Association between serum osteocalcin and atherosclerosis in Type-2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The past few decades have seen a marked increase in the macrovascular complications of Type-2 diabetes mellitus (T2DM) such as coronary heart disease, peripheral arterial disease, and cerebrovascular disease. This has been predominantly attributed to the increased atherosclerosis in these patients. Atherosclerosis usually remains an asymptomatic condition and this poses a significant challenge in its early diagnosis and timely intervention. Hence, there is an immediate need for exploring novel tools to aid in the early detection of atherosclerosis, especially in T2DM patients. Osteocalcin (OC), synthesized by osteoblasts, is a protein hormone found in the skeletal system. This protein is considered as a marker for bone density and in recent times has been gaining interest due to its protective role in cerebrovascular diseases(CVD). METHODS: We conducted a cross-sectional study and evaluated the association between serum OC levels and atherosclerosis in 113 T2DM patients. Carotid intima-media thickness (CC-IMT) was used as an estimate of atherosclerosis and patients were divided into two groups (CC-IMT < 0.9 and ≥ 0.9). Correlation of serum OC levels and glycemic parameters and lipid profiles were studied and compared between both groups. RESULTS: There is a significant negative correlation between the CC-IMT estimates and serum OC levels. CC-IMT also has a significant association with other biochemical parameters such as fasting blood sugar, glycated hemoglobin and high-density lipoprotein. CONCLUSION: Although the independent association of serum OC could not be established in the T2DM patient population, overall, the results favor low serum OC as a prognostic marker for atherosclerosis.

Unveiling the masked native blood group following thalidomide therapy in a thalassemia patient: A 5 WHY analysis approach.

Blood grouping discrepancy in patients with hematological disorders can occur due to red cell sensitization following transfusion, transplantation, and pregnancy or pre-analytical errors. Prompt initiation of root cause analysis is vital to avoid complications of wrong blood transfusion. We present an unusual case of Rh mismatched grouping report of 24 year old female thalassemia patient being managed in our hospital since 2015. Her current type and screen were observed as O Rh D negative with negative antibody screen while the historical blood group was O Rh D positive. The pre-analytical errors were ruled out and blood grouping performed from fresh sample also demonstrated as O Rh D negative despite antigen enhancement techniques and had no recent transfusion history. We sought to reason out the possibilities for discordant Rh grouping report, historical and present group through "Funnel based problem solving 5 WHY analysis" approach. The review of the past clinical history revealed that the patient had undergone Rh mismatch bone marrow transplant (Rh D positive donor and Rh D negative recipient) at 5 years of age which soon resulted in graft failure. Yet, she continued to receive Rh D positive blood thereafter with no development of anti-D which explains the historical blood group. Recently the patient was started on thalidomide, the Hb F inducer drug, which helped in maintaining her hemoglobin level between 9 and 10 g/dl without transfusion support for two months. This allowed unmasking of native Rh D negative blood and the review of clinical history played a significant role in resolution of grouping discrepancy.

Clinical research training and capacity building for prevention and control of non-communicable diseases: A programme in India.

BACKGROUND.: Non-communicable diseases (NCDs)-a term which includes diabetes, cardiovascular disease, cancers, chronic respiratory diseases, and mental illness-are now the major cause of death in India and pose healthcare and economic challenges. There is an urgent need for enhanced clinical research training and capacity building for NCD prevention and control in India. METHODS.: We describe a multi-pronged approach funded in part by the US National Institutes of Health Fogarty International Center, which was initiated in 2001, to train Indian present and future scientists/doctors in NCD prevention and control. The approaches used were annual national seminars, intensive training courses, in-house workshops, short-term training sessions in the USA and monthly video conferences. RESULTS.: During 2001-2016, a total of 3650 undergraduate, postgraduate and faculty from medical colleges and institutes from almost all states in India and several neighbouring countries participated in seminars and other capacity-building workshops held at the Madras Diabetes Research Foundation, Chennai and at six other medical colleges; 883 delegates participated in the in-house workshops, 463 in the intensive interactive sessions; 244 in workshops on advanced techniques in genomics; and 37 in short-term training sessions held in the USA. CONCLUSION.: Through this unique capacity-building programme, more than 5000 individuals representing faculty and students from various medical colleges and research institutes across, and beyond, India, underwent training in the prevention and control of NCDs.

