Search

We aimed to evaluate and compare the clinical, biochemical and radiological profile and outcomes of patients with ectopic ACTH syndrome (EAS) and Cushing disease (CD) treated over a period of 10 years (2013-2022).In this ambispective observational study, we collected data for 146 patients with ACTH-dependent CS (EAS, n = 23; CD, n = 94; occult ACTH source, n = 29). Relevant details were filled in a predesigned proforma and outcomes were ascertained at the most recent visit.EAS was more common in males (65.2 vs. 27.6%, p 0.001). Patients with EAS had a shorter duration of symptoms [12 (6-12) vs. 31.5 (15-48) months, p 0.001] and were more likely to have hypokalemia (82.6 vs. 21.0%, p = 0.001), pedal edema (65.2 vs. 34.2%, p = 0.015), weight loss (34.8 vs. 4.0%, p 0.001) and systemic infection (30.4 vs. 6.5%, p = 0.006). They also had significantly higher 8 a.m. serum cortisol, midnight serum and salivary cortisol and 8 a.m. plasma ACTH levels. Bronchial carcinoid (n = 10, 43.5%) was the most common etiology of EAS. Bilateral adrenalectomy was performed in 11 (47.8%) patients with EAS. Eight patients (34.8%) with EAS died at the last follow-up, of whom 7 (87.5%) had metastatic disease. In CD group, overall remission rate was 69.4% (56.1%, early and 13.3%, delayed) and 26.3% of patients with an initial remission had recurrence.Bronchial carcinoid was the most common cause of EAS in our cohort. Bilateral adrenalectomy was performed in approximately every 1 in 2 patients with EAS and approximately every 1 in 3 patients expired till the last follow-up.

To evaluate the differences in the continuous glucose monitoring system (CGMS) profiles of women in early pregnancy stratified based on different HbA1c levels known to be predictive of gestational diabetes mellitus (GDM) at 24-28 weeks of gestation (≥ 5.2%) and adverse pregnancy outcomes (≥ 5.5%) in Indian women. We enrolled women at 8Ninety-six women were enrolled at 14.0 ± 3.2 weeks of gestation. Of these, 38 were found to have early GDM (diagnosed before 20 weeks of gestation) on evaluation. Of 96 women, 33 (34.4%) had HbA1c value ≥ 5.5% [11 (19.0%) with normoglycaemia and 22 (57.9%) with GDM]. The women with elevated HbA1c differed significantly from those with HbA1c 5.5% for all evaluated parameters. The differences for overall women were10 mg/dl (0.56 mmol/l) for 1-h postprandial glucose (difference of 0.78 mmol/l), 2-h postprandial glucose (difference of 0.59 mmol/l), peak postprandial glucose (difference of 0.75 mmol/l), and 1-h postprandial glucose excursion (difference of 0.59 mmol/l). Of 58 women with normoglycaemia, 29 (50.0%) had an HbA1c value ≥ 5.2%. In comparison, in the normoglycaemic group of women with and without HbA1c ≥ 5.2% (known to be predictive of future GDM), the results were significant for 1-h (difference of 0.44 mmol/l), 2-h (difference of 0.278 mmol/l), and peak postprandial glucose (difference of 0.35 mmol/l). The results suggest that women with elevated HbA1c (≥ 5.5%) in early pregnancy significantly differ from those with HbA1c 5.5% in all glycaemic parameters evaluated in this study, suggesting that HbA1c at this cut-off has a role to play in early pregnancy.

There is an unmet need to evaluate the burden of cardiometabolic risk factors in young South Asian adults, who are not preselected for glycaemia.To evaluate young North Indian men (aged 20-50 years) for burden of cardiometabolic risk factors, in relation to parameters of homeostatic model assessment for insulin resistance (HOMA-IR) and beta-cell function (oral disposition index [oDI]).Study participants were invited in a fasting state. Sociodemographic, anthropometric, and medical data were collected, and 75 g oral glucose tolerance test was performed with serum insulin and plasma glucose estimation at 0, 30, and 120 min. Participants were divided into quartiles for HOMA-IR and oDI (category 1: Best HOMA-IR/oDI quartile; category 3: Worst HOMA-IR/oDI quartile) and composite HOMA-IR/oDI phenotypes (phenotype 1: Best quartile for both HOMA-IR and oDI; phenotype 4: Worst quartile for both HOMA-IR and oDI) were derived.We evaluated a total of 635 men at a mean (± SD) age of 33.9 ± 5.1 years and body mass index of 26.0 ± 3.9 kg/mThe burden of cardiometabolic risk factors is high among young Asian Indian men. Our findings highlight the importance of using parameters of insulin resistance and beta-cell function in phenotyping individuals for cardiometabolic risk.

