectivesElectronic data capture (EDC) tools can improve data quality gathered in clinical trials and may be more cost-effective. However, limited data is available on the adoption of EDC tools in randomized controlled trials (RCT) conducted in India. The objective of the current study was to determine the EDC adoption rate in RCTs in India. MethodsWe invited investigators of registered RCTs in India to an online survey. The questionnaire included questions on the use of EDC and features available. An EDC sophistication level (range 1 - 6) was computed. Respondents were also asked about barriers to the implementation of EDC. The EDC adoption rate (EAR) was defined as the proportion of clinical trials where EDC with a sophistication level of 2 or more was used. Multivariable logistic regression was used to identify factors that predicted EDC adoption. Results321 responses were received for 400 unique trials (participation rate of 21%), with an EAR of 27.5% (95% confidence intervals : 23.4% to 32.1%, n = 110). The number of sites influenced EDC adoption (odds ratio : 1.26, 95% CI : 1.12 - 1.47, p = 0.001) on multivariable analysis. EAR did not increase over time. The key barriers identified for not using an EDC were lack of technical support (170, 63.0%) and software cost (132, 48.9%). ConclusionsThe survey shows a low EAR in randomized trials registered in India. The barriers identified in the survey would need systematic solutions to improve the EAR in the future.

FASE-family and social engagement model for prevention and management of self harm behavior-a study protocol for cluster randomized control trial in India.

BackgroundSuicide is a substantial public health concern for countries worldwide. Effective preventive and curative interventions for self-harm behavior (SHB) are imperative for nations with an alarmingly high rate of suicide and self-harm behaviors. The intervention protocol named FASE (Family and Social Engagement) consists of comprehensive assessment, Attachment-Based Family Therapy (ABFT), and community linkages for people presenting with suicide or self-harm in emergency departments of tertiary hospitals.MethodsThis article reports the design and protocol for a cluster randomized control trial for suicide prevention and management. After the developed intervention is pilot tested in a tertiary hospital in Kerala, the intervention will be scaled up to be implemented in various tertiary hospitals in Kerala. Each hospital emergency department will be considered a cluster, and these clusters will be randomized to the intervention group and control group in a 1:1 ratio. The eligible people from the intervention clusters will undergo a baseline assessment, a structured moderate intense intervention with twelve sessions spread across 6 months by the trained social workers supervised by the Mental health team, and a follow-up assessment at the end. Participants will be recruited after obtaining consent and explaining the study. The primary outcome includes suicidality measured by the Depressive Symptom Inventory–Suicidality Subscale (DSI-SS), Depression, Anxiety and Stress Scale (DASS), MOS Social Support Survey, and Brief resilience scale (BRS).DiscussionKnowledge generated from this trial can significantly affect new programmatic policy and clinical guidelines that will improve the reduction of suicide rates in the country.Trial registrationProspectively registered in Clinical Trial Registry India (ICMR-NIMS) on 18/10/2021 (ref number- REF/2021/10/048264).

The impact of a direct to beneficiary mobile communication program on reproductive and child health outcomes: a randomised controlled trial in India

BackgroundDirect-to-beneficiary communication mobile programmes are among the few examples of digital health programmes to have scaled widely in low-resource settings. Yet, evidence on their impact at scale is limited. This...

A realist process evaluation of the INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) randomized controlled trial in India

AimsWe aimed to determine what key resources, mechanisms, and contextual factors are necessary to integrate depression and diabetes treatment into low-resource settings. MethodsA realist evaluation framework was employed to conduct a comparative case study. Data were collected through document review, key informant interviews (n=4), activity logs, and interviews with implementing health care providers (n=11) to test and refine program theories for collaborative care. ResultsEfforts to enhance patient care coordination (i.e., adapting clinics’ patient flow and resources, on-going trainings, and on-site support for care coordinators) improved implementation of depression treatment by usual care diabetes physicians. Clinician's avoidance of the term depression was identified as a barrier to mental health counseling and treatment. ConclusionsThe variations in organizational features and processes linked to implementation activities across two clinics provided an opportunity to examine how and why different contextual factors help or hinder the implementation process. Findings from this study demonstrate that successful implementation of an integrated depression and diabetes care model is feasible in a low-resource setting, while the revised program theories provide an explanatory framework of coordinated care implementation processes that can inform future efforts to disseminate and scale this care model.

Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India

Chronic pulmonary aspergillosis has a 5-year mortality of 50-80% globally, and the optimal duration of treatment for chronic pulmonary aspergillosis remains unclear. We aimed to compare the effect of 6-months of oral itraconazole with 12-months of oral itraconazole on chronic pulmonary aspergillosis clinical outcomes. In this single-centre, open-label, randomised controlled trial conducted in one chest clinic in Chandigarh, India, we screened consecutive patients with chronic pulmonary aspergillosis who were naive to antifungal treatment and randomised eligible patients, using block randomisation, to receive a starting dose of 400 mg/day of oral itraconazole for either 6 months or 12 months. There was no masking of participants or investigators. We excluded patients who were unable to provide informed consent; had an intake of any antifungal drugs for more than 3 weeks in the preceding 6 months; had active Mycobacterium tuberculosis or non-tuberculous mycobacterial pulmonary disease; and had allergic, subacute, or invasive forms of aspergillosis. The primary outcome was the proportion of patients having relapse 2 years after treatment initiation. We performed an intention-to-treat analysis for all outcomes. The study is registered with ClinicalTrials.gov, NCT03920527. We recruited participants between July 1, 2019, and Aug 31, 2021. We screened 250 patients, of which 164 were included in the trial. 81 patients were randomised to the 6-month group and 83 patients were randomised to the 12-month group. The study population was 78 (48%) women and 86 (52%) men, and the mean age of participants was 44·3 (SD 13·3) years. The proportion of patients experiencing relapse was significantly lower in the 12-month group, 31 (38%) had a relapse in the 6-month group compared with 8 (10%) in the 12-month group, with an absolute risk reduction of 0.29 [95% CI 0·16-0·40]. The mean time to first relapse was 23 months in the 12-month group, which is significantly longer than the mean of 18 months in the 6-month group (p<0.0001). There were 16 deaths in total, eight in each group. Ten (12%) of 81 patients in the 6-months group and 18 (22%) of 83 patients in the 12-months group had adverse effects, with none requiring treatment modification. Nausea and anorexia were the most common adverse events in both groups. Treatment of chronic pulmonary aspergillosis with 12 months of oral itraconazole was superior to 6 months of oral itraconazole in reducing relapses at 2 years. Itraconazole should be given for at least 12 months for treating chronic pulmonary aspergillosis. None. For the Hindi translation of the abstract see Supplementary Materials section.

A pilot multicentre cluster randomised trial to compare the effect of trauma life support training programmes on patient and provider outcomes

IntroductionTrauma accounts for nearly 10% of the global burden of disease. Several trauma life support programmes aim to improve trauma outcomes. There is no evidence from controlled trials to show...

Effect of a maternal counselling intervention delivered by community health workers on child nutrition: secondary analysis of a cluster randomised controlled trial in India

BackgroundIndia suffers from a double burden of malnutrition and anaemia. The Karnataka anaemia project indicated that a counselling intervention delivered by community health workers improved anaemia cure rates.ObjectiveTo evaluate the effect of maternal counselling on nutritional aspects of anaemia prevention.MethodsSecondary analysis of a cluster randomised controlled trial (55 simultaneously randomised villages using random number generator in Chamrajnagar district, Northern India). In the intervention group mothers of anaemic children received five monthly counselling sessions plus usual care (iron and folic acid supplements), while mothers of anaemic children in the control group received usual care alone. Daily intake of nutrients related to anaemia prevention, i.e. iron (mg) and vitamin C (mg), was estimated using the 24-h dietary recall method at baseline and 6 months follow-up. Linear and logistic mixed regression models were used to assess between-groups difference in changes in nutrients intake from baseline to end of follow-up. Data collectors and analysts were blinded to the group assignment.ResultsParticipants were 534 (intervention n = 303; usual treatment n = 231) anaemic children, aged 1 to 5 years and their caregivers, of whom 521(intervention n = 299 from 28 villages; usual treatment n = 222 from 27 villages) were retained at 6 months follow-up and included in the analysis. This study provides inconclusive evidence of improvement in the intake of nutrients that prevent anaemia from baseline to follow-up among the intervention compared to the control group; increase in iron intake was 0.24 mg/day (95% CI -0.67; 1.15) and increase in vitamin C intake was 4.61 mg/day (95% CI -0.69, 9.91). Although encouraging, it is notable that the overall intake of nutrients that prevent anaemia remained well below the national recommended daily allowance.ConclusionThis study provides inconclusive evidence of the effect of parental counselling on nutritional aspects of anaemia prevention. The results highlight the need to devise multi-component anaemia-prevention interventions that include facilitators of the availability of nutritious food and should be evaluated in studies that are adequately powered to detect nutritional changes.Trial registrationInternational Standard Randomized Controlled Trial Number ISRCTN68413407, prospectively registered on 17/12/2013.

Yoga Program for Type 2 Diabetes Prevention (YOGA-DP) Among High-Risk People: Qualitative Study to Explore Reasons for Non-participation in a Feasibility Randomized Controlled Trial in India.

Background: Yoga-based interventions can be effective in preventing type 2 diabetes mellitus (T2DM). We developed a Yoga program for T2DM prevention (YOGA-DP) among high-risk people and conducted a feasibility randomized controlled trial (RCT) in India. The objective of this study was to identify and explore why potential participants declined to participate in the feasibility RCT.Methods: An exploratory qualitative study, using semi-structured interviews, was conducted at a Yoga center in New Delhi, India. Fourteen people (10 women and four men) who declined to participate in the feasibility RCT were interviewed, and 13 of them completed the non-participant questionnaire, which captured their socio-demographics, diets, physical activities, and reasons for declining.Results: Three types of barriers were identified and explored which prevented participation in the feasibility RCT: (1) personal barriers, such as lack of time, perceived sufficiency of knowledge, preferences about self-management of health, and trust in other traditional and alternative therapies; (2) contextual barriers, such as social influences and lack of awareness about preventive care; and (3) study-related barriers, such as lack of study information, poor accessibility to the Yoga site, and lack of trust in the study methods and intervention.Conclusions: We identified and explored personal, contextual, and study-related barriers to participation in a feasibility RCT in India. The findings will help to address recruitment challenges in future Yoga and other RCTs.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: CTRI/2019/05/018893.

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

SummaryBackgroundAlthough therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia.MethodsWe did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385.FindingsWe screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention.InterpretationTherapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available.FundingNational Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation.TranslationsFor the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.