Search

Ovarian hyperstimulation syndrome (OHSS) usually occurs in patients undergoing assisted reproduction techniques and ovulation induction. Its variant, spontaneous ovarian hyperstimulation syndrome, a potentially life-threatening disorder, is uncommon and only a few cases have been reported in association with hypothyroidism. This study analysed five patients with untreated chronic hypothyroidism presenting with multicystic ovaries, isosexual precocious puberty, and delayed bone age; subsequently, the follow-up and regression of ovarian pathology was assessed. Two patients had presented to the emergency department with menorrhagia and hypotension, of these, one had ovarian torsion at presentation. Three patients presented to the outpatient department: one for evaluation of short stature, one for premature menarche, and another with polycystic ovaries. They were all diagnosed with long-standing, untreated chronic hypothyroidism. There was regression of the size of the cystic ovaries on subsequent follow-up. In all these patients, long-standing hypothyroidism had resulted in ovarian hyperstimulation syndrome. The potentially life-threatening complications of this syndrome may be prevented by careful screening and a strong index of clinical suspicion at the outset.

Understanding the health culture of tribal community is important as health problems among tribal communities and their care is influenced by sociocultural factors, which will help in the implementation of health services. The conventional way of improving the access for the general populations may not suit the tribal populations owing to their distinct culture and owing to health systems factors as well. A stepwise process was followed for the development of a protocol to study to strengthen the implementation of National Programme for Prevention and Control of Non-Communicable Diseases. The study was planned to be carried out across six tribal districts of India. A detailed protocol was built around Implementation Research Logic Model, primarily as a method for planning, executing, reporting, and synthesizing the implementation.

Introduction: Thyroid storm is an uncommon but life-threatening presentation of thyrotoxicosis with a mortality rate of 10%. Our objective was to study the demographics, clinical and biochemical characteristics, and outcomes of inpatients diagnosed with thyroid storm in the Indian context. Methods: This retrospective study was conducted by analysing the institutional electronic medical records (EMR) of all patients admitted with thyroid storm from 2004 to 2020 with a Burch–Wartofsky score (BWS) of ≥45. Results: Thirty-five patients with a BWS ≥45 were included, of whom 71.4% were women, with a mean age of 44.9 ± 10.2 years. 43% did not have any prior history of thyrotoxicosis. Graves’ disease was the most common underlying aetiology (71.4%), followed by toxic multinodular goitre (14.3%). Cardiovascular (94.3%) and gastrointestinal-hepatic dysfunction (88.6%) were the most common clinical manifestations. Features of Central nervous system (CNS) dysfunction were seen in only 42.3% of patients diagnosed with a thyroid storm. The Japanese Thyroid Association (JTA) criteria diagnosed only 26 patients (74.3%) with “definite” thyroid storm. The mortality rate was 8.6%, and all three patients expired within 48 hours of admission. Conclusion: Nearly one in every two patients with thyroid storm had previously undiagnosed thyrotoxicosis. Toxic multinodular goitre is a notable aetiology in Indians. Features of CNS dysfunction, considered relatively specific for thyroid storm, were less prominent in our series. The JTA criteria might alter the classification of some patients diagnosed with a thyroid storm, when compared to the BWS score due to fewer CNS features among Indian patients.

Abstract Aims The widely used dynamic disposition index, derived from oral glucose tolerance testing, is an integrative measure of the homeostatic performance of the insulin‐glucose feedback control. Its collection is, however, time consuming and expensive. We, therefore, pursued the question if such a measure can be calculated at baseline/fasting conditions using plasma concentrations of insulin and glucose. Methods A new fasting‐based disposition index (structure parameter inference approach‐disposition index [SPINA‐DI]) was calculated as the product of the reconstructed insulin receptor gain (SPINA‐GR) times the secretory capacity of pancreatic beta cells (SPINA‐GBeta). The novel index was evaluated in computer simulations and in three independent, multiethnic cohorts. The objectives were distribution in various populations, diagnostic performance, reliability and correlation to established physiological biomarkers of carbohydrate metabolism. Results Mathematical and in‐silico analysis demonstrated SPINA‐DI to mirror the hyperbolic relationship between insulin sensitivity and beta‐cell function and to represent an optimum of the homeostatic control. It significantly correlates to the oral glucose tolerance test based disposition index and other important physiological parameters. Furthermore, it revealed higher discriminatory power for the diagnosis of (pre)diabetes and superior retest reliability than other static and dynamic function tests of glucose homeostasis. Conclusions SPINA‐DI is a novel simple reliable and inexpensive marker of insulin‐glucose homeostasis suitable for screening purposes and a wider clinical application.

Congenital adrenal hyperplasia (CAH) comprises a heterogeneous group of autosomal recessive disorders impairing adrenal steroidogenesis. Most cases are caused by mutations in the CYP21A2 gene resulting in 21-hydroxylase (21-OH) deficiency (21-OHD). The genetics of 21-OH CAH is complexed by a highly homologous pseudogene CYP21A1P imposing several limitations in the molecular analysis. Therefore, genetic testing is still not a part of routine CAH diagnosis and is mainly dependent on 17-hydroxy progesterone (OHP) measurements. There are very few reports of CYP21A2 gene analysis from India and there is no comprehensive review available on genetic testing and the spectrum of CYP21A2 mutations from the country. This review focuses on the molecular aspects of 21-OHD and the genetic studies on CYP21A2 gene reported from India. The results of these studies insist the compelling need for large-scale CYP21A2 genetic testing and newborn screening (NBS) in India. With a high disease prevalence and consanguinity rates, robust and cost-effective genetic testing for 21-OH CAH would enable an accurate diagnosis in routine clinical practice. Whereas establishing affordable genotyping assays even in secondary care or resource-poor settings of the country can identify 90% of the mutations that are pseudogene derived, initiatives on reference laboratories for CAH across the nation with comprehensive genetic testing facilities will be beneficial in those requiring extended analysis of CYP21A2 gene. Further to this, incorporating genetic testing in NBS and carrier screening programmes will enable early diagnosis, better risk assessment and community-based management.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Background: Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index

Abstract We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson’s correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r − 0.23, p = 0.01), McAuley index (r − 0.65, p

