A mentored hands-on training model for scaling up implementation and intervention research in India: "connecting the dots".

Despite the high burden of mental disorders in low- and middle-income countries (LMICs), less than 25% of those in need have access to appropriate services, in part due to a scarcity of locally relevant, evidence-based interventions and models of care. To address this gap, researchers from India and the United States and the Indian Council of Medical Research (ICMR) collaboratively developed a "Grantathon" model to provide mentored research training to 24 new principal investigators (PIs). This included a week-long didactic training, a customized web-based data entry/analysis system and a National Coordination Unit (NCU) to support PIs and track process objectives. Outcome objectives were assessed via scholarly output including publications, awards received and subsequent grants that were leveraged. Multiple mentorship strategies including collaborative problem-solving approaches were used to foster single-centre and multicentre research. Flexible, approachable and engaged support from mentors helped PIs overcome research barriers, and the NCU addressed local policy and day-to-day challenges through informal monthly review meetings. Bi-annual formal review presentations by all PIs continued through the COVID-19 pandemic, enabling interim results reporting and scientific review, also serving to reinforce accountability. To date, more than 33 publications, 47 scientific presentations, 12 awards, two measurement tools, five intervention manuals and eight research grants have been generated in an open-access environment. The Grantathon is a successful model for building research capacity and improving mental health research in India that could be adopted for use in other LMICs.

MoCA in five Indian languages: A brief screening tool to diagnose dementia and MCI in a linguistically diverse setting.

INTRODUCTION AND OBJECTIVES: Early dementia diagnosis in low and middle-income countries (LMIC) is challenging due to limited availability of brief, culturally appropriate, and psychometrically validated tests. Montreal Cognitive Assessment (MoCA) is one of the most widely used cognitive screening tests in primary and secondary care globally. In the current study, we adapted and validated MoCA in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam) and determined the optimal cut-off points that correspond to screening for clinical diagnosis of dementia and MCI. METHODS: A systematic process of adaptation and modifications of MoCA was fulfilled. A total of 446 participants: 214 controls, 102 dementia, and 130 MCI were recruited across six centers. RESULTS: Across five languages, the area under the curve for diagnosis of dementia varied from 0.89 to 0.98 and MCI varied from 0.73 to 0.96. The sensitivity, specificity and optimum cut-off scores were established separately for five Indian languages. CONCLUSIONS: The Indian adapted MoCA is standardized and validated in five Indian languages for early diagnosis of dementia and MCI in a linguistically and culturally diverse population.

Non-communicable diseases as a major contributor to deaths in 12 tribal districts in India.

Background & objectives: Non-communicable diseases (NCDs) are the leading cause of death in India. Although studies have reported a high prevalence of NCD in tribal populations, there are limited data pertaining mortality due to NCDs. Therefore, in this study we estimated the proportion of deaths due to NCDs among 15 yr and older age group in tribal districts in India. Methods: We conducted a community-based survey in 12 districts (one per State) with more than 50 per cent tribal population. Data were collected using a verbal autopsy tool from the family member of the deceased. The estimated sample size was 452 deaths per district. We obtained the list of deaths for the reference period of one year and updated it during the survey. The cause of death was assigned using the International Classification of Diseases-10 classification and analyzed the proportions of causes of death. The age-standardized death rate (ASRD) was also estimated. Results: We surveyed 5292 deaths among those above 15 years of age. Overall, NCDs accounted for 66 per cent of the deaths, followed by infectious diseases (15%) and injuries (11%). Cardiovascular diseases were the leading cause of death in 10 of the 12 sites. In East Garo Hills (18%) and Lunglei (26%), neoplasms were the leading cause of death. ASRD due to NCD ranged from 426 in Kinnaur to 756 per 100,000 in East Garo Hills. Interpretation & conclusions: The findings of this community-based survey suggested that NCDs were the leading cause of death among the tribal populations in India. It is hence suggested that control of NCDs should be one of the public health priorities for tribal districts in India.

