Prescription-based cost analysis of medicines for cardiovascular risk factors at Indian Council of Medical Research-Rational Use of Medicine Centre Hospitals of India.

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.

Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences.

BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

An observational multi-centric COVID-19 sequelae study among health care workers.

Background: India has seen more than 43 million confirmed cases of COVID-19 as of April 2022, with a recovery rate of 98.8%, resulting in a large section of the population including the healthcare workers (HCWs), susceptible to develop post COVID sequelae. This study was carried out to assess the nature and prevalence of medical sequelae following COVID-19 infection, and risk factors, if any. Methods: This was an observational, multicenter cross-sectional study conducted at eight tertiary care centers. The consenting participants were HCWs between 12 and 52 weeks post discharge after COVID-19 infection. Data on demographics, medical history, clinical features of COVID-19 and various symptoms of COVID sequelae was collected through specific questionnaire. Finding: Mean age of the 679 eligible participants was 31.49 ± 9.54 years. The overall prevalence of COVID sequelae was 30.34%, with fatigue (11.5%) being the most common followed by insomnia (8.5%), difficulty in breathing during activity (6%) and pain in joints (5%). The odds of having any sequelae were significantly higher among participants who had moderate to severe COVID-19 (OR 6.51; 95% CI 3.46-12.23) and lower among males (OR 0.55; 95% CI 0.39-0.76). Besides these, other predictors for having sequelae were age (≥45 years), presence of any comorbidity (especially hypertension and asthma), category of HCW (non-doctors vs doctors) and hospitalisation due to COVID-19. Interpretation: Approximately one-third of the participants experienced COVID sequelae. Severity of COVID illness, female gender, advanced age, co-morbidity were significant risk factors for COVID sequelae. Funding: This work is a part of Indian Council for Medical Research (ICMR)- Rational Use of Medicines network. No additional financial support was received from ICMR to carry out the work, for study materials, medical writing, and APC.

Epidemic of Vitamin D Deficiency and Its Management: Awareness among Indian Medical Undergraduates.

Vitamin D deficiency is prevalent across all age groups in epidemic proportions. The purpose of this study was to acquire a baseline assessment and create awareness among medical students regarding vitamin D. A cross-sectional, voluntary survey was conducted among undergraduate medical students. Data were collected using a questionnaire which assessed the level of knowledge students had with regard to where vitamin D comes from, what it does for health, how much is recommended, factors that affect its levels, and deficiency management. Majority of students were unaware that vitamin D deficiency has attained epidemic proportions. Though bone and skeletal disorders as a complication of vitamin D deficiency were known, a large number were unaware of systemic consequences (diabetes mellitus, cardiovascular diseases, and cancers). Only one-third of respondents were aware of duration and timing of sun exposure required for adequate serum vitamin D levels. However, we observed lack of awareness among students regarding the various biochemical forms, dose, and duration of vitamin D supplementation for treatment of nutritional deficiency. Our study highlighted a lack of knowledge about the importance of vitamin D, worldwide prevalence of vitamin D deficiency, and its management among medical students. Promoting vitamin D health awareness, if replicated across populations, could lead to positive health outcomes globally.

Vitamin D Supplements in the Indian Market.

It is now known that vitamin D deficiency is a worldwide health problem. In our country, as food fortification is lacking, supplementation with pharmaceutical preparations is the only means of treatment of vitamin D deficiency. We aimed to study the composition and availability of various vitamin D preparations in the Indian market, data about which was collected from annual drug compendium. The preparations were assessed for total number, different formulations, constituents and amount of each constituent present in the formulation. Vitamin D3 is available in the form of cholecalciferol, alfacalcidiol and calcitriol as single ingredient products and in combination with calcium and other micronutrients. Most of the supplements contain calcitriol (46.5%) or alfacalcidiol (43%) as tablets (51.1%) and capsules (35.2%). Cholecalciferol, the preferred form for prophylaxis and treatment of vitamin D deficient states, constitutes only 10% of the available market preparations. High market sales of calcium supplements containing calcitriol indicate increasing intake of calcitriol rather than cholecalciferol; which could predispose to toxicity. There is a need for marketing and rational prescribing of the appropriate vitamin D supplement in ostensibly healthy Indian population. Implementation of population-based education and intervention programmes with enforcement of strict regulations could generate awareness and curb unsupervised intake of vitamin D containing dietary supplements. This health challenge mandates effective nutritional policies, fortification and supplementation programmes and partnership between government, healthcare and industry to safeguard the health of Indian population at large.