Abstract Objective Chronic obstructive airway disease (COPD) is characterized by airflow limitation due to airway and/or alveolar abnormalities with significant extra‐pulmonary manifestations. Bone health impairment is an extra‐pulmonary complication of COPD which is less well studied in India. Moreover, it can contribute to significant morbidity and mortality. Hence, we aim to estimate the prevalence of osteoporosis and metabolic parameters of adverse bone health in patients with COPD. Methods In this case control study, male subjects aged 40–70 years with COPD attending the respiratory outpatient clinic in a tertiary care hospital were recruited over a period of 2 years and the control population were derived from the historical cohort who were apparently healthy with no obvious diseases. Metabolic parameters of bone health measured from fasting blood samples were calcium, albumin, alkaline phosphatase, phosphorous, parathormone, creatinine, 25‐hydroxy vitamin D, and testosterone. Bone mineral density (BMD) was estimated using DXA scan and the World Health Organization (WHO) criteria was used to categorize into osteoporosis, osteopenia, and normal BMD based on the T‐score at femoral neck, lumbar spine and distal forearm. Pulmonary function tests and 6 minute walk test were performed if they had not been done in the previous 3 months. The associations of COPD with osteoporosis were analyzed using linear regression analysis and effect size are presented as beta with 95% confidence interval. Results Of the 67 participants with COPD enrolled in the study, osteoporosis was present in 61% (41/67) and osteopenia in an additional 33% (22/67) of the cases, which was higher when compared to the control population (osteoporosis 20% [50/252] and osteopenia 58% [146/252]). In regression modeling, there was a trend toward adverse bone health with advanced age, low body mass index, low forced expiratory volume in 1 second and testosterone deficiency in COPD. Conclusion Individuals with COPD have a substantially higher prevalence of osteoporosis and osteopenia, up to almost twice that of the general population, with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. Hence, bone health assessment should be a part of comprehensive COPD care to prevent adverse consequences due to poor bone health.

Background/objective: Parathyroid carcinoma is a rare entity presenting as parathyroid hormone (PTH) dependent hypercalcemia. Our objective was to report a case of metastatic parathyroid carcinoma in a middle-aged woman, who presented with refractory hypercalcemia and the strategies we used to induce remission. Case report: A 47 year old lady with a past history of a left superior parathyroid adenoma excision, presented with recurrent PTH dependent hypercalcemia. An ultrasonography of the neck and parathyroid scintigraphy were normal. Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) scan picked up metabolically active lesions in the lingular segment of the left lung and another lesion in the diaphragmatic pleura of the left hemi-thorax. Following metastectomy of the lung nodules, she developed symptomatic hypocalcemia with a reduction of serum PTH levels. The histopathology and immunoprofile were consistent with metastatic carcinoma. The PTH levels started rising 2 months after the surgery, with calcium levels remaining stable on cinacalcet, denosumab and cabozantinib. Discussion: Parathyroid carcinoma is a rare endocrine malignancy with typically indolent, yet progressive course. There is no consensus on the treatment and follow-up of parathyroid carcinoma, owing to its rarity. The greatest likelihood of cure is achieved if complete resection of all malignant tissue is successful at the time of initial surgery. Surgical reduction of the tumor mass may also render the patient's hypercalcemia more amenable to medical treatment with hydration, potent intravenous bisphosphonates, denosumab and cinacalcet. Conclusion: Surgical debulking of the metastatic lesions, followed by medical management of hypercalcemia offers promising results in the management of metastatic parathyroid carcinoma.

Objective: Parkinson's disease (PD) is a neurodegenerative condition that is characterized by bradykinesia, rigidity, and gait instability. Inherent to this condition is an increased predisposition to falls and fractures. Bone health in Parkinson's disease in India has not been studied thus far. This study aimed to assess the bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA) in Indian men with PD and compare them with matched controls. Methodology: A case-control study done at a tertiary care center from southern India. Bone biochemistry, BMD, TBS, and HSA were assessed. Results: Among 40 cases and 40 age, gender, and body mass index (BMI)-matched controls, there was no significant difference in BMD between both groups. The mean (SD) TBS at the lumbar spine [1.349 (0.090)] was significantly (P = 0.019) lower in men with PD as compared to matched controls [1.401 (0.089)]. Among the parameters of HSA, the buckling ratios were significantly higher at the femoral neck [11.8 (2.2) vs 9.4 (2.2); P = 0.001] and inter-trochanteric region [9.4 (2.1) vs 7.8 (1.4); P = 0.002] among cases as compared to matched controls. Vitamin D deficiency was significantly higher in this cohort of patients as was bone turnover marker indicating bone loss and a high bone turnover state. Conclusion: A comprehensive bone health assessment comprising BMD, TBS, and HSA may be required to capture all aspects of bone strength in Indian men with PD as BMD assessment as a stand-alone tool may not suffice to obtain all information pertaining to fracture risk in these individuals.

Abstract Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research.

BackgroundAsian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India.MethodsThe IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43–50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived.ResultsEchocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy.ConclusionsOur study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality.ISRCTN registration number13432279

A 57-year-old housewife presented with complaints of sudden onset of chest pain and dyspnea. Computed tomography angiography revealed saddle-shaped pulmonary emboli in the main pulmonary artery and its branches. Evaluation for the cause of pulmonary embolism revealed a heterogeneously enhancing lesion arising from the anterior aspect of the lower pole of the left kidney. She had no hematuria, flank pain, or any palpable abdominal mass. She underwent a left open radical nephrectomy with inferior vena cava thrombectomy. Given that only 10% of patients present with the classic triad, it is often difficult to diagnose renal cell carcinoma in the early stages. Therefore, a high index of suspicion in patients with atypical presentations can lead to an early diagnosis.

Abstract Objective The objective of this paper was to present the results of our study of the utility of bone mineral density (BMD) measurements at various segments of distal forearm in predicting central‐site osteoporosis and deteriorated trabecular microarchitecture. Methods This was a cross‐sectional study and BMD at the femoral neck, lumbar spine, and distal forearm were assessed using the dual‐energy X‐ray absorptiometry (DXA) scanner and bone microarchitecture at lumbar spine by trabecular bone score (TBS). The utility of forearm BMD in predicting osteoporosis as well as the deteriorated TBS was assessed by a receiver operating characteristic analysis. Results A total of 352 postmenopausal women with mean (SD) age of 60.7 (6.8) years were included. The odds of having osteoporosis at femoral neck [odds ratio (OR) = 14.1, 95% confidence interval (CI): 7.8–25.2] and lumbar spine (OR = 7.5, 95% CI: 4.6–12.1) was highest with the mid‐distal radius. A derived T‐score cut off ≤ −1.6, −1.9, and −1.7 at any segment of the forearm was elucidated to predict osteoporosis at the central‐site, femoral neck, and lumbar spine, respectively, with sensitivity of 80%–88% and specificity of 60%–70%. The T‐scores at all three forearm segments ≤ −1.2 showed fair performance in predicting degraded trabecular microarchitecture. The T‐scores thus derived were further validated in cohort of 360 Bengali postmenopausal women. Conclusion BMD assessment at the forearm may be utilized in prediction of trabecular microarchitecture and central site osteoporosis at the femoral neck and lumbar spine in postmenopausal women.

