Comparative effectiveness and safety of prasugrel and ticagrelor in patients of acute coronary syndrome undergoing percutaneous transluminal coronary angioplasty: A propensity score-matched analysis.

Evidence on comparative effectiveness and safety of prasugrel and ticagrelor post-percutaneous transluminal coronary angioplasty is scarce in Indian population. In a 1:1 propensity score-matched cohort with 71 individuals in each group, the incidence of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization was not significantly different in prasugrel and ticagrelor group (7.04% vs 9.86%; absolute difference, 2.8%; HR, 0.65; 95% CI, 0.21-2.1; p = 0.49). There was no significant difference in bleeding (5.63% vs 9.86%; absolute difference, -4.20%; 95% CI, -13.0%-4.5%) and dyspnea (7.04% vs 12.7%; absolute difference, -5.60%; 95% CI, -15.4%-4.1%).

Treatment Cost Along With Pattern of Disease and Therapy in the Intensive Care Unit of a Tertiary Care Teaching Hospital in India.

Background The intensive care unit (ICU) represents an important platform for conducting drug utilization analysis using defined daily dose (DDD)/100 bed-days and the financial burden of treatment as patients are seriously ill and are often suffering from chronic critical illnesses. Therefore, in this study, we evaluated the drug utilization patterns and cost of treatment in the ICU. Methods A retrospective observational analysis of the medical records obtained for the medical ICU of an apex tertiary care teaching hospital in central India was conducted for a period of three years from 2017 to 2019. All the patients admitted to the medical ICU during the study tenure were included in the study. Patients hospitalized in neonatal intensive care unit (NICU), pediatric intensive care unit (PICU), and surgical ICU were excluded from the study. The socio-demographic and clinical data, utilization of different classes of drugs, WHO-Anatomic Therapeutic Chemical (WHO-ATC) classification, DDD/100 bed days, hospital stay, etc. were analyzed. A partial pharmaco-economic analysis of the average cost of admission to patients was done. Results Data from 280 patients was assessed. The mean age was 47 ± 19.18 years and 58% were males. Antibiotics and injections were prescribed to 96% and 97.5% of the patients, respectively, during their ICU stay (median: seven days). Antimicrobial drugs were most frequently prescribed (n=1096, 68%); the most common were beta-lactams and carbapenems, followed by drugs acting on the central nervous system (5%) and cardiovascular system (4.3%). Cefoperazone/sulbactum, ceftriaxone, and piperacillin/tazobactam were the most utilized antibiotics with 8, 16, and 6 DDD/100 bed-days, respectively, while proton pump inhibitors, analgesics, and anti-epileptics were the most frequently prescribed non-antimicrobial drug class. The median cost of treatment per ICU admission was Indian Rupees (INR) 23,347 (IQR 12,552- 65,524). Conclusion Drug utilization assessment provides crucial information for understanding the usage of drugs in the settings of the ICU, and should be conducted regularly to help in the proper planning and implementation of rational drug use. Treatment costs reflect the high economic burden seen in ICU admissions.

Usefulness of the PRECISE-DAPT score at differentiating between ticagrelor and prasugrel for dual antiplatelet therapy initiation.

As a part of dual antiplatelet therapy (DAPT), prasugrel or ticagrelor is prescribed along with aspirin to patients of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to assess if the PRECISE-DAPT score, which provides prediction of bleeding during DAPT, could be used to choose between prasugrel and ticagrelor for DAPT initiation. 181 patients out of which 71 received prasugrel and 110 received ticagrelor were enrolled in this prospective cohort study. PRECISE-DAPT score was calculated for everyone and was used to dichotomize patients into two subgroups (score <25 and ≥25). After balancing potential confounders in baseline characteristics of the subgroups using propensity scores, comparison of a composite outcome of 4-point major adverse cardiovascular events (4P-MACE) (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization due to stent thrombosis) and bleeding (any type as defined by the Bleeding Academic Research Consortium) within 1-year post-PCI was performed among the subgroups using Cox proportional hazards regression. Prasugrel was associated with lower and comparatively higher 4P-MACE events in subgroups with score ≥25 (HR: 0.17; 95% CI, 0.04-0.77) and score <25 (HR: 3.58; 95% CI, 0.62-20.70) respectively. For bleeding outcome, prasugrel trended towards more clinical benefit for scores ≥25 (HR: 0.44; 95% CI, 0.10-1.93) than <25 (HR: 0.93; 95% CI, 0.13-6.58). Therefore, prasugrel was associated with better clinical effectiveness and trended towards a lower bleeding risk compared to ticagrelor within 1-year post-PCI for those with a high PRECISE-DAPT score (≥25). This finding requires validation through larger studies.

