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Background: Selective publication of studies has important scientific, ethical, and public health implications. Aim: We studied selective publication among mood disorder research protocols registered in the Clinical Trials Registry of India (CTRI) database. We also examined the frequency and nature of protocol deviations among the published articles. Methods: Using a systematic search strategy, we examined the publication status of all mood disorder-related research protocols registered in the CTRI database from inception till December 31, 2019. Logistic regression analysis was used to identify variables associated with selective publication. Results: Of 129 eligible protocols identified, only a third (n = 43, 33.3%) were published in literature; among those published, only 28 (21.7%) were placed in MEDLINE indexed journals. Protocol deviations were observed in more than half of the published papers (n = 25, 58.1%); many of these (41.9%) were related to sample size deviations, though, importantly, deviations in primary and secondary outcomes were also noted (16.2%). Retrospective registration of trials (odds ratio, 2.98, 95% confidence interval, 1.32--6.71) was significantly associated with publication; other variables, such as funding status or multicentric sampling, were not associated with eventual publication. Conclusions: Two out of three mood disorder research protocols registered in India do not translate into published research. These findings from a low- and middle-income country with limited spending on health care research and development represent wastage of resources and raise scientific and ethical concerns about unpublished data and futile patient participation in research. [ABSTRACT FROM AUTHOR]

Introduction: In 2019, the Central Drugs Standard Control Organization (CDSCO) introduced the New Drugs and Clinical Trials Rules 2019 (NDCTR), which separated the research guidelines for "Clinical Trials" and "Biomedical and Health Research." As a result, guidelines issued by Indian Council of Medical Research were stated to apply to academic clinical trials (ACTs). This change is important because academic studies are crucial for scientific advancement and repurposing of approved drugs in health-care industry. However, conducting an ACT can pose challenges. We assessed the level of awareness, knowledge, and challenges faced by investigators. Our aim is to overcome some of these challenges and encourage more academic studies for the betterment of healthcare and scientific knowledge in India. Methodology: The study was conducted in two phases after obtaining approval from the Institutional Ethics Committee (EC) of three tertiary care hospitals in Mumbai. In the first phase, the number of ACTs was assessed from the clinical trial registry India website, while the number of registered and re-registered ECs were assessed from the CDSCO website. The second phase involved assessing investigator awareness and knowledge about ACTs using a prevalidated questionnaire with a content validity index score of 0.93. Results: In 2020, the highest numbers of studies were registered, with the highest numbers of registered and re-registered ECs from Maharashtra. All participants completed the questionnaire and were aware of the need to follow guidelines for clinical trials. Sixty-seven percent of participants knew that the guidelines for ACTs differed from those of sponsored clinical trials, but only 58% were aware of the exact definition of an ACT as per NDCTR, 2019. Eighty-five percent of participants knew who could initiate an ACT, but only 27% knew about the applicability of results of an ACT and 33% had in-depth knowledge about the required approvals, while only 10% knew the archival period. Although 71% of participants had knowledge about serious adverse event reporting, few answered in-depth questions correctly. Only 31 participants reported facing varied challenges. Conclusion: To conduct ACTs effectively and contribute to healthcare and scientific advancement, it is crucial to enhance investigators' existing knowledge about ACTs. [ABSTRACT FROM AUTHOR]

Background: The Clinical Trials Registry of India (CTRI) was launched in July 2007 and will enter its tenth year in 2017. While its mission is to encourage prospective trial registration, CTRI does permit retrospective trial registration. Against this backdrop, the present audit was carried out with the primary objective of assessing the nature and extent of trials retrospectively registered with CTRI. Methods: All studies registered in the year 2016 were searched within CTRI using the keyword "CTRI/2016." The total number of trials registered in that year, their phase, the source of funding and their nature (Interventional or observational; whether postgraduate theses or otherwise, source of funding (pharmaceutical industry/Government of India/Institute Funded), whether prospectively or retrospectively registered were noted. We also tested for the association between the nature of the trial and retrospective registration using the Chi-square test and generated crude odds ratios with 95% confidence intervals. Results: A total of 1147 studies were registered in 2016, of which 719 (63%) were retrospectively registered. Interventional studies formed the majority of studies at n = 926 (81%), while postgraduate theses constituted half of the studies (384; 53%). Postgraduate theses (relative to all other studies) were twice as likely to be retrospectively registered (cOR 2.4 [1.8, 3.0], p < 0.0001). Studies funded by the pharmaceutical industry were four times more likely to be registered prospectively relative to nonindustry funded studies (cOR 4.4 [3.2, 5.9], p < 0.0001). Conclusion: Given that CTRI will be insisting on prospective registration effective April 1, 2018, and as trial registration is an ethical, scientific and moral imperative, prospective registration must always be done as prerequisite to participant protection. [ABSTRACT FROM AUTHOR]

Background: When we were unable to identify an electronic data capture (EDC) package that supported our requirements for clinical research in resource-limited regions, we set out to build our own reusable EDC framework. We needed to capture data when offline, synchronize data on demand, and enforce strict eligibility requirements and complex longitudinal protocols. Based on previous experience, the geographical areas in which we conduct our research often have unreliable, slow internet access that would make web-based EDC platforms impractical. We were unwilling to fall back on paper-based data capture as we wanted other benefits of EDC. Therefore, we decided to build our own reusable software platform. In this paper, we describe our customizable EDC framework and highlight how we have used it in our ongoing surveillance programs, clinic-based cross-sectional studies, and randomized controlled trials (RCTs) in various settings in India and Ecuador.Objective: This paper describes the creation of a mobile framework to support complex clinical research protocols in a variety of settings including clinical, surveillance, and RCTs.Methods: We developed ConnEDCt, a mobile EDC framework for iOS devices and personal computers, using Claris FileMaker software for electronic data capture and data storage.Results: ConnEDCt was tested in the field in our clinical, surveillance, and clinical trial research contexts in India and Ecuador and continuously refined for ease of use and optimization, including specific user roles; simultaneous synchronization across multiple locations; complex randomization schemes and informed consent processes; and collecting diverse types of data (laboratory, growth measurements, sociodemographic, health history, dietary recall and feeding practices, environmental exposures, and biological specimen collection).Conclusions: ConnEDCt is customizable, with regulatory-compliant security, data synchronization, and other useful features for data collection in a variety of settings and study designs. Furthermore, ConnEDCt is user friendly and lowers the risks for errors in data entry because of real time error checking and protocol enforcement. [ABSTRACT FROM AUTHOR]

