Search

Chaitanya Dutt,1 Joao Eduardo Nunes Salles,2 Shashank Joshi,3 Tiny Nair,4 Subhankar Chowdhury,5 Ambrish Mithal,6 Viswanathan Mohan,7 Ravi Kasliwal,8 Satyawan Sharma,9 Jan Tijssen,10 Nikhil Tandon11 1Research and Development, Torrent Pharmaceuticals Ltd, Ahmedabad, Gujarat, India; 2Discipline of Endocrinology, Medical Sciences of Santa Casa de São Paulo, São Paulo, Brazil; 3Department of Endocrinology, Lilavati Hospital, Mumbai, Maharashtra, India; 4Department of Cardiology, PRS Hospital, Thiruvananthapuram, Kerala, India; 5Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India; 6Department of Endocrinology & Diabetes, Max Healthcare, New Delhi, India; 7Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India; 8Medanta- The Medicity, Gurgaon, Haryana, India; 9Department of Cardiology, Bombay Hospital and Medical Research Center, Mumbai, Maharashtra, India; 10Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; 11Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Chaitanya Dutt, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel +91 9825606901, Email Cdutt@torrentpharma.comAbstract: The epidemic of obesity or adiposity-based chronic diseases presents a significant challenge with the rising prevalence of morbidities and mortality due to atherosclerotic cardiovascular diseases (ASCVD), especially in low- and middle-income countries (LMIC). The underlying pathophysiology of metabolic inflexibility is a common thread linking insulin resistance to cardiometabolic-based chronic disease (CMBCD), including dysglycemia, hypertension, and dyslipidemia progressing to downstream ASCVD events. The complex CMBCD paradigm in the LMIC population within the socio-economic and cultural context highlights considerable heterogeneity of disease predisposition, clinical patterns, and socio-medical needs. This review intends to summarize the current knowledge of CMBCD. We describe recently established or emerging trends for managing risk factors, assessment tools for evaluating ASCVD risk, and various pharmacological and non-pharmacological measures particularly relevant for LMICs. A CMBCD model positions insulin resistance and β-cell dysfunction at the summit of the disease spectrum may improve outcomes at a lower cost in LMICs. Despite identifying multiple pathophysiologic disturbances constituting CMBCD, a large percentage of the patient at risk for ASCVD remains undefined. Targeting dysglycemia, dyslipidemia, and hypertension using antihypertensive, statins, anti-glycemic, and antiplatelet agents has reduced the incidence of ASCVD. Thus, primordial prevention targeting pathophysiological changes that cause abnormalities in adiposity and primary prevention by detecting and managing risk factors remains the foundation for CMBCD management. Therefore, targeting pathways that address mitochondrial dysfunction would exert a beneficial effect on metabolic inflexibility that may potentially correct insulin resistance, β cell dysfunction and, consequently, would be therapeutically effective across the entire continuum of CMBCD.Keywords: mitochondrial modulator, insulin resistance, diabetes mellitus, dyslipidemia hypertension, non-high-density lipoprotein-cholesterol, triglycerides, apolipoprotein B