Evaluation of the Anxiolytic Effect of Ramelteon in Various Rat Models of Anxiety.

Background Melatonin was found to have anxiolytic properties in several animal and human studies. The melatonin receptor agonist ramelteon might also have a similar anxiolytic action. Objectives The objective of the study was to evaluate the effect of ramelteon in various rat models of anxiety and to explore the possible mechanism of action. Methods The anxiolytic effect was compared between the control group, diazepam group (1 mg/kg and 0.5 mg/kg), and ramelteon group (0.25 mg/kg, 0.5 mg/kg, and 1 mg/kg) by an elevated plus maze, light-dark box, hole board apparatus, and open field test in Sprague Dawley rats. Antagonists flumazenil, picrotoxin, and Luzindole were used to explore the possible mechanism of action of ramelteon if it showed an anxiolytic property. Results Ramelteon as a standalone drug did not show an anxiolytic effect. However, a combination of ramelteon (1 mg/kg) and diazepam (0.5 mg/kg) showed an anxiolytic effect. Conclusion Further studies can evaluate the use of a fixed-dose combination of ramelteon and already-approved anxiolytic drugs to reduce the dose of the latter.

How to choose and interpret a statistical test? An update for budding researchers.

Postgraduate medical students are often not able to select and interpret the findings of statistical tests during their thesis or research projects. To go ahead with selection of tests to be performed, researchers need to determine the objectives of study, types of variables, analysis and the study design, number of groups and data sets, and the types of distribution. In this review, we summarize and explain various statistical tests to help postgraduate medical students to select the most appropriate techniques for their thesis and dissertation.

A multicentre point prevalence survey (PPS) of antimicrobial use amongst admitted patients in tertiary care centres in India.

OBJECTIVES: Data from point prevalence surveys (PPSs) in India are scarce. Conducting PPSs is especially challenging in the absence of electronic medical records, a lack of dedicated resources and a high patient load in resource-poor settings. This multicentre survey was conducted to provide background data for planning and strengthening antimicrobial stewardship programmes across the country. METHODS: This inpatient PPS was conducted over 2 weeks in May 2019 simultaneously across five study centres in India. Data about patient characteristics, indications for antimicrobials use and details of each antimicrobial prescribed including supportive investigation reports were collected in predesigned forms. RESULTS: A total of 3473 admitted patients in wards and ICUs were covered across five study centres. Of these, 1747 (50.3%) patients were on antimicrobials, with 46.9% patients being on two or more antimicrobials. Out of the total antimicrobials prescribed, 40.2% of the antimicrobials were prescribed for community-acquired infection requiring hospitalization followed by surgical prophylaxis (32.6%). Third-generation cephalosporins and drugs from the 'Watch' category were prescribed most commonly. Only 22.8% of the antimicrobials were based on microbiology reports. CONCLUSIONS: The survey demonstrated a high use of antimicrobials in admitted patients with a considerable proportion of drugs from the 'Watch' category. The targets for interventions that emerged from the survey were: improving surgical prophylaxis, decreasing double anaerobic cover, initiating culture of sending cultures and de-escalation with targeted therapy.

Prasugrel Versus Ticagrelor in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: a Systematic Review and Meta-analysis of Randomized Trials.

PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and ticagrelor or prasugrel is the mainstay of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to systematically perform a head-to-head comparison of ticagrelor vs prasugrel in terms of efficacy and safety. METHODS: We searched PubMed/Medline, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomized controlled trials (RCTs). The primary outcome was adverse cardiovascular events and secondary outcome was bleeding events. A random-effects meta-analysis was used to obtain the pooled estimate of each outcome. RESULTS: Nine RCTs with a total number of 6990 patients (3550 treated with prasugrel and 3481 treated with ticagrelor) were included. No significant difference between prasugrel and ticagrelor was observed in terms of mortality (OR 0.86, 95% CI 0.66 to 1.13, P = 0.28), major adverse cardiovascular events (MACEs) (OR 0.85, 95% CI 0.70 to 1.03, P = 0.10), non-fatal myocardial infarction (OR 0.78, 95% CI 0.57 to 1.06, P = 0.11), stroke (OR 1.02, 95% CI 0.60 to 1.72, P = 0.95), stent thrombosis (OR 0.76, 95% CI 0.47 to 1.21, P = 0.25), thrombolysis in myocardial infarction (TIMI) defined major (OR 0.94, 95% CI 0.19 to 4.67, P = 0.94), minor (OR 0.35, 95% CI 0.08 to 1.62, P = 0.18) and minimal (OR 0.48, 95% CI 0.19 to 1.18, P = 0.11) bleeding and Bleeding Academic Research Consortium (BARC) defined bleeding (OR 1.06, 95% CI 0.82 to 1.36, P = 0.68). CONCLUSION: In patients with ACS undergoing PCI, both prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events.