Type 1 diabetes (T1DM) is associated with cognitive deficits, and age at diagnosis is thought to play a substantial role. However, there are limited data for the cognitive performance in young adults, in relation to the age of diabetes onset. The lack of information is particularly striking in the context of developing regions.This cross-sectional study was performed from August 2018 to July 2020. We included adult participants with T1DM, stratified by the age of diabetes onset (till 6 years of age, between 7 to 12 years of age, and 13 to 18 years of age) and compared them with the control group (no diabetes or pre-diabetes). We filled a structured case record proforma for all participants and recorded relevant socio-demographic and medical details. Detailed neuropsychological assessment with 13 psychological tests representing four cognitive domains was carried-(1) attention, working memory and executive functions; (2) learning and memory; (3) visuoperceptual functions; and (4) information processing speed.We evaluated 100 individuals, 73 (men 48.0%) with T1DM and 27 (men 51.9%) without T1DM. After adjustment for age, gender and education, the mean differences in composite Z scores (for the four cognitive domains) between participants with T1DM and without T1DM were 0.08 for attention, working memory and executive functions (p = 0.614); 0.07 for learning and memory (p = 0.694); 0.05 for visuoperceptual (p = 0.784); and 0.22 for information processing speed (p = 0.305). No significant differences were found for the three subgroups of individuals with T1DM, when compared with the control group. Effect size (Cohen's d) for the individual tests (n = 13) ranged from - 0.36 to + 0.39, and none of the comparisons were statistically significant. Amongst the participants with T1DM, higher education had a significant positive association with three of the four cognitive domains evaluated.To conclude, our findings suggest minimal differences in the cognitive functioning of patients with T1DM with different age of onset of diabetes compared to healthy controls, when evaluated in early adulthood. This is possibly the first study from South Asia with an in-depth and comprehensive assessment of cognitive functions in patients with T1DM, using a detailed neuropsychological battery.

Overt diabetes in pregnancy is defined as hyperglycemia first recognized during pregnancy which meets the diagnostic threshold of diabetes in non-pregnant adults. This case-based narrative review aims to describe this unique condition and discuss the potential implications for its accurate diagnosis and management.We conducted a literature search in PubMed for relevant articles published in English language up to January 2022. Women with overt diabetes have a higher risk for adverse pregnancy outcomes and postpartum diabetes, compared to their counterparts with gestational diabetes mellitus (GDM). Such women often need aggressive management, including early and prompt initiation of insulin therapy, and a close follow-up during pregnancy and in the postpartum period. Not all pregnant women with overt diabetes have persistent diabetes in the postpartum period. Early diagnosis, especially during the first trimester, and fasting plasma glucose elevation (≥ 126 mg/dl or 7 mmol/L) at the time of initial diagnosis are predictors of postpartum diabetes.Both GDM and overt diabetes in pregnancy are hyperglycemic conditions first recognized during pregnancy, but the two conditions differ in severity; the latter is a more severe form of hyperglycemia associated with worse maternal and fetal outcomes, and a higher risk of postpartum diabetes.

OBJECTIVE The aim of this cross-sectional study was to comprehensively assess bone health in women with prior gestational diabetes mellitus, including bone microarchitecture (TBS), bone mineral density (BMD, DXA) and bone turnover (osteocalcin). DESIGN, PATIENTS AND MEASUREMENTS Study participants underwent a detailed anthropometric, biochemical and hormone assessment, including insulin and osteocalcin measurement. BMD was measured at lumbar spine, femur neck and total hip using DXA and TBS derived from lumbar spine DXA images using TBS iNsight software. RESULTS A total of 240 women (mean age: 33.3 ± 5.0 years; median postpartum duration: 34 [interquartile range 13.0-54.5] months were evaluated. At the current visit, 115 (47.9%) and 36 (15%) women had prediabetes and diabetes, respectively. Women with dysglycemia (diabetes/prediabetes) had a higher BMD at all three sites, compared to those with normoglycemia; however, the difference was not statistically significant. Women with dysglycemia had a significantly lower TBS (1.32 ± 0.09 vs. 1.35 ± 0.09; p = .038). In the fully adjusted model, the odds ratio for association between diabetes and low TBS was 2.92 (95% confidence interval: 1.20, 7.08; p = .018). Women with dysglycemia had significantly lower serum osteocalcin levels (18.6 ± 8.5 ng/ml vs. 21.5 ± 9.7 ng/ml; p = .018). HOMA-IR (r = -.285, p

Introduction We aimed to evaluate whether SARS-CoV-2 infection is associated with beta cell dysfunction and progression of glycemic and cardiometabolic variables in an established cohort. Methods Study participants (n = 352, 46.9% men) underwent a detailed evaluation at two time points: (a) pre-COVID (2016–19) and (b) peri-COVID (2020–21). At the second visit, SARS-CoV-2 infection was determined on the basis of a quantitative S1/S2 IgG antibody test (DiaSorin Liaison) and/or a documented history of infection. Results A total of 159 (45.2%) participants were seropositive for SARS-CoV-2, of whom 122 (76.7%) had mild/asymptomatic infection. Progression in body mass index (BMI) category [34 (21.4%) vs. 22 (11.4%), p = 0.011] was seen in a significantly higher proportion of the participants in the infected group compared to the non-infected group. Progression in glycemic and insulin indices [homeostasis model assessment of insulin resistance (HOMA-IR), Matsuda index, and oral disposition index (oDI)] categories was also evident in a larger proportion of participants in the infected group; however, the difference was not statistically significant. On logistic regression analysis, the association between SARS-CoV-2 infection and BMI category progression was statistically significant [fully adjusted OR 2.14 (95% CI, 1.18–3.90; p = 0.013)]. Conclusion In this longitudinal study, predominant mild/asymptomatic SARS-CoV-2 infection was associated with increase in BMI, but not with worsening of beta cell function and insulin resistance, nor glycemic progression.