Effectiveness of self-management programmes in diabetes management: A systematic review.

BACKGROUND: Diabetes is a major noncommunicable disease, which is increasing, and approximately 415 million people are affected around the globe. Since diabetes is a lifelong disease, patients require better understanding and knowledge of the condition to become self-reliant in making diabetes-related decisions. AIMS: This systematic review was performed to assess the effectiveness of diabetes self-management programs in people with type 2 diabetes. METHODS: A comprehensive literature search was undertaken to identify all published English language articles through EBSCO discovery services in the following electronic database: Science Direct, CINAHL Plus with Full Text, MEDLINE, and Access Medicine. Studies were published from January 2000 to October 2015. The initial search retrieved 37 566 studies and based on the inclusion criteria, 14 studies were selected for review. RESULTS: Of 14 studies, most findings favoured diabetes self-management. But the overall effectiveness of individual interventions was not conclusive. A wide variety of interventions was used including diabetes education as a major component in self-management programs. CONCLUSION: Interventions used varied strategies in differing composition, and further work is needed to find out the effectiveness of individual interventions.

Surmised total leucocyte counts miscalculate the parasite index of Plasmodium vivax malaria patients of tertiary and primary care settings in South-Western India.

BACKGROUND: For the calculation of parasite index (PI) by microscopy method, an assumed total leucocyte count (TLC) of 8,000/µL is used conventionally. However, due to obvious variation in the population and individual TLCs, use of 8,000/µL may result in either over/underestimation of the PI. METHODS: This study was aimed at ascertaining the utility of 8,000/µL TLC, as well as other assumed TLCs, with respect to measured TLC for the calculation of PI. A tertiary care hospital and five primary health centres were the base for the prospective study conducted among microscopically proven, symptomatic Plasmodium vivax mono-infection patients aged ≥18 years. PIs calculated by assumed TLCs ranging from 4,000-11,000/µL were compared with those calculated by measured TLCs. Geometric mean with 95% confidence interval, Bland-Altman plot and Wilcoxon signed rank test were used for statistical analysis. RESULTS: A total of 284 P. vivax mono-infection patients, including 156 from a tertiary care hospital and 128 from five primary health centres, were recruited in the study. Assumed TLCs below 5,000 cell/µL and above 5,500 cell/µL in tertiary care setting resulted in significant (p <0.05) underestimation and overestimation, respectively. However, in primary health centres, it was an assumed TLC of 5,000 cell/µL, below and above which there was significant (p <0.05) underestimation and overestimation observed, respectively. CONCLUSIONS: Assumed TLC of 8,000/µL is not suitable for the calculation of PI. Either actual TLC of the patient should be measured or a representative TLC should be derived for the population under investigation for any study requiring calculated PI by microscopy.

Therapeutic assessment of chloroquine-primaquine combined regimen in adult cohort of Plasmodium vivax malaria from a tertiary care hospital in southwestern India.