Objective: Maturity-onset diabetes of the young (MODY) type 5 is caused by an autosomal dominant mutation in the HNF1B gene. Our objective was to report a case of a young girl with bicornuate uterus and recurrent renal stones with diabetes mellitus (DM) without a family history that was diagnosed to be MODY 5. Case Report: A 12-year-old girl presented with recurrent renal stones that were managed with lithotripsy and double-J stenting at various time points. At the age of 14 years, she was found to have a bicornuate uterus with an absent cervix and vagina. She was diagnosed with DM at the age of 16 years without a preceding history of osmotic symptoms or steatorrhea. Although there was no family history of young-onset diabetes, given her long-standing history of müllerian abnormalities, renal cysts, and pancreatic hypotrophy, she was evaluated for MODY. Using the next-generation sequencing, she was found to be positive for a reported HNF1B gene pathogenic mutation c.494G>A (p.Arg165His), confirming a diagnosis of MODY 5. Discussion: There is a significant overlap in clinical criteria for type 2 DM and MODY in the Asian Indian population. The HNF1B gene mutation is difficult to diagnose as none of the clinical manifestations are pathognomonic and many lack a family history of DM. Diagnostic algorithms with specific clinical and biochemical criteria along with pancreatic imaging can help in case detection and direct toward particular genetic mutation analysis. Conclusion: We suggest that genetic testing be offered to patients with otherwise unexplained DM and such genitourinary anomalies.

Background: Skeletal fluorosis is a metabolic bone disease that results from the chronic ingestion of fluoride. Although there are national programs in place to raise awareness and curtail this disease condition, skeletal fluorosis continues to cause crippling deformities in areas where it continues to be endemic. Method: ology: An observational study was undertaken at a university-affiliated teaching hospital in southern India. Clinical, biochemical features and densitometric variables including bone mineral density (BMD) and trabecular bone score (TBS) were assessed. Results: All patients (n = 9) hailed from fluorosis-endemic Indian states and the source of drinking water was from a bore-well in all cases. The mean (±SD) age and BMI were 45.6(±11.0) years and 25.6 (±8.4) kg/m2 respectively. Dental mottling was present in five subjects. Five subjects each had vitamin D deficiency with osteomalacia. The mean (±SD) urine fluoride was 2.9(±1.4) ppm. The bone mineral density showed a sclerotic pattern, with the mean (±SD) TBS being 1.607 (±0.160). All patients were initiated on calcium and cholecalciferol supplements and those with osteomalacia were treated with calcitriol. Conclusion: While fluorosis continues to be a challenge in endemic regions, the presence of osteomalacia proves to be a treatable component of the disease condition. There seems to be an unmet need for more aggressive defluoridation techniques and the provision of safe drinking water in susceptible individuals.

Background: Osteoporosis and sarcopenia are important aspects of motor neuron disease (MND). Individuals with amyotrophic lateral sclerosis (MND-ALS) have an increased risk of falls and fractures. Currently, the standard of care does not involve a routine assessment of bone mineral density (BMD) and body composition in these patients. We aimed to assess BMD, bone mineral parameters and body composition in men with MND and compared them with healthy controls. Methods: Consecutive males between 50 and 80 years of age diagnosed as MND-ALS by revised El Escorial criteria and able to walk unassisted attending Neurology outpatient clinic were recruited into the study. Age, gender and body mass index (BMI) matched healthy controls were recruited from the local community. BMD and body composition were assessed by dual-energy x-ray absorptiometry (DXA). Bone mineral parameters and bone turnover markers (BTMs) were also assessed in them. Results: A total of 30 subjects with MND-ALS and 33 controls were recruited. The mean age (years) was 59.2 in cases and 61.2 in controls. The mean BMD (g/cm2) between the two groups was similar; however, BTMs were significantly higher in the MND group (P < 0.05). Subjects with MND-ALS had significantly lower mean appendicular lean mass (ALM) (19.9 versus 22.4 kg; P = 0.007) and ALM corrected for BMI than the healthy control group (0.858 versus 0.934 kg/kg/m2; P = 0.034). Sarcopenic obesity (Percentage fat mass >27% + ALM/BMI

Objectives: The purpose of this study was to establish the prevalence of diabetes-specific psychological distress (DSPD) among patients with type 2 diabetes mellitus (T2DM) using the “Problem areas in diabetes” (PAID) scale at a teaching hospital in southern India. Other objectives included observing the relationship between socio-demographic factors and DSPD and, finally exploring the level of acceptance of the PAID scale by Asian–Indian patients. Methods: The patients with T2DM aged >18 years attending the diabetes outpatient clinic were recruited. They completed two sets of questionnaires; PAID and a satisfactory questionnaire, which included socio-demographic characteristics and questions relating to the acceptance of PAID. Statistical analysis was performed using Stata 13.1 and Excel. Results: A total of 253 questionnaires were completed, including 157 (62.1%) male and 96 (37.9%) female patients. The prevalence of DSPD was 32.8% (83/253). Younger age (OR 3.65, 95% CI 1.36–9.80) and presence of retinopathy (OR 2.60, 95% CI 1.12–6.04) were significantly associated with DSPD. However, it was observed that one-third of the patients had an elevated level of distress regardless of socio-demographic or clinical factors. PAID was well accepted by the participants and 84.6% (214/253) were pleased to complete it again. Conclusion: About one-third of the patients with T2DM had DSPD. Psychological distress was higher in the younger age group and those with retinopathy. PAID is an easy, well-accepted questionnaire and would serve as a useful tool to screen for DSPD.

Background and Aims: The measuring tools used for assessment of neuropathy include various questionnaires, monofilament testing, Biothesiometry and the gold standard test, nerve conduction studies (NCS). This study aims to evaluate the diagnostic accuracies of Michigan Neuropathy Screening Instrument (MNSI), Biothesiometry, Semmes Weinstein Monofilament (SWMF), Sural Radial Amplitude Ratio (SRAR) and minimal F wave latency as compared to conventional NCS and arrive at a simple diagnostic algorithm for early detection of Diabetic Peripheral Neuropathy (DPN). Methods: In a cross-sectional observational study on 48 Type 2 diabetes mellitus patients, MNSI, Biothesiometry, SWMF and NCS including F waves and SRAR were done and diagnostic accuracies (sensitivity, specificity, positive and negative predictive values) calculated taking NCS as gold standard. Results: MNSI, Biothesiometry, SWMF, SRAR and minimal F wave latency had a sensitivity of 64.3%, 78.6%, 14.3%, 100% and 78.6% and specificity of 67.7%, 52.9%, 94.1%, 23.53% and 76.47% respectively, with reference to NCS. Based on combined sensitivities and specificities, we arrived at a simple algorithm for early diagnosis of DPN, which showed that DPN could either be diagnosed or ruled out in 75% of the patients by a combination of the Biothesiometry, SRAR and left lower limb minimal F wave latency results. Conclusions: In the setting of an outpatient, multidisciplinary diabetic clinic, simple tests such as questionnaires, monofilament testing and biosthesiometer could be performed with greater ease while considering NCS as the gold standard. This algorithm, combining Biothesiometry, SRAR and left lower limb minimal F wave latency would be less time consuming and help in early diagnosis of DPN.

ObjectivesHypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD.MethodsA two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11).ResultsHUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05).ConclusionHeterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder due to enzyme defects in adrenal steroidogenesis. Several genes code for these enzymes, out of which mutations in the CYP21A2 gene resulting in 21 hydroxylase deficiency, contribute to the most common form of CAH. However, pseudogene imposed challenges complicate genotyping CYP21A2 gene, and there is also a lack of comprehensive molecular investigations in other genetic forms of CAH in India. Here, we describe a cost-effective, highly specific, and sensitive Allele Specific PCR (ASPCR) assay designed and optimized in-house to screen eight common pathogenic mutations in the CYP21A2 gene. We have also established and utilized a multiplex PCR assay for target enrichment and Next-generation sequencing (NGS) of CYP11B1, CYP17A1, POR, and CYP19A1 genes. Following preliminary amplification of the functional gene CYP21A2, ASPCR based genotyping of eight common mutations - P30L, I2G, 8BPdel, I172N, E6CLUS (I235N, V236E, M238K) V281L, Q318X, and R356W was carried out. These results were further validated using Sanger and Next-generation sequencing. Once optimized to be specific and sensitive, the advantage of ASPCR in CYP21A2 genotyping extends to provide genetic screening for both adult and paediatric subjects and carrier testing at a low cost and less time. Furthermore, multiplex PCR coupled NGS has shown to be cost-effective and robust for parallel multigene sequencing in CAH.

Early onset hypertension is one of many major medical disorders that have evolved over the current millennium across both the developing as well as the developed world. Though various mechanisms have been postulated for the evolution of hypertension in these individuals, one of the most relevant ones is that of low birth weight and its association with hypertension. Barker from historical evidence has postulated the foetal onset adult disease (FOAD) or Thrifty phenotype on Low Birth Weight (LBW) associated hypertension. Later, Brenner highlighted the importance of low nephron mass and future implications. In this review we elaborate the mechanisms that were postulated for LBW-related hypertension as well the potential antihypertensive therapy that may be used in these individuals.

No abstract available

Background: To improve the control of hypertension in low- and middle-income countries, we trialed a community-based group program co-designed with local policy makers to fit within the framework of India's health system. Trained accredited social health activists (ASHAs), delivered the program, in three economically and developmentally diverse settings in rural India. We evaluated the program's implementation and scalability.Methods: Our mixed methods process evaluation was guided by the United Kingdom Medical Research Council guidelines for complex interventions. Meeting attendance reports, as well as blood pressure and weight measures of attendees and adherence to meeting content and use of meeting tools were used to evaluate the implementation process. Thematic analysis of separate focus group discussions with participants and ASHAs as well as meeting reports and participant evaluation were used to investigate the mechanisms of impact.Results: Fifteen ASHAs led 32 community-based groups in three rural settings in the states of Kerala and Andhra Pradesh, Southern India. Overall, the fidelity of intervention delivery was high. Six meetings were delivered over a 3-month period to each of the intervention groups. The mean number of meetings attended by participants at each site varied significantly, with participants in Rishi Valley attending fewer meetings [mean (SD) = 2.83 (1.68)] than participants in West Godavari (Tukeys test, p = 0.009) and Trivandrum (Tukeys test, p < 0.001) and participants in West Godavari [mean (SD) = 3.48 (1.72)] attending significantly fewer meetings than participants in Trivandrum [mean (SD) = 4.29 (1.76), Tukeys test, p < 0.001]. Culturally appropriate intervention resources and the training of ASHAs, and supportive supervision of them during the program were critical enablers to program implementation. Although highly motivated during the implementation of the program ASHA reported historical issues with timely remuneration and lack of supportive supervision.Conclusions: Culturally appropriate community-based group programs run by trained and supported ASHAs are a successful and potentially scalable model for improving the control of hypertension in rural India. However, consideration of issues related to unreliable/insufficient remuneration for ASHAs, supportive supervision and their formal role in the wider health workforce in India will be important to address in future program scale up.Trial Registration: Clinical Trial Registry of India [CTRI/2016/02/006678, Registered prospectively].

Aims: To correlate the waist-to-height ratio (WHt-R) with Matsuda index of the Oral Glucose Tolerance Test (OGTT) and other surrogate indices of fasting insulin resistance/sensitivity and to derive a cut-off value for the WHt-R in lean, normoglycaemic males from Southern India. Methods: A cohort of 105 lean, normoglycaemic males (mean BMI: 19.2 ± 2.6 kg/m2) underwent OGTT. Surrogate indices of insulin resistance viz, the Homeostatic model assessment of Insulin Resistance (HOMA-IR), the Quantitative Insulin sensitivity Check Index (QUICKI), the Fasting glucose to insulin ratio (FG-IR), the McAuley's index and the Triglyceride/HDL-C ratio were correlated with the Matsuda and the Insulinogenic indices. The cut-off value for WHt-R to predict insulin resistance was obtained using Receiver operating characteristics (ROC) with Area under curve (AUC) at 95% confidence interval (CI). The P value

# Background Diabetes mellitus (DM) is a global public health concern, with significant increase in the transitioning low- and middle-income countries (LMICs), such as India, with limited resources and poor health care systems. Recognising the need for innovative, feasible, targeted interventions for diabetes care, a non-randomized, controlled, phase II clinical trial was conducted in a rural revenue block in Tamil Nadu, India. This pilot trial tested the non-inferiority of the trained community health workers (CHWs) in delivering education, screening for diabetes complications using a protocol-based referral for physician consultation for management, assisted by an android application (App) for patient tracking. Understanding the perceptions of key stakeholders including patients and health workers is crucial for upscaling and sustaining these novel interventions for diabetes care. This study explored the perspectives and views of patients with DM and diabetes CHWs who participated in the pilot trial. # Methods Using qualitative research methodology, individual in-depth interviews were conducted in the local vernacular (Tamil) language among the two diabetes CHWs and purposively chosen 24 patients until the data saturation was reached. Participant information sheets, consent forms and a detailed topic guide were developed. Interviews were transcribed verbatim, translated into English and thematic analysis was conducted. # Results Five main themes emerged during interviews with diabetes CHWs: deeper understanding of the disease; belonging and strengthening; ease of use of digital technology and a timesaver for patient tracking; cultural sensitivity; stigma and change in attitudes over time. Interviews with patients highlighted four major themes: convenience; cost reduction; improved knowledge and perceptions on health. Benefits were perceived by both patients and diabetes CHWs, in the domains of convenience, access, cost and knowledge. Perceptions of changes in health were mixed with room for improvement in the digital App. # Conclusions Training CHWs in resource limited settings in supporting community diabetes care, assisted by digital technology for tracking is acceptable to the patients and will help shift the care pathway for Diabetes closer to the patients in a rural setting. This qualitative study identified a number of areas for improvement and potential barriers that will need to be addressed prior to scaling up in similar resource constrained settings.