Glycemic control has remained an enigma despite a large number of anti-diabetic drugs being available. Clinical practice and guidelines have focussed largely on optimal and rational use of anti-diabetes drugs to achieve care goals. This study aims to delineate factors impacting glycemic control from real-world data. Retrospective, cross-sectional data comprising 15,689 prescriptions from 4647 people living with diabetes and attending an endocrine clinic over a 5-year period was extracted from EMR (electronic medical records) of the clinic. Data pertaining to drugs prescribed, glycemic control attained and patient behavioral factors like diet, drug and exercise adherence was analysed to delineate the contribution of patient or care team-dependent factors towards glycemic control. Factors related to patient behavior affected glycemic control linearly with statistically lower HbA1c in people with better adherence to diet, medications and exercise. People who did any self-monitoring of blood glucose at home had significantly better glycemic control. On the other hand, a number of medications were negatively associated with glycemic control. Hypoglycemia had no impact on glycemic control. A number of visits to treating physician were positively associated with glycemic control but impact plateaued after 6 visits. Patient behavior and activation-related factors are predominant drivers of glycemic control.

Alzheimer's disease (AD) is a multifactorial neurological disorder associated with neuropathological and neurobehavioral changes, like cognition and memory loss. Pathological hallmarks of AD comprise oxidative stress, formation of insoluble β-amyloid (Aβ) plaques, intracellular neurofibrillary tangles constituted by hyperphosphorylated tau protein (P-tau), neurotransmitters dysbalanced (DA, NE, 5-HT, GABA and Glutamate) and metal deposition. Chronic exposure to metals like aluminium and copper causes accumulation of Aβ plaques, promotes oxidative stress, neuro-inflammation, and degeneration of cholinergic neurons results in AD-like symptoms. In the present study, rats were administered with aluminium chloride (200 mg/kg p.o) and copper sulfate (0.5 mg/kg p.o) alone and in combination for 28 days. Allicin (10 and 20 mg/kg i.p) was administered from day 7 to day 28. Spatial and recognition memory impairment analysis was performed using Morris water maze, Probe trial, and Novel Object Recognition test. Animals were sacrificed on day 29, brain tissue was isolated, and its homogenate was used for biochemical (lipid peroxidation, nitrite, and glutathione), neuro-inflammatory (IL-1β, IL-6 and TNF- α), neurotransmitters (DA, NE, 5-HT, GABA and Glutamate), Aβ(1-42) level, Al concentration estimation, and Na+/K+-ATPase activity. In the present study, aluminium chloride and copper sulfate administration increased oxidative stress, inflammatory cytokines release, imbalanced neurotransmitters' concentration, and promoted β-amyloid accumulation and Na+/K+-ATPase activity. Treatment with allicin dose-dependently attenuated these pathological events via restoration of antioxidants, neurotransmitters concentration, and inhibiting cytokine release and β-amyloid accumulation. Moreover, allicin exhibited the neuroprotective effect through antioxidant, anti-inflammatory, neurotransmitters restoration, attenuation of neuro-inflammation and β-amyloid-induced neurotoxicity.

Aims/Introduction This study aims to evaluate the prevalence of and factors associated with non‐alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Materials and Methods This cross‐sectional study (2018–2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75‐g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography. Results We evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9–38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11‐fold higher in women with prior GDM (95% confidence interval 1.16–3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD. Conclusions The prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long‐term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women., This study evaluated the prevalence and risk factors of non‐alcoholic fatty liver disease in Indian women with prior gestational diabetes mellitus diagnosed using International Association of Diabetes and Pregnancy Study Groups criteria. Ultrasonography of abdomen was used to define non‐alcoholic fatty liver disease status. Prevalence of non‐alcoholic fatty liver disease was significantly higher in women with prior gestational diabetes mellitus (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%).

The aim of the study was to evaluate the differences in the continuous glucose monitoring system (CGMS)-based glycemic parameters between women with normoglycemia and early gestational diabetes mellitus (GDM) identified on the basis of mild fasting plasma glucose elevation (FPG, 5.1-5.5 mmol/L) and/or post-load plasma glucose elevation (PLG, 1-h ≥ 10.0 mmol/L or 2-h ≥ 8.5 mmol/L).This cross-sectional study included women with singleton pregnancy (8An isolated FPG threshold, especially the higher cutoff ≥ 5.6 mmol/L, can potentially miss a large proportion of women (nearly three-fourths) diagnosed with GDM per WHO 2013 criteria. Eventually, such women fare significantly differently from normoglycemic women in various CGMS parameters of clinical interest.

Gestational diabetes has serious health effects during pregnancy and childbirth. We estimated the occurrence of gestational diabetes mellitus (GDM) among pregnant women in a secondary care hospital in Haryana.It was a hospital-based cross-sectional study, done in an ante-natal clinic (ANC) at a sub-district hospital (SDH), Faridabad district of Haryana, India. Eligible pregnant women attending the ANC clinic were recruited. An oral glucose tolerance test (OGTT) with 75 g of glucose was done with a collection of blood for fasting blood sugar (FBS) and two-hour post-OGTT blood glucose. A pre-tested semi-structured interview schedule was administered. Both the modified International Association of the Diabetes and Pregnancy Study Groups criteria (IADPSGC) and the Diabetes in Pregnancy Study Group of India (DIPSI) criteria were used. Data were presented as percentages, means, standard deviation, and 95% confidence interval (CI). Bi-variable and multi-variable logistic regressions were done. The level of significance was set at 0.05.Of the 623 eligible participants, 66.1% were within the 20-25 age group. The GDM was found in 14.1% (95%CI: 11.5-17.1) participants as per modified IADPSG criteria and 6.7% (95%CI: 4.9-9.0) participants as per DIPSI criteria, respectively. Increasing age [adjusted odds ratio (AOR): 1.24 (95% CI: 1.05-1.47), p=0.008] and increasing years of schooling [AOR: 1.19 (1.01-1.41), p=0.032] were significantly associated with GDM by DIPSI criteria. Family history of DM was also found to have an increased odds with GDM using modified IADPSG criteria [AOR 2.87 (95% CI: 1.09-7.54), p=0.032]. Conclusion: Considerable proportion of pregnant women were found to have GDM in a Sub-district hospital at Ballabgarh in north India. The study highlighted the need and generated evidence about the feasibility of GDM screening utilizing routine staff in a secondary care facility.