Preparedness of primary & secondary care health facilities for the management of non-communicable diseases in tribal population across 12 districts in India.

Background and objectives: Non-communicable diseases (NCDs) are highly prevalent in the tribal populations; however, there are limited data regarding health system preparedness to tackle NCDs among these populations. We estimated the availability of human resources, equipment, drugs, services and knowledge of doctors for NCD management in the selected tribal districts in India. Methods: A cross-sectional survey was conducted in 12 districts (one from each State) with at least 50 per cent tribal population in Andaman and Nicobar Islands, Himachal Pradesh, Madhya Pradesh, Odisha and eight northeastern States. Primary health centres (PHCs), community health centres (CHCs) and district/sub-district hospitals (DHs) were surveyed and data on screening and treatment services, human resources, equipment, drugs and information systems indicators were collected and analysed. The data were presented as proportions. Results: In the present study 177 facilities were surveyed, including 156 PHCs/CHCs and 21 DHs. DHs and the majority (82-96%) of the PHCs/CHCs provided outpatient treatment for diabetes and hypertension. Overall, 97 per cent of PHCs/CHCs had doctors, and 78 per cent had staff nurses. The availability of digital blood pressure monitors ranged from 35 to 43 per cent, and drugs were either not available or inadequate. Among 213 doctors, three-fourths knew the correct criteria for hypertension diagnosis, and a few correctly reported diabetes diagnosis criteria. Interpretation & conclusions: The results of this study suggest that the health system of the studied tribal districts was not adequately prepared to manage NCDs. The key challenges included inadequately trained workforce and a lack of equipment and drugs. It is suggested that capacity building and, procurement and distribution of equipment, drugs and information systems to track NCD patients should be the key focus areas of national programmes.

Picture-naming test for a linguistically diverse population with cognitive impairment and dementia.

BACKGROUND: Picture-naming tests (PNTs) evaluate linguistic impairment in dementia due to semantic memory impairment, impaired lexical retrieval or perceptual deficits. They also assess the decline in naming impairment at various stages of dementia and mild cognitive impairment (MCI) that occurs due to progressive cognitive impairment. With the increasing numbers of people with dementia globally, it is necessary to have validated naming tests and norms that are culturally and linguistically appropriate. AIMS: In this cross-sectional study we harmonized a set of 30 images applicable to the Indian context across five languages and investigated the picture-naming performance in patients with MCI and dementia. METHODS & PROCEDURES: A multidisciplinary expert group formed by the Indian Council of Medical Research (ICMR) collaborated towards developing and adapting a picture naming test (PNT) known as the ICMR-PNT in five Indian languages: Hindi, Bengali, Telugu, Kannada and Malayalam. Based on cross-cultural adaptation guidelines and item-wise factor analysis and correlations established separately across five languages, the final version of the ICMR-PNT test was developed. A total of 368 controls, 123 dementia and 128 MCI patients were recruited for the study. Psychometric properties of the adapted version of the ICMR-PNT were examined, and sensitivity and specificity were examined. OUTCOMES & RESULTS: The ICMR-PNT scores in all languages combined were higher in controls compared with patients with dementia and MCI (F2, 615 = 139.85; p < 0.001). Furthermore, PNT scores for MCI was higher in comparison with patients with dementia in all languages combined (p < 0.001). The area under the curve across the five languages ranged from 0.81 to 1.00 for detecting dementia. There was a negative correlation between Clinical Dementia Rating (CDR) and ICMR-PNT scores and a positive correlation between Addenbrooke's Cognitive Examination-III (ACE-III) and ICMR-PNT scores in control and patient groups. CONCLUSIONS & IMPLICATIONS: The ICMR-PNT was developed by following cross-cultural adaptation guidelines and establishing correlations using item-wise factor analysis across five languages. This adapted PNT was found to be a reliable tool when assessing naming abilities effectively in mild to moderate dementia in a linguistically diverse context. WHAT THIS PAPER ADDS: What is already known on this subject Picture-naming evaluates language impairment linked to naming difficulties due to semantic memory, lexical retrieval or perceptual disturbances. As a result, picture naming tests (PNTs) play an important role in the diagnosis of dementia. In a heterogeneous population such as India, there is a need for a common PNT that can be used across the wide range of languages. What this study adds to existing knowledge PNTs such as the Boston Naming Test (BNT) were developed for the educated, mostly English-speaking, Western populations and are not appropriate for use in an Indian context. To overcome this challenge, a PNT was harmonized in five Indian languages (Hindi, Bengali, Telugu, Kannada and Malayalam) and we report the patterns of naming difficulty in patients with MCI and dementia. The ICMR-PNT demonstrated good diagnostic accuracy when distinguishing patients with mild to moderate dementia from cognitively normal individuals. What are the potential or actual clinical implications of this work? With the growing number of persons suffering from Alzheimer's disease and other forms of dementia around the world, its critical to have culturally and linguistically relevant naming tests and diagnosis. This validated ICMR-PNT can be used widely as a clinical tool to diagnose dementia and harmonize research efforts across diverse populations.

