LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries.

INTRODUCTION: Real-world evidence on insulin glargine 100 U/ml (Gla-100) initiation in Indian type 2 diabetes mellitus (T2DM) individuals is limited. The present study aimed to evaluate the effectiveness of Gla-100 in insulin-naïve T2DM participants from India. METHODS: This post hoc analysis includes real-world data of insulin-naïve Indian participants with T2DM who started Gla-100 treatment in two Asian registries: FINE ASIA and GOAL. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, insulin dose, and incidence of hypoglycemia from baseline to 6 months were assessed. RESULTS: A total of 955 participants with T2DM were identified and analyzed. The mean [standard deviation (SD)] age and duration of diabetes were 54.7 (9.8) years and 9.8 (6.3) years, respectively. Mean HbA1c and FPG were significantly reduced after 6 months of Gla-100 treatment [- 2.07 (1.4) %; - 94.4 (65.2) mg/dl, respectively]. HbA1c targets of < 7.0% and < 7.5% were achieved by 292 (30.6%) and 589 (61.7%) study participants, respectively. The overall incidence of hypoglycemia was low (n = 52; 5.4%); only two participants (0.2%) reported severe hypoglycemia. Insulin was titrated with a mean (SD) increment of 2.5 (5.6) U/day after 6 months, leading to a mean Gla-100 dose of 18.2 (8.9) U/day. Mean body weight remained unchanged from baseline to 6 months (- 0.1 kg). CONCLUSION: In routine clinical practice, Gla-100 significantly improved glycemic parameters after 6 months of treatment with a low risk of hypoglycemia and no weight change in participants with T2DM.

The LongitudinAl Nationwide stuDy on Management And Real-world outComes of diabetes in India over 3 years (LANDMARC trial).

INTRODUCTION: LANDMARC (CTRI/2017/05/008452), a prospective, observational real-world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan-India regions over a period of 3 years. METHODS: Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. RESULTS: Of the 6234 participants enrolled, 5273 completed 3 years follow-up. At the end of 3-years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3-years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3-years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3-years, majority (67.7%-73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP-IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years. CONCLUSION: These 3-year trends highlight the burden of uncontrolled glycemia and cumulative diabetes-related complications, emphasizing the importance of optimizing diabetes management in India.

Two-year trends from the LANDMARC study: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcome in patients with type 2 diabetes mellitus.

INTRODUCTION: There are limited data on the real-world management of diabetes in the Indian population. In this 2-year analysis of the LANDMARC study, the management of type 2 diabetes mellitus (T2DM) and related complications were assessed. METHOD: This multicenter, observational, prospective study included adults aged ≥25 to ≤60 years diagnosed with T2DM (duration ≥2 years at enrollment) and controlled/uncontrolled on ≥2 anti-diabetic agents. This interim analysis at 2 years reports the status of glycaemic control, diabetic complications, cardiovascular (CV) risks and therapy, pan-India including metropolitan and non-metropolitan cities. RESULTS: Of the 6234 evaluable patients, 5318 patients completed 2 years in the study. Microvascular complications were observed in 17.6% of patients (1096/6234); macrovascular complications were observed in 3.1% of patients (195/6234). Higher number of microvascular complications were noted in patients from non-metropolitan than in metropolitan cities (p < .0001). In 2 years, an improvement of 0.6% from baseline (8.1%) in mean glycated haemoglobin (HbA1c) was noted; 20.8% of patients met optimum glycaemic control (HbA1c < 7%). Hypertension (2679/3438, 77.9%) and dyslipidaemia (1776/3438, 51.7%) were the predominant CV risk factors in 2 years. The number of patients taking oral anti-diabetic drugs in combination with insulin increased in 2 years (baseline: 1498/6234 [24.0%] vs. 2 years: 1917/5763 [33.3%]). While biguanides and sulfonylureas were the most commonly prescribed, there was an evident increase in the use of dipeptidyl peptidase-IV inhibitors (baseline: 3049/6234, 48.9% vs. 2 years: 3526/5763, 61.2%). CONCLUSION: This longitudinal study represents the control of T2DM, its management and development of complications in Indian population. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2017/05/008452.