Hypersensitivity reactions against exogenous insulin are a rare clinical entity after the advent of recombinant human insulin; however, there are still case reports wherein patients develop hypersensitivity reactions against insulin. We present the case of a type 1 diabetes mellitus patient who developed type 1 hypersensitivity reaction against subcutaneous insulin. He had recurrent episodes of diabetic ketoacidosis after developing hypersensitivity reactions against insulin, requiring multiple hospital admissions. When he presented to us, he was on both insulin infusion and subcutaneous insulin, requiring a daily insulin dose of about 800 units and having severe insulin hypersensitivity reactions and hyperglycemia. He had multiple subcutaneous erythematous nodules at the insulin injection sites, however, had no evidence of systemic allergy. Investigations revealed eosinophilic leukocytosis, and high IgE levels and skin biopsy showing evidence of insulin hypersensitivity. He was desensitized to insulin according to Heinzerling et al. insulin desensitization protocol and subsequently with immunomodulation therapy using steroids (pulse methylprednisolone) and mycophenolate mofetil as well as by installation of insulin pump.

Nelson’s syndrome is an infrequent pituitary mass with an incidence of 8–43% in adults and 25–66% in children that develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s disease. It is one of the most challenging of all endocrine conditions. The frequent aggressiveness of the underlying ACTH-secreting pituitary adenoma (corticotrophinoma) necessitates regular biochemical and radiological screening. Current evidence favours a lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in the year post TBA as factors that may predict the occurrence of Nelson’s syndrome. Though, computerized tomography (CT)/magnetic resonance imaging (MRI) have led to the early diagnosis and improvement in management. Nelson’s related tumours are sometimes detected late, through clinical manifestations of invasion and compression of the surrounding structures. With this perspective in mind, we describe a 22 year old gentleman 10 years after TBA who presented with right sided hemiparesis due to a corticotroph adenoma.

Objectives: The objective was to compare body composition, metabolic characteristics, and insulin resistance between obese (body mass index [BMI] ≥25 kg/m2) polycystic ovary syndrome (PCOS) and nonobese PCOS (BMI

# Background The epidemic of type 2 diabetes mellitus is growing at large globally, more so in Low- and Middle-Income Countries (LMIC) like India, who concurrently battles the burden of infectious diseases. In such a health setting, people with diabetes (PWD) often receive sub-optimal care due to lack of understanding, physician-patient time, social support, and financial resources. Thus, there is a need for innovative, feasible, targeted interventions that strengthen health system to reduce the impact of diabetes in the rural communities in India. We hypothesised that structured interventions delivered by trained community health workers (CHWs) would improve outcomes in PWD and sought to demonstrate non-inferiority compared to standard care. # Methods A phase II, non-randomized, controlled clinical trial was conducted in a rural block in Tamil Nadu, India. Two sub-center areas (cluster) each were allocated to the control and intervention arms, with 50 participants in each cluster. The control group received standard care routinely provided and the intervention group received interventions namely – CHW delivered, Engage communities, Screen, Examine, Refer and Follow up with the aid of ‘education tools’ and a ‘tablet based SmartHealth Application for follow-up’. Non-inferiority of the intervention in terms of early case detection, reduction in number of unnecessary physician consultations and glycaemic control was demonstrated using generalized estimating equation (GEE) for repeated measures with exchangeable correlation structure, adjusting for age, duration of diabetes and family history of diabetes. # Results Baseline characteristics of both groups were comparable. CHWs were successfully able to Engage, Screen, Examine, Refer and Follow-up patients in the community. The multipronged interventions delivered by CHWs were demonstrated to be non-inferior to standard care, with significant difference in case detection rate (P=0.003), early recognition of complications, reduction in unnecessary physician consultations (P=0.041) and better glycaemic control (P=0.036). # Conclusions The study has shown promising results in the limited sample size and a small geographic area and has been able to show that the task shifting to frontline community health workers for diabetes care works in this rural population. We recommend a scale up of the intervention by conducting a multicentric randomized controlled trial including cost-effectiveness analysis and taking into account stakeholders’ opinions regarding this model of diabetes care.

Summary: Background: Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods: We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings: Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40·0% (95% uncertainty interval [UI] 39·4–40·7) to 50·3% (50·0–50·5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46·3% (95% UI 46·1–46·5) in 2017, compared with 28·7% (28·5–29·0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Funding: Bill & Melinda Gates Foundation.

Summary: Background: Lymphatic filariasis is a neglected tropical disease that can cause permanent disability through disruption of the lymphatic system. This disease is caused by parasitic filarial worms that are transmitted by mosquitos. Mass drug administration (MDA) of antihelmintics is recommended by WHO to eliminate lymphatic filariasis as a public health problem. This study aims to produce the first geospatial estimates of the global prevalence of lymphatic filariasis infection over time, to quantify progress towards elimination, and to identify geographical variation in distribution of infection. Methods: A global dataset of georeferenced surveyed locations was used to model annual 2000–18 lymphatic filariasis prevalence for 73 current or previously endemic countries. We applied Bayesian model-based geostatistics and time series methods to generate spatially continuous estimates of global all-age 2000–18 prevalence of lymphatic filariasis infection mapped at a resolution of 5 km2 and aggregated to estimate total number of individuals infected. Findings: We used 14 927 datapoints to fit the geospatial models. An estimated 199 million total individuals (95% uncertainty interval 174–234 million) worldwide were infected with lymphatic filariasis in 2000, with totals for WHO regions ranging from 3·1 million (1·6–5·7 million) in the region of the Americas to 107 million (91–134 million) in the South-East Asia region. By 2018, an estimated 51 million individuals (43–63 million) were infected. Broad declines in prevalence are observed globally, but focal areas in Africa and southeast Asia remain less likely to have attained infection prevalence thresholds proposed to achieve local elimination. Interpretation: Although the prevalence of lymphatic filariasis infection has declined since 2000, MDA is still necessary across large populations in Africa and Asia. Our mapped estimates can be used to identify areas where the probability of meeting infection thresholds is low, and when coupled with large uncertainty in the predictions, indicate additional data collection or intervention might be warranted before MDA programmes cease. Funding: Bill & Melinda Gates Foundation.