Effect of vitamin D on bone strength in older African Americans: a randomized controlled trial.

There is controversy over whether African Americans have higher vitamin D requirements than recommended by the Institute of Medicine. We previously reported that maintaining serum 25(OH)D above 30 ng/mL does not prevent age-related bone loss. Herein, we report that bone strength is also unaffected by maintaining this level in this population. INTRODUCTION: The role of vitamin D in bone strength has not been investigated in the African American (AA) population. METHODS: A 3-year randomized controlled trial was designed to examine the effect of vitamin D supplementation on physical performance, bone loss, and bone strength in healthy older AA women. A total of 260 postmenopausal AA women, ages ≥ 60 years were randomized to a vitamin D3 or placebo arm. Vitamin D3 dose was adjusted to maintain serum 25OHD > 30 ng/mL. Bone mineral density, femoral axis length, and femoral neck (FN) width were measured by dual-energy X-ray absorptiometry. Composite indices of FN strength [compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI)] were computed. RESULTS: The mean age of participants was 68.2 ± 4.9 years. Baseline characteristics between groups were similar. The average dose of vitamin D3 was 3490 ± 1465 IU/day in the active group. The mean serum 25OHD was 46.8 ± 1.2 ng/mL versus 20.7 ± 1.1 ng/mL in the active versus placebo group. Serum 25OHD did not correlate with any composite indices. The longitudinal differences observed in FN width, CSI, BSI, and ISI in both groups were not statistically significant (all p values > 0.05). Further, there was no group × time interaction effect for any of the composite indices (all p values > 0.05). CONCLUSION: Maintaining serum 25OHD > 30 ng/mL (75 nmol/L) does not affect bone strength in older AA women. There is no evidence to support vitamin D intake greater than the recommended RDA by the Institute of Medicine in this population for bone strength.

White paper on venomous snakebite in India.

Venomous snakebite is one of the leading preventable causes of mortality and morbidity with tremendous socio-economic impact on the family and nation. Venomous snakebite has been relisted as a neglected tropical disease after having been removed off the list in 2013. This paper discusses the various reasons which could be attributed to the high mortality and morbidity due to venomous snakes and also provides recommendations on policy decisions, improvement on the quality of venom and anti-snake venom and in promoting awareness on how to avoid snakebite.

Indian Council of Medical Research consensus document on hepatocellular carcinoma.