BACKGROUND: Of late there have been accounts of therapeutic failure and chloroquine resistance in Plasmodium vivax malaria especially from Southeast Asian regions. The present study was conducted to assess the therapeutic efficacy of chloroquine-primaquine (CQ-PQ) combined regimen in a cohort of uncomplicated P. vivax mono-infection. METHODS: A tertiary care hospital-based prospective study was conducted among adult cohort with mono-infection P. vivax malaria as per the World Health Organization's protocol of in vivo assessment of anti-malarial therapeutic efficacy. Participants were treated with CQ 25 mg/kg body weight divided over 3 days and PQ 0.25 mg/kg body weight daily for 2 weeks. RESULTS: Of a total of 125 participants recruited, 122 (97.6%) completed day 28 follow up, three (2.4%) participants were lost to follow-up. Eight patients (6.4%) were ascertained to have mixed P. vivax and Plasmodium falciparum infection by nested polymerase chain reaction test. The majority of subjects (56.8%, 71/125) became aparasitaemic on day 2 followed by 35.2% (44/125) on day 3, and 8% (10/125) on day 7, and remained so thereafter. Overall only one therapeutic failure (0.8%, 1/125) occurred on day 3 due to persistence of fever and parasitaemia. CONCLUSIONS: CQ-PQ combined regimen remains outstandingly effective for uncomplicated P. vivax malaria and should be retained as treatment of choice in the study region. One case of treatment failure indicates possible resistance which warrants constant vigilance and periodic surveillance.

Diagnostic validation of selected serological tests for detecting scrub typhus.

Clinical diagnosis of scrub typhus is often difficult because the symptoms are very similar to those of other febrile illness such as dengue, leptospirosis, malaria and other viral hemorrhagic fevers. Though better diagnostic tests are available for rickettsial diseases and scrub typhus elsewhere, the Weil-Felix test is still commonly used in India, mainly because microimmunofluorescence assays (M-IFA) were not available in India till recently and relevant staff had insufficient training. The present study was performed to investigate the performance of M-IFA, IgM ELISA, and Weil-Felix test on 546 non-repeated serum samples from subjects suspected of having scrub typhus. One hundred and forty-three of these 546 samples were positive by M-IFA; these cases were also confirmed clinically to have scrub typhus based on their dramatic responses to doxycycline therapy. IgM ELISA was positive in 122 of the 143 M-IFA positive cases and the Weil-Felix test in 96. Though the Weil-Felix test is a heterophile agglutination test, it was found in this study to have good specificity but far too little sensitivity to use as a routine diagnostic test. IgM ELISA can be a good substitute for M-IFA. Incorporation of multiple prototype antigens on M-IFA slides is likely one of the reasons for its superior performance. As newer and better diagnostic assays become available for scrub typhus diagnosis in developed countries, it will be imperative to also use such tests in other endemic countries to prevent over- or under-diagnosis of scrub typhus.

Awareness of chronic disease related health benefits of physical activity among residents of a rural South Indian region: a cross-sectional study.

BACKGROUND: Physical activity trends for a lower-middle income country like India suggest a gradual decline in work related physical activity and no concomitant increase in leisure time physical activity. Perceived health benefits of physical activity and intention to increase physical activity have been established as independent correlates of physical activity status. In India, not much is known about peoples' perceptions of health benefits of physical activity and their intention to increase physical activity levels. This study was performed to understand peoples' perceptions and awareness about health benefits of physical activity in a rural South Indian region. METHODS: This cross-sectional study was conducted using a multistage cluster sampling design. A content validated, field tested questionnaire was administered in person by a trained interviewer in the participants' native language. The questionnaire assessed the participants' perceptions about their lifestyle (active or sedentary), health benefits of physical activity and need for increasing their physical activity. In addition, the participant's physical activity was assessed using version 2 of global physical activity questionnaire. Frequencies and percentages were used to summarise perceived health benefits of physical activity and other categorical variables. Age and body mass index were summarised using mean ± SD, whereas physical activity (MET.min.wk -1) was summarised using median and interquartile range. RESULTS: Four hundred fifty members from 125 randomly selected households were included in the study, of which 409 members participated. 89% (364) of participants felt they lead an active lifestyle and 83.1% (340) of participants did not feel a need to increase their physical activity level. 86.1%, (352) of the participants were physically active. Though 92.4% (378) of participants felt there were health benefits of physical activity, majority of them (75.1%) did not report any benefit related to chronic diseases. None mentioned health benefits related to heart disease or stroke. CONCLUSION: There is low awareness of chronic disease related benefits of physical activity and participants do not see a need to increase their physical activity level. Public health awareness programs on importance and health benefits of physical activity would be useful to counter the anticipated decline in physical activity.