Background: Clinical Trials Registry - India (CTRI) was established in July 2007 and today hosts thousands of trials, a significant fraction of them registered in the last couple of years. We wished to undertake an up-to-date analysis of specific fields of the registered trials. In doing so we discovered problems with the quality of the data, which we describe in this paper.Methods: We downloaded CTRI records and reformatted the data into an SQLite database, which we then queried. We also accessed ClinicalTrials.gov records as needed.Results: We discovered various categories of problems with the data in the CTRI database, including (1) a lack of clarity in the classification of Types of Study, (2) internal inconsistencies, (3) incomplete or non-standard information, (4) missing data, (5) variations in names or classification, and (6) incomplete or incorrect details of ethics committees. For most of these problems, error rates have been calculated, over time. Most were found to be in single digits, although others were significantly higher. We suggest how data quality in future editions of CTRI could be improved, including (1) a more elaborate and structured way of classifying the Type of Study, (2) the use of logic rules to prevent internal inconsistencies, (3) less use of free text fields and greater use of drop-down menus, (4) more fields to be made compulsory, (5) the pre-registration of individuals' and organizations' names and their subsequent selection from drop-down menus while registering a trial, and (6) more information about each ethics committee, including (a) its address and (b) linking the name of the trial site to the relevant ethics committee. As we discuss problems with the data of specific fields, we also examine - where possible - the quality of the data in the corresponding fields in ClinicalTrials.gov, the largest clinical trial registry in the world.Conclusions: It is a scientific and ethical obligation to correctly record all information pertaining to each trial run in India. CTRI is a valuable database that has proved its worth in terms of improving the record of trials in the country. The suggestions made herein would improve it further. [ABSTRACT FROM AUTHOR]

While many studies suggested the isolated effects of plyometric and whole-body vibration exercises on physical performance variables, only few studies have compared the acute effects of plyometric and whole-body vibration on the occurrence of post-activation potentiation and the resultant improvements in performance. Therefore, we aimed to compare the acute effects of plyometric exercises and whole-body vibration training on physical performance in collegiate basketball players. Twenty-four collegiate male basketball players (age 20.8 ± 2.02 years, height 1.79 ± 0.7 m, and weight 71.2 ± 7.6 kg) participated in this randomized crossover study. Subjects were received both plyometric and whole-body vibration exercises after a 48-h washed-out period. Countermovement Jump height, sprint, and agility time were measured at baseline, 4- and 12-min post-plyometric, and whole-body vibration exercises. The result suggests a positive effect of both the plyometric and whole-body vibration exercises on countermovement jump and agility time (p = 0.001). While the countermovement jump height and agility were higher in the plyometric group (mean difference 1.60 cm and 0.16 s, respectively), the sprint performance was higher in the whole-body vibration group. However, these differences were statistically non-significant between the two groups (p > 0.05). This study suggests that both plyometric and whole-body vibration exercises may improve post-activation potentiation, which leads to better physical performance. Trial registration CTRI/2019/05/019059. Registered with the Clinical trials registry, India on 10/05/2019. http://ctri.nic.in/Clinicaltrials/advsearch.php. [ABSTRACT FROM AUTHOR]

Background: Progress has been made in the reduction of under-five mortality in India; however, neonatal mortality is reducing at a slower rate. Efforts are required to bring down neonatal mortality in order to attain the Sustainable Development Goal-3. Prevention of sepsis among the high-risk, vulnerable low birth weight neonates by a newer intervention with probiotic supplementation is promising.Methods: A phase III, multicenter, randomized, double-blind, placebo-controlled study is being conducted at six sites in India. A total of 6144 healthy low birth weight (LBW) infants fulfilling the eligibility criteria would be enrolled within the first week of life, after obtaining written informed consent from the parents of the infant. Randomization in 1:1 ratio, stratified by site, sex, and birth weight, would be done through an interactive web response system (IWRS) using a standard web browser and email service. Vivomixx®, a probiotic containing a mix of 8 strains of bacteria, in a suspension form standardized to deliver 10 billion CFU/ml, or an organoleptically similar placebo would be fed to enrolled infants in a 1-ml/day dose for 30 days. The follow-up of enrolled infants for 60 days would take place as per a pre-specified schedule for recording morbidities and outcome assessments at the six participating sites. Screening for morbidities would be conducted by trained field workers in the community, and sick infants would be referred to designated clinics/hospitals. A physician would examine the referred infants presenting with complaints and clinical signs, and blood samples would be collected from sick infants for diagnosis of neonatal sepsis by performing sepsis screen and blood culture. Appropriate treatment would be provided as per hospital protocol. The study would be implemented as per the MRC guideline for the management of Global Health Trials in accordance with ICH-GCP and Indian Regulatory guidelines. A contract research organization would be engaged for comprehensive monitoring and quality assurance. The final analysis would be conducted in a blinded manner as per the statistical analysis plan (SAP) to estimate the primary outcomes of sepsis, possible serious bacterial infection (PSBI), and secondary outcomes. The codes will be broken after DMC permission. The protocol has been reviewed by the Research Ethics Committee of the Liverpool School of Tropical Medicine (REC-LSTM), from Research Ethics Committees of the six subject recruitment participating sites.Discussion: This adequately powered and well-designed trial would conclusively answer the question whether probiotics can prevent neonatal sepsis in the high-risk group of low birth weight infants as indicated by a pilot study in 1340 LBW infants, evidence from systematic reviews of hospital-based studies, and a primary study on healthy newborns in Orissa. Results of the study would be generalizable to India and other low-middle-income countries.Trial Registration: Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197 . Registered on 16 May 2019. [ABSTRACT FROM AUTHOR]