Biosimilars: current scientific and regulatory considerations.

The widespread use of biologics has paved way for newer options in therapeutics for once incurable illnesses. Their large and complex protein structure, post-translational modifications, elaborate manufacturing/production process and risk for immunogenicity adds to the uniqueness of a biologic product. Patent expiration of innovator biologics has led to the development of biosimilars; biologics similar /comparable to the reference product in terms of quality, safety and efficacy. We discuss the clinical safety and regulatory requirements for biosimilars in various countries across the world. Future holds promise for biosimilars to provide affordable, efficacious and safe treatment to a vast majority of patients with significant cost savings to the nation.

Evaluation of anti-inflammatory activity, effect on blood pressure & gastric tolerability of antidepressants.

BACKGROUND & OBJECTIVES: Antidepressants are being used as analgesics for various pain related disorders like neuropathic and non neuropathic pain. Although their analgesic activity is well recognized but anti-inflammatory potential of antidepressants is still inconclusive. Since the antidepressants are used for longer duration, it becomes important to elucidate effect of anti-depressants on blood pressure and gastric mucosa. This study was undertaken to evaluate the anti-inflammatory potential of various antidepressant drugs as well as their effect on blood pressure and gastric tolerability on chronic administration in rats. METHODS: Rat paw oedema model was used for studying anti-inflammatory activity, single dose of test drug (venlafaxine 20 and 40 mg/kg, amitryptline 25 mg/kg, fluoxetine 20 mg/kg) was administered intraperitoneally 45 min prior to administration of 0.1 ml of 1 per cent carrageenan in sub-planter region. Oedema induced in test group was compared with normal saline treated control group. For studying effect on blood pressure and gastric tolerability, test drugs were administered for 14 days. Blood pressure was recorded on days 0, 7 and 14 using tail cuff method. On day 14, 4 h after drug administration, rats were sacrificed and stomach mucosa was examined for ulcerations. RESULTS: Pretreatment of rats with venlafaxine (40 mg/kg) resulted in a significant decrease in paw oedema as compared to control (2.4 ± 0.15 to 1.1 ± 0.16 ml, P<0.01). Similarly, in the group pretreated with fluoxetine, significant decrease in paw oedema was observed in comparison to control (P<0.05). Significant change in mean blood pressure was seen in rats pretreated with venlafaxine 40 mg/kg (126.7 ± 4.2 to 155.2 ± 9.7, P<0.05) and fluoxetine (143.5 ± 2.6 to 158.3 ± 1.2, P<0.05) on day 7. No significant difference with regard to gastric tolerability was observed among groups. INTERPRETATION & CONCLUSIONS: Our findings showed significant anti-inflammatory activity of venlafaxine (40 mg/kg) and fluoxetine but these drugs were also associated with an increase in blood pressure. No significant change in mean ulcer index was observed among groups.

Fatal methotrexate toxicity: could it have been avoided?

Methotrexate is used judiciously, only when specifically indicated. However, in this case the patient had a fatal outcome after only three doses. A young nulliparous woman diagnosed as having high-risk persistent trophoblastic disease was considered for multidrug chemotherapy. However, because of persistent low-grade fever it was decided to give only single agent, methotrexate. She developed severe toxicity which proved fatal, even before the first course could be completed. Analysing causes of this rare, unexpected outcome of methotrexate administration, suggested that estimation of serum levels can be a useful tool in monitoring patients showing hypersensitivity but this facility is rarely available especially in low-resource countries. Pharmacogenetical analysis of blood/tissue sample may be useful to help in identifying patients likely to show hypersensitivity reaction.