Osteocalcin and Metabolic Syndrome.

Introduction: Metabolic syndrome which is a syndrome complex that is associated with insulin resistance. Osteocalcin (OC), a bone derived protein has been found to decrease insulin resistance and stimulate production of insulin from the pancreas. Serum osteocalcin levels correlate with body mass index (BMI) and waist circumference. Thus, serum osteocalcin levels in metabolic syndrome could potentially be a new area to explore therapeutically. However, its role in clinical practice needs to be established. Methods: We conducted a cross-sectional study on patients, who visited Kasturba Hospital, Manipal between September 2018 and September 2020, to study the relationship between Serum Osteocalcin and the parameters of metabolic syndrome. All patients above the age of 18 years who satisfied the NCEP-ATP III guidelines (Asian adaptation) for metabolic syndrome were considered for the study. Patients who had thyroid and parathyroid disorders, bone malignancies, osteoporosis, liver failure and renal dysfunction were excluded. Results: A total of 115 subjects were analyzed. As serum osteoclacin increased, there was a significant decrease in fasting blood glucose levels (r = -.748, P < .05) and a significant increase in serum HDL levels (r = .617, P < .01). There was no correlation found between serum osteocalcin and BMI/waist circumference in this study. Finally, it was observed that individuals with fewer components of metabolic syndrome had a significantly higher serum osteocalcin when compared with individuals with a higher number of components of metabolic syndrome (P < .01). Conclusion: This data further confirmed the association between serum OC and parameters of metabolic syndrome such as FBS and serum HDL. It also found that increased serum OC was associated with fewer components of the metabolic syndrome indicating that OC could have a positive metabolic impact and may prevent atherosclerotic risk.

Design of dual hormone blood glucose therapy and comparison with single hormone using MPC algorithm.

The complete automated control and delivery of insulin and glucagon in type 1 diabetes is the developing technology for artificial pancreas. This improves the quality of life of a diabetic patient with the precise infusion. The amount of infusion of these hormones is controlled using a control algorithm, which has the prediction property. The control algorithm model predictive control (MPC) predicts one step ahead and infuses the hormones continuously according to the necessity for the regulation of blood glucose. In this research, the authors propose a MPC control algorithm, which is novel for a dual hormone infusion, for a mathematical model such as Sorenson model, and compare it with the insulin alone or single hormone infusion developed with MPC. Since they aim for complete automatic control and regulation, unmeasured disturbances at a random time are integrated and the performance evaluation is projected through statistical analysis. The blood glucose risk index (BGRI) and control variability grid analysis (CVGA) plot gives the additional evaluation for the comparative results of the two controllers claiming 88% performance by dual hormone evaluated through CVGA plot and 2.05 mg/dl average tracking error, 2.20 BGRI. The MPC developed for dual hormone significantly performs better and the time spent in normal glycaemia is longer while eliminating the risk of hyperglycaemia and hypoglycaemia.

Blood glucose regulation and control of insulin and glucagon infusion using single model predictive control for type 1 diabetes mellitus.

This study elaborates on the design of artificial pancreas using model predictive control algorithm for a comprehensive physiological model such as the Sorensen model, which regulates the blood glucose and can have a longer control time in normal glycaemic region. The main objective of the proposed algorithm is to eliminate the risk of hyper and hypoglycaemia and have a precise infusion of hormones: insulin and glucagon. A single model predictive controller is developed to control the bihormones, insulin, and glucagon for such a development unmeasured disturbance is considered for a random time. The simulation result for the proposed algorithm performed good regulation lowering the hypoglycaemia risk and maintaining the glucose level within the normal glycaemic range. To validate the performance of the tracking of output and setpoint, average tracking error is used and 4.4 mg/dl results are obtained while compared with standard value (14.3 mg/dl).