Background: Better drug regimens for mass drug administration (MDA) could accelerate the Global Programme to Eliminate Lymphatic Filariasis (LF). This community study was designed to compare the safety and efficacy of MDA with IDA (ivermectin, diethylcarbamazine and albendazole) or DA (diethylcarbamazine and albendazole) in India. Methodology/Principal findings: This two-armed, open-labelled, block randomised, community study was conducted in LF endemic villages in Yadgir district, Karnataka, India. Consenting participants ≥5 years of age were tested for circulating filarial antigenemia (CFA) and microfilaremia (Mf) before treatment with a single oral dose of IDA or DA. Adverse events (AEs) were monitored actively for two days and passively for five more days. Persons with positive CFA or Mf tests at baseline were retested 12-months post-treatment to assess treatment efficacy. Baseline CFA and Mf—rates were 26.4% and 6.9% in IDA and 24.5% and 6.4% in DA villages respectively. 4758 and 4160 participants received IDA and DA. Most AEs were mild after both treatments; fewer than 0.1% of participants experienced AEs with severity > grade 1. No serious AEs were observed. Fever, headache and dizziness were the most common AEs. AE rates were slightly higher after IDA than DA (8.3% vs. 6.4%, P<0.01). AEs were more frequent in females and Mf-positives after either treatment, but significantly more frequent after IDA (40.5% vs 20.2%, P < 0.001). IDA was more effective for clearing Mf than DA (84% vs. 61.8%, P < 0.001). Geometric mean Mf counts per 60μl in retested Mf-positives decreased by 96.4% from 11.8 after IDA and by 90.0% from 9.5 after DA. Neither treatment was effective for clearing CFA. Conclusions/Significance: IDA had an acceptable safety profile and was more effective for clearing Mf than DA. With adequate compliance and medical support to manage AEs, IDA has the potential to accelerate LF elimination in India. Trial registration: Clinical Trial Registry of India (CTRI No/2016/10/007399) Author summary: Lymphatic filariasis (LF) is a major neglected tropical disease that is caused by filarial nematode worms. The strategies of the Global Programme to Eliminate Lymphatic Filariasis, launched in 2000, are mass drug administration (MDA) of antifilarial medications to kill the parasites and reduce transmission and morbidity management and disability prevention for those who are already affected by the disease. Recent clinical trials have shown that a single co-administered dose of ivermectin, diethylcarbamazine and albendazole (IDA) is more effective for clearing microfilariae (Mf) from the blood than the traditional two-drug regimen (DA). That is important, because blood Mf are essential for mosquitoes to transmit the parasite. As part of a large multicenter study, we assessed the safety of IDA and compared the efficacy of IDA and DA for clearing parasites from the blood. We treated almost 9,000 people in Wuchereria bancrofti endemic villages with either IDA or DA. Adverse events (AE) were monitored actively for two days and passively for another five days. AE rates were slightly higher after IDA than DA, but AEs were mild and self-limited. Infected persons, adults and females had higher AE rates in both treatment areas. We retested infected persons one year after treatment. IDA was significantly more effective for clearing Mf and reducing blood Mf counts than DA. Neither treatment was effective for clearing circulating filarial antigenemia. Our large study showed that IDA was well tolerated and more effective than DA. This new treatment has the potential to hasten LF elimination in India and many other countries. [ABSTRACT FROM AUTHOR]

Context: The elderly in India form a heterogeneous subset of the population with significant disease burden variations. However, there are no data available regarding the type of research studies conducted in an elderly population in India. Aims: The aim of this study was to analyze the research studies conducted in the elderly population in India based on data from the Clinical Trials Registry of India (CTRI). Settings and Design: This was an "audit" of available data on the CTRI website. Participants and Methods: Following exemption from the Institutional Ethics Committee, all studies in the elderly population registered in CTRI from its inception (July 2007 to August 2019) were reviewed. Data captured with respect to geographical distribution, study designs used, therapy area, trial registration, and funding. Statistical Analysis Used: The variables were analyzed using descriptive statistics using SPSS version 16.0. Results: Out of a total of 21,400 studies in CTRI, a total of 99 (0.46%) studies involved only elderly patients. Of these studies, 60 (60.6%) were interventional, whereas 39 (39.4%) were observational. Of all the interventional studies, 17 (28%) tested drugs, 26 (43%) tested a lifestyle intervention, and the rest were nutraceuticals, Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy, and physiotherapy. Postgraduate theses constituted 60 (60.6%) studies. Eighty-seven (87.9%) were academic projects, eight (8.1%) were government-funded studies, and only four (4%) were pharmaceutical-sponsored studies. The most commonly studied therapy area was the central nervous system, followed by community medicine and orthopedics. Conclusions: This study depicts the underrepresentation of the geriatric population in clinical studies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To present a descriptive analysis of the clinical studies registered in the Clinical Trials Registry – India (CTRI) and deduce its impact. METHODS: We searched the CTRI databease for all registered clinical studies from July 20, 2007 to May 31, 2018. Extracted data were analyzed in three time periods i.e., Periods 1, 2, and 3 based on the major activities and milestones of the CTRI. In addition, comparative registrations of the various Primary Registries of the WHO were compiled and registration policy of Indian journals with regard to trial registration assessed. RESULTS: A total of 20,160 clinical studies were submitted to the CTRI in the designated study period. Of the registered 14,341 clinical studies, 10,485 (76.3%) were interventional trials which were either regulatory (n = 2004), academic non-regulatory (n = 3855), or those conducted as part of PG thesis (n = 4626) trials. Regulatory trials registration numbers varied according to the Indian regulatory scenario. PG thesis trial registrations showed a steep rise, although unlike regulatory trials, these were mostly retrospective registrations. CTRI registration numbers were comparable to that in other Primary Registries. Instructions to authors of 48% indexed Indian journals made a mention of trial registration. CONCLUSIONS: The CTRI has a strong global presence and has enhanced the transparency of regulatory trials as well as academic research particularly thesis-based work. The latter is expected to help improve standard of research and prevent repetitive research. Additional support from Indian journal editors by strict implementation of prospective registration is crucial for increasing compliance by researchers. [ABSTRACT FROM AUTHOR]

