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Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction

Garg M, Khanna D, Kalra S, Balakumar P

Fundam Clin Pharmacol, 2016 Oct;30(5):394-405.
PMID: 27148865 DOI: 10.1111/fcp.12204

Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.
Fulltext Defining Disease Progression and Drug Durability in Type 2 Diabetes Mellitus

Kalra S, Kamaruddin NA, Visvanathan J, Santani R

Eur Endocrinol, 2019 Aug;15(2):67-69.
PMID: 31616495 DOI: 10.17925/EE.2019.15.2.67

This communication shares insights into the definition of disease progression and drug durability in type 2 diabetes. Disease progression may be defined as gradual worsening of beta-cell function, clinically observed as an increase in drug dosage, drug frequency or number of glucose lowering drugs needed to maintain HbA1c control; and/or a ≥0.5% rise in HbA1c, unexplained by acute, modifiable factors, while using the same drug regimen; and/or as the occurrence or worsening of cardiovascular or microvascular complications, in spite of standard care, over a pre-specified time period. Durability of a drug or a drug combination may be defined as its ability to postpone or delay progression of disease, in a safe and well tolerated manner. Thus, all drugs that are able to prevent disease progression (i.e., postpone loss of glycaemic control, need for intensification of therapy or onset or worsening of complications) may be termed 'durable'.
Fulltext Correction to: Impact of migraine on workplace productivity and monetary loss: a study of employees in banking sector in Malaysia

Wong LP, Alias H, Bhoo-Pathy N, Chung I, Chong YC, Kalra S, et al.

J Headache Pain, 2020 Aug 18;21(1):104.
PMID: 32811428 DOI: 10.1186/s10194-020-01172-9

An amendment to this paper has been published and can be accessed via the original article.
Fulltext Impact of migraine on workplace productivity and monetary loss: a study of employees in banking sector in Malaysia

Wong LP, Alias H, Bhoo-Pathy N, Chung I, Chong YC, Kalra S, et al.

J Headache Pain, 2020 Jun 08;21(1):68.
PMID: 32513174 DOI: 10.1186/s10194-020-01144-z

BACKGROUND/OBJECTIVE: Productivity and monetary loss due to migraine in the workplace may be substantial. This study aimed to determine the impact of migraine on productivity and monetary lost among employees in the banking sectors, in a multiethnic middle income country.
METHODS: A cross-sectional online survey was conducted among employees in two multinational banks in Malaysia between April and July 2019. Screening for migraine was conducted using the self-administered ID-Migraine™ questionnaire. Migraine-related disability (MIDAS) and headache frequency were recorded. Impact of migraine on work productivity and activities were evaluated using the Work Productivity and Activity Impairment (WPAI) questionnaire.
RESULTS: Of the 1268 employees who submitted complete responses, 47.2% (n = 598) were screened positive for migraine. Strikingly, the mean percent productivity loss at work (presenteeism) was almost 20-fold higher than the mean percent work time missed due to migraine (absenteeism) (39.1% versus 1.9%). The mean percent productivity loss in regular activity (activity impairment) and overall work productivity loss (work impairment) was 38.4% and 39.9%, respectively. It was also found that the costs related to presenteeism (MYR 5392.6) (US$1296) was 3.5-fold higher than absenteeism (MYR1,548.3) (US$370). Highest monetary loss related to presenteeism was reported in migraineurs with frequency of headache of above 3 days (MYR 25,691.2) (US$6176), whereas highest monetary loss related to absenteeism was reported in migraineurs with MIDAS grade IV (MYR 12,369.1) (US$2973). Only 30% of migraineurs of MIDAS grade IV reported taking prescribed medication. Notably, a vast majority (96%) of migraineurs who had three or lower episodes of migraine per month did not seek treatment.
CONCLUSION: The significant impact of migraine on work productivity and regular activity, appears to lead to substantial monetary loss attributed to not only absenteeism, but more importantly to presenteeism. This study also highlights the unmet needs in migraine management among employees in the banking sector.
Fulltext Choice of insulin in type 2 diabetes: a Southeast Asian perspective

Kalra S, Thai HQ, Deerochanawong C, Su-Yen G, Mohamed M, Latt TS, et al.

Indian J Endocrinol Metab, 2017;21(3):478-481.
PMID: 28553609 DOI: 10.4103/ijem.IJEM_82_17

Southeast Asia faces a diabetes epidemic, which has created significant challenges for health care. The unique Asian diabetes phenotype, coupled with peculiar lifestyle, diet, and healthcare-seeking behavior, makes it imperative to develop clinical pathways and guidelines which address local needs and requirements. From an insulin-centric viewpoint, the preparations prescribed in such pathways should be effective, safe, well tolerated, nonintrusive, and suitable for the use in multiple clinical situations including initiation and intensification. This brief communication describes the utility of premixed or dual action insulin in such clinical pathways and guidelines.
Earlier diagnosis of peripheral neuropathy in primary care: A call to action

Gad H, Kalra S, Pinzon R, Gracia RN, Yotsombut K, Coetzee A, et al.