Oral melatonin improves the detection of parasitemia in malaria.

INTRODUCTION: Malaria is a growing global threat and a major cause of mortality in the tropics. The gold standard diagnosis is peripheral blood smear examination. It has been demonstrated that melatonin acts as messenger molecule in malaria pathophysiology. This concept was used to evolve a clinical study wherein use of exogenous melatonin could improve the chance of detection of the parasite. METHODOLOGY: In a prospective study, 80 consecutive patients seen in the Department of Medicine at Kasturba Hospital, Manipal, suspected to have malarial fever were enrolled with proper informed consent, and randomly assigned to the groups given oral melatonin 3mg (melatonin group, n = 40) or placebo (control group, n = 40). Blood samples were collected for peripheral smear examination at baseline and then at two, three, four and five hours after drug administration. The primary end point was the parasite detection index. RESULTS: Baseline characteristics of patients were comparable. In the melatonin group, there was a significant increase of 0.0943 ± 0.22 in the mean parasite index from 0.217 ± 0.42 pre-melatonin to 0.3114 ± 0.5 post-melatonin (p = 0.001), compared to a difference of 0.0025 ± 0.22 in mean parasite index before and after placebo in the control group (p = 0.95). The maximum rise in parasite detection was seen at five hours after melatonin. CONCLUSIONS: In a single centre study, for the first time, it has been shown that a significantly higher proportion of patients was diagnosed with malaria on peripheral smear after oral melatonin administration, maximal at five hours after administration of melatonin.

Predictive performance of traditional and novel lipid combined anthropometric indices to identify prediabetes.

BACKGROUND AND AIMS: Diabetes mellitus is one of the critical public health challenges in the Indian healthcare scenario. Novel anthropometric indices are promising surrogate markers to detect prediabetes compared to the traditional anthropometric indices that only reflect gross obesity. Thus, the authors aim to analyse the potential of three novel lipid combined anthropometric indices in predicting prediabetes in the Asian Indian population. METHODS: We conducted an age and gender-matched case-control study to identify the predictors of prediabetes. Prediabetes was diagnosed as per the American Diabetes Association (ADA) guidelines 2010. The traditional anthropometric measurements including waist circumference (WC), waist to hip ratio (WHR) and body mass index (BMI) were executed using standardised methods. Fasting lipid profile was obtained and using standardised formulas, the novel lipid combined anthropometric indices such as lipid accumulation product (LAP), visceral adiposity index (VAI) and triglyceride glucose index (TyG index) were derived. TyG related indices such as triglyceride glucose-waist circumference (TyG-WC) and triglyceride glucose-body mass index (TyG-BMI) were also calculated. RESULTS: The novel lipid combined anthropometric indices LAP, VAI, TyG index, TyG-WC and TyG-BMI were significantly higher in subjects with prediabetes of both the genders (p < 0.05). During receiver operating characteristic (ROC) curve evaluation, TyG index (AUC = 0.802) was the superior predictive measure in males, while in females, TyG-WC (AUC = 0.767) was the best among all the markers. CONCLUSION: TyG index and TyG-WC seem to be a superior indicator of prediabetes in the Asian Indian population in comparison with other anthropometric indices to screen prediabetes.

Syndrome of inappropriate antidiuretic hormone release as the initial presentation of adenocarcinoma of the colon.