An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants.

Background: Nanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. Methods: In this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18-45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC0-120h], maximum observed drug concentration [Cmax], time to reach maximum drug concentration [Tmax], terminal half-life [T½el], and terminal elimination rate constant [Kel]) were estimated using baseline corrected data and analyzed using analysis of variance. Results: Among the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC0-120h. Similarly, Cmax of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC0-120h and Cmax were 23.22% and 26.51%, respectively. The Tmax, T½el, and Kel were comparable for both the formulations. No adverse effects were noted with either of the two formulations. Conclusions: Nanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants.

One-year trends from the LANDMARC trial: A 3-year, pan-India, prospective, longitudinal study on the management and real-world outcomes of type 2 diabetes mellitus.

INTRODUCTION: Longitudinal data on management and progression of type 2 diabetes mellitus (T2DM) in India are scarce. LANDMARC (CTRI/2017/05/008452), first-of-its-kind, pan-India, prospective, observational study aimed to evaluate real-world patterns and management of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrolment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. The first-year trends for glycaemic control, therapy and diabetic complications, including those from metropolitan and non-metropolitan cities are reported here. RESULTS: Of 6236 enrolled participants, 5654 completed 1 year in the study. Although the overall mean glycated haemoglobin (HbA1c) improved by 0.5% (baseline: 8.1%) at 1 year, only 20% of the participants achieved HbA1c <7%. Participants from metropolitan and non- metropolitan cities showed similar decrease in glycaemic levels (mean change in HbA1c: -0.5% vs. -0.5%; p = .8613). Among diabetic complications, neuropathy was the predominant complication (815/6236, 13.1% participants). Microvascular complications (neuropathy, nephropathy and retinopathy) were significantly (p < .0001) higher in non-metropolitan than metropolitan cities. Hypertension (2623/6236, 78.2%) and dyslipidaemia (1696/6236, 50.6%) continued to be the most commonly reported cardiovascular risks at 1 year. After 1 year, majority of the participants were taking only oral anti-diabetic drugs (OADs) (baseline: 4642/6236 [74.4%]; 1 year: 4045/6013 [67.3%]), while the proportion of those taking insulin along with OADs increased (baseline: 1498/6236 [24.0%] vs. 1 year: 1844/6013 [30.7%]). Biguanides and sulfonylureas were the most used OADs. The highest increase in use was seen for dipeptidyl peptidase-IV inhibitors (baseline: 3047/6236 [48.9%]; 1 year: 3529/6013 [58.7%]). Improvement in all glycaemic parameters was significantly (p < .0001) higher in the insulin vs. the insulin-naïve subgroups; in the insulin-naïve subgroup, no statistical difference was noted in those who received >3 vs. ≤3 OADs. CONCLUSIONS: First-year trends of the LANDMARC study offer insights into real-world disease progression, suggesting the need for controlling risk factors and timely treatment intensification in people with T2DM.

The state-of-art of design and research for Pelton turbine casing, weight estimation, counterpressure operation and scientific challenges.

The Pelton turbine is the most widespread and efficient impulse hydropower turbine. The Pelton casing is a static, but key component: the internal hydrodynamic phenomena affect the performance of the hydropower plant, the vibration of the equipment and water quality (dissolved oxygen downstream). However, the literature information is very fragmented and not well organized, so that the design is generally based on empirical rules and on proper know-how of hydropower companies. In this paper, the state-of-the-art of the Pelton casing is reviewed and organized under three macro areas: hydraulics, mechanics (vibrations and weight) and aeration. The preliminary design procedure is described and discussed in light of recent scientific results, and the open questions and research challenges are highlighted. Innovative case studies are described (including counterpressure operation) and a dataset of installed casings (not available in literature) is elaborated to derive an empirical equation to estimate the casing weight. The efficiency can be improved by 3% by an optimal fluid dynamic design and a better understanding of the internal hydrodynamics. Proper inserts can improve the hydraulic efficiency by 2%, reduce the weight (by about 12%) and better bear the vibrations. Several scientific questions are still open, and a better understanding of the fluid structure interaction is needed to improve efficiency, operation and water quality.