This document aims to assist oncologists in making clinical decisions encountered while managing their patients with hepatocellular carcinoma (HCC), specific to Indian practice, based on consensus among experts. Most patients are staged by Barcelona Clinic Liver Cancer (BCLC) staging system which comprises patient performance status, Child-Pugh status, number and size of nodules, portal vein invasion and metastasis. Patients should receive multidisciplinary care. Surgical resection and transplant forms the mainstay of curative treatment. Ablative techniques are used for small tumours (<3 cm) in patients who are not candidates for surgical resection (Child B and C). Patients with advanced (HCC should be assessed on an individual basis to determine whether targeted therapy, interventional radiology procedures or best supportive care should be provided. In advanced HCC, immunotherapy, newer targeted therapies and modern radiation therapy have shown promising results. Patients should be offered regular surveillance after completion of curative resection or treatment of advanced disease.

A community-based pragmatic, controlled trial for preventing and reducing oral diseases among 1-6-year-old children visiting Anganwadi centers, under the Integrated Child Development Scheme, India.

BACKGROUND: Early childhood caries (ECC) has reached epidemic proportions affecting millions of children worldwide. Its prevention becomes imperative owing to the significant morbidity and financial implications involved with its treatment. The Integrated Child Development Scheme (ICDS), launched in India to provide mid-day meals, pre-school education and primary healthcare to children, can be utilised to counsel and deliver oral health education to mothers. The purpose of the study is to compare the effect of an oral health care package (OHCP) with usual care on the change in dental disease status among 1 to 3-year-old children at Anganwadi centres (AWC) in periurban areas of Chandigarh and rural areas of Cuttack, Orissa over a follow-up period of three years. METHODS: Two geographically distant ICDS blocks would be selected at each of the two study sites and would be randomly allocated to intervention and control group. Closely located AWCs under each of the selected blocks shall constitute the study setting. OHCP would be delivered to the mothers of the 1-6-year-old children enrolled in the AWCs of the experimental group whereas mothers under control group would receive usual care advice available at the AWCs. DISCUSSION: ECC prevention had conventionally focused upon testing effectiveness of programs targeting behaviour change among the caregivers and children, but surprisingly minimal efforts have been made to seek translation of these efforts into reduction of ECC at the community level. The present study has two components; testing effect of altering maternal and child behavioral aspects on ECC incidence through cohort follow up of 1-3-year-old children for three consecutive years and cross-sectional follow up of all available 1-6-year old children at the selected AWCs at regular intervals to look for change in prevalence of ECC at community level. In other regions of the world surveys of ECC prevalence before and after the intensive educational programs have shown a significant reduction in ECC prevalence. A similar decline can be anticipated through this program. TRIAL REGISTRATION: This trial has been prospectively registered at Clinical Trials Registry, India (CTRI/2019/02/017556, 08 February 2019).

Type 2 Diabetes and Aging: A Not so Sweet Scenario for Bone.

Type 2 diabetes and fractures are associated with substantial mortality and morbidity in the aging population. Given the normal to high bone mineral density, skeletal fragility in type 2 diabetes is an intriguing topic of ongoing research. An improved understanding of the underlying mechanisms and regulators of bone pathology in diabetes is needed to formulate targeted prevention and intervention strategies in this high risk population. Although the changes in bone induced by aging and disease are divergent, the pathogenetic mechanisms of aging and type 2 diabetes, thus far known, are not mutually exclusive. These mechanisms may provide deeper insight into the quantitative and qualitative deficits to further our knowledge of diabetes-specific bone pathology.

Trabecular bone score (TBS) in postmenopausal African American women.

UNLABELLED: Trabecular bone score (TBS) is a newly developed parameter that can be derived from DXA scans of the spine and may reflect bone quality. This study provides TBS values in healthy postmenopausal women of African descent. INTRODUCTION: African American women have a lower risk for osteoporotic fractures as a result of higher bone density and better bone quality. We examined TBS in postmenopausal African American women since there are no previous reports in this population. METHODS: This was a study of healthy African American volunteers using baseline values prior to their participation in two vitamin D intervention studies conducted at an ambulatory research center of an academic health center. RESULTS: The study population consisted of 518 healthy postmenopausal African American women with a mean age of 66 years and a BMI of 30.1. Mean TBS (L1 to L4) was 1.300(.100 SD). Significant negative correlations were found between TBS and age and BMI. None of the biochemical variables were significantly correlated with TBS whereas the various bone density sites were correlated with TBS. CONCLUSION: TBS values for African American women are higher than those reported in the literature for white women and are inversely related to age and BMI.