Background: Suicide is a major public health challenge globally and specifically in India where 36.6% and 24.3% of all suicides worldwide occur in women and men, respectively. The United Nations Sustainable Development Goals uses suicide rate as one of two indicators for Target 3.4, aimed at reducing these deaths by one third by 2030. India has no examples of large-scale implementation of evidence-based interventions to prevent suicide; however, there is a sizeable evidence base to draw on for suicide prevention strategies that have been piloted in India or proven to be effective regionally or internationally.Method: The SPIRIT study is designed as a cluster-randomized superiority trial and uses mixed methods to evaluate the implementation, effectiveness and costs of an integrated suicide prevention programme consisting of three integrated interventions including (1) a secondary-school-based intervention to reduce suicidal ideation among adolescents, (2) a community storage facility intervention to reduce access to pesticides and (3) training for community health workers in recognition, management, and appropriate referral of people identified with high suicidal risk.Discussion: Combining three evidence-based interventions that tackle suicide among high-risk groups may generate a synergistic impact in reducing suicides at the community level in rural areas in India. Examination of implementation processes throughout the trial will also help to prepare a roadmap for policymakers and researchers looking to implement suicide prevention interventions in other countries and at scale.Trial Registration: Clinical Trial Registry of Indian Council of Medical Research, India: CTRI/2017/04/008313. Registered on 7 April 2017. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18256&EncHid=&userName=SPIRIT Trial registry was last modified on 28 June 2019. [ABSTRACT FROM AUTHOR]

Background: While lay-health worker models for mental health care have proven to be effective in controlled trials, there is limited evidence on the effectiveness and scalability of these models in rural communities in low- and middle-income countries (LMICs). Atmiyata is a rural community-led intervention using local community volunteers, called Champions, to identify and provide a package of community-based interventions for mental health, including evidence-based counseling for persons with common mental disorders (CMD).Methods: The impact of the Atmiyata intervention is evaluated through a stepped wedge cluster randomized controlled trial (SW-CRCT) with a nested economic evaluation. The trial is implemented across 10 sub-blocks (645 villages) in Mehsana district in the state of Gujarat, with a catchment area of 1.52 million rural adults. There are 56 primary health centers (PHCs) in Mehsana district and villages covered under these PHCs are equally divided into four groups of clusters of 14 PHCs each. The intervention is rolled out in a staggered manner in these groups of villages at an interval of 5 months. The primary outcome is symptomatic improvement measured through the GHQ-12 at a 3-month follow-up. Secondary outcomes include: quality of life using the EURO-QoL (EQ- 5D), symptom improvement measured by the Self-Reporting Questionnaire-20 (SRQ-20), functioning using the World Health Organization's Disability Assessment Scale (WHO-DAS-12), depression symptoms using the Patient Health Questionnaire (PHQ-9), anxiety symptoms using Generalized Anxiety Disorder Questionnaire (GAD-7), and social participation using the Social Participation Scale (SPS). Generalized linear mixed effects model is employed for binary outcomes and linear mixed effects model for continuous outcomes. A Return on Investment (ROI) analysis of the intervention will be conducted to understand whether the intervention generates any return on financial investments made into the project.Discussion: Stepped wedge designs are increasingly used a design to evaluate the real-life effectiveness of interventions. To the best of our knowledge, this is the first SW-CRCT in a low- and middle-income country evaluating the impact of the implementation of a community mental health intervention. The results of this study will contribute to the evidence on scaling-up lay health worker models for mental health interventions and contribute to the SW-CRCT literature in low- and middle-income countries.Trial Registration: The trial is registered prospectively with the Clinical Trial Registry in India and the Clinical Trial Registry number- CTRI/2017/03/008139. URL http://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=70845.17209. Date of registration- 20/03/2017. [ABSTRACT FROM AUTHOR]

