Efficacy and safety of sacubitril/valsartan compared with enalapril in patients with chronic heart failure and reduced ejection fraction: Results from PARADIGM-HF India sub-study.

OBJECTIVES: To determine efficacy and safety of sacubitril/valsartan compared with enalapril in Indian patients of PARADIGM-HF trial. METHODS: A randomized, double-blind, active-controlled, phase III sub-study (NCT01035255) was conducted between April 2010 and May 2014. Patients with chronic heart failure (HF), aged >18 years with left ventricular ejection fraction ≤40% were randomized (1:1) to receive either sacubitril/valsartan 200 mg twice-daily or enalapril 10 mg twice-daily. The primary endpoint was to compare efficacy of sacubitril/valsartan to enalapril in delaying time-to-first occurrence of the composite endpoint (cardiovascular [CV] death or HF hospitalization). RESULTS: The trial was stopped after a median follow-up of 27 months, because the boundary for benefit with sacubitril/valsartan had crossed. Among 637 Indian patients in PARADIGM-HF (sacubitril/valsartan, n = 322 and enalapril, n = 315), the primary outcome, CV death, and the first hospitalization for HF occurred in 21.81% and 24.76% (HR 0.89; 95% CI, 0.646-1.231), 17.45% and 20.63% (HR 0.87; 95% CI, 0.605-1.236), and 7.48% and 9.52% (HR 0.78; 95% CI, 0.461-1.350) patients in the sacubitril/valsartan and enalapril group, respectively. The all-cause mortality (19.0% vs. 21.9%) and adverse events (78.4% vs. 82.2%) were comparatively lower in the sacubitril/valsartan than enalapril group. No significant difference was seen between the benefits of treatment in Indian and the total PARADIGM-HF cohort (p value for interaction >0.05). CONCLUSION: Results support the use of sacubitril/valsartan in Indian patients with chronic HF with reduced ejection fraction with treatment benefits similar to global PARADIGM-HF cohort.

The Management of Severe Asthma - An Indian Perspective.

Epidemiologically the burden of asthma in India is alarming with a median prevalence of 7%. As the symptoms of asthma ascend the severity ladder, the prediction of the cause of asthma is important from the treatment point of view. The GINA 2020 states that the management of asthma should be individualized as per the patient depending on patient phenotype. The goal of asthma treatment is to achieve good control of symptoms, to reduce exacerbations and to improve quality of life. Guidelines recommend adapting the level of treatment to the level of disease severity, and this approach has been demonstrated to be effective in the majority of asthma patients overall. However, it is known that a small but significant proportion of patients do not achieve adequate control despite optimized treatment, and these patients are frequently prescribed high doses of oral steroids in an attempt to achieve control. For patients with severe uncontrolled asthma, monoclonal antibodies (mAbs) against IgE or IL-5 are available as add-on treatments to inhaled corticosteroid (ICS) plus long-acting ß2-agonist (LABA) therapy. With a plethora of available modalities, the fact still remains that there is a large treatment gap and the number of people living with asthma in India is predicted to be around 30 million. This article reviews the phenotypes/endotypes of asthma described in India and the current therapies for management.

Prevalence of Hyperuricemia in Indian Subjects attending Hyperuricemia Screening Programs-A Retrospective Study.

Objectives: To determine the prevalence of hyperuricemia (HU) in patients with hypertension (HTN) and type 2 diabetes mellitus (T2DM) in the Indian setting. Methods: A retrospective analysis of patients undergoing screening for HU in health clinics across India between April to May 2017 was carried out. Data regarding demographics, history of T2DM and HTN and uric acid levels (easy touch uric acid monitoring system) were recorded during the program. Results: Data from 3044 screening programs was analysed. The mean age of the study population was 47.9 years; about two-thirds of the subjects were males. Of the 29391 subjects screened, 25.8% were found to have HU. The proportion of diabetics, hypertensives and diabetic hypertensives who had HU was 33.6%, 35.1%, and 34.4% respectively. A trend towards increased prevalence of HU was seen with increasing age and increased duration of diseases like HTN and diabetes. Conclusion: High prevalence of HU was observed in T2DM and HTN and in patients with both co-morbidities. Age-wise analysis revealed an increasing trend of HU with age. Further, the prevalence of HU also increased with increasing duration of T2DM and HTN.

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.

OBJECTIVE: To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. MATERIALS AND METHODS: In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. RESULTS: A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as "very good to good", whereas according to physician's assessment, "very good to good" tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. CONCLUSION: Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.

The rise and fall of felbamate as a treatment for partial epilepsy--aplastic anemia and hepatic failure to blame?

