Evaluation of methods for assigning causes of death from verbal autopsies in India.

Background: Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (COD) in countries where medical certification of death is low. Computer-coded verbal autopsy (CCVA), an alternative method to PCVA for assigning the COD is considered to be efficient and cost-effective. However, the performance of CCVA as compared to PCVA is yet to be established in the Indian context. Methods: We evaluated the performance of PCVA and three CCVA methods i.e., InterVA 5, InSilico, and Tariff 2.0 on verbal autopsies done using the WHO 2016 VA tool on 2,120 reference standard cases developed from five tertiary care hospitals of Delhi. PCVA methodology involved dual independent review with adjudication, where required. Metrics to assess performance were Cause Specific Mortality Fraction (CSMF), sensitivity, positive predictive value (PPV), CSMF Accuracy, and Kappa statistic. Results: In terms of the measures of the overall performance of COD assignment methods, for CSMF Accuracy, the PCVA method achieved the highest score of 0.79, followed by 0.67 for Tariff_2.0, 0.66 for Inter-VA and 0.62 for InSilicoVA. The PCVA method also achieved the highest agreement (57%) and Kappa scores (0.54). The PCVA method showed the highest sensitivity for 15 out of 20 causes of death. Conclusion: Our study found that the PCVA method had the best performance out of all the four COD assignment methods that were tested in our study sample. In order to improve the performance of CCVA methods, multicentric studies with larger sample sizes need to be conducted using the WHO VA tool.

Challenges in Accessing and Delivering Maternal and Child Health Services during the COVID-19 Pandemic: A Cross-Sectional Rapid Survey from Six States of India.

BACKGROUND/OBJECTIVES: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India. METHODS: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020. The sample size included 540 MCH patients, 18 gynaecologists, 18 paediatricians, 18 district immunisation officers and 108 frontline health workers. Bivariate analysis and multivariable analysis were used to assess the association between sociodemographic characteristics, and challenges faced by the patients. RESULTS: More than one-third of patients (n = 212; 39%) reported that accessing MCH services was a challenge during the lockdown period, with major challenges being transportation-related difficulties (n = 99; 46%) unavailability of hospital-based services (n = 54; 23%) and interrupted outreach health services (n = 39; 18.4%). The supply-side challenges mainly included lack of infrastructural preparedness for outbreak situations, and a shortage of human resources. CONCLUSIONS/RECOMMENDATIONS: A holistic approach is required that focuses on both preparedness and response to the outbreak, as well reassignment and reinforcement of health care professionals to continue catering to and maintaining essential MCH services during the pandemic.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

Community Perspectives on Men's Role in the Utilisation of Maternal Health Services Among Saharia Tribes in Gwalior, Madhya Pradesh, India: Insights from a Qualitative Study.

BACKGROUND: Utilization of maternal health care services by tribal population could be detrimental in reducing high maternal mortality in Madhya Pradesh, India. A growing body of evidence indicates the positive association between male involvement and increased use of antenatal care services. Further research is required to understand barriers and possible solutions to develop culturally appropriate interventions to engage men to promote the utilization of maternal health care services. METHODS: The study used qualitative data collected through 8 focus group discussions with men and women and 8 key informant interviews with either a community representative or health worker in two blocks dominated by Saharia tribes in Gwalior district, Madhya Pradesh, India in 2018. Information on the perception of utilization of maternal and child health services, male involvement, challenges and opportunities were elicited using a structured guide. Framework analysis was used to analyse the data. RESULTS: Findings document barriers at the individual (poor knowledge, fear of loss of wage, choice of home as a place of delivery), community (practices that reinforced the prevailing gender norms) and health care facility level (quality and attitude of health care providers) to male engagement in utilization of maternal health services. Community perceptions on possible solutions to address these were more likely to be gender exploitative interventions. CONCLUSION: To promote utilization of maternal health care services among Saharia tribes, this study highlights the importance of developing gender sensitive interventions that addresses the individual, community and health care facility level barriers of male involvement and do not reinforce existing gender norms.

Clinical Trials Registry - India: A decadal perspective.

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.

Letter on: "An analysis of deficiencies in the data of interventional drug trials registered with Clinical Trials Registry - India".

An article published in this journal analyses the deficiencies in the data of interventional drug trials registered with Clinical Trials Registry - India. We wish to rebut some of the inferences and highlight the pitfalls of a purely automated analysis of registry data as posited by the authors.

Overview of Ayurveda trials registered with Clinical Trial Registry-India: Need for customized data set items.

