Subhankar Chatterjee

Ezetimibe Plus Moderate-dose Simvastatin After Acute Coronary Syndrome: What Are We IMPROVEing On?

The recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is the first study to demonstrate a significant benefit of another medication (ezetimibe) on top of statin therapy in patients who have recently experienced an acute coronary syndrome. Despite the fact that ezetimibe led to positive results on the primary endpoint, the clinical benefit translated to real-life practice is only modest at best. However, this is the first major trial to demonstrate a significant benefit of a lipid medication in addition to statins. We explore the strengths and weaknesses of IMPROVE-IT in the context of current-day acute coronary syndrome practice, where high-dose statins now are prescribed widely.

Lorcaserin for the treatment of obesity? A closer look at its side effects.

Obesity is developing into a pandemic in countries like the USA, the UK and India.1–3 The WHO projects that by 2015, about 700 million adults will be clinically obese.4 Obesity is a major public health problem, beyond the disability directly related to excessive adiposity, and it also increases the risk of several chronic diseases such as hypertension, sleep apnoea, diabetes, coronary artery disease and cancer. Clearly, obesity is a serious threat, imposing a vast economic burden on the healthcare system.5 Obesity is the second most common preventable cause of death, second only to tobacco use.6 Evidence suggests that weight reduction substantially lowers the risk of related comorbidities and fosters their therapeutic management.7 ,8 Although bariatric surgery has emerged as the most clinically effective strategy for decreasing body weight for people with morbid obesity (body mass index (BMI) ≥40) or for those who cannot be managed otherwise,9 it is a very invasive procedure with significant risks.10 ,11 At this juncture, behavioural therapy, lifestyle modification and pharmacotherapy remain the mainstays of treatment. The most appealing solution for the public in general would be a ‘weight loss pill’. Several drugs have been tested since the 1960s, such as thyroid hormone, dinitrophenol, various forms of amphetamines, aminorex, fenfluramine, phenylpropanolamine, rimonabant, orlistat and sibutramine. All but phentermine, phendimetrazine and orlistat have been banned because of serious side effects. Aminorex was introduced in 1965 in Switzerland and was found to cause pulmonary hypertension. Lorcaserin (ADP356; Trade name: Belviq marketed by Arena Pharmaceuticals) and topiramate/phentermine (Qsymia) are the most recent additions to the armamentarium of antiobesity medications.12 Lorcaserin is a novel drug acting selectively as a 5-HT2C receptor agonist in the hypothalamus …

A higher dietary ratio of long-chain omega-3 to total omega-6 fatty acids for prevention of COX-2-dependent adenocarcinomas.

Compelling evidence that daily low-dose aspirin decreases risk for a number of adenocarcinomas likely reflects the fact that a modest but consistent inhibition of cyclooxygenase-2 (COX-2) activity can have a meaningful protective impact on risk for such cancers. The cancer-promoting effects of COX-2 are thought to be mediated primarily by prostaglandin E2 (PGE2), synthesized from arachidonic acid. The long-chain omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), abundant in many fatty fish, can interfere with the availability of arachidonate to COX-2 by multiple complementary mechanisms; moreover, the PGE3 produced by COX-2 from EPA is a competitive inhibitor of the receptors activated by PGE2. These considerations have given rise to the hypothesis that a high dietary intake of EPA/DHA, relative to omega-6 (from which arachidonate is generated), should lessen risk for a number of adenocarcinomas by impeding PGE2 production and activity—while not posing the risk to vascular health associated with COX-2-specific nonsteroidal antiinflammatory agents. Analyses that focus on studies in which the upper category of fish consumption (not fried or salt-preserved) is 2 or more servings weekly, and on studies that evaluate the association of long-term fish oil supplementation with cancer risk yields a number of findings that are consistent with the hypothesis. Further studies of this nature may help to clarify the impact of adequate regular intakes of long-chain omega-3 on cancer risk, and perhaps provide insight into the dose-dependency of this effect.

Dietary Salt Restriction in Heart Failure: Where Is the Evidence?

Several dietary guidelines, health organizations and government policies recommend population-wide sodium restriction to prevent hypertension and related comorbidities like heart failure (HF). The current European Society of Cardiology and American College of Cardiology/American Heart Association Heart Failure guidelines recommend restricting sodium in HF patients. However, these recommendations are based on expert opinion (level C), leading to wide variability in application and lack of consensus among providers pertaining to dietary salt restriction. To evaluate the strength of current evidences to recommend dietary salt restriction among HF patients, we performed a comprehensive literature review and explored the safety and efficacy of such recommendations.