Syndrome of inappropriate antidiuretic hormone release (SIADH) is a condition defined by the unsuppressed release of antidiuretic hormone (ADH) from the pituitary gland or nonpituitary sources or its continued action on vasopressin receptors. Of the many causes of SIADH, an important one includes tumours that secrete ADH. We describe a rare case of a patient with colonic adenocarcinoma presenting initially as SIADH. A 60-year-old man presented with confusion and vomiting. Over the previous month he had fatigue and loss of weight. Baseline investigations showed a low serum sodium level of 108mmol/l. He was euvolaemic on examination and fulfilled the criteria for SIADH. Further evaluation and imaging tests revealed that the patient had adenocarcinoma of the colon. It is remarkable that our patient did not present with any of the cardinal symptoms/signs suggestive of colorectal carcinoma including haematochezia, change in bowel habits or iron-deficiency anaemia. Initial therapy with hypertonic saline, fluid restriction and salt diet for management of SIADH was unsuccessful. Tolvaptan was added to the treatment regimen and the patient improved dramatically. Oncology consultation was initiated, and chemotherapy for the carcinoma was planned.

Factors associated with outcomes in organophosphate and carbamate poisoning: a retrospective study.

Organophosphate and carbamate (OPC) poisoning is a major global health hazard requiring immediate medical intervention. Atropine (ATR) is an essential antidote in organophosphate and carbamate poisoning, with the inclusion of cholinesterase reactivators and other anticholinergics, namely pralidoxime (PAM) and glycopyrrolate (GPR). This study aimed to compare the efficacy of various treatment regimens and identify the factors affecting mortality. The data of patients presented at the emergency unit with the consumption of OPC compounds between the years 2013 and 2017 were retrospectively reviewed. The study population was then categorized into four treatment patterns (1) ATR alone, (2) ATR and PAM, (3) ATR and GPR, (4) ATR, PAM and GPR. The outcome of the patients was assessed in terms of survival, intubation, ICU days, and days of ventilation and hospitalization. Univariate and multivariate analyses were performed to investigate the risk factors associated with mortality and odds ratio (OR). A total of 441 patients were included in the study, of which 69.16% were males, and 375 patients survived. Consumption of poison with a suicidal intention was reported in 98.19% of the patients, and the treatment with ATR and PAM (42.86%) was observed to have lower days of ventilation in comparison to the treatment with ATR and GPR (p = 0.003). Patients requiring intubation were also lowest in the group treated with ATR and PAM (27.51%). The age group of > 50 years (OR 4.275 [CI 2.179-8.387]), male gender (OR 2.608 [CI 1.258-5.406]), and the treatment pattern with ATR, PAM and GPR (OR 2.233 [CI 1.002-4.040]) were independently associated with mortality. In summary, male gender, elderly population, and treatment patterns followed adversely affected the outcome in patients with OPC poisoning.

Acute tension hydrothorax in chronic liver disease secondary to spontaneous diaphragmatic rupture.

Pleural effusion in liver cirrhotics is more commonly transudative. A transudative pleural effusion secondary to ascites in decompensated cirrhosis is also known as hepatic hydrothorax and is usually due to fluid seepage through congenital pores in the diaphragm. The patient, a known case of decompensated chronic liver disease, presented with a massive, left-sided, rapidly accumulating and transudative pleural effusion secondary to spontaneous diaphragmatic rupture. Clinically, he developed sudden onset shortness of breath and became hypotensive. This is a rare entity, and was confirmed on CT thorax revealing a focal segment defect ~1.6 cm over the left hemidiaphragm. Ascites treatment consisting of diuretics with salt restriction and repeated thoracentesis with albumin replacement improved his symptoms and lead to a complete resolution of the effusion.

Posterior reversible encephalopathy syndrome due to hypercalcaemia: a rare cause.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity described by Hinchey et al in late 90's, characterised by variable associations of seizure activity, consciousness impairment ranging from confusion to coma, headaches, visual abnormalities, nausea/vomiting and focal neurological signs. Common causes are accelerated hypertension, eclampsia, preeclampsia, cytotoxic drug use and autoimmune diseases like systemic lupus erythematosus.We report a case of PRES in a 62-year-old female patient due to hypercalcemia secondary to vitamin D toxicity on treatment with calcium supplements and vitamin D for secondary hypoparathyroidism. She had seizures and visual defects on presentation which recovered completely with treatment of hypercalcemia.