Introduction Our aim is to propose an evidence-based strategy for screening postpartum dysglycemia. Methods This study included adult non-pregnant women who were diagnosed with gestational diabetes (GDM) using International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria during their index pregnancy (2012–2019). Eligible participants underwent a concurrent oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) test. A detailed questionnaire documenting relevant personal and medical history was filled, and the relevant anthropometric parameters were recorded. Results We evaluated data from 377 women at a mean (± SD) age of 32.1 ± 4.6 years and at a median duration of 15 (10–33) months following childbirth. Diabetes was diagnosed in 42 (11.1%) women. Use of a combination cutoff [fasting plasma glucose (FPG) ≥ 6.1 mmol/L or glycated hemoglobin (HbA1c) ≥ 6.0% (42 mmol/mol)] avoided OGTT in 80.9% of the study cohort, without missing the diagnosis of diabetes in any study subject. The diagnosis was missed in 2.4% of women with diabetes (and 0.3% of whole cohort) using only the FPG criterion (≥ 5.6 mmol/L) or HbA1c criterion [HbA1c ≥ 5.7% (39 mmol/mol)] alone. These tests avoided the need for an OGTT in 75.3% and 65.5% of women, respectively. Conclusions The proposed strategies are likely to be both patient- and physician-friendly and have the potential to address several barriers for postpartum screening among women with prior GDM.

Background and aims Diabetes and coronavirus disease 2019 (COVID-19) share a bidirectional relationship. Hyperglycemia occurring in the setting of either previously diagnosed or undiagnosed diabetes is known to be associated with poor outcomes. Here, we aim to provide a simple and practical guidance on the diagnosis and management of hyperglycemia in admitted patients with COVID-19. Methods The guidance is formulated based on experience of authors and relevant literature on the subject searched using Pubmed. Results Every patient admitted to a COVID care facility should be investigated for hyperglycemia using a combination of tests including capillary blood glucose, fasting plasma glucose and HbA1c. Oral glucose lowering drugs can be considered in patients with mild COVID illness who have mild hyperglycemia [pre-meal blood glucose of

Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes.To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia.This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021.A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care.The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight.A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome.This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals.Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

Background and Aim The coronavirus disease 2019 (COVID-19) outbreak has rapidly crossed international boundaries and placed increasing demands on healthcare facilities worldwide. Patients with diabetes and uncontrolled blood glucose levels are at increased risk for poor clinical outcomes and in-hospital mortality related to COVID-19. Therefore, achieving good glycaemic control is of paramount importance among hospitalised patients with COVID-19. Basal-bolus insulin therapy is a safe and effective intervention for the management of hyperglycaemia in hospitalised patients. The aim of this article is to provide a practical guidance for the use of the basal-bolus insulin regimen in hospitalised patients with COVID-19 and diabetes mellitus. Methods This guidance document was formulated based on the review of available literature and the combined personal experiences of the authors. We provide a comprehensive review on the use of the basal-bolus insulin regimen, including its principles, rationale, indications, prerequisites, initiation, and dose titration, and also suggest targets for blood glucose control and different levels of capillary blood glucose monitoring. Various case scenarios are used to illustrate how optimal glucose control can be achieved, such as through adjustments in doses of prandial and basal insulin, the use of correctional insulin dosing and changes in the timing and content of major and minor meals. Conclusion The practical guidance for the use of the basal-bolus insulin regimen in hospitalised patients with COVID-19 and diabetes mellitus presented here can be used for patients admitted to hospital for indications other than COVID-19 and for those in ambulatory care. Electronic supplementary material The online version of this article (10.1007/s13300-020-00873-3) contains supplementary material, which is available to authorized users.

Background: There is no published literature on the profile of patients with tall stature (TS) from India. This study aimed to evaluate the etiological and clinical profile of patients with TS referred to our hospital. Materials and Methods: We performed a retrospective review of records of patients referred to us for evaluation of TS (January 2007 to March 2020). Relevant clinical, anthropometric, biochemical, and radiological data at presentation were recorded, and the final diagnosis reviewed. Results: The study included 16 subjects (6 boys, 10 girls) with a mean age at presentation of 13.2 ± 3.6 years. Most subjects were pubertal (n = 10) and belonged to the overweight or obese category (n = 10). The mean height and height standard deviation score (SDS) were 172.3 ± 20.3 cm and 3.6 ± 1.5, respectively, while mean mid-parental height (MPH) and MPH SDS were 168.8 ± 8.8 cm and 1.2 ± 0.9, respectively. The etiological diagnoses were familial TS (n = 9), acrogigantism (n = 3), obesity-related TS (n = 2), constitutional advancement of growth (n = 1), and Marfan syndrome (n = 1). The mean height SDS in subjects with acrogigantism was 6.4 ± 1.2 compared to 3.0 ± 0.6 in those with other etiologies of TS. Only one girl with familial TS and significantly increased predicted adult height (+4.56 SDS) opted for sex steroid therapy. Conclusion: Familial TS is the most common diagnosis among patients referred for evaluation to our hospital. One should consider the possibility of acrogigantism in patients with growth acceleration, extreme TS, and markedly increased gap between height SDS and MPH SDS. Most patients with familial TS require reassurance and sex steroid therapy should be reserved for highly selected cases.