J Peripher Nerv Syst, 2024 Mar;29(1):28-37.
PMID: 38268316 DOI: 10.1111/jns.12613

Peripheral neuropathy (PN) often remains undiagnosed (~80%). Earlier diagnosis of PN may reduce morbidity and enable earlier risk factor reduction to limit disease progression. Diabetic peripheral neuropathy (DPN) is the most common PN and the 10 g monofilament is endorsed as an inexpensive and easily performed test for DPN. However, it only detects patients with advanced neuropathy at high risk of foot ulceration. There are many validated questionnaires to diagnose PN, but they can be time-consuming and have complex scoring systems. Primary care physicians (PCPs) have busy clinics and lack access to a readily available screening method to diagnose PN. They would prefer a short, simple, and accurate tool to screen for PN. Involving the patient in the screening process would not only reduce the time a physician requires to make a diagnosis but would also empower the patient. Following an expert meeting of diabetologists and neurologists from the Middle East, South East Asia and Latin America, a consensus was formulated to help improve the diagnosis of PN in primary care using a simple tool for patients to screen themselves for PN followed by a consultation with the physician to confirm the diagnosis.
ISPAD Clinical Practice Consensus Guidelines: Fasting during Ramadan by young people with diabetes

Deeb A, Elbarbary N, Smart CE, Beshyah SA, Habeb A, Kalra S, et al.

Pediatr Diabetes, 2020 02;21(1):5-17.
PMID: 31659852 DOI: 10.1111/pedi.12920
Fulltext A Practitioner's Toolkit for Insulin Motivation in Adults with Type 1 and Type 2 Diabetes Mellitus: Evidence-Based Recommendations from an International Expert Panel

Kalra S, Bajaj S, Sharma SK, Priya G, Baruah MP, Sanyal D, et al.

Diabetes Ther, 2020 Mar;11(3):585-606.
PMID: 31981212 DOI: 10.1007/s13300-020-00764-7

AIM: To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner's toolkit for insulin motivation in the management of diabetes mellitus (DM).
BACKGROUND: Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization.
REVIEW RESULTS: After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy.
CONCLUSIONS: In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.
Fulltext Asian Best Practices for Care of Diabetes in Elderly (ABCDE)

Kalra S, Dhar M, Afsana F, Aggarwal P, Aye TT, Bantwal G, et al.

Rev Diabet Stud, 2022 Jun 30;18(2):100-134.
PMID: 35831938 DOI: 10.1900/RDS.2022.18.100

The elderly population with diabetes is diverse with the majority experiencing a decline in physical and mental capabilities, impacting the entire diabetes management process. Therefore, a need for geriatric-specific guidelines, especially for the Asian population, was identified and subsequently developed by an expert panel across government and private institutions from several Asian countries. The panel considered clinical evidence (landmark trials, position papers, expert opinions), recommendations from several important societies along with their decades of clinical experience and expertise, while meticulously devising thorough geriatric-specific tailored management strategies. The creation of the ABCDE best practices document underscores and explores the gaps and challenges and determines optimal methods for diabetes management of the elderly population in the Asian region.
Fulltext Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel

Kalra S, Shaikh S, Priya G, Baruah MP, Verma A, Das AK, et al.

Diabetes Ther, 2021 Feb;12(2):465-485.
PMID: 33367983 DOI: 10.1007/s13300-020-00973-0

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.
Fulltext Correction to: Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel

Kalra S, Shaikh S, Priya G, Baruah MP, Verma A, Das AK, et al.

Diabetes Ther, 2021 Sep;12(9):2627-2629.
PMID: 34363138 DOI: 10.1007/s13300-021-01120-z
Fulltext Expert Opinion: Patient Selection for Premixed Insulin Formulations in Diabetes Care

Kalra S, Czupryniak L, Kilov G, Lamptey R, Kumar A, Unnikrishnan AG, et al.

Diabetes Ther, 2018 Dec;9(6):2185-2199.
PMID: 30390228 DOI: 10.1007/s13300-018-0521-2

Premixed insulins are an important tool for glycemic control in persons with diabetes. Equally important in diabetes care is the selection of the most appropriate insulin regimen for a particular individual at a specific time. Currently, the choice of insulin regimens for initiation or intensification of therapy is a subjective decision. In this article, we share insights, which will help in rational and objective selection of premixed formulations for initiation and intensification of insulin therapy. The glycemic status and its variations in a person help to identify the most appropriate insulin regimen and formulation for him or her. The evolution of objective glucometric indices has enabled better glycemic monitoring of individuals with diabetes. Management of diabetes has evolved from a 'glucocentric' approach to a 'patient-centered' approach; patient characteristics, needs, and preferences should be evaluated when considering premixed insulin for treatment of diabetes.Funding: Novo Nordisk, India.