A Cost Variation Analysis of Drugs Available in the Indian Market for the Management of Thromboembolic Disorders.

Introduction Cardiovascular diseases (CVDs) have become one of the major causes of mortality among the Indian population. The costs of anticoagulant, antiplatelet, and fibrinolytic drugs that are used to treat various thromboembolic disorders and used as prophylactics for individuals at high risk of CVDs vary widely in the Indian pharmaceutical market. The aim of this study was to evaluate the cost variation of different brands of drug formulations and to compare the branded prices of the formulations with their corresponding generic and ceiling prices. Materials and methods This study followed an analytical method. Costs of various drugs were obtained from the October - December 2019 edition of the Current Index of Medical Specialities (CIMS) and December 2019 edition of the Monthly Index of Medical Specialities (MIMS) India. Cost ratio and percentage variation in cost per tablet/capsule/injection of different drugs available in the Indian market and manufactured by different pharmaceutical companies were calculated. Comparison of the branded prices with generic and ceiling prices was also performed for different drugs by using information available from official websites. Results Percentage variation in cost among the commonly prescribed drugs for the management of thromboembolic disorders was found to be highest for prasugrel 10 mg tablet (1,408.44%) while it was lowest for fondaparinux 2.5 mg / 0.5 ml injection (20%). Among the commonly prescribed drugs that are under Drugs Prices Control Order (DPCO) price control, streptokinase 1.5 MIU injection had the highest cost variation (132.02%) while enoxaparin 60 mg / 0.6 ml injection had the lowest (4.99%). Among some of the important formulations under the Jan Aushadhi scheme (JAS), acenocoumarol 2 mg tablet had the highest cost variation (680.09%) and cilostazol 50 mg tablet had the lowest (55.46%). Conclusions Wide differences exist in the costs of various anticoagulants, antiplatelets, and fibrinolytics available in the Indian market. The prescribing physician should be aware of theses variations and prescribe medicines accordingly, keeping in mind the financial status of the patients.

Risperidone-induced Somnambulism: A Case Report and Brief Review of Literature.

Atypical antipsychotic drugs have been recommended as the first-line agents in the treatment of schizophrenia. They are usually not associated with extrapyramidal symptoms and hyperprolactinemia. There is no previously reported case on somnambulism associated with risperidone intake. We report a case of risperidone-induced somnambulism in a schizophrenic patient. Somnambulism occurred while the patient was on a dose of 3 mg of risperidone per day. The dose was reduced to 2 mg per day along with the addition of clonazepam 0.5 mg daily at night. No further episode of somnambulism was reported after this. This case suggests the association of risperidone with occurrence of somnambulism. Further evidence to strengthen the causality of this needs to be gathered. This calls for prompt pharmacovigilance reporting of adverse drug events associated especially with antipsychotics.

Ticagrelor-Induced Prolongation of the QTc Interval.

BACKGROUND: Ticagrelor has been accepted as a class I antiplatelet agent in patients undergoing percutaneous coronary angioplasty (PTCA). There have been cases reported on ticagrelor being associated with various cardiac conduction defects. But there is no evidence of QTc prolongation associated with the drug as of yet. CASE PRESENTATION: A 64-year-old male who underwent PTCA was given ticagrelor. A baseline electrocardiogram (ECG) showed a QTc of 402 ms. He returned after 1.5 months with complaints of shortness of breath. An ECG revealed a prolonged QTc of 468 ms. Ticagrelor was discontinued in view of ticagrelor-induced dyspnea and the patient was started on clopidogrel. The other medications were kept unchanged. The patient returned after a month without any complaints. A follow-up ECG showed a reduced QTc of 425 ms. CONCLUSION: We present a case of ticagrelor-induced QTc prolongation. To our knowledge, this is the first case to be reported on the same. The Naranjo algorithm for causality assessment gave a total score of 6 indicating that the adverse drug reaction falls under the probable category.