Objective Data for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design. Methods Study participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection. Results We evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001). Conclusion SARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.

IntroductionGestational diabetes mellitus (GDM), once considered a transient condition during pregnancy, is now a firmly established risk factor for type 2 diabetes mellitus (T2DM). Women whose blood glucose levels do not return to normal soon after giving birth are particularly at high risk of developing established diabetes and consequent heart and blood vessel disease. Lifestyle interventions are recommended for women with GDM to prevent or delay the subsequent development of T2DM. Recent systematic reviews and meta-analyses have suggested postpartum lifestyle interventions may be beneficial in reducing the risk of developing diabetes in women with GDM, however, included studies were generally small, many had a high risk of bias and subsequent data have become available with new trials likely to complete in the next couple of years. In addition, to the best of our knowledge, formal systematic review and meta-analysis of other approaches to preventing diabetes in this population (e.g. pharmacotherapy) has not been attempted. Therefore, an updated systematic review is needed and will be formulated as a living systematic review to ensure the inclusion of emerging studies.Methods and analysisA living systematic review and a prospective meta-analysis to examine the effectiveness of postpartum interventions in reducing the risk of developing T2DM in women with recent GDM.Ethics and disseminationEthics committee approval is not required. The data included will be from published studies, and a continued living systematic review and prospective meta-analysis will occur once a year for the next five years. Results of the review will be disseminated at relevant meetings.PROSPERO registration numberCRD42021279891Strengths and limitations of this studyA living systematic review will allow continuous surveillance of emerging literature on different lifestyle interventions in women with a history of GDM and allow identification of effective strategies for diabetes prevention.We estimate considerable heterogeneity of interventions which may limit our ability to make clear conclusions.

Background The growing burden of hypertension and diabetes is one of the major public health challenges being faced by the health system in India. Clinical Decision Support Systems (CDSS) that assist with tailoring evidence-based management approaches combined with task-shifting from more specialized to less specialized providers may together enhance the impact of a program. We sought to integrate a technology “CDSS” and a strategy “Task-shifting” within the Government of India’s (GoI) Non-Communicable Diseases (NCD) System under the Comprehensive Primary Health Care (CPHC) initiative to enhance the program’s impact to address the growing burden of hypertension and diabetes in India. Methods We developed a model of care “I-TREC” entirely calibrated for implementation within the current health system across all facility types (Primary Health Centre, Community Health Centre, and District Hospital) in a block in Shaheed Bhagat Singh (SBS) Nagar district of Punjab, India. We undertook an academic-community partnership to incorporate the combination of a CDSS with task-shifting into the GoI CPHC-NCD system, a platform that assists healthcare providers to record patient information for routine NCD care. Academic partners developed clinical algorithms, a revised clinic workflow, and provider training modules with iterative collaboration and consultation with government and technology partners to incorporate CDSS within the existing system. Discussion The CDSS-enabled GoI CPHC-NCD system provides evidence-based recommendations for hypertension and diabetes; threshold-based prompts to assure referral mechanism across health facilities; integrated patient database, and care coordination through workflow management and dashboard alerts. To enable efficient implementation, modifications were made in the patient workflow and the fulcrum of the use of technology shifted from physician to nurse. Conclusion Designed to be applicable nationwide, the I-TREC model of care is being piloted in a block in the state of Punjab, India. Learnings from I-TREC will provide a roadmap to other public health experts to integrate and adapt their interventions at the national level. Trial registration CTRI/2020/01/022723.