Felbamate has been approved for refractory partial seizures since the early nineties. Due to safety concerns regarding its use, namely, in aplastic anemia and hepatic failure, felbamate's use has been restricted and a 'Black Box' warning has been inserted. Nonetheless, it is a useful drug in refractory cases of partial epilepsy. There are certain precautions which can prevent and minimize the serious idiosyncratic reactions associated with felbamate, thereby providing an option in refractory cases where no other drug works.

Practice of Pain Management by Indian Healthcare Practitioners: Results of a Paper Based Questionnaire Survey.

Objective. Understanding factors while selecting an analgesic and its usage pattern by Indian healthcare practitioners (HCPs). Methods. Questionnaire-based survey was conducted among six healthcare specialties. Results. Total 448 HCPs participated. Patient's age (72.8%, 74.4%, 87.5%, and 78.9%) and duration of therapy (70.8%, 66.2%, 69.6%, and 73.6%) were main attributes for selecting an opioid according to general practitioners (GPs), dentists, consulting physicians (CPs), and surgeons, respectively. Patient's age was important factor while selecting NSAID according to 77.60%, 66.91%, and 84.20% of GPs, dentists, surgeons, respectively. For mild pain, paracetamol was the choice according to 77%, 78.57% and 74% of GPs, CPs, and surgeons, respectively. For moderate pain, 77%, 87.50%, 68%, and 80.30% of GPs, CPs, surgeons and orthopedicians, respectively, preferred the use of paracetamol + tramadol combination. For moderate pain, NSAID + paracetamol and paracetamol+diclofenac were used by 68.94% and 47.73% of orthopedicians, respectively. Lack of pain clinic (38.8%) in city was commonly cited reason for not referring patients to pain clinics. Conclusion. Patient's age, duration of therapy, comorbid conditions, frequency of dosing, and severity of pain are important parameters while selecting analgesics. Paracetamol and its combinations are commonly used for mild and moderate pain, respectively. Pain clinics currently have limited presence in India.

A drug utilization study of cognition enhancers in dementia in a tertiary care hospital in mumbai.

BACKGROUND: Cognitive decline is one of the important factors undermining the quality of life in geriatric patients. Although the WHO has declared 'Dementia' as a priority health condition.Cognitive neuropharmacology is still in its infancy and there is no general consensus on the use of cognition enhancing (CE) drugs in humans. Since drug utilization data of CEs in dementia are scarce, we conducted a study to describe the observed patterns of CE drug use, compare it to the current recommendations and conduct a preliminary cost analysis. METHODS: A prospective cross sectional drug utilization study of 100 prescriptions of patients of both sexes and all ages suffering from dementia attending the Neurology and Psychiatry clinics was undertaken as per the WHO - DUS and the STROBE guidelines. RESULTS: In all, the 100 prescriptions contained 322 drugs, out of which, 168 were CE drugs. 38.2% of the drugs were prescribed by generic names. Donepezil, Memantine, Piracetam, Rivastigmine and Gallantamine were prescribed to 76%, 34%, 8%, 6% and 0%, respectively. The PDD/DDD ratio of Donepezil and Memantine were 1.36 and 0.94, respectively. The average cost per prescription was INR 626.29 or USD 9.5. CONCLUSION: Principles of rational prescribing were followed. Donepezil and Memantine were the most commonly prescribed drugs and hence should be included in the hospital drug schedule. Piracetam should not be prescribed because of doubtful benefits and high cost. Antipsychotics should be used in geriatric dementia patients very judiciously. A major part of the total cost per prescription was borne by the patient.

A cross-sectional study to evaluate the awareness and attitudes of physicians towards reducing the cost of prescription drugs, Mumbai.

BACKGROUND: In India, about half of the total health expenditure is spent on medicines. The projected increase in various diseases coupled with the skyrocketing drug prices have further compounded the drug cost burden. We conducted a study to assess the awareness, attitudes, and practices of physicians with regard to various cost containment measures and the factors affecting them. METHODS: A cross-sectional, questionnaire-based, observational study was conducted over a period of 3 months among 200 physicians, after permission from the Institutional Ethics Committee, at the Grant Medical College and Sir J J Group of Hospitals, Mumbai. The STROBE (Strengthening The Reporting of OBservational studies in Epidemiology) guidelines were followed. RESULTS: Cost considerations were important to 97 % of government doctors (GDs) and 72 % of private doctors (PDs). Eighty percent of both GDs and PDs said that safety and efficacy were more important than cost. Seventy-one percent of GDs and 65 % of PDs knew about the various cost reduction methods. Twenty-four percent of GDs and 65 % of PDs said that they graded drugs according to cost. Ninety-four percent of GDs and 73 % of PDs said that patent protection should not be extended to life-saving drugs. Sixty-four percent of GDs and 10 % of PDs, and 20 % of GDs and 10 % of PDs were in favor of the stepwise introduction of drugs and the use of generics, respectively. Factors precluding the use of cheaper alternatives were narrow therapeutic index drugs (43.5 %) and fear of substandard quality (38.5 %). CONCLUSION: Doctors are indeed concerned about the high cost of drugs. More awareness needs to be created about the use of cheaper generics. The government has a very important role to play in reducing the cost of prescription drugs and making healthcare affordable.