Baseline characteristics of participants in the LANDMARC trial: A 3-year, pan-india, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

INTRODUCTION: Longitudinal data on progression, complications, and management of type 2 diabetes mellitus (T2DM) across India are scarce. LANDMARC (CTRI/2017/05/008452), the first pan-India, longitudinal, prospective, observational study, aims to understand the management and real-world outcomes of T2DM over 3 years. METHODS: Adults (≥25 to ≤60 years old at T2DM diagnosis; diabetes duration ≥2 years at enrollment; controlled/uncontrolled on ≥2 anti-diabetic agents) were enrolled. Baseline characteristics were analyzed using descriptive statistics. RESULTS: Of the 6279 recruited participants, 6236 were eligible for baseline assessment (56.6% [n/N = 3528/6236] men; mean ± SD age: 52.1 ± 9.2 years, diabetes duration: 8.6 ± 5.6 years). mean ± SD HbA1c, fasting plasma glucose, and postprandial glucose values were 64 ± 17 mmol/mol (8.1 ± 1.6%), 142.8 ± 50.4 mg/dl, and 205.7 ± 72.3 mg/dl, respectively. Only 25.1% (n/N = 1122/6236) participants had controlled glycemia (HbA1c < 53 mmol/mol, <7%). Macrovascular and microvascular complications were prevalent in 2.3% (n/N = 145/6236) and 14.5% (n/N = 902/6236) participants, respectively. Among those with complications, non-fatal myocardial infarction (n/N = 74/145, 51.0%) and neuropathy (n/N = 737/902, 81.7%) were the most reported macrovascular and microvascular complication, respectively. Hypertension (n/N = 2566/3281, 78.2%) and dyslipidemia (n/N = 1635/3281, 49.8%) were the most reported cardiovascular risks. Majority (74.5%; n/N = 4643/6236) were taking oral anti-diabetic drugs (OADs) only, while 24.4% (n/N = 1522/6236) participants were taking OADs+insulin. Biguanides (n/N = 5796/6236, 92.9%) and sulfonylureas (n/N = 4757/6236, 76.3%) were the most reported OADs. Basal (n/N = 837/6236, 13.4%) and premix (n/N = 684/6236, 11.0%) insulins were the most reported insulins. CONCLUSIONS: Baseline data from LANDMARC help understand the clinical/medical profile of study participants and underscore the extent of suboptimal glycemic control and prevalence of associated complications in a vast majority of Indians with T2DM.

Suboptimal glycemic control among subjects with diabetes mellitus in India: a subset analysis of cross-sectional wave-7 (2016) data from the International Diabetes Management Practices Study (IDMPS).

OBJECTIVE: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. METHODS: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. RESULTS: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. CONCLUSION: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

Spontaneous Bilateral Subdural Hematoma in a Patient with Falciparum Malaria.

A 70-year old female presented with complaints of fever with chills, headache for 15 days and altered sensorium for 7 days. Peripheral blood smear showed ring form of P. falciparum and CT brain revealed bilateral subdural hematoma. Patient received Artesunate based combination therapy and recovered completely without surgical intervention within 8 days of admission.

Prevalence and real-world assessment of central aortic blood pressure in adult patients with essential hypertension uncontrolled on single anti-hypertensive agents.

