Received the first dose of study drug 4612 (97.0) (96.7) Received the second dose of the study drug 4586 (96.4) (96.5) Received both doses of the study drug 4581 (96.3) (96.3) no. = number; % = percentage

From the proximate composition of Sauropus androgynus leaf it was observed that its nutritive value is superior to other commonly consumed leafy vegetables in India. In an attempt to popularise this vegetable for human consumption, certain preparations (traditional recipes in Andhra Pradesh, India) were made with the leaf and palatability tests conducted. These tests showed that the leaf was quite acceptable to the consumer. Sauropus androgynus leaf was previously reported to contain considerable amounts of the alkaloid papavarine (580 mg per 100 gm fresh leaf). Excessive consumption of the leaf reportedly caused dizziness, drowsiness, constipation, etc. Before it could be recommended for wide and frequent use, further work on the subject is necessary to set safe levels for its consumption.

In this first systematic review of CAD in India, prevalence of risk factors is high, treatments delayed and use of evidence based treatments variable.

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Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Sir,A 62-year-old, 76-kg male, with a bilateral osteoarthritis knee, scheduled for right knee replacement was a known hypertensive for 4 years, controlled on tablet amlodipine 10 mg and clonidine 100 mg once daily. History, examination and investigations revealed no abnormality. Combined spinal epidural anesthesia was accomplished with an 18 G epidural catheter inserted at L 2-3 level and 2.5 ml of 0.5% heavy bupivacaine injected intrathecally at L 3-4 level, using a 27 G sprottee-type spinal needle. Maximum sensory loss up to T 10 dermatome was achieved after 7 min.A tourniquet was applied over the right thigh and pressure was maintained at 230 mmHg. After 90 min, the surgeon was reminded of the tourniquet time every 10 min. Throughout the surgery (including the cementing with methyl-methacrylate), the patient remained hemodynamically stable. Inspite of repeated reminders, the surgery lasted 155 min and then the tourniquet was released.Before tourniquet deflation, his pulse rate was 72/min, regular, blood pressure 130/76 mmHg and 97% SpO 2 . Immediately after deflating the tourniquet, his heart rate came down to 18/min and blood pressure declined to 70/42 mmHg and then became unrecordable with a complaint of uneasiness. Instantly, he was given 0.6 mg atropine intravenously and 100% oxygen by a mask. His heart rate increased to 102/min and blood pressure to 140/84 mmHg and his complaint of uneasiness subsided. The patient remained hemodynamically stable post-operatively. There was no sensory loss or motor weakness.Tourniquet deflation causes the release of blood that has low pH, low pO 2 , high pCO 2 , high lactate and K 1 into systemic circulation, which leads to a decline in blood pressure. This decline could be further aggravated by volume shift back to the limb on deflation of tourniquet, a post-ischemic reactive hyperemia (vasodilatation) and a decrease in peripheral vascular resistance. This leads to a decrease in mean systemic blood pressure of 14-19 mmHg and a mean increase in heart rate of 6-12 beats per minute (1) and can cause severe myocardial depression (as in our case) and rarely cardiac arrest. As the duration of tourniquet inflation increases, the pH and pO 2 of blood in the limb decrease significantly and adenosine, lactate and pCO 2 increase (Po0.05) (2). The maximum recommended time of tourniquet inflation is 2 h for lower limb surgery (1).Previous studies have shown that factors contributing to tourniquet-induced ischemia-reperfusion injury are activation of granulocytes (3), release of oxygen-free radicals (4) and tumor necrosis factor-a (5). The patient had taken oral clonidine pre-operatively, which has been shown to accentuate the hypotension following tourniquet deflation by inhibiting noradrenaline release (6). The release of tourniquet leads to hypotension more commonly in older patients (57 AE 8 years) vs. 50 AE 4 years (Po0.005), patients with underlying cardiovascular disease and longer duration of surgery [120 AE 14 vs. 60 AE 27 min (Po0.001) (7)]. Even our patient was elderly (62 y...

Idiosyncratic drug-induced liver injury (DILI) is damage to liver occurring at recommended dose of a drug in contrast to toxic or predictable DILI. Although it is common in first-generation antiepileptic drugs (AEDs), it is rare in newer AEDs such as topiramate. Topiramate commonly causes neurological adverse effects such as psychomotor slowing and somnolence. Hepatotoxicity by topiramate is rare and has been previously reported in combination with other drugs such as valproate and carbamazepine. Here, we report a case of topiramate-induced asymptomatic elevation of liver enzymes in an adult man diagnosed with alcohol dependence syndrome and alcohol withdrawal complicated with seizures.

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