A drug utilization study of psychotropic drugs prescribed in the psychiatry outpatient department of a tertiary care hospital.

BACKGROUND: Psychiatric disorders are one of the major causes of morbidity. Development of newer drugs like SSRIs and atypical antipsychotics has altered the treatment paradigms. Various factors like cost of drugs, local paradigms, etc. play a role in the selection of drug therapy and hence, affect the outcome. Keeping this in mind, we conducted a study to delineate the various drugs used in psychiatric disorders, to find discrepancies, if any, between the actual and the ideal prescribing pattern of psychotropic drugs and to conduct a cost analysis. MATERIAL AND METHODS: After our institutional ethics committee approved, a retrospective cross sectional drug utilization study of 600 prescriptions was undertaken. Preparation of the protocol and conduct of the study was as per the WHO - DUS and the STROBE guidelines. RESULTS: Drug use indicators - In 600 prescriptions, 1074 (88.25%) were psychotropic drugs. The utilization from the National and WHO EML was 100% and 90%, respectively. Average number of psychotropic drugs per prescription was 1.79 ± 1.02 (SD). 22.5% of the prescriptions contained psychotropic FDCs. 76.01% of drugs were prescribed by generic name. Percentage of psychotropic drugs prescribed from the hospital drug schedule and psychotropic drugs actually dispensed from the hospital drug store were 73.1% and 62.3%, respectively. Drug utilization pattern in different psychiatric disorders - Most commonly prescribed drugs for schizophrenia, bipolar disorders, depression and anxiety disorders were trifluoperazine + trihexiphenydyl (63.9%), carbamazepine (17.2%), amitriptyline (34.9%), and diazepam (23.8%), respectively. The least commonly prescribed drugs were levosulpiride (1.7%), lithium (1.3%), bupropion (4.7%) and clozapine (1.9%), respectively. The PDD/DDD ratio of three drugs - haloperidol, pimozide and amitriptyline - was equal to one. The cost borne by the hospital was 116, i.e., 65.2% of the total cost. The cost index of clozapine was 11.2. CONCLUSION: Overall, the principles of rational prescribing were followed. The hospital drug schedule should include more SSRIs. The practice of using 1(st) generation/ typical anti-psychotics as the first line was as per current recommendations. Anti-cholinergics should be used only in selected cases of patients on anti-psychotics. The use of diazepam should be curtailed and it should be used for short term only.

A study to assess completeness of project application forms submitted to Institutional Ethics Committees (IEC) of a tertiary care hospital.

OBJECTIVES: To review Ethics Committee (EC) application forms and to find out similarities and differences in content of five ECs forms in India. MATERIALS AND METHODS: THE COMPLETENESS OF EC APPLICATION FORMS WAS ASSESSED ON THE FOLLOWING THEMES: title, study team, sponsor responsibility, scientific aspects, patient safety, regulatory permissions, Informed consent process from 2008-2009. Application forms (available online) of 5 ECs were studied and compared. RESULTS: A total of 445 application forms were analyzed, 382 were academic, 63 were sponsored. The common deficiencies in academic studies were inappropriate titles (25.13%), lack of budget details (90%). More than 95% studies had not mentioned the method of recruitment. The issue of vulnerability was not marked in more than 50% of studies. Compensation for participation/injury was poorly stated in academic (99%) studies. Among industry sponsored studies, 98% were compliant with regulatory permissions and 41% were CTRI registered. The information pertaining to Informed Consent was mentioned in all forms. Comparative analysis of application forms of 5 ECs showed that the requirements for submission were similar except 1-2 ECs asked for additional information like percentage of time allotted by investigator for studies, GCP training of study team, certification by investigator regarding accuracy of local versions of Informed consent. CONCLUSION: Our study recommends that increased awareness and vigilance by investigators of academic studies regarding submission of applications to EC will increase efficiency and speed of review process. A common application form for all ECs across India would be an important step to achieve uniformity in functioning of ethics committees.