Background: Lack of research data is one of the major challenges identified in traditional medicine (TM). Further, there is an urgent need to strengthen and streamline clinical research processes as well as develop research databases in TM. The Clinical Trials Registry-India (CTRI), a free, online primary register of the WHO's International Clinical Trials Registry Platform, undertakes registration of all clinical trials being conducted in India, including TM trials. However, as the CTRI data set items are primarily designed to capture information of interventional trials of the conventional system of medicine, key fields relevant to the TM system are not adequately captured in the CTRI. Aims and Objectives: The current study was conceptualized with the objective to review the type and quality of trials registered in the CTRI as well as identify the specific data set items in CTRI which may be customized as per Ayurveda studies. Materials and methods: The trials registered from July 1, 2018, to March 31, 2020, were analyzed to decipher the kind of research being undertaken in the field of Ayurveda. These trials were manually reviewed independently by two Ayurveda reviewers to gain insights into the discrepancies. Along with these analysis, brainstorming sessions with Ayurveda experts were also held. Results: The fields which were identified and need tweaking and customization were the fields "health condition" and "intervention/comparator agent." Conclusions: These modifications in the CTRI would enable the capture of more effective Ayurveda-specific information which would in turn help to standardize and streamline research practices as well as raise the standard of research.

An overview of primary registries of WHO's international clinical trial registry platform.

INTRODUCTION: WHO's International Clinical Trials Registry Platform (ICTRP) has 17 primary registries that collect the information on the minimum set of items of trial information that appear in the register and these registries are also endorsed by the International Committee of Medical Journal Editors. OBJECTIVE: The objective of this study is to describe the profile of all the primary registries including Clinical Trial Registry­India (CTRI), through features such as magnitude, domain of registration, flagging, audit trail, language, mandatory requirements, and result disclosure. METHODOLOGY: The profiling of all registries was based on countries and zones, year of establishment, registrant, flagging, conflict of interest, language, documents, result disclosure, type of study, mode of registration, mandate of registration, quality check method, individual patient data statement and translation of content facility. The mode of search used was online which included advanced search, basic search and also from the audio/video manual on their website. RESULTS: There are 17 primary registries of ICTRP, the first one International Standard Randomised Controlled Trial Number (ISRCTN) of England being initiated in year 2000 and the most recent being Lebanese registry, in September 2019. The trials registered with these registries range from 301 in Cuba to 53972 in European union's EU Clinical Trials Register. The primary registries in WHO registry network are diverse in functionalities and practices. The characteristics of online registers vary in content and features and to achieve coordinated level of data quality, across all the different registries and to keep a balance in standards of the data collected and validation of that data, the registries are adhering to the minimum data set items laid down by ICTRP. CONCLUSION: The very process of registering the clinical studies helps in promoting the research methods and also raising the standards of research, especially among young researchers. It also helps in reducing the duplicity of research.

Clinical Trials Registry - India: An overview and new developments.

The Clinical Trials Registry - India (CTRI), launched over 10 years ago, is a free, searchable online platform for registration of clinical trials being conducted in India and as well as countries which do not have a Primary Registry of their own. The objective of the present article is to appraise the current status and the new developments of CTRI, which registers all types of clinical studies, including postgraduate theses. The CTRI which was until now allowing both prospective and retrospective registration is moving towards only prospective trial registration. From April 1, 2018, only those trials where the first patient enrollment has not yet commenced will be registered. Further, the CTRI is in the process of implementing structured summary results disclosure of all interventional clinical trials in the near future.

Atypical Articular Presentations in Indian Children With Rheumatic Fever.

BACKGROUND: The objective of the study was to describe the clinical characteristics of atypical articular presentations during the initial outbreak and recurrence in patients with acute rheumatic fever (ARF) in the paediatric age group. METHODS: This was a retrospective, observational study conducted between January 2012 and December 2014 on all suspected cases of acute rheumatic fever (ARF) fulfilling either WHO 2004 or Australian guidelines with atypical articular manifestations ie, presence of at least one of the following features: duration of symptoms more than 3 weeks; monoarthritis/arthralgia; involvement of small joints of hand and feet and/or cervical spine and/or hip joint; and, not responding to salicylates in 1 week. RESULTS: 'Atypical' pattern was present in 63% (39/62) of patients with articular manifestations, of which arthralgia was a common manifestation (57%). Polyarticular afflictions were predominately non-migratory (additive) in both atypical (74%; 29/39) and typical (82%; 18/23) groups. Monoarticular (33%) affliction of the joints constituted a significant disease manifestation. Time from onset to diagnosis was >3 weeks in 79% of patients while small joints involvement and axial joint involvement occurred in half of the cases (51%). Inadequate response to NSAIDs was found in three (7%) cases. CONCLUSION: Atypical manifestations in ARF may well be mistaken for a connective tissue disorder, post streptococcal reactive arthritis and septic arthritis. Physicians should be made aware of these features to prevent diagnostic dilemma, and to effect institution of appropriate management including penicillin prophylaxis.

Evaluation of the American Heart Association 2015 revised Jones criteria versus existing guidelines.