India’s growing problem of injecting drug misuse

India needs to invest in proved treatments that reduce harm in people who inject drugs, write Susan Wherley and Subhankar Chatterjee

Molecular blockade of angiogenic factors: A new therapeutic tool for the treatment of abnormal uterine bleeding

Dear Editor, Abnormal uterine bleeding (AUB) has been one of the most common gynecological symptoms among adolescent and peri‐menopausal age group.[1] Combined oral contraceptive pills (OCP), progestin, non‐steroidal anti‐inflammatory drugs (NSAIDs), anti‐fibrinolytic agents, danazol, and gonadotropin releasing hormone (GnRH) agonists are presently advised as pharmacotherapeutic agents.[2] Combined OCPs are targeting the bungled co‐ordination of unopposed estrogen stimulation and hampered progestational induction of tissue factor (TF) and plasminogen activator inhibitor‐1 (PAI‐1) in anovulatory dysfunctional uterine bleeding (DUB). It counteracts the proliferative and angiogenic effect of estrogen on endometrium.[3] GnRH agonists like leuprolide and androgenic synthetic steroid like danazol induce chemical menopause by reducing follicle stimulating hormone and luteinizing hormone. However, their use is associated with various adverse effects. NSAIDs like naproxen and mefenamic acid are used to reduce the vasodilating prostaglandin imbalance in case of ovulatory DUB.[2] Although, the basic pathophysiological mechanism of AUB lies around the impaired hemostasis with vascular derangement and disturbed neo‐angiogenesis, the current medical strategies are not directed to attack the step of disturbed angiogenesis. This correspondence is an attempt to propose a hypothetical view on the use of molecular angiogenic factor inhibitors in the treatment of AUB.

Death by insecticide

Organophosphate containing pesticides cause many deaths by poisoning in rural India. Subhankar Chatterjee and Haris Riaz consider the problem

Rabies: beware of the dog

India’s least populous state, Sikkim, has made great progress toward eliminating rabies. Can the rest of the country follow its lead and reduce the huge burden of this universally fatal disease? Subhankar Chatterjee and Haris Riaz report

SGLT-2 Inhibitors and Peripheral Artery Disease: A Statistical Hoax or Reality?

Inhibitors of sodium-glucose cotransporters type-2 are the most recent addition to the armamentarium of oral antidiabetic agents. This class of drugs has shown promising results in glycemic control and most importantly to reduce cardiovascular disease (CVD) mortality risk. Despite the encouraging data, there is concern regarding their potential for causing or worsening peripheral artery disease (PAD), which may increase the risk of lower extremity amputations. Following the publication of results of CANVAS and CANVAS-R trials, which revealed that leg and mid-foot amputations occurred about twice as often in patients treated with canagliflozin compared to placebo, the Food and Drug Administration (FDA) in the United States issued a black box warning of leg and foot amputations associated with canagliflozin use. In this article, our main aim is to review the available evidence in preclinical and clinical studies regarding SGLT-2 inhibitors and PAD events, the possible mechanisms related to increased risk of amputation, to evaluate whether it is a class effect or individual drug effect, and most importantly, implications for their continued use as antidiabetic agents. It also raises the issue of including PAD events among the end-points when assessing future antihyperglycemic agents. Thus, we also tried to analyze whether outcomes of SGLT2 inhibitors trials mostly focused on stroke, myocardial infarction, heart failure, and peripheral vascular disease-related outcomes remained underrated.

Mountford Joseph Bramley: A pioneering thyroidologist and the first principal of Asia's oldest medical college.

Mountford Joseph Bramley was one of the educationists whose sincere efforts are undeniable in the making of modern India. After achieving the Member of the Royal College of Surgeons diploma, he joined the Malta Garrison as a Hospital Assistant and was soon promoted to the rank of Assistant Surgeon of the Rifle Brigade. Following his arrival in India in 1826, he held several important medical posts in the British service. He was one of the early researchers to investigate the role of iodine in the causation of goitre. He was appointed as the first Principal of the Medical College of Bengal, the oldest medical college in Asia, in 1835. Bramley was an educationist from the very core of his heart, and he always wished for the betterment of his students. He died early at the age of 34 years. His legacy as a pioneer in the fields of medical education and endocrinology, specifically thyroidology, has largely been shrouded in a miasma of time.