Management of type 2 diabetes mellitus: insights into prescribing trends

Background: Recently, management of type 2 diabetes mellitus (T2DM) has changed with advent of novel agents like DPP4i, SGLT2i and GLP-1 agonist. Of these, DPP4i have emerged as promising agents as monotherapy and as an add-on to metformin for improved glycaemic control.  This survey was planned to explore current prescribing trends of physicians of India for the management of T2DM.Methods: This was a prospective, cross sectional, questionnaire-based survey of physicians and endocrinologist across different geographic areas in India. A survey questionnaire consisting of 10 questions related to management of T2DM in real-world clinical settings was prepared, validated in a small group of physicians and then administered to physicians and endocrinologists.Results: Responses from 502 physicians were received. About 60% physicians prefer DPP4i as first add-on to metformin followed by sulfonylurea (SU) (30%). Amongst DPP4i, vildagliptin and sitagliptin were preferred by 48% and 28% physicians respectively as first add-on to metformin. For patients uncontrolled on metformin + SU therapy, 54 % physicians prefer DPP4i as second add-on. Vildagliptin is perceived to have the better efficacy and safety data, as suggested by 40% and 43% physicians respectively. Large number of physicians (48%) were hesitant to prescribe teneligliptin due to insufficient data. SGLT2 inhibitors are preferred as third add-on by 44% physicians.Conclusions: DPP4i are being increasingly preferred by physician as an add-on to metformin. Among DPP4i, the survey revealed that vildagliptin is the most preferred DPP4i as an add-on to metformin possibly owing to its established safety and efficacy data

Clinical challenges with excipients in insulin formulations and role of concentrated insulin

Most of the insulin formulations in clinical use contain phenol, meta-cresol or both as excipients. These excipients in insulin preparations provide stability and have antimicrobial properties. However, they are reported to be associated with undesirable side-effects especially localised allergic reactions. Amount of excipients injected per unit dose of insulin is a major determining factor in causation of these reactions. This review discusses the excipients in different insulin formulations available in India with potential of precipitating undesirable effects and the use of concentrated insulins to reduce these complications. To avoid the detrimental effects associated with excipients, removal of preservatives or use of insulin preparations devoid of excipients can be an option. Besides these approaches, one approach that can be considered is the use of concentrated insulin to reduce the volume of insulin dose and thereby the excipients. Concentrated insulins address the high insulin requirements of the growing population of patients with type 2 diabetes who require higher insulin doses. Concentrated insulins help in reduction of dose volume as well as amount of excipients injected per unit dose of insulin. U200 (concentrated r-DNA Human Insulin Premix 30/70-200 IU/ml) can be advantageous with better absorption from smaller quantity injected, lesser variability in absorption, lesser pain and discomfort due to smaller quantity, lesser chances of hypoglycaemia all of which can lead to better patient compliance. Thus, concentrated insulin U200 can be one of the alternatives to prevent/reduce clinical complications with excipients in insulins

Adjuvant drugs in management of osteoarthritis: spotlight on type II collagen

Osteoarthritis (OA) is a common musculoskeletal disorder that affects large and small joints and is seen in all ages due to diverse aetiologies. Pain, joint stiffness and limitation of daily activities affects the quality of life of individuals with OA. Conventional analgesics like non-steroidal anti-inflammatory drugs affect pain and inflammatory component but do not target the disease pathogenesis. Damage to the joint cartilage is central to the pathogenesis of OA. Better understanding of the pathogenesis has led to evolution of various adjuvant drugs in management of OA. Among them, undenatured type II collagen induces immune tolerance and thereby provide benefits by reducing the joint damage. Studies assessing efficacy and safety of undenatured type II collagen in OA have shown to reduce clinical symptoms like pain, joint stiffness and improvement in physical activities, and thus improving the quality of life. It is well tolerated and safe for use in OA. This article discusses the pathophysiology of OA with inflammation and beyond, and overviews the various drugs that are used as adjuvants in the management of OA with special focus on the use of type 2 collagen

Ternatin and improved synthetic variants kill cancer cells by targeting the elongation factor-1A ternary complex.

Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series of cyclic peptides with partially elucidated structures, we designed synthetic variants of ternatin, a cytotoxic and anti-adipogenic natural product whose molecular mode of action was unknown. The new ternatin variants are cytotoxic toward cancer cells, with up to 500-fold greater potency than ternatin itself. Using a ternatin photo-affinity probe, we identify the translation elongation factor-1A ternary complex (eEF1A·GTP·aminoacyl-tRNA) as a specific target and demonstrate competitive binding by the unrelated natural products, didemnin and cytotrienin. Mutations in domain III of eEF1A prevent ternatin binding and confer resistance to its cytotoxic effects, implicating the adjacent hydrophobic surface as a functional hot spot for eEF1A modulation. We conclude that the eukaryotic elongation factor-1A and its ternary complex with GTP and aminoacyl-tRNA are common targets for the evolution of cytotoxic natural products

Epidemiologic study of myelodysplastic syndromes in a multiethnic, inner city cohort

Little is known about the epidemiology of MDS in minority populations. The IPSS and newly released IPSS-R are important clinical tools in prognostication of patients with MDS. Therefore, we conducted a retrospective epidemiological analysis of MDS in an ethnically diverse cohort of patients. Demographics, disease characteristics, and survival were determined in 161 patients seen at Montefiore Medical Center from 1997 to 2011. We observed that Hispanics presented at a younger age than blacks and whites (68 vs. 73.7 vs. 75.6 years); this difference was significant (p = 0.01). A trend towards greater prevalence of thrombocytopenia in Hispanics was observed, but this was not significant (p = 0.08). No other differences between the groups were observed. Overall median survival after diagnosis was the highest among Hispanics (8.6 years) followed by blacks (6.2 years) and Caucasians (3.7). Adjusted hazard ratios however did not show significant differences in risk of death between the groups. The IPSS-R showed slightly better discrimination when compared to the IPSS in this cohort (Somers Dxy 0.39 vs. 0.35, respectively) but observed survival more was more closely approximated by IPSS than by IPSS-R. Our study highlights the possibility of ethnic differences in the presentation of MDS and raises questions regarding which prognostic system is more predictive in this population

Osmotic controlled drug delivery system (OSMO technology) and its impact on diabetes care

Recently, focus on the development of controlled release drug delivery system has increased, as existing drugs exhibit certain pharmacokinetic limitations. The major goal of designing sustained release formulations is to improve the drug performance by prolonged duration of drug action, decreased frequency of dosing and reduced side effects by using smallest quantity of drug administered by the most suitable route. Osmotic-controlled release oral delivery system (OSMO technology) is the most promising strategy based system for sustained delivery of drug. Drug can be delivered in a controlled manner over a long period of time by the process of osmosis. Osmotic drug delivery system appears to be a promising solution for the limitations of conventional extended release formulations by virtue of their distinguished technological features. The present review describes briefly about various controlled drug delivery systems with special focus on advantages of osmotic-controlled release oral delivery system related to diabetes therapy and improved compliance

A study of bronchial asthma in school going children in Southern part of Rajasthan

Background: Asthma is a chronic and common inflammatory disease involving mainly large airways of lungs. Childhood asthma is common chronic illness among school going children and is usually underdiagnosed and undertreated. The aim of the present study was to find out of the prevalence of Bronchial asthma in school going children of age group 6-12 years in southern part of Rajasthan (India), and its relation with gender, socio-economic status and heredity.Methods: A questionnaire-based study has been carried out in 1500 children of 6 to 12 years age group in four schools of Udaipur city (Rajasthan, India) with a response rate of 60.23% (904/1500).Results: The overall prevalence of asthma observed is 4.75% (43/904). The prevalence is higher among boys (5.55%) as compared to girls (3.75%). Further the prevalence is higher in upper (7.18%) and upper middle class (7.14%) children as compared to lower middle (4.84%) and upper lower class (2.01%) socioeconomic status. The children with positive family history of asthma also have higher prevalence (26.31%) of asthma.Conclusions: The prevalence of childhood asthma in Udaipur city is relatively lower and supports the already reported relation with gender, socioeconomic status and heredity.

Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

Abstract Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60]).</jats:p

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council