OBJECTIVES: To compare the diagnostic yield of acute rheumatic fever (ARF) by the American Heart Association/ American College of Cardiology (AHA/ACC) 2015 revised Jones criteria with the WHO 2004 and Australian guidelines 2012. METHODS: Retrospective observational study in 93 cases of suspected ARF admitted to the Division of Paediatric Cardiology between January 2012 and December 2014. WHO 2004, Australian guidelines and AHA/ACC 2015 Jones criteria were applied to assess definite and probable ARF. RESULTS: Of the 93 cases, 50 were diagnosed as the first episode of ARF and 43 as a recurrence of the condition. Subclinical carditis was a predominant presentation (38%) in the first episode group (p<0.01) whereas in the recurrence group carditis (88%) was the main presentation (p<0.01). Among the joint manifestations, the majority of patients in both the first episode group and the recurrence group presented with arthralgia. Of all the patients with suspected ARF (50), 34% of cases did not fulfil the standard Jones criteria 2004; however, 86% qualified as having ARF on applying the Australian and AHA/ACC 2015 criteria. Surprisingly in the recurrence group only 67% of the patients fulfilled AHA/ACC 2015 despite the modifications incorporated beyond WHO 2004; however, all the patients fulfilled the Australian guidelines either as definite (88.4%) or probable (11.6%). Inclusion of subclinical carditis, polyarthralgia and monoarthritis as major criteria influenced the diagnosis to definite ARF in 20%, 10% and 4% of patients, respectively. CONCLUSIONS: The clinical manifestations of ARF, comprising subclinical carditis and arthralgia, are possibly milder in the Indian population; hence, inclusion of subclinical carditis, polyarthralgia and monoarthritis as major criteria in the newer guidelines has improved the diagnostic yield of ARF. In the absence of a gold standard for the diagnosis of ARF, it is not possible to comment on sensitivity and specificity.

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

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

Maternal and Perinatal Outcome of Life Threatening Obstetrical Complications Requiring Multiple Transfusions.

INTRODUCTION: Obstetrical haemorrhage is the direct cause of maternal mortality, which can be prevented by timely recognition followed by quick and adequate treatment. AIM: To evaluate maternal and perinatal outcome of life threatening obstetric complications requiring multiple transfusions. MATERIALS AND METHODS: It is an observational study conducted on 112 antenatal and postnatal women admitted in a tertiary level hospital, requiring blood and blood products transfusion of >1.5 liters in 24 hours, over a period of 15 months (Aug 2011 to Oct 2012). The demographic and obstetrical profile, amount transfused, mode of delivery, duration of hospital stay, maternal and neonatal morbidity and mortality was evaluated. STATISTICAL ANALYSIS: Statistical analysis of the data was performed using chi-squared test. RESULTS: There were 95 women who presented in antepartum period and 17 in the postpartum. Multigravidas comprised of 70 women, 81 had unsupervised pregnancies and 33 women presented in shock. At admission, 76 peripartum women had severe anaemia and 62 had coagulopathy. Obstetrical hysterectomy was done for 33 women and total 17 women expired. Haemorrhage was the most common indication for transfusion. The mean blood transfusion and volume replacement in 24 hours was 4.2 units & 2.25 liters respectively. The mean hospital stay was 10-15 days. Intra-uterine death at the time of admission was present in 40 women and 72 had live births. After birth, 21 babies required neonatal intensive care, of which 6 expired. CONCLUSION: Antenatal care is important to prevent complications though pregnancy is always unpredictable. Patients' condition at admission is single most important factor often influencing the maternal and perinatal outcome.

Issues of sample size in sensitivity and specificity analysis with special reference to oncology.

Sample size is one of the basics issues, which medical researcher including oncologist faces with any research program. The current communication attempts to discuss the computation of sample size when sensitivity and specificity are being evaluated. The article intends to present the situation that the researcher could easily visualize for appropriate use of sample size techniques for sensitivity and specificity when any screening method for early detection of cancer is in question. Moreover, the researcher would be in a position to efficiently communicate with a statistician for sample size computation and most importantly applicability of the results under the conditions of the negotiated precision.

Share of tobacco related cancers: gender and time gaps-Indian scenario.