Background: Unhealthy dietary behaviour–high intake of fat, sugar, and salt, and low intake of fruits and vegetables–is a major risk factor for chronic diseases. There is a lack of evidence-based interventions to promote healthy dietary intake among Indian populations. Therefore, we tested the effectiveness of an information technology-enabled 'SMART Eating' intervention to reduce the intake of fat, sugar and salt, and to increase the intake of fruits and vegetables. Methods: In Chandigarh, a North Indian city, a cluster randomized controlled trial was implemented in twelve geographical clusters, based on the type of housing (i.e., LIG: Low-income group; MIG; Middle-income group, and HIG: High-income group–a proxy for socio-economic status). Computer-generated randomization was used to allocate clusters to intervention and comparison arms after pairing on the basis of socioeconomic status and geographical distance between clusters. The sample size was 366 families per arm (N = 732). One adult per family was randomly selected as an index case to measure the change in the outcomes. For behaviour change, a multi-channel communication approach was used, which included information technology–short message service (SMS), email, social networking app and 'SMART Eating' website, and interpersonal communication along with distribution of a 'SMART Eating' kit—kitchen calendar, dining table mat, and measuring spoons. The intervention was implemented at the family level over a period of six months. The comparison group received pamphlets on nutrition education. Outcome measurements were made at 0 and 6 months post-intervention at the individual level. Primary outcomes were changes in mean dietary intakes of fat, sugar, salt, and fruit and vegetables. Secondary outcomes included changes in body mass index (BMI), blood pressure, haemoglobin, fasting plasma glucose (FPG), and serum lipids. Mixed-effects linear regression models were used to determine the net change in the outcomes in the intervention group relative to the comparison group. Results: Participants' mean age was 53 years, a majority were women (76%), most were married (90%) and 51% had completed a college degree. All families had mobile phones, and more than 90% of these families had access to Internet through mobile phones. The intervention group had significant net mean changes of -12.5 g/day (p<0.001), -11.4 g/day (p<0.001), -0.5 g/day (p<0.001), and +71.6 g/day (p<0.001) in the intake of fat, sugar, salt, and fruit and vegetables, respectively. Similarly, significant net changes occurred for secondary outcomes: BMI -0.25 kg/m2, diastolic blood pressure -2.77 mm Hg, FPG -5.7 mg/dl, and triglycerides -24.2mg/dl. The intervention had no effect on haemoglobin, systolic blood pressure, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol. Conclusion: The IT-enabled 'SMART Eating' intervention was found to be effective in reducing fat, sugar, and salt intake, and increasing fruit and vegetable consumption among urban adults from diverse socio-economic backgrounds. Trial registration: Clinical Trial Registry of India CTRI/2016/11/007457. [ABSTRACT FROM AUTHOR]

Background: Stroke has emerged as a leading cause of death in rural India. However, well-tested healthcare interventions to reduce stroke mortality in rural under-resourced settings are lacking. The aim of this study is to evaluate the effect of a community-based preventive intervention on stroke mortality in rural Gadchiroli, India.Methods: The study is a two-arm, parallel group, cluster randomised controlled trial in which 32 villages will be randomised to the intervention and the enhanced usual care (EUC) arm. In the intervention arm, individuals ≥50 years of age will be screened for hypertension, diabetes and stroke by trained Community Health Workers (CHWs). Screened individuals who are positive will be referred to a mobile outreach clinic which will visit the intervention villages periodically. A physician in the clinic will confirm the diagnosis, provide guideline-based treatment and follow up patients. The CHWs will make home visits once a month to ensure medication compliance and counsel patients to reduce salt consumption and quit tobacco and alcohol. In the EUC arm, households will be provided information on the ill effects of tobacco use and steps to quit it. Individuals from both the arms will have access to the government's national programme for the prevention and control of non-communicable diseases, where treatment for hypertension, diabetes and preventive treatment after stroke is available at the nearest primary health centres (PHCs). The intervention will be implemented for 3.5 years. The primary outcome will be a reduction in stroke mortality in the last 2.5 years of the intervention.Discussion: This trial will provide important information regarding the feasibility and effect of a community-based preventive intervention package on stroke mortality in a rural under-resourced setting and can inform India's non-communicable diseases prevention and control programme. If successful, such an intervention can be scaled up in the rural regions of India and other countries.Trial Registration: Clinical Trials Registry of India: CTRI/2015/12/006424. Registered on 8 December 2015. [ABSTRACT FROM AUTHOR]

Background: Serial lactate measurement is found to predict mortality in septic shock. Majority of patients with perforation peritonitis for emergency laparotomy are in sepsis and mortality rate is substantial. However, lactate dynamics has not been studied in this patient population. Methods: After institutional ethics clearance and informed written consent, 113 patients with suspected or proven perforation peritonitis presenting for emergency laparotomy were recruited in this prospective observational trial. Baseline Mannheim peritonitis index (MPI), SOFA and APACHE II score were calculated. Lactate values were obtained at baseline, immediate and 24-h postoperative period. Primary outcome was 28-day mortality. Results: Mortality was 15.04% at 28 days. Age, SOFA, qSOFA, APACHE, preoperative lactate, MPI and site of perforation were significantly different between survivors and non-survivors. Arterial lactate values at preoperative (cut off 2.75 mmol/L), immediate postoperative (cut off 2.8 mmol/L) and 24 h-postoperative period (cut off 2.45 mmol/L) independently predicted mortality at day 28. Combination of MPI and 24-h lactate value was best predictor of mortality with AUC 0.99. Conclusion: Preoperative, immediate postoperative and 24-h postoperative lactate value independently predict 28-day mortality in perforation peritonitis patients undergoing emergency laparotomy. Combination of MPI and 24-h lactate value is the most accurate predictor of mortality. Trial registration: Clinical Trial Registry of India - CTRI/2018/01/011103 [ABSTRACT FROM AUTHOR]