With millions of people getting affected with COVID-19 pandemic caused by a novel severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), people living with post COVID-19 Symptoms (PCS) are expected to rise in the future· The present study aimed at assessing PCS comprehensively and its associated factors among COVID-19 recovered adult population in north India.MethodsIn a tertiary health centre at Delhi, an online based cross-sectional study was conducted using a semi-structured questionnaire, developed by employing a nominal group technique, in aged 18 years and above who were SARS-CoV-2 positive during the month of January to April 2021. Socio-demographic, various potential risk factors, including pre-existing morbidities, vaccination status, and severity of acute COVID-19 illness, information on acute illness for management and a spectrum of PCS were collected between June 16 to July 28, 2021. Each participant was contacted telephonically before sending the survey link. PCS were presented as relative frequency; chi-square test, odds ratio, including adjusted, were calculated to rule out association between PCS and potential predictors.ResultsA total of 773 of 1801 COVID recovered participants responded to the link reaching a participation rate of 42·9%, with a median age of 34 years (IQR 27 to 44). Male respondents were 56·4%. Around 33·2% of them had PCS at four or more weeks, affecting almost all body organ systems. The most prevalent PCS were fatigue (79·3%), pain in the joins (33·4%), muscle (29·9%), hair loss (28·0%), headache (27·2%), breathlessness (25·3%), sleep disturbance (25·3%) and cough (24·9%). The prevalence of PCS was reduced to 12·8% at 12 weeks after positive test. Factor such as female gender, older age, oxygen supplementation during the acute illness, working in healthcare care facilities, the severity of acute illness, and pre-existing co-morbid were risk factors for PCS. Further, vaccination (second dose) reduced the odds of developing PCS by 45% compared to unvaccinated participants (aOR 0·65; 95%CI 0·45-0·96). Finally, 8·3% of participants rated their overall health status was either poor or very poor following COVID-19 illness.ConclusionsThe PCS involves almost all organ systems, regardless of the severity of acute COVID-19 illness. Two doses of vaccine help to reduce development of PCS.Research in ContextEvidence before this studyAlthough the evidence is mounting in prolonged COVID-19 symptoms among COVID-19 survivors, to date, the full range of such post-COVID-19 symptoms (PCS) is not yet fully understood. There is a lack of studies that assessed PCS comprehensively among persons who have recovered from the COVID-19illness. For example, limited data are available on psychosocial, behavioral, and oral manifestations related to PCS. Further, there is a paucity of studies that included a wide range of determinants of PCS and the association of vaccination with the development of PCS across the world. Our study is the first such study conducted among COVID-19 recovered persons who with a majority of them employed in a tertiary health care institute of north India.Added value of this studyOur study, for the first time, investigated a wide range of post-COVID-19 manifestations among COVID-19 recovered persons in organ-specific and psychosocial behavioral aspects, making this the largest categorization of PCS currently (in total 16). The study included telephonic calls to each eligible candidate which helped in ensuring the COVID-19 status at the time of the study. Since the participants either were employees in the hospital or their dependents that enhance the accuracy of reporting PCS. The most prevalent symptom was unspecific PCS (85.6%), e.g., fatigue, followed by musculoskeletal manifestations (49·8%), Ear, Nose and Throat symptoms (47·5%), neurological (47·0%), cardio-respiratory (42·4%, gastrointestinal (36·2%), ocular symptoms (31·9%), dermatological symptoms (31·5%), and cardio-vascular (24·5%) symptoms, and mental health symptoms (23·7%). The rest of the organ specific symptoms were observed in less than 20% of the respondents. Older age, female gender, pre-existing co-morbid, oxygen supplementation during acute illness, the severity of illness, working in health care institutions were associated with PCS. Vaccination after the second dose was protective against PCS compared to non-vaccinated participants. Further, our study also reported a rating of the overall health status among COVID survivors, whereby around 8.3% of them reported being a poor or very poor health.Implications of all the available evidencePCS affects a multi-organ organ system, irrespective of the severity of acute-phase COVID-19 illness and hospitalization. Such persistent COVID-19 symptoms, compounded by its heterogeneity among COVID survivors can pose a substantial burden to the affected individuals and their families and additional challenges for healthcare delivery and public health service. The current study shows that one in three individuals experience persistent COVID-19 symptoms. Since the COVID pandemic is still ongoing across the world, therefore, the number of people experiencing PCS is likely to be increased substantially further. An integrated PCS care strategy, but not limited to organ-specific healthcare disciplines, others such as psychosocial support, including counseling and education, rehabilitation, community-based rehabilitation programs will be required for management. Prioritization of PCS care to elder and co-morbid patients should be recommended. Expediting the vaccination drive will be helpful to reduce the development of persistent COVID-19 symptoms. Research, collaborative and multidisciplinary, is required to understand the underlying pathophysiology mechanism for PCS.

Various studies have shown a positive co-relation between Vitamin D deficiency and severity of Allergic Rhinitis (AR) based on subjective symptoms. AR is also associated with serum eosinophilia and raised levels of various interleukins (IL)—particularly IL-4, IL-5 and IL-13. To compare serum Vitamin D levels, IL-4, IL-5, and IL-13 levels, and eosinophilia in AR patients with healthy controls and co-relate disease severity using Sino-nasal Outcome Test-22 (SNOT-22) score in patients with Vitamin D deficiency. 30 patients and 30 healthy controls were recruited. 10 ml blood sample was drawn from each patient and healthy control. It was then processed to evaluate absolute eosinophil count, serum levels of Vitamin D, and IL-4, IL-5, and IL-13. 93.33% of patients with AR and 70% of healthy controls had decreased Vitamin D levels (below 25 ng/ml). The mean Vitamin D levels was 10.50 ± 2.34 ng/ml and 17.54 ± 2.84 ng/ml in the patient and control group, respectively (p = 0.001). But there was no significant co-relation between SNOT-22 score and Vitamin D level, and between interleukin levels in patient and control group. Vitamin D deficiency is associated with Allergic Rhinitis and therefore, checking Vitamin D levels in patients with AR can be considered as routine practice in outpatient clinics. However, co-relation between severity of Allergic Rhinitis and Vitamin D levels and the proven therapeutic role of Vitamin D in Allergic Rhinitis is still debatable and thus, requires large sample size randomised controlled trials.

This is a diagnostic test research study to evaluate the various existing methods of thyroid examination and their comparison with the novel modified Rose method. It also aims to measure inter-examiner variation in clinical findings based on the level of education and training, as compared to ultrasonography.This cross-sectional study was conducted at a tertiary care hospital with 83 patients presenting to surgery OPD with neck swelling. Each patient was examined by one trained Junior Resident and a Surgery Consultant with all the four methods and with ultrasonography. Data was analysed by Stata-14, agreement between the two categorical variables was assessed by Kappa. In case of continuous variable agreement was assessed by Intra class correlation and Bland-Altman plot.Modified Rose method by the consultant has the highest sensitivity (98%) and diagnostic odds (210) as compared to others but its specificity ranges from 46.7-91.1% to diagnose retro-sternal extension of a goiter. It has 93.98% agreement for identification of nodules. It has a high specificity (Consultant - 100%, Resident - 95.5%) with relatively lower sensitivity (Consultant - 94%, Resident - 86.8%) to diagnose solitary thyroid nodule (STN) but the sensitivity and specificity for diagnosing a multinodular goitre (MNG) was high. However, the highest sensitivity to diagnose STN was highest with Crile's method, but specificity was low. Lahey's method was a better clinical method to palpate lymph nodes compared to the other three.Examination in modified Rose's position is a better method of clinical examination of thyroid especially in patients with occult substernal extension. Lahey's method is a better method to examine cervical lymph nodes.