Bone quality assessment in type 2 diabetes mellitus.

UNLABELLED: The increased risk for fractures in type 2 diabetes mellitus (T2DM) despite higher average bone density is unexplained. This study assessed trabecular bone quality in T2DM using the trabecular bone score (TBS). The salient findings are that TBS is decreased in T2DM and low TBS associates with worse glycemic control. INTRODUCTION: Type 2 diabetes mellitus is a risk factor for osteoporotic fractures despite high average bone mineral density (BMD). The aim of this study was to compare BMD with a noninvasive assessment of trabecular microarchitecture, TBS, in women with T2DM. METHODS: In a cross-sectional study, trabecular microarchitecture was examined in 57 women with T2DM and 43 women without diabetes, ages 30 to 90 years. Lumbar spine BMD was measured by dual-emission x-ray absorptiometry (DXA), and TBS was calculated by examining pixel variations within the DXA images utilizing TBS iNsight software. RESULTS: Mean TBS was lower in T2DM (1.228 ± 0.140 vs. 1.298 ± 0.132, p = 0.013), irrespective of age. Mean BMD was higher in T2DM (1.150 ± 0.172 vs. 1.051 ± 0.125, p = 0.001). Within the T2DM group, TBS was higher (1.254 ± 0.148) in subjects with good glycemic control (A1c ≤ 7.5 %) compared to those (1.166 ± 0.094; p = 0.01) with poor glycemic control (A1c > 7.5 %). CONCLUSION: In T2DM, TBS is lower and associated with poor glycemic control. Abnormal trabecular microarchitecture may help explain the paradox of increased fractures at a higher BMD in T2DM. Further studies are needed to better understand the relationship between glycemic control and trabecular bone quality.

Management of Intraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common childhood intraocular malignancy. Delayed presentation due to a lack of awareness and advanced intraocular tumors are a common scenario in low-middle income countries (LMICs). Remarkable treatment advances have been made in the past few decades allowing globe salvage in advanced intraocular RB (IORB) including systemic chemotherapy with focal consolidation and targeted treatments like intraarterial chemotherapy and intravitreal chemotherapy. However, a lack of availability and affordability limits the use of such advances in LMICs. External beam radiotherapy, despite risk of second cancers in RB with germline mutations, still remains useful for recalcitrant RB not responding to any other treatment. When choosing conservative treatment for advanced IORB, the cost and long duration of treatment, morbidity from multiple evaluation under anesthesias (EUAs), side effects of treatment and risk of treatment failure need to be taken into account and discussed with the parents. In this article, the authors discuss the ICMR consensus guidelines on the management of IORB.

Epidemiology, Diagnosis and Genetics of Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common intraocular tumor in childhood. It is mainly caused by mutations in both alleles of the RB1 tumor suppressor gene that is found on chromosome 13 and regulates the cell cycle. Approximately 8000 children are diagnosed with RB globally each year, with an estimated 1500 cases occurring in India. The survival rate of RB has improved to more than 90% in the developed world. Leukocoria and proptosis are the most common presenting features of RB in Asian Indian populations. Most cases of RB are diagnosed by fundus examination followed by ultrasound. The International Classification of Retinoblastoma is the most used scheme for the staging and classification of intraocular RB in India. Prenatal testing and preimplantation genetic testing for RB may be beneficial in high-risk families. Histopathologic risk factors such as massive choroidal invasion and post-laminar optic nerve help in predicting the occurrence of metastasis in children with RB, while presence of microscopic residual disease requires aggressive adjuvant treatment in eyes enucleated for group E RB. The review provides a consensus document on diagnosis and genetics of RB in India.