Management of women with systemic lupus erythematosus.

With improvements in survival rates for women with systemic lupus erythematosus (SLE) in the last few decades, the focus has now shifted towards the management of the associated complications. These include cancer, cardiovascular disease, osteoporosis and early menopause. These co-morbidities are believed to be the result of a complex interplay between the inflammatory process and disease treatment, and they complicate the management. A majority of women with SLE suffer considerable morbidity in the prime of their life. A team of multidisciplinary specialists is required to ensure aggressive and comprehensive management of risk factors, treatment of symptoms and prevention of complications to ensure successful outcomes.

Etoricoxib attenuates effect of antihypertensives in a rodent model of DOCA-salt induced hypertension.

While it is known that non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 (COX-2) inhibitors influence BP, the exact relationship and underlying mechanisms are still unclear. We investigated the effect of etoricoxib, a selective COX-2 inhibitor on the antihypertensive efficacy of atenolol; beta-blocker, ramipril; angiotensin converting enzyme inhibitor and telmisartan; angiotensin receptor blocker in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a mineralocorticoid volume expansion model. Etoricoxib attenuated the antihypertensive-induced reduction of systolic (atenolol; P < .001, ramipril; P = .011, telmisartan; P = .003) and mean arterial pressure (atenolol; P < .001, ramipril; P = .032, telmisartan; P = .023). These results demonstrate that COX-2 dependent mechanisms play a significant role in blood pressure regulation, and etoricoxib-induced COX-2 inhibition blunts the therapeutic effect of different classes of antihypertensives in this mineralocorticoid volume expansion model of hypertension.

Predictive value of symptoms for quality of life in first-episode schizophrenia.

BACKGROUND: Management of the disease symptomatology impacts the long-term functioning and quality of life (QOL) in psychotic patients. AIM: The aim of this research was to study the association between psychiatric symptoms (positive, negative and general psychopathology symptoms) and QOL in first-episode schizophrenia patients. METHODS: Fifty-five first-episode drug-naïve schizophrenia outpatients were recruited from a tertiary care hospital in New Delhi, India. WHOQOL-Bref (World Health Organization Quality of Life) Scale was used to assess multi-dimensional domains of QOL (physical, psychological, social and environmental health). The patients were evaluated clinically using PANSS and followed up for 6 months. Multivariate analyses were carried out to outline the symptoms which are predictive of QOL in these patients. RESULTS: Physical well-being as assessed with WHOQOL-Bref is significantly impacted by the positive, negative and general psychopathology symptoms of the disease. General psychopathology symptoms demonstrated a strong relationship with different facets of QOL. These symptoms are predictive of physical (P=0.025) and psychological health (P=0.026), social relationships (P=0.009) and environmental QOL (P=0.022). CONCLUSIONS: The general psychopathology symptoms significantly impact QOL in a diverse manner. Negative symptoms have a greater influence than positive symptoms on subjective QOL. CLINICAL IMPLICATIONS: The antipsychotics focus on primary positive and negative disease symptoms. There is a need to develop a holistic approach (target non-psychotic symptoms intensively) in the disease management to prevent further long-term impairment of QOL.

Lupus: novel therapies in clinical development.

There have been significant advancements in understanding the immunopathogenesis of systemic lupus erythematosus. However, the developments in therapeutics have been rather slow. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been approved for the treatment of this disease after more than 50 years. Numerous biological agents are being developed which target the B cells, T cells, and various cytokines. Among anti-B cell therapy, drugs target CD20+ cells (ocrelizumab, SBI-087), CD22+ cells (epratuzumab) \or the receptors of tumor necrosis factor (TNF) superfamily (atacicept, LY2127399, A-623). Monoclonal antibodies targeting interferon alpha (IFN-α) and gamma (IFN-γ) and interleukins (IL-6, 10) are being investigated for SLE. Novel targets include toll like receptors, phosphodiesterases, CD40 ligand and retinoid receptors. This review discusses various drugs which are in different phases of clinical trials and hold promise for patients suffering from this chronic debilitating disease.