Summary: Background: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. Methods: We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000–17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. Findings: While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000–7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910–68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. Interpretation: To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. Funding: Bill & Melinda Gates Foundation.

Background Various indicators of socioeconomic position (SEP) may have opposing effects on the risk of hypertension in disadvantaged settings. For example, high income may reflect sedentary employment, whereas greater education may promote healthy lifestyle choices. We assessed whether education modifies the association between income and hypertension in 3 regions of South India at different stages of epidemiological transition. Methods and Results Using a cross‐sectional design, we randomly selected villages within each of rural Trivandrum, West Godavari, and Rishi Valley. Sampling was stratified by age group and sex. We measured blood pressure and anthropometry and administered a questionnaire to identify lifestyle factors and SEP, including education, literacy, and income. Logistic regression was used to assess associations between various components of SEP and hypertension, and interaction analyses were used to determine whether educational attainment modified the association between income and hypertension. Trivandrum, the region of highest SEP, had the greatest prevalence of hypertension, whereas Rishi Valley, the lowest SEP region, had the least. Overall, greater income was associated with greater risk of hypertension. In interaction analyses, there was no evidence that educational attainment modified the association between income and hypertension. Conclusions Education is widely considered to ameliorate the risk of hypertension in high‐income countries. Why this effect is absent in rural India merits investigation.

Obesity indicators are known to predict the presence of type 2 diabetes mellitus (T2DM); however, evidence for which indicator best identifies undiagnosed T2DM in the Indian population is still very limited. In the present study we examined the utility of different obesity indicators to identify the presence of undiagnosed T2DM and determined their appropriate cut point for each obesity measure. Individuals were recruited from the large-scale population-based Kerala Diabetes Prevention Program. Oral glucose tolerance tests was performed to diagnose T2DM. Receiver operating characteristic (ROC) curve analyses were used to compare the association of different obesity indicators with T2DM and to determine the optimal cut points for identifying T2DM. A total of 357 new cases of T2DM and 1352 individuals without diabetes were identified. The mean age of the study participants was 46⋅4 (sd 7⋅4) years and 62 % were men. Waist circumference (WC), waist:hip ratio (WHR), waist:height ratio (WHtR), BMI, body fat percentage and fat per square of height were found to be significantly higher (P < 0⋅001) among those with diabetes compared with individuals without diabetes. In addition, ROC for WHR (0⋅67; 95 % 0⋅59, 0⋅75), WHtR (0⋅66; 95 % 0⋅57, 0⋅75) and WC (0⋅64; 95 % 0⋅55, 0⋅73) were shown to better identify patients with T2DM. The proposed cut points with an optimal sensitivity and specificity for WHR, WHtR and WC were 0⋅96, 0⋅56 and 86 cm for men and 0⋅88, 0⋅54 and 83 cm for women, respectively. The present study has shown that WHR, WHtR and WC are better than other anthropometric measures for detecting T2DM in the Indian population. Their utility in clinical practice may better stratify at-risk patients in this population than BMI, which is widely used at present.

BACKGROUND:New methods are required to manage hypertension in resource-poor settings. We hypothesised that a community health worker (CHW)-led group-based education and monitoring intervention would improve control of blood pressure (BP). METHODS AND FINDINGS:We conducted a baseline community-based survey followed by a cluster randomised controlled trial of people with hypertension in 3 rural regions of South India, each at differing stages of epidemiological transition. Participants with hypertension, defined as BP ≥ 140/90 mm Hg or taking antihypertensive medication, were advised to visit a doctor. In each region, villages were randomly assigned to intervention or usual care (UC) in a 1:2 ratio. In intervention clusters, trained CHWs delivered a group-based intervention to people with hypertension. The program, conducted fortnightly for 3 months, included monitoring of BP, education about hypertension, and support for healthy lifestyle change. Outcomes were assessed approximately 2 months after completion of the intervention. The primary outcome was control of BP (BP < 140/90 mm Hg), analysed using mixed effects regression, clustered by village within region and adjusted for baseline control of hypertension (using intention-to-treat principles). Of 2,382 potentially eligible people, 637 from 5 intervention clusters and 1,097 from 10 UC clusters were recruited between November 2015 and April 2016, with follow-up occurring in 459 in the intervention group and 1,012 in UC. Mean age was 56.9 years (SD 13.7). Baseline BP was similar between groups. Control of BP improved from baseline to follow-up more in the intervention group (from 227 [49.5%] to 320 [69.7%] individuals) than in the UC group (from 528 [52.2%] to 624 [61.7%] individuals) (odds ratio [OR] 1.6, 95% CI 1.2-2.1; P = 0.001). In secondary outcome analyses, there was a greater decline in systolic BP in the intervention than UC group (-5.0 mm Hg, 95% CI -7.1 to -3.0; P < 0.001) and a greater decline in diastolic BP (-2.1 mm Hg, 95% CI -3.6 to -0.6; P < 0.006), but no detectable difference in the use of BP-lowering medications between groups (OR 1.2, 95% CI 0.8-1.9; P = 0.34). Similar results were found when using imputation analyses that included those lost to follow-up. Limitations include a relatively short follow-up period and use of outcome assessors who were not blinded to the group allocation. CONCLUSIONS:While the durability of the effect is uncertain, this trial provides evidence that a low-cost program using CHWs to deliver an education and monitoring intervention is effective in controlling BP and is potentially scalable in resource-poor settings globally. TRIAL REGISTRATION:The trial was registered with the Clinical Trials Registry-India (CTRI/2016/02/006678).

BACKGROUND:Diabetes triples the risk of developing tuberculosis (TB). This study was designed to determine the prevalence of past and current TB disease and Latent TB infection (LTBI) in type 2 Diabetes Mellitus (NIDDM) patients. DESIGN:This was a prospective descriptive study on all NIDDM patients attending a Diabetic clinic. Detailed history, included details of previous history of TB (Past TB)and symptoms of active TB and a thorough physical exam was also done. When clinical suspicion of TB was present, appropriate investigations were carried out to diagnose 'Current TB'. Subsequently, 200 consecutive patients who were negative for Past and Current TB were screened for Latent TB infection (LTBI) by tuberculin skin test. RESULTS:Of 1000 NIDDM patients enrolled, 43(4.3%) had Past TB. Of remaining 957 patients, 50 were evaluated for New TB on the basis of suggestive symptoms and 10(1%) patients were confirmed to have Current TB. Risk factors for Past or Current TB 'DM-TB' in comparison with 'DM Only' group were; male sex (72% VS 57%; P = 0.033), manual laborer (28% VS 15%; P = 0.012), smoking (26% VS 14%; P = 0.015), alcohol consumption (23% VS 9%; P