Introduction: Glucosamine dietary supplements are commonly used for the management of osteoarthritis (OA). However, clinical trials have reported varying outcomes with regard to joint function and disease progression. One of the possible reasons for variability in observed effects of glucosamine could be that, unlike prescription drugs, the quality of manufactured dietary supplements is not closely monitored in many countries. Therefore, there is the possibility that the actual amount of glucosamine present in a dietary supplement is different from that claimed on the label. The quality control of glucosamine supplements is further complicated by the unavailability of a simple and effective analytical method for the analysis of glucosamine. Therefore, the aim of this study was to develop a simple analytical method that could be easily adapted by the pharmaceutical industry for routine analysis of glucosamine. Aims: To develop a novel high-performance liquid chromatography (HPLC) method for the quantification of glucosamine, and determine the amount of glucosamine present in a sample of dietary supplements commercially available in Australia and India. Methods: Chromatographic separation of glucosamine was achieved using a zwitter-ionic hydrophilic interaction liquid chromatography column with a mobile phase consisting of 60% acetonitrile and 40% of 85 mM ammonium acetate, at a flow rate of 0.3 mL/min and column temperature 40°C. The developed method was validated for intra- and inter-day linearity, accuracy, precision, and reproducibility. The newly-developed method was subsequently used to analyse 12 glucosamine supplements. Results: The developed method was selective for glucosamine, which had a retention time of 5.9 min. The standard curve was linear with a correlation coefficient (r2) exceeding 0.99, over the range of 10–200 μg/mL for glucosamine. The relative standard deviations for intra- and inter-day accuracy, precision and reproducibility were all less than 4%. The amount of glucosamine determined in six Australian and six Indian glucosamine supplements ranged between 98.7–101.7% and 85.9–101.8% of the labelled values, respectively. Discussion: Unlike previous HPLC methods, this newly-developed HPLC technique does not require pre-derivatisation and can separate glucosamine from both hydrochloride and sulphate salts, and from other amino sugars, such as chondroitin sulphate present in dietary supplements. This simple and effective technique can be employed by analytical laboratories for the quality control of glucosamine dietary supplements. Conclusion: The current study has developed a new analytical technique using HPLC-Corona CAD, which can analyse underivatised glucosamine hydrochloride and sulphate within 6 minutes. Using the novel assay, we confirmed that unlike the tested Australian dietary supplements, only half of the tested Indian products had a glucosamine content within ±10% of what was claimed on the label. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVD) are rising in India resulting in major health system challenges. Methods: Eighteen primary health centre (PHC) clusters in rural Andhra Pradesh were randomised over three, 6-month steps to an intervention comprising: (1) household CVD risk assessments by village-based community health workers (CHWs) using a mobile tablet device; (2) electronic referral and clinical decision support for PHC doctors; and (3) a tracking system for follow-up care. Independent data collectors screened people aged ≥ 40 years in 54 villages serviced by the PHCs to create a high CVD risk cohort (based on WHO risk charts and blood pressure thresholds). Randomly selected, independent samples, comprising 15% of this cohort, were reviewed at each 6-month step. The primary outcome was the proportion meeting systolic blood pressure (SBP) targets (<140mmHg). Findings: Eight-four percent of the eligible population (n = 62,254) were assessed at baseline (18.4% at high CVD risk). Of those at high risk, 75.3% were followed up over two years. CHWs screened 85.9% of the baseline cohort and doctors followed up 70.0% of all high risk referrals. There was no difference in the proportion of people achieving SBP targets (41.2% vs 39.2%; adjusted odds ratio (OR) 1.01 95% CI 0.76–1.35) or receiving BP-lowering medications in the intervention vs control periods respectively. There was a high discordance in risk scores generated by independent data collectors and CHWs, resulting in only 37.2% of the evaluation cohort exposed to the intervention. This discordance was mainly driven by fluctuating BP values (both normal variability and marked seasonal variations). In the pre-specified high risk concordant subgroup, there was greater use of BP-lowering medications in the intervention period (54.3% vs 47.9%, OR 1.22, 95% CI 1.03–1.44) but no impact on BP control. Conclusions: The strategy was well implemented with increased treatment rates among high risk individuals assessed by CHWs, however effects on BP were not demonstrated. Use of guideline-recommended BP thresholds for identifying high risk individuals substantially affected the reproducibility of risk assessment, and thus the ability to reliably evaluate the effectiveness of the intervention. In addition, unanticipated seasonal variation in BP in the context of a stepped-wedge trial highlights the inherent risks of this study design. Trial registration: Clinical Trials Registry of India CTRI/2013/06/ 003753. [ABSTRACT FROM AUTHOR]

Background: Biased results from poorly reported trials can mislead decision-making in health care at all levels, from treatment decisions for the individual patient to formulation of national public health policies.Objective: To evaluate the quality of reporting of randomized controlled trials (RCTs) in ten Indian dental journals over the period 2011-2012.Materials and Methods: This study included all RCTs published as full-text articles reported in ten Indian dental journals over the period from 2011 to 2012. The relevant trials were identified by searching Medline. Hand searching of the journals was also carried out by three of the authors to check if any potential trial was missing. Each article was assessed against the Consolidated Standards of Reporting Trials criteria tool, as described by Schulz et al. (2010).Results: The mean number of criteria present per article was 12.2 (standard deviation [SD] =2.2) and only 5 of 106 articles got total possible score. Most of the articles (69%) did not mention about justification for sample size calculation, 89% of the articles did not mention about allocation concealment, 86% of the articles did not mention about funding and 63% of the articles did not mention about limitations of the study.Conclusion: The quality of reporting of Randomized clinical trials in ten Indian academic journals was poor. [ABSTRACT FROM AUTHOR]