Deepa Joshi,1 Prashant GJ,1 Shohini Ghosh,1 Anookh Mohanan,1 Shashank Joshi,2 Viswanathan Mohan,3 Subhankar Chowdhury,4 Chaitanya Dutt,1 Nikhil Tandon5 1Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India; 2Lilavati Hospital, Mumbai, India; 3Dr. Mohan’s Diabetes Specialities Centre (Madras Diabetes Research Foundation), Tamil Nadu, India; 4Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, India; 5Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Deepa Joshi, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel + 91 7971315571, Email deepajoshi@torrentpharma.comBackground: TRC150094, a novel mitochondrial modulator, reduces insulin resistance and is expected to improve the trinity of dysglycemia, dyslipidemia, and hypertension. In this multi-dose phase-2 study, we evaluated the safety and efficacy of TRC150094 in diabetic subjects with dyslipidemia receiving standard of care.Methods: A randomized, multicenter, double-blind, placebo-controlled, parallel-group, Phase 2 study was conducted in 225 subjects from July 2013 to August 2015. The key inclusion criteria were body mass index of 23– 35 kg/m2, age between 30 and 65 years, fasting glucose of ≥ 126 or glycated hemoglobin (HbA1c) of ≥ 6.4% stabilized on treatment with ≤ 2 oral hypoglycemic agents, apolipoprotein-B (apo-B) ≥ 100 mg/dL, serum triglyceride (TG) ≥ 150 mg/dL, systolic blood pressure (SBP) ≥ 130 mmHg, and diastolic blood pressure (DBP) ≥ 85 mmHg with/without antihypertensive treatment. The subjects were randomly assigned to one of three TRC150094 doses (25, 50, or 75 mg) or placebo for 24 weeks. The outcomes assessed included fasting plasma glucose (FPG), insulin, mean arterial blood pressure (MAP), and apoB. In addition, safety and tolerability were assessed.Results: A reduction for dose up to 50 mg was noted for FPG in the range of 13.9 to 21.7 mg/dL (p < 0.05 for TRC150094 25 and 50 mg), fasting insulin reduction in the range 2.7 to 6.0 mU/L (all doses, p > 0.05), and improved HOMA-IR (− 2.0 to − 2.5) (all doses, p > 0.05) compared to placebo after 24 weeks of treatment. Furthermore, a significant reduction in MAP in the range 3.1 to 4.2 mmHg (p < 0.05 for TRC150094 25 and 75 mg) was noted. In addition, TRC150094 treatment was weight neutral, had a favorable effect on lowering atherogenic lipid fractions, including non-HDL cholesterol (− 6.8 mg/dL at 50 mg dose). Adverse events were mild to moderate in nature and not dose-related. One adverse event not related to treatment led to the discontinuation of the study. Overall, TRC150094 was safe and well tolerated for up to 24 weeks.Conclusion: In this study, TRC150094 treatment in the dose range of 25 to 50 mg showed improvement in various components of CMBCD, ie, dysglycemia, dyslipidemia, and hypertension.Trial Registration: This study was registered in the Clinical Trial Registry of India. Trial registration number: CTRI/2013/03/003444. Date of registration: 4th March 2013.Keywords: cardiometabolic-based chronic disease, mitochondrial modulator, type 2 diabetes, non-HDL cholesterol, hypertension, dyslipidemia

Dominic Pilon,1 Kruti Joshi,2 Neeta Tandon,2 Marie-Hélène Lafeuille,1 Rhiannon L Kamstra,1 Bruno Emond,1 Patrick Lefebvre2 1Groupe d’analyse, Ltée, Montréal, QC, Canada; 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Poor antipsychotic (AP) adherence is a key issue in patients with schizophrenia. First-generation antipsychotic (FGA) and second-generation antipsychotic (SGA) long-acting injectable therapies (LAI) may improve adherence compared to oral antipsychotics (OAP). The objective of the study was to compare treatment adherence and persistence in Medicaid patients with schizophrenia initiated on first-generation long-acting injectable therapies (FGA-LAI) or second-generation long-acting injectable therapies (SGA-LAI) versus OAP.Methods: Adults with schizophrenia initiated on FGA-LAI, SGA-LAI, or OAP on or after January 2010 were identified using a six-state Medicaid database (January 2009– March 2015). Outcomes were assessed during the 12 months following treatment initiation. Index medication adherence was assessed using the proportion of days covered ≥80%, while persistence was assessed as no gap of ≥30, ≥60, or ≥90 days between days of supply. Outcomes were compared between FGA/SGA-LAI and OAP cohorts using chi-squared tests and adjusted odds ratios (OR).Results: During follow-up, AP polypharmacy was more common in FGA-LAI patients (N=1,089; 36%; P=0.029) and less common in SGA-LAI patients (N=2,209; 27%; P

Nidhi Tandon, Vijay Ramakrishnan, Shaji K Kumar Division of Hematology, Mayo Clinic, Rochester, MN, USA Abstract: The incorporation of various novel therapies has resulted in a significant survival benefit in newly diagnosed and relapsed patients with multiple myeloma (MM) over the past decade. Despite these advances, resistance to therapy leads to eventual relapse and fatal outcomes in the vast majority of patients. Hence, there is an unmet need for new safe and efficacious therapies for continued improvement in outcomes. Given the role of epigenetic aberrations in the pathogenesis and progression of MM and the success of histone deacetylase inhibitors (HDACi) in other malignancies, many HDACi have been tried in MM. Various preclinical studies helped us to understand the antimyeloma activity of different HDACi in MM as a single agent or in combination with conventional, novel, and immune therapies. The early clinical trials of HDACi depicted only modest single-agent activity, but recent studies have revealed encouraging clinical response rates in combination with other antimyeloma agents, especially proteasome inhibitors. This led to the approval of the combination of panobinostat and bortezomib for the treatment of relapsed/refractory MM patients with two prior lines of treatment by the US Food and Drug Administration. However, it remains yet to be defined how we can incorporate HDACi in the current therapeutic paradigms for MM that will help to achieve longer disease control and significant survival benefits. In addition, isoform-selective and/or class-selective HDAC inhibition to reduce unfavorable side effects needs further evaluation. Keywords: HDAC inhibitors, Panobinostat, epigenetics, myeloma, relapse