BackgroundCardiometabolic disorders are frequently observed among those who have obesity as measured by body mass index (BMI). However, there is limited data available on the cardiometabolic profile of those who are non-obese by BMI but with a high body fat percentage (BFP), a phenotype frequently observed in the Indian population. We examined the prevalence of individuals with normal weight obesity (NWO) and the cardiometabolic profile of NWO individuals at high risk for type 2 diabetes(T2D) in a south Asian population.Material and methodsIn the Kerala Diabetes Prevention Program, individuals aged between 30 to 60 years were screened using the Indian Diabetes Risk Score(IDRS) in 60 rural communities in the Indian state of Kerala. We used data from the baseline survey of this trial for this analysis which included 1147 eligible high diabetes risk individuals(IDRS >60). NWO was defined as BMI within the normal range and a high BFP (as per Asia-pacific ethnicity based cut-off); Non-obese (NO) as normal BMI and BFP and overtly obese (OB) as BMI ≥25 kg/m2 irrespective of the BFP. Data on demographic, clinical and biochemical characteristics were collected using standardized questionnaires and protocols. Body fat percentage was assessed using TANITA body composition analyser (model SC330), based on bioelectrical impedance.ResultsThe mean age of participants was 47.3 ± 7.5 years and 46% were women. The proportion with NWO was 32% (n = 364; 95% CI: 29.1 to 34.5%), NO was 17% (n = 200) and OB was 51% (n = 583). Among those with NWO, 19.7% had T2D, compared to 18.7% of those who were OB (p value = 0.45) and 8% with NO (p value = 0.003). Among those with NWO, mean systolic and diastolic blood pressure were 129 ± 20; 78 ± 12 mmHg, compared to 127 ± 17; 78±11 mmHg among those with OB (p value = 0.12;0.94) and 120 ± 16; 71±10 mmHg among with NO (p valueConclusionsAlmost one-third of this South Asian population, at high risk for T2D, had normal weight obesity. The significantly higher cardiometabolic risk associated with increased adiposity even in lower BMI individuals has important implications for recognition in clinical practice.

BackgroundLower serum 25-hydroxyvitamin D [25(OH)D] is associated with greater adiposity and adverse cardiometabolic risk profile. The evidence is inconsistent among South Asian Indians. We aimed to examine associations between 25(OH)D and cardiovascular (CVD) risk markers in a rural and urban cohort from South India.Subjects/methodsIn this cross sectional study, 373 individuals (men, n = 205) underwent detailed CVD risk marker assessment including anthropometry [body mass index (BMI), waist, (WC) and hip circumferences (HC)], body composition analysis using dual energy x-ray absorptiometry (DXA), blood pressure and biochemical analysis (glucose, insulin and lipids). The distribution of CVD risk factors were compared across serum 25(OH)D levels, stratified as deficiency (ResultsThe mean and standard deviation (SD) of age, BMI and 25(OH)D levels were 41.4 (1.1) years, 25.5 (4.8) kg/m2 and 23.4 (10.4) ng/ml respectively. The prevalence of 25(OH)D deficiency was 39.9% in this cohort. Individuals in the 25(OH)D deficiency category had significantly higher mean (SD) BMI [26.6 (5.1) kg/m2], waist circumference [89.9 (12.5) cm] and total fat mass [20.6 (7.9) kg] compared with the Vitamin D sufficient group [BMI: 24.0 (4.4); WC 84.7 (12.0); total fat mass: 15.2 (6.8)]. Significantly inverse associations were observed with DXA measured total and regional fat depots with 25(OH)D levels, while anthropometric indices of adiposity showed significant inverse association only in women. After adjusting for total fat mass, no significant associations were observed between 25(OH)D and the cardiometabolic traits.ConclusionsOur results confirm that lower 25(OH)D is independently associated with both total and regional adiposity, but not with cardiometabolic traits, in this population.

Context: The size and morphology of the adrenal glands are affected by several physiological and pathological conditions. Radiologists need to be aware of the normal thickness of adrenal gland to accurately assess patients with suspected adrenal pathology. However, there is limited data on the normal size of the adrenal glands. Moreover, this has not been studied in our population. Aims: To study the normal thickness of adrenal gland on computerized tomography (CT) in Indian adult population. Settings and Design: Retrospective study in a tertiary care hospital in Southern India. Subjects and Methods: Our study included 586 adults who underwent a CT abdominal angiogram over 15 months, and excluding patients with clinical or imaging evidence of adrenal disease. The measurements made included: the maximum thickness of the body, medial and lateral limbs, measured perpendicular to the long axis. Results: The median age was 51 (range: 18–85) years. The mean maximum thickness of the adrenal body, medial, and lateral limbs were 7.2 ± 1.8, 4.1 ± 1.1, and 4.3 ± 1.1 mm on the right side and 8.8 ± 1.9, 4.7 ± 1.1, and 4.9 ± 1.3 mm on the left. The cumulative thickness of the body and the limbs were 15.6 ± 3.7 mm and 18.4 ± 3.8 mm on the right and left sides, respectively. There was a statistically significant difference in all the measurements between the right and left adrenal glands (all P values = 0.000) and between men and women, being larger in men (P value

Abstract Background Hypertension is a major risk factor for cardiovascular disease, a leading cause of premature death and disability in India. Since access to health services is poor in rural India and Accredited Social Health Activists (ASHAs) are available throughout India for maternal and child health, a potential solution for improving hypertension control is by utilising this available workforce. We aimed to develop and implement a training package for ASHAs to identify and control hypertension in the community, and evaluate the effectiveness of the training program using the Kirkpatrick Evaluation Model. Methods The training program was part of a cluster randomised feasibility trial of a 3-month intervention to improve hypertension outcomes in South India. Training materials incorporated details on managing hypertension, goal setting, facilitating group meetings, and how to measure blood pressure and weight. The 15 ASHAs attended a five-day training workshop that was delivered using interactive instructional strategies. ASHAs then led community-based education support groups for 3 months. Training was evaluated using Kirkpatrick’s evaluation model for measuring reactions, learning, behaviour and results using tests on knowledge at baseline, post-training and post-intervention, observation of performance during meetings and post-intervention interviews. Results The ASHAs’ knowledge of hypertension improved from a mean score of 64% at baseline to 76% post-training and 84% after the 3-month intervention. Research officers, who observed the community meetings, reported that ASHAs delivered the self-management content effectively without additional assistance. The ASHAs reported that the training materials were easy to understand and useful in educating community members. Conclusion ASHAs can be trained to lead community-based group educational discussions and support individuals for the management of high blood pressure. Trial Registration The feasibility trial is registered with the Clinical Trials Registry - India (CTRI) CTRI/2016/02/006678 (25/02/2016).