OBJECTIVE: To assess the prevalence of high central aortic pressure (CAP) in Indian patients with uncontrolled essential hypertension while on anti-hypertensive monotherapy. Also, to determine correlation between brachial blood pressure (BBP) and CAP, and ascertain if it is impacted by anti-hypertensive drug class and patients' age. METHODS: In this real-world, observational, prospective study, patients (30-70 years) with uncontrolled BBP (systolic BP [SBP] ≥140 mmHg or diastolic BP [DBP] ≥90 mmHg) were enrolled. Treatment was adjusted at Visit 1 (baseline), based on BBP and at treating physicians' discretion. Primary endpoint was proportion of patients with uncontrolled central aortic SBP (>125 mmHg) at baseline. Secondary endpoints were comparison of BBP and CAP across drugs classes and age groups at baseline and Visit 2 (End-of-study, ∼8 weeks post-baseline), and proportion of patients with uncontrolled central SBP at end-of-study. RESULTS: Of 2030 patients screened, 1949 patients reported at baseline and 1740 patients completed end-of-study visit. Central SBP was >125 mmHg for 84.3% patients at baseline, and 48% patients at end-of-study. Interestingly, at end-of-study, 6.6% patients still had uncontrolled brachial SBP and controlled central SBP, while 13.6% patients had uncontrolled central SBP and controlled brachial SBP. At both visits, brachial SBP and central SBP showed positive correlation across most drug classes and age groups. At baseline, ACE inhibitors showed better efficacy than other drug classes. At end-of-study, BP control was better with fixed-dose combinations, though free-drug combinations were more frequently prescribed. CONCLUSION: Measurement of CAP along with BBP can be vital in management of hypertension. CTRI REGISTRATION NUMBER: CTRI/2015/10/006302.

Emerging therapies for diverticular disease of the colon.

Diverticular disease (DD) of the colon is common. This paper reviews the evidence supporting the role of some of the conventional medical therapies such as fiber and nonabsorbable antibiotics in the treatment of DD. More importantly, it will review the emerging body of evidence supporting the use of 5-aminosalicylic acid and probiotics for symptomatic or complicated DD. Possible mechanisms supporting the role of 5-aminosalicylates will also be discussed. On the basis of strength of the evidence supporting each medical intervention, recommendations will be graded in an evidence-based fashion. Finally, an evidence-based algorithmic approach is proposed for the medical management of DD. This paper does not discuss the use of absorbable antibiotics such as ciprofloxin and metronidazole, which are discussed in all standard textbooks. The purpose of this paper is to discuss newer recommendations.

Drug-induced pancreatitis: an update.

BACKGROUND AND AIMS: Many frequently prescribed drugs are suspected to cause acute pancreatitis (AP). The goal of this paper is to bring to light the often occult but real problem of drug-induced pancreatitis (DIP). METHODS: We searched the National Library of Medicine/Pubmed for reported cases of DIP from 1966 to April 30, 2004. Medications implicated in AP are classified based on the strength of evidence into one of three classes of drugs associated with pancreatitis. We reviewed the top 100 prescription medications in the United States for their association with AP. RESULTS: Class I medications (medications implicated in greater than 20 reported cases of acute pancreatitis with at least one documented case following reexposure): didanosine, asparaginase, azathioprine, valproic acid, pentavalent antimonials, pentamidine, mercaptopurine, mesalamine, estrogen preparations, opiates, tetracycline, cytarabine, steroids, trimethoprim/sulfamethoxazole, sulfasalazine, furosemide, and sulindac. Class II medications (medications implicated in more than 10 cases of acute pancreatitis): rifampin, lamivudine, octreotide, carbamazepine, acetaminophen, phenformin, interferon alfa-2b, enalapril, hydrochlorothiazide, cisplatin, erythromycin, and cyclopenthiazide. Class III medications (all medications reported to be associated with pancreatitis). Of the top 100 most frequently prescribed medications in the United States, 44 have been implicated in AP, 14 of them fall into either Class I or II of medications associated with AP. CONCLUSIONS: Among adverse drug reactions, pancreatitis is often-ignored because of the difficulty in implicating a drug as its cause. The physician should have a high index of suspicion for DIP, especially in specific subpopulations such as geriatric patients who may be on multiple medications, HIV+ patients, cancer patients, and patients receiving immunomodulating agents.