Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

AIM: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. METHODS: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. RESULTS: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. CONCLUSION: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

Safety of hydroxychloroquine in healthcare workers for COVID-19 prophylaxis.

BACKGROUND & OBJECTIVES: Hydroxychloroquine (HCQ), reported to inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in in vitro studies, has been recommended for prophylaxis of COVID-19 in healthcare workers (HCWs). The objective of this study was to assess short-term adverse events (AEs) of HCQ in HCWs. METHODS: This cross-sectional study among consenting HCWs taking prophylaxis and working in hospitals with COVID-19 patients used online forms to collect details of HCWs, comorbidities, prophylactic drugs used and AEs after the first dose of HCQ. Verification of dose and AEs was done by personal contact. Multivariate logistic regression analysis was done to determine the effect of age, gender and dose of HCQ on AE. RESULTS: Of the 1303 HCWs included, 98.4 per cent (n=1282) took HCQ and 66 per cent (n=861) took 800 mg as first day's dose. Among the 19.9 per cent (n=259) reporting AEs, 1.5 per cent (n=20) took treatment for AE, none were hospitalized and three discontinued HCQ. Gastrointestinal AEs were the most common (172, 13.2%), with less in older [odds ratio (OR) 0.56, 95% confidence interval (CI) 0.35-0.89], with more in females (OR 2.46, 95% CI 1.78-3.38) and in those taking a total dose of 800 mg on day one compared to a lower dose. Hypoglycaemia (1.1%, n=14), cardiovascular events (0.7%, n=9) and other AEs were minimal. INTERPRETATION & CONCLUSIONS: HCQ prophylaxis first dose was well tolerated among HCWs as evidenced by a low discontinuation. For adverse effects, a small number required treatment, and none required hospitalization. The study had limitations of convenience sampling and lack of laboratory and electrocardiography confirmation of AEs.

Development and impact of a massive open online course (MOOC) for antimicrobial stewardship.

Background: The University of Dundee and the BSAC developed a massive open online course (MOOC) to address the global need for education to support antimicrobial stewardship in low- and middle-income countries. Methods: An interactive course, Antimicrobial Stewardship: Managing Antibiotic Resistance, was developed and delivered via the FutureLearn© platform. The course ran over four 6 week periods during 2015 and 2016 supported by educators and was evaluated via data on uptake and feedback from learners on impact on clinical practice. Results: In total, 32 944 people, 70% of them healthcare professionals, from 163 countries joined the course from Europe (49%), Asia (16%), Africa (13%), North America (9%), Australia (8%) and South America (5%). Between 33% and 37% of joiners in each run completed at least one step in any week of the course and 219 participants responded to a post-course survey. The course was rated good or excellent by 208 (95%) of the participants, and 83 (38%) intended to implement stewardship interventions in their own setting. A follow-up survey 6 months later suggested that 49% had implemented such interventions. Conclusions: The MOOC has addressed a global learning need by providing education free at the point of access, and learning from its development will help others embarking upon similar educational solutions. Initial quantitative and qualitative feedback suggests it has engaged participants and complements traditional educational methods. Measuring its real impact on clinical practice remains a challenge. The FutureLearn© platform offers flexibility for MOOCs to be sustainable through modification to remove educator facilitation but maintain active participant discussion.

ICMR programme on Antibiotic Stewardship, Prevention of Infection & Control