We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia.This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour.The guidance can be generalized to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present.

The aim of this study was to investigate the concordance of dysglycaemia (prediabetes or diabetes) and cardiometabolic traits between women with a history of gestational diabetes mellitus (GDM) and their spouses. Using hospital medical records, women with GDM (diagnosed between 2012 and 2016) and their spouses were invited to participate in the study and to attend a scheduled hospital visit in a fasting state. Sociodemographic, anthropometric and medical data were collected, and a 75 g OGTT with serum insulin estimation, HbA1c measurement and fasting lipid profile were performed at the visit. Prediabetes and diabetes were defined using ADA criteria and the metabolic syndrome was defined using IDF criteria. A total of 214 couples participated in the study. Women were tested at a mean ± SD age of 32.4 ± 4.6 years and median (quartile [q]25–q75) of 19.5 (11–44) months following the index delivery, while men were tested at a mean ± SD age of 36.4 ± 5.4 years. A total of 72 (33.6%) couples showed concordance for dysglycaemia, while 99 (46.3%) and 51 (23.8%) couples were concordant for overweight/obesity and the metabolic syndrome, respectively. A total of 146 (68.2%) couples showed concordance for any of the above three factors. The presence of dysglycaemia in one partner was associated with an increased risk of dysglycaemia in the other partner (OR 1.80 [95% CI 1.04, 3.11]). Similarly, being overweight/obese (OR 2.19 [95% CI 1.22, 3.93]) and presence of the metabolic syndrome (OR 2.01 [95% CI 1.16, 3.50]) in one partner was associated with an increased risk of these conditions in the other partner. Both women and men were more likely to have dysglycaemia if they had a partner with dysglycaemia. Women with a partner with dysglycaemia had a significantly higher BMI, waist circumference and diastolic BP, and a significantly higher probability of low HDL-cholesterol (

Dynamic tests are often considered as the backbone of endocrinology. These tests involve the use of an exogenous agent to manipulate the body's hormonal milieu for the diagnosis and characterization of an endocrine disorder. They are especially helpful in the evaluation of certain endocrine conditions, such as disorders of growth and pubertal maturation and disorders of sex development. A great deal of heterogeneity exists across clinicians with regard to the usage, methodology, and interpretation of these tests. This review outlines various dynamic tests used to evaluate adrenal and gonadal function in pediatric and adult endocrinology, along with their clinical application and interpretation.

Aims To confirm non-inferiority of insulin degludec/insulin aspart (IDegAsp) once-daily (OD) versus insulin glargine (IGlar) U100 OD + insulin aspart (IAsp) OD for HbA1c after 26 weeks, and compare efficacy and safety between groups at W26 + W38. Methods A 38-week, randomised, open-label, treat-to-target (HbA1c Results For W0–W26, mean percentage-change (standard deviation) HbA1c was: IDegAsp, −1.1 (0.9); IGlar U100 + IAsp, −1.1 (0.8); estimated treatment difference: 0.07% (95% confidence interval [CI]: −0.06; 0.21) confirmed non-inferiority. At W26 and W38, target HbA1c achievement, and mean fasting and postprandial glucose were similar across groups. At W38, more subjects achieved target HbA1c without hypoglycaemia with IDegAsp (22.5%) than with IGlar U100 + IAsp (21.1%), with significantly fewer nocturnal episodes (W0–W38, estimated rate ratio: 0.61 [95% CI: 0.40; 0.93]). Safety profiles were similar across treatment groups throughout. Conclusions IDegAsp OD/BID are effective treatment intensification options versus multiple injection basal–bolus therapies, achieving similar glycaemic control, with significantly less nocturnal hypoglycaemia.

Drug therapy in diabetes care along the duration of diabetes has been documented scarcely in literature, especially from Indian subcontinent. An audit of an endocrine practice from New Delhi was conducted to understand the current diabetes practice and its direct cost to the patient. Aims: The aim of this study was to analyze the current trend in the use of antidiabetes as well as other drugs for comorbidities along the duration of diabetes. The study also aimed to analyze the direct drug cost to patients. Settings and Design: Retrospective cross-sectional study. Subjects and Methods: Data captured in clinic electronic medical records of an endocrine practice was analyzed. Statistical Analysis Used: Data was analyzed descriptively using machine learning codes on python platform. Results: Records of 489 people who attended the clinic during the 6-month period were retrieved. Data of 403 people with diabetes were analyzed after exclusion of incomplete data. Use of antidiabetic drug increased from 1.44 (0.78) [mean (standard deviation)] in people with a duration of diabetes