Creatine and low-dose lithium supplementation separately alter energy expenditure, body mass, and adipose metabolism for the promotion of thermogenesis.

Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

Management of Extraocular Retinoblastoma: ICMR Consensus Guidelines.

Retinoblastoma (RB) is the most common intraocular malignancy of childhood. Advanced stage presentation of RB is common in low middle-income countries (LMICs) due to lack of awareness, social taboos associated with enucleation, seeking alternative conservative treatment options, and poor accessibility to health care. Over the last few decades, there have been significant advancements in the management of extraocular RB (EORB) which have improved outcomes and helped in minimizing treatment-related toxicities. The incorporation of multimodality approaches including chemotherapy, surgery, and radiotherapy (RT) has shown promising results; however, prognosis remains poor especially in LMICs. In this article, authors have discussed the ICMR consensus guidelines on the management of EORB, including metastatic RB.

Somatic mutational landscape across Indian breast cancer cases by whole exome sequencing.

Breast cancer (BC) has emerged as the most common malignancy among females. The genomic profile of BC is diverse in nature and complex due to heterogeneity among various geographically different ethnic groups. The primary objective of this study was to carry out a comprehensive mutational analysis of Indian BC cases by performing whole exome sequencing. The cohort included patients with a median age of 48 years. TTN, TP53, MUC16, SYNE1, and OBSCN were the frequently altered genes found in our cohort. The PIK3CA and KLC3 genes are driver genes implicated in various cellular functions and cargo transportation through microtubules, respectively. Except for CCDC168 and PIK3CA, several gene pairings were found to be significantly linked with co-occurrence. Irrespective of their hormonal receptor status, RTK/RAS was observed with frequently altered signaling pathways. Further analysis of the mutational signature revealed that SBS13, SBS6, and SBS29 were mainly observed in our cohort. This study supplements the discovery of diagnostic biomarkers and provides new therapeutic options for the improved management of BC.

A review on electronic nose for diagnosis and monitoring treatment response in lung cancer.

Lung cancer is one of the common malignancies with high mortality rate and a poor prognosis. Most lung cancer cases are diagnosed at an advanced stage either due to limited resources of infrastructure, trained human resources, or delay in clinical suspicion. Low-dose computed tomography has emerged as a screening tool for lung cancer detection but this may not be a feasible option for most developing countries. Electronic nose is a unique non-invasive device that has been developed for lung cancer diagnosis and monitoring response by exhaled breath analysis of volatile organic compounds. The breath-print have been shown to differ not only among lung cancer and other respiratory diseases, but also between various types of lung cancer. Hence, we postulate that the breath-print analysis by electronic nose could be a potential biomarker for the early detection of lung cancer along with monitoring treatment response in a resource-limited setting. In this review, we have consolidated the current published literature suggesting the use of an electronic nose in the diagnosis and monitoring treatment response of lung cancer.

MicroRNAs in exhaled breath condensate: A pilot study of biomarker detection for lung cancer.

INTRODUCTION: Quantitation of microRNAs secreted by lung cells can provide valuable information regarding lung health. Exhaled breath condensate (EBC) offers a non-invasive way to sample the secreted microRNAs, and could be used as diagnostic tools for lung cancer. MATERIALS & METHODS: EBC samples from twenty treatment-naïve patients with pathologically confirmed lung cancer and twenty healthy subjects were profiled for miRNAs expression. Selected microRNAs were further validated, using quantitative-PCR, in an independent set of 10 subjects from both groups. RESULTS: A total of 78 miRNAs were found to be significantly upregulated in the EBC of lung cancer patients compared to the control group. Six of these 78 miRNAs were shortlisted for validation. Of these, miR-31-3p, let7i, and miR-449c were significantly upregulated, exhibited good discriminatory power. DISCUSSION: Differential expression of miRNAs secreted by lung cells could be quantitated in EBC samples, and could be used as a potential non-invasive tool for early diagnosis of lung cancer.