Background: Hypofractionated radiotherapy is the current standard for adjuvant radiotherapy across many centres. Further hypofractionation may be possible but remains to be investigated in non-Caucasian populations with more advanced disease, with a higher proportion of patients requiring mastectomy as well as tumour bed boost. We are reporting the design of randomized controlled trial testing the hypothesis that a 1-week (5 fractions) regimen of radiotherapy will be non-inferior to a standard 3-week (15 fractions) schedule.Methods: We describe a multicentre, randomized controlled trial recruiting patients at large academic centres across India. Patients without distant metastases who merit adjuvant radiotherapy will be eligible for inclusion in the study. Patients in the control arm will receive adjuvant radiotherapy to the breast or chest wall (with/without regional nodes) to a dose of 40 Gy/15 fractions/3 weeks, while those in the experimental arm will receive a dose of 26 Gy/5 fractions/1 week (to the same volume). The use of a simultaneous integrated boost (dose of 8 Gy and 6 Gy, respectively) is allowed in patients who have undergone breast conservation. A sample size of 2100 patients provides an 80% power to detect a non-inferiority of 3% in the 5-year locoregional recurrence rate with a one-sided type I error of 2.5%, assuming that the locoregional recurrence rate in the control arm is 5% at 5 years (corresponding to a hazard ratio of 1.63). Patients will be recruited over a period of 5 years and followed up for a further 5 years thereafter.Discussion: If a five-fraction regimen of breast cancer is proven to be non-inferior, this will result in a significant improvement in the access to radiotherapy, as well as reduced costs of treatment. The trial gives an opportunity to standardize and quality-assure radiotherapy practices across the nation at the same time. Along with the results of the FAST-Forward trial, the safety of this intervention in advanced node-positive disease requiring regional nodal radiation will be established.Trial Registration: The trial has been registered at the Clinical Trial Registry of India (CTRI) vide registration number: CTRI/2018/12/016816 (December 31, 2018) as well as the ClinicalTrial.gov website at NCT03788213 (December 28, 2018). [ABSTRACT FROM AUTHOR]

Background: Data on the cost-effectiveness of lifestyle-based diabetes prevention programs are mostly from high-income countries, which cannot be extrapolated to low- and middle-income countries. We performed a trial-based cost-effectiveness analysis of a lifestyle intervention targeted at preventing diabetes in India.Methods: The Kerala Diabetes Prevention Program was a cluster-randomized controlled trial of 1007 individuals conducted in 60 polling areas (electoral divisions) in Kerala state. Participants (30-60 years) were those with a high diabetes risk score and without diabetes on an oral glucose tolerance test. The intervention group received a 12-month peer-support lifestyle intervention involving 15 group sessions delivered in community settings by trained lay peer leaders. There were also linked community activities to sustain behavior change. The control group received a booklet on lifestyle change. Costs were estimated from the health system and societal perspectives, with 2018 as the reference year. Effectiveness was measured in terms of the number of diabetes cases prevented and quality-adjusted life years (QALYs). Three times India's gross domestic product per capita (US$6108) was used as the cost-effectiveness threshold. The analyses were conducted with a 2-year time horizon. Costs and effects were discounted at 3% per annum. One-way and multi-way sensitivity analyses were performed.Results: Baseline characteristics were similar in the two study groups. Over 2 years, the intervention resulted in an incremental health system cost of US$2.0 (intervention group: US$303.6; control group: US$301.6), incremental societal cost of US$6.2 (intervention group: US$367.8; control group: US$361.5), absolute risk reduction of 2.1%, and incremental QALYs of 0.04 per person. From a health system perspective, the cost per diabetes case prevented was US$95.2, and the cost per QALY gained was US$50.0. From a societal perspective, the corresponding figures were US$295.1 and US$155.0. For the number of diabetes cases prevented, the probability for the intervention to be cost-effective was 84.0% and 83.1% from the health system and societal perspectives, respectively. The corresponding figures for QALY gained were 99.1% and 97.8%. The results were robust to discounting and sensitivity analyses.Conclusions: A community-based peer-support lifestyle intervention was cost-effective in individuals at high risk of developing diabetes in India over 2 years.Trial Registration: The trial was registered with Australia and New Zealand Clinical Trials Registry ( ACTRN12611000262909 ). Registered 10 March 2011. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of the combination of hydroxychloroquine (HCQ) and standard personal protective equipment (PPE) compared to the use of standard personal protective equipment alone on the proportion of laboratory confirmed COVID-19 infections among frontline healthcare workers(HCWs) in India TRIAL DESIGN: HOPE is an investigator initiated multi-centre open-label parallel group randomized controlled trial.Participants: All HCWs currently working in an environment with direct exposure to patients with confirmed COVID-19 infection are eligible to participate in the trial. The trial aims to be conducted across 20-30 centres (public and private hospitals) in India. HCWs who decline consent, who have a confirmed COVID-19 infection, those who are already on chloroquine/HCQ for any indication, or if pregnant or breast-feeding, or have known QT prolongation or are on medications that when taken with HCQ can prolong the QTc will be excluded.Intervention and Comparator: The interventions to be compared in this trial are standard practice (use of recommended PPE) and HCQ plus standard practice. In the standard practice arm, HCWs will use recommended PPE as per institutional guidelines and based on their roles. They will be discouraged from taking HCQ to prevent contamination and contacted every week for the duration of the study to ascertain if they have taken any HCQ. Any such use will be reported as a protocol violation. In the intervention arm, HCWs will be administered 800mg of HCQ as a loading dose on the day of randomization (as two 400mg doses 12hrs apart) and subsequently continued on 400mg once a week for 12 weeks. This will be in addition to the use of recommended PPE as per institutional guidelines and based on their roles. HCWs will collect the drug once every week from designated research and pharmacy staff at site. A weekly phone reminder will be provided to participants in this arm to ensure compliance. An ECG will be performed between 4-6 weeks in this arm and if the QTc is prolonged (greater than 450milliseconds), the drug will be stopped. Follow-up will however continue. Participants in both arms will receive a weekly phone call for evaluation of the primary outcome, to monitor protocol compliance and development of any adverse events (in the HCQ group).Main Outcomes: Participants will be followed on a weekly basis. The primary outcome is the proportion of HCWs developing laboratory confirmed COVID-19 infection within 6 months of randomization. We will also evaluate a number of secondary outcomes, including hospitalization related to suspected/confirmed COVID-19 infection, intensive care unit or high-dependency unit admission due to suspected/confirmed COVID-19 infection, all-cause mortality, need for organ support ( non-invasive or invasive ventilation, vasopressors and renal replacement therapy), ICU and hospital length of stay, readmission, days off work and treatment-related adverse events.Randomisation: Randomisation will be conducted through a password-protected, secure website using a central, computer-based randomisation program. Randomisation will be stratified by participating institutions and by the role of HCW - nursing, medical and other. Participants will be randomised 1:1 to either standard practice only or HCQ plus standard practice. Allocation concealment is maintained by central web-based randomisation BLINDING (MASKING): This is an unblinded study: study assigned treatment will be known to the research team and participant. Bias will be mitigated through an objective end point (laboratory confirmed COVID-19 infection).Numbers To Be Randomised (sample Size): A total of 6,950 HCWs will be enrolled (3475 to the intervention) and (3475 to the standard practice group) to detect a 25% relative reduction, or 2.5% absolute reduction, in the infection rate from an estimated baseline infection rate of 10%, with 80% statistical power using a two-sided test at 5% level of significance. Available data from China and Italy indicate that the rate of infection among frontline healthcare workers varies between 4% to 12%. We therefore assumed a baseline infection rate of 10% among HCWs. This sample size allows for a potential loss to follow-up rate of 10% and a potential non-compliance rate of 10% in both the treatment and control arms.Trial Status: HOPE protocol version 3.0 dated June 3rd 2020. Recruitment started on 29th June 2020 and currently 56 participants have been enrolled. Planned completion of enrolment is January 31st 2021.Trial Registration: Clinical Trials Registry of India: CTRI/2020/05/025067 (prospectively registered) Date of registration: 6th May 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expedited dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). [ABSTRACT FROM AUTHOR]