A pilot point prevalence study of antimicrobial drugs in indoor patients of a teaching hospital in Central India.

AIM: To evaluate the point prevalence of antimicrobial drug use by using point prevalence survey method. METHODOLOGY: A cross-sectional point prevalence study was done on patients admitted in AIIMS Bhopal hospital. This study included all inpatients receiving an antimicrobial that were on the ward at 8 AM on a specific day in May 2018. Information regarding age, gender, occupation, income group, diagnosis, patient's present/past medical history, treatment, any adverse drug reactions, and investigations are recorded in a pro forma. RESULTS: A total of 77 patients (31.95%) were included out of total 241 patients who received at least one antimicrobial. Of patients who received at least one antimicrobial, diagnosis was mentioned in 83.11% of prescriptions. Targeted treatment was given to 10.38% of patients. Reasons for antimicrobial were recorded in 12.98% of patients. Most common healthcare infection recorded was catheter-associated urinary tract infections followed by postoperative surgical site infections. Penicillin with beta lactamase inhibitors was most commonly prescribed antibiotic group followed by third generation cephalosporins and fluoroquinolones. Stop or review date was recorded in 19.48% of patients. Parenteral administration was given to 30.55% of patients. Compliance to guidelines was followed in 64.11% of patients. Local antibiotic guideline and antibiogram were available in hospital. Biomarkers were utilized in 9.77% of patients to guide the choice of therapy. CONCLUSION: Availability of antibiotic policy, antibiogram, local antibiotic guidelines, drugs, and therapeutic committee were some of the encouraging findings. Diagnosis was mentioned in majority of prescriptions. Most patients were prescribed oral antimicrobial drugs, which can reduce complications with parenteral route. Underutilizations of microbiological facilities, prolonged use of antibiotics for surgical prophylaxis, and polypharmacy were areas of concern.

Early onset gestational diabetes mellitus: A case report and importance of early screening.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Screening for GDM is usually done at 24-28 weeks of gestation. In this case, we report a 31-year-old woman who developed gestational diabetes at 6 weeks in two successive pregnancies. She was in the perceived high-risk group to develop gestational diabetes. The first pregnancy terminated in spontaneous abortion at 10 weeks. In the second pregnancy, institution of insulin therapy at diagnosis was associated with a successful outcome. This case highlights the need of screening for gestational diabetes at the first antenatal visit in the high-risk group.

Statin induced diabetes and its clinical implications.

Statins are one of the most commonly used drugs in the world based on their potential to prevent adverse cardiovascular events. These cholesterol-lowering drugs received a US Food and Drug Administration warning, in February 2012, regarding increased risk of incident diabetes and impaired glycemic control in patients who already have diabetes. The possible association of diabetes with statin therapy has started a wave of discussion in the medical community. A number of meta-analyses conducted in recent years have demonstrated that the association is real although causality has not been proved yet. Individual statins differ with respect to their diabetogenic property; women and elderly persons appear to be at increased risk. Various aspects of statin's adverse effect on glycemic control remain to be explored. As further research in this area continues, physicians might still take some precautions to make risk benefit ratio more favorable for the patients.

Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome.

AIM: The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries, especially in the Middle East and in Southeast Asia. This plant has been a focus of much research. This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome. MATERIALS AND METHODS: This prospective study was conducted at a tertiary health care center in North India. After confirmation of diagnosis, 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. Written informed consent was taken from all the patients enrolled. Approval from the institutional ethical committee was also obtained. The patients were divided into two groups of 30 each. In group I (the standard group), patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks. In group II (the N. sativa group), the patients were advised tablet atorvastatin 10 mg once a day, tablet metformin 500 mg twice a day, and N. sativa oil 2.5 ml twice daily for a period of 6 weeks. Fasting and postprandial blood glucose, fasting lipid profile, and waist circumference were recorded before therapy and after completion of therapy. RESULT: The treatment group showed significant (P < 0.05) improvement with reference to total cholesterol, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (P < 0.05). CONCLUSION: N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome. N. sativa oil has a significant activity in diabetic and dyslipidemic patients.