Background and Objectives: Currently available DXA (Dual energy X-ray Absorptiometry) scanners utilise bone mineral density (BMD) of Caucasian population to calculate T scores and categorise BMD. We studied the influence of various databases on classification of BMD in south-Indian postmenopausal women aged above 50 years. Methodology: This was a cross-sectional study. Hologic DXA scanner was used to estimate BMD at lumbar spine (LS) and femoral neck (FN). T scores of ≤-2.5, -2.4 to -1, -0.9 to +1 were diagnostic of osteoporosis, osteopenia and normal respectively. Three reference databases(Italian, Korean and north Indian) were used to recalculate T scores. The agreement (K=kappa) between manufacturer provided database and the other databases was studied. The impact of different databases in diagnosing osteoporosis in subjects with FN fracture was assessed. Results: A total of 1956 postmenopausal women with mean (SD) age of 62 (4.3) years and 211 femoral neck(FN) fracture subjects with mean(SD) age of 68 (7.2) years were recruited. In subjects with fracture, osteoporosis at FN was found in 72% with Caucasian, 88% with North Indian, 56% with Italian, and 45% with Korean database. On comparing manufacturer provided database with the other population-specific reference, there was perfect agreement with north Indian (κ = 0.81 [FN], κ = 0.82 [LS]) and good agreement with the Italian database (κ = 0.78 [FN], κ = 0.74 [LS]). Conclusion: North-Indian database identified most of the participants with FN fracture as having osteoporosis and had perfect agreement with the manufacturer's database. Follow up studies will further validate the impact of utilizing this database in clinical practice.

Background: Paget's disease of bone (PDB) is uncommonly reported from India. We attempted to study the clinical and imaging features and management of participants who presented with PDB. Materials and Methods: In this retrospective study, clinical and imaging profile, biochemistry, and treatment outcomes of participants with PDB (n = 48) were obtained. Results: The mean age was 60 ± 11.3 years and 35% were women. Twenty percent were asymptomatic. Many (87%) had polyostotic involvement. Sixty percent (n = 29) underwent treatment with zoledronic acid and rest with oral bisphosphonates, and all achieved remission. Conclusion: Most of the pagetic participants had polyostotic disease and one-fifth were asymptomatic. All participants had disease remission following treatment.

Aims and Objectives: The aim of the study is to examine the adequacy and accuracy of ultrasound-guided fine-needle aspiration cytology (US-FNAC) in thyroid nodules ≥1 cm and to analyze the clinical, sonological, and cytological features in predicting thyroid malignancy. Materials and Methods: US-FNAC was done on 290 patients from December 2013 to December 2014 by the radiologist. The Thyroid Imaging Reporting and Data System (TIRADS) was used to record the sonological features. FNAC samples were reported by a dedicated cytopathologist. Accuracy was calculated by comparing US-FNAC, clinical features and ultrasound (US) features for those who had final histopathology till April 2017. Results: The adequacy of US-FNAC in this study was 80.2%. Thyroidectomy was performed in 128/290 (44.1%). The sensitivity and specificity of US-FNAC in this study is 83.9 and 76.3%, respectively, with a positive predictive value of 85.2%, negative predictive value of 74.4%, and an accuracy of 81% in predicting malignancy in thyroid nodules ≥1 cm. The malignancy rate in benign FNAC sample was 25% (10/40), and was 69% (8/13) in those with a follicular lesion of undetermined significance (FLUS). Around 80% of benign and 89% of FLUS had follicular variant of papillary carcinoma of thyroid (FVPTC). US-FNAC, a high TIRADS score, and US features such as marked hypoechogenicity, taller than wide, irregular margins, microcalcification, and clinical features, such as hard in consistency and significant cervical lymph nodes, were important in predicting malignancy (P < 0.001). Conclusions: The accuracy of US-FNAC in this study is 81%. The US-FNAC, a high TIRADS score, a hard thyroid nodule, and significant cervical lymph nodes are important in predicting malignancy. The accuracy rate in benign and atypia undetermined significance categories needs to improve in this study. Further research to help in decreasing false negative rates of FVPTC will help in increasing the accuracy of US-FNAC in the present study.

Objective: Analysis of BRAF V600E mutation in thyroid fine needle aspirates (FNA) is an important adjunct to cytology, particularly among FNA placed in the “indeterminate category.” However, such a prospective evaluation of FNA obtained from patients with thyroid nodules has been lacking from India. Material and Methods: FNA from 277 patients were prospectively evaluated for BRAF mutations by Sanger's sequencing. A subset of 30 samples was also analyzed by pyrosequencing using the PyroMark BRAF mutation kit. Results: Overall, 27.2% of FNA samples were positive for mutations including 19 (35.8%) of the 53 histologically confirmed papillary thyroid carcinoma (PTC), 2 of the 25 follicular variants of PTC, and 1 anaplastic thyroid carcinoma. Only 1 (2.7%) of the 37 samples in the atypia of undetermined significance/follicular lesion of unknown significance category was BRAF positive. The sensitivity of cytology improved marginally from 67.1% to 68.3% when evaluated with BRAF. Further, a comparison of the clinicopathological characteristics of BRAF positive and negative PTCs showed a significant association (P = 0.05) between lymph node metastasis and BRAF positivity. Conclusion: BRAF positivity was lower than that reported from East Asia with the test being useful in confirming malignancies among the suspicious of malignancy and malignant categories.

Background: Obesity is sweeping across continents and is a major public health concern of the modern society. Aims: The main objective of this study was to study the demographic, anthropometric and dietary patterns of the morbidly obese and study region wise variation in their nutrient intake. Materials and Methods: The study was conducted on 101 morbidly obese individuals from different regions of India who attended the Bariatric clinic of a tertiary care hospital in India. Their socio-demographic details, anthropometric measurements were collected. The dietary assessment was done using a 24 hour dietary recall and a food frequency questionnaire. The study was approved by the Institutional review board and informed consent was obtained from them. Results: More than 3/4th of the patients were females and 61 per cent had Type 2 diabetes mellitus. The mean age of the male and female population was 41.3 + 15.5 years and 36.7 + 11.9 years respectively. Their mean BMI was 41kg/m2. The mean daily intake of calories was more than 2200kcal/day with a gross deficit in the intake of micronutrients. Bonferroni Test showed that there was region wise variation in dietary intake, South Indian female population had the lowest intake of the micronutrients and those from East India had the highest intake. In the male population, there was a significant regional difference in intake of Proteins (p=0.039) and Energy (p=0.024). Independent Sample T test showed that South Indian had the highest intake of Energy and proteins. Anthropometric measures showed positive relation with various macronutrient intakes. Conclusion: The obese patients require intense counselling by a dedicated team of an endocrinologist, psychiatrist, dietician, bariatric surgeon and a social worker to make achievable changes in the quality of life of the morbidly obese patients. Regional influences must be considered when counselling the patient.