INTRODUCTION: Cancer is one of the leading causes of mortality in Indian population with control approach of varied kind which the health system of the country needs to prioritize. The tobacco related cancer which account for major share of all the cancers could be largely controlled through primary prevention a strategy effective in terms of resources hence take priority in terms of cancer control activities. It would be worthwhile to study the cancer of sites and relative magnitude of the cancers which are tobacco related and are amenable for prevention. MATERIALS AND METHODS: The age specific cancer incidence rates of cancer as available from the consolidated reports of the National Cancer Registry Program of Indian Council of Medical Research for the years 1990-96 an 2001-04 were utilized for computing proportion of tobacco related cancers which included population based cancer registries at Bangalore, Bhopal, Barshi a rural registry in Maharashtra, Chennai, Delhi and Mumbai. As defined cancer of the sites oral cavity, lip, tongue, oropharynx, hypopharnx, pharynx, oesophagus, larynx, lung, urinary bladder were considered as tobacco related cancers. The statistical evaluation of proportion of tobacco related cancers between two time periods under consideration was carried out by proportion test. RESULTS: There was a significant decline of proportion of tobacco related cancers from 1990-96 to 2003 for all the registries except Bhopal where around 50% of the total cancers attributed to tobacco habits for the two time periods under consideration. The Barshi also reported a decline but was not statistically significant. In females the proportion of tobacco related cancers ranged between 17% in Bangalore 10% in Delhi for the two time periods under review. All the registries showed significant decline in proportion of tobacco related cancers for the periods under consideration, except Delhi and Bhopal, while rural registry at Barshi revealed an increase of 3.3 %. The gender difference of the proportion of tobacco related cancers ranges between 19.8% to 34% during the period 1990-96, while it was 18.5% to 35% for the period 2001-03. While examining the difference between gender gap between the two time periods, the results from Mumbai registry revealed significant decline.

Laparoscopy:as a first line diagnostic tool for infertility evaluation.

INTRODUCTION: The role of diagnostic and therapeutic hystero-laparoscopy in women with infertility is well established. It is helpful not only in the identification of the cause but also in the management of the same at that time. MATERIALS AND METHODS: In this study, the aim was to analyse the results of 203 women on whom laparoscopy for the evaluation of infertility was done. This study was carried out at a tertiary level hospital from 2005 to 2012. The study group included 121 women with primary infertility and 82 women with secondary infertility. Women with incomplete medical records and isolated male factor infertility were excluded from the study. RESULTS: It was observed that tubal disease was the responsible factor in 62.8% women with primary infertility and 54.8% women with secondary infertility followed by pelvic adhesions in 33% and 31.5%, ovarian factor in 14% and 8.5%, pelvic endometriosis in 9.9% and 6.1% women respectively. Thus tubal factor infertility is still a major cause of infertility in developing countries and its management at an early stage is important to prevent an irreversible damage. At the same time, it also directs which couples would be benefited from assisted reproductive technologies (ART).

Changing trends in use of laparoscopy: a clinical audit.

Aim. To find out the changing trends in indications for use of laparoscopy for diagnostic or operative procedures in gynaecology. Methods. This was a clinical audit of 417 women who underwent laparoscopic procedures over a period of 8 years from January 2005 to December 2012 in the Department of Obstetrics and Gynaecology at a tertiary care centre in Delhi. Results. A total of 417 diagnostic and operative laparoscopic procedures were performed during the period from January 2005 to December 2012. Out of 417 women, 13 women were excluded from the study due to inadequate data. 208 (51.4%) women had only diagnostic laparoscopy whereas 196 (48.6%) patients had operative laparoscopy after the initial diagnostic procedure. Change in trend of diagnostic versus operative procedures was observed from 2005 to 2012. There was increase in operative procedures from 10 (37.03%) women in 2005 as compared to 51 (73.91%) in 2012. The main indication for laparoscopy was infertility throughout the study period (61.38%), followed by chronic pelvic pain (CPP) (11.38%) and abnormal uterine bleeding (AUB) (9.4%). Conclusion. Over the years, there has been a rise in the rate of operative laparoscopy. Though the indications for laparoscopy have remained almost similar during the years, laparoscopy for diagnosis and treatment of CPP and AUB has now increased.

Infusional chemotherapy and medication errors in a tertiary care pediatric cancer unit in a resource-limited setting.

BACKGROUND: Drug administration is a multiprofessional process. The high toxicity and low therapeutic index of chemotherapy drugs make medication errors a significant problem, resulting in excessive patient morbidity and cost. OBJECTIVE: An audit of the delivery of infusional chemotherapy among pediatric inpatients was planned, with the objective of improving practice and minimizing errors. METHOD: An observational study was conducted between January and August 2012. Patients were followed up from their premedication until the completion of postchemotherapy hydration and/or rescue drugs. Errors were recorded and classified by error type, cause, severity, unit location, medication involved, and harm caused. RESULTS: A total of 205 observations were made and 23(13.6%) errors recorded, of which 6 were intercepted. No life-threatening adverse drug event was recorded. The most important risk factor predisposing to errors was admission to nonpediatric ward (P=0.004). Documentation errors and incorrect infusion time were the 2 most common errors, whereas the most frequent error node was administration error. Appropriate steps were taken to prevent their reoccurrence. CONCLUSIONS: This study helped provide important information about the rate and epidemiology of medication errors, emphasizing on the role of audit in enabling development of appropriate error-reducing strategies, particularly in the context of quality assurance in hospitals.