Background: The Indian National Program for Cardiovascular Disease, Diabetes, Cancer and Stroke (NPCDCS) was introduced to provide non-communicable disease (NCD) care through primary healthcare teams including Accredited Social Health Activists (ASHAs). Since ASHAs are being deployed to provide NCD care on top of their regular work for the first time, there is a need to understand the current capacity and challenges faced by them.Methods: A desktop review of NPCDCS and ASHA policy documents was conducted. This was followed by group discussions with ASHAs, in-depth interviews with their supervisors and medical officers and group discussions with community members in Guntur, Andhra Pradesh, India. The multi-stakeholder data were analysed for themes related to needs, capacity, and challenges of ASHAs in providing NCD services.Results: This study identified three key themes-first, ASHAs are unrecognised as part of the formal NPCDCS service delivery team. Second, they are overburdened, since they deliver several NPCDCS activities without receiving training or remuneration. Third, they aspire to be formally recognised as employees of the health system. However, ASHAs are enthusiastic about the services they provide and remain an essential link between the health system and the community.Conclusion: ASHAs play a key role in providing comprehensive and culturally appropriate care to communities; however, they are unrecognised and overburdened and aspire to be part of the health system. ASHAs have the potential to deliver a broad range of services, if supported by the health system appropriately.Trial Registration: The study was registered with "Clinical Trials Registry - India" (identifier CTRI/2018/03/012425 ). [ABSTRACT FROM AUTHOR]

Background: Like other women in India, female sex workers (FSWs) frequently experience violence from their intimate partners (IPs)-a reality that increases their risk of acquiring HIV or other sexually transmitted infections. Less is known about the nature of these intimate relationships or what aspect of the relationship increases the risk of IP violence (IPV). We measured the prevalence and determinants of IPV on FSWs in the context of north Karnataka, India, characterized by high HIV-prevalence and extreme poverty.Methods: Overall 620 FSWs with an IP participated in a baseline survey conducted for an on-going cluster-randomised controlled trial aiming to evaluate the impact of a multi-level intervention on IPV reduction. We characterize the nature of intimate relationships and explored determinants of severe physical and/or sexual IP violence using univariable and multivariable analyses.Results: The median age of participants was 35 years with 10 years of duration in an intimate relationship. Though most relationships originated from a sex work encounter, 84% stated that IPs did not know they were currently practicing sex work. In past 6 months, the experience of emotional violence was 49% (95%CI:45.2-53.2), physical 33% (95%CI:29.5-37.1) and sexual violence 7% (95%CI:4.8-8.9), while 24% (95%CI:21.0-27.9) FSWs experienced recent severe physical and/or sexual violence from IPs. Factors associated with recent IPV included experience of physical and/or sexual violence from their clients in last 6 months (AOR 2.20; 95%CI: 1.29-3.75), sexual intercourse in the past 1 month when their IP was under the influence of alcohol (AOR 2.30; 95%CI: 1.47-3.59) and providing financial support to their IP (AOR 2.07; 95%CI: 1.28-3.34).Conclusions: The association between increased risk of violence and provision of financial support to an IP is indicative of gendered power dynamics as men remain dominant irrespective of their financial dependency on FSWs. Interventions are needed that address inequitable gender norms which makes FSWs tolerate violence even though she is not financially dependent on IP. Higher likelihood of violence in presence of alcohol use and FSWs' previous experience of workplace violence linked to IPV call for strengthening the crisis management systems within community-based organisations that can address all forms of violence and associated risk factors.Trial Registration: Clinical Trials NCT02807259. [ABSTRACT FROM AUTHOR]

The article discusses several issues involving various research on clinical trial registration in India. In so many years, clinical trials registration has been improved into more essentials and mandatory compared from desirable and voluntary. The policy on clinical trial registration made by the International Committee of Medical Journal Editors' (ICMJE) aims to ensure that the information about the emergence and design of clinical trials would be protected from other unregistered researchers.