Susan C Bolge,1 Amir Goren,2 Neeta Tandon1 1Health Economics and Outcomes Research, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 2Health Outcomes Practice, Kantar Health, New York, NY, USA Objective: To examine reasons why rheumatoid arthritis patients discontinued subcutaneous (SQ) anti-tumor necrosis factor (anti-TNF) treatment in the past 12 months, so as to help inform successful, uninterrupted therapy.Methods: Data were collected in March and April 2011 using self-reported, internet-based questionnaires. Study inclusion criteria comprised: rheumatoid arthritis diagnosis; discontinuation of SQ anti-TNF medication (adalimumab, certolizumab, etanercept, or golimumab) within the past 12 months; aged ≥18 years; United States residency; and consent to participate. Patients reported primary and other reasons for discontinuation of their most recently discontinued anti-TNF.Results: Questionnaires from 250 patients were analyzed; 72.8% were female, 80.8% were white, and median age was 51 years. Patients had discontinued etanercept (n=109), adalimumab (n=98), certolizumab (n=24), or golimumab (n=19) within the past 12 months. When prompted about their primary reason for discontinuation, lack of effectiveness (40.8%) was cited most often, followed by injection experience (18.4%). Combining prompted primary and other reasons for discontinuation, 60.8% of patients reported lack of effectiveness, while 40.8% reported injection experience, which included: pain/burning/discomfort after injection (14.4%); pain/burning/discomfort during injection (13.2%); injection reactions such as redness/swelling after injection (12.4%); dislike of self-injection (11.6%); dislike of frequency of injection (10.4%); and fear of injection/needles (6.8%). Conclusion: From the patient perspective, there are unmet needs with regard to the effectiveness and injection experience associated with SQ anti-TNF medications, which may lead to discontinuation. Treatment options with a better injection experience may address these needs. These results demonstrate the importance of including the patient perspective when making prescribing decisions or payer access and coverage decisions. Keywords: persistence, subcutaneous injection, anti-TNF

Nuri I Akkus,1 Abdulrahman Abdulbaki,1 Enrique Jimenez,2 Neeraj Tandon2 1Department of Cardiology, Louisiana State University Health Sciences Center Shreveport, Shreveport, LA, USA; 2Department of Cardiology, Overton Brooks VA Medical Center, Shreveport, LA, USA Abstract: Atherectomy is a procedure which is performed to remove atherosclerotic plaque from diseased arteries. Atherosclerotic plaques are localized in either coronary or peripheral arterial vasculature and may have different characteristics depending on the texture of the plaque. Atherectomy has been used effectively in treatment of both coronary and peripheral arterial disease. Atherectomy devices are designed differently to either cut, shave, sand, or vaporize these plaques and have different indications. In this article, current atherectomy devices are reviewed. Keywords: coronary artery disease, peripheral arterial disease

AimsGuidelines recommend hemoglobin A1c (HbA1c) as a diagnostic test for type 2 diabetes, but its accuracy may differ in certain ethnic groups.MethodsThe prevalence of type 2 diabetes by HbA1c, fasting glucose, and 2 h glucose was compared in 3016 participants from Chennai and Delhi, India from the CARRS-2 Study to 757 Indians in the U.S. from the MASALA Study. Type 2 diabetes was defined as fasting glucose ≥ 7.0 mmol/L, 2-h glucose ≥ 11.1 mmol/L, or HbA1c ≥ 6.5%. Isolated HbA1c diabetes was defined as HbA1c ≥ 6.5% with fasting glucose

A comparative study on fatigue life of deep groove radial ball bearings possessing conventional and micro-grooved outer races by experimental investigation is discussed in this paper. This research has been carried out to explore and understand the fatigue life of a micro-grooved ball bearing (MGB) with a circumferential micro-groove on outer race by conducting long duration tests under dry condition (i.e. wiping out the applied grease from the races by using tissue paper and lint free cloth) and compare the results with same size SKF BB1B 420206 conventional bearing (CB) at the identical operating parameters. Frictional torque (FT), bulk temperature, and overall vibration level of the test bearings (CB and MGB) at the maximum load zone have been measured at 800 N (pH = 1.7 GPa) radial load and 1800 rpm (4.2 m/s) for the entire duration (7.8 million revolutions) of the experiments. Comparison of the surface conditions of the bearing components by means of the captured scanning electron microscope (SEM) images, roundness and deviation in profile of the races measured by co-ordinate measuring machine (CMM), and photographs captured before and after the experiment indicates lesser damage of the MGB components as compared to the conventional cases. Moreover, the initiation of fatigue failure in CBs is faster as compared to the MGBs for the same test condition, indicating longer bearing life in MGBs as compared to the CBs. [ABSTRACT FROM AUTHOR]