Background: Women with recent gestational diabetes mellitus (GDM) have increased risk of developing type 2 diabetes mellitus (T2DM). We aimed to determine whether a resource- and culturally-appropriate lifestyle intervention could prevent glycaemic deterioration in South Asia. Methods: This was an open-label parallel-group randomised trial. Women with GDM from 19 urban hospitals in India, Sri Lanka and Bangladesh underwent an oral glucose tolerance test (OGTT) 3-18 months post-partum. Those without T2DM were randomised to a 12-month lifestyle intervention focused on diet and physical activity or usual care. The primary outcome was the proportion with worsening category of glycaemia based on OGTT using American Diabetes Association criteria: 1) normal glucose tolerance to pre-diabetes (impaired fasting glucose and/or impaired glucose tolerance) or T2DM; or 2) pre-diabetes to T2DM. Secondary outcomes included new-onset T2DM, and change in body weight. Findings: 1823 women underwent OGTT at a median of 6·9 months post-partum. After excluding 162 (8·9%) with T2DM, 1612 (37·5% with pre-diabetes and 62·5% with normoglycaemia) were randomised between November 2017 and January 2020. Baseline mean age was 30·9 years (SD 4·9), mean BMI was 26·6 kg/m 2 (SD 4·7). Among participants randomised to the intervention, 79·7% were exposed to all programme content although pandemic lockdowns impacted the delivery model. After 14·5 months median follow-up, 1308 (81·2%) participants had primary outcome data. The intervention, compared to usual care, did not reduce worsening glycaemic status (25·5% vs. 27·1%; hazard ratio, 0·92 [95% CI: 0·76‒1·12]) or any secondary outcome. There was no evidence of heterogeneity of intervention effect by baseline characteristics. Interpretation: A large proportion of South Asian women in urban centres develop dysglycaemia soon after a GDM-affected pregnancy. A low-intensity lifestyle intervention, substantially modified due to the COVID-19 pandemic, did not prevent subsequent deterioration in glycaemic status. Alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001) and ClinicalTrials.gov (NCT03305939). Funding: Global Alliance for Chronic Disease grants from the Indian Council of Medical Research (NO.58/1/1/GACD/NCD-II) and Australian National Health and Medical Research Council (1093171). Additional funding was received from USV Pharmaceuticals Ltd. and Lupin Pharmaceuticals Ltd. for sub-studies (data not reported here). Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by Human Research Ethics Committees of the All India Institute of Medical Sciences (India), icddr,b (Bangladesh), Faculty of Medicine, University of Kelaniya (Sri Lanka) and the University of Sydney (Australia)

Aim: To refine and contextually adapt a postpartum lifestyle intervention for prevention of type 2 diabetes mellitus (T2DM) in women with prior gestational diabetes mellitus (GDM) in Bangladesh, India, and Sri Lanka.Materials and Methods: In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted with women with current diagnosis of GDM, and health care professionals involved in their management, to understand relevant local contextual factors for intervention optimization and implementation. This paper describes facilitators and barriers as well as feedback from participants on how to improve the proposed intervention. These factors were grouped and interpreted along the axes of the three main determinants of behavior–capability, opportunity, and motivation. IDIs and FGDs were digitally recorded, transcribed, and translated. Data-driven inductive thematic analysis was undertaken to identify and analyze patterns and themes.Results: Two interrelated themes emerged from the IDIs and FGDs: (i) The lifestyle intervention was acceptable and considered to have the potential to improve the existing model of care for women with GDM; and (ii) Certain barriers such as reduced priority of self-care, and adverse societal influences postpartum need to be addressed for the improvement of GDM care. Based on the feedback, the intervention was optimized by including messages for family members in the content of the intervention, providing options for both text and voice messages as reminders, and finalizing the format of the intervention session delivery.Conclusion: This study highlights the importance of contextual factors in influencing postpartum care and support for women diagnosed with GDM in three South Asian countries. It indicates that although provision of postpartum care is complex, a group lifestyle intervention program is highly acceptable to women with GDM, as well as to health care professionals, at urban hospitals.

Background Hypertension and diabetes are among the most common and deadly chronic conditions globally. In India, most adults with these conditions remain undiagnosed, untreated, or poorly treated and uncontrolled. Innovative and scalable approaches to deliver proven-effective strategies for medical and lifestyle management of these conditions are needed. Methods The overall goal of this implementation science study is to evaluate the Integrated Tracking, Referral, Electronic decision support, and Care coordination (I-TREC) program. I-TREC leverages information technology (IT) to manage hypertension and diabetes in adults aged ≥30 years across the hierarchy of Indian public healthcare facilities. The I-TREC program combines multiple evidence-based interventions: an electronic case record form (eCRF) to consolidate and track patient information and referrals across the publicly-funded healthcare system; an electronic clinical decision support system (CDSS) to assist clinicians to provide tailored guideline-based care to patients; a revised workflow to ensure coordinated care within and across facilities; and enhanced training for physicians and nurses regarding non-communicable disease (NCD) medical content and lifestyle management. The program will be implemented and evaluated in a predominantly rural district of Punjab, India. The evaluation will employ a quasi-experimental design with mixed methods data collection. Evaluation indicators assess changes in the continuum of care for hypertension and diabetes and are grounded in the Reach, Effectiveness, Adoption Implementation, and Maintenance (RE-AIM) framework. Data will be triangulated from multiple sources, including community surveys, health facility assessments, stakeholder interviews, and patient-level data from the I-TREC program’s electronic database. Discussion I-TREC consolidates previously proven strategies for improved management of hypertension and diabetes at single-levels of the healthcare system into a scalable model for coordinated care delivery across all levels of the healthcare system hierarchy. Findings have the potential to inform best practices to ultimately deliver quality public-sector hypertension and diabetes care across India. Trial registration The study is registered with Clinical Trials Registry of India (registration number CTRI/2020/01/022723). The study was registered prior to the launch of the intervention on 13 January 2020. The current version of protocol is version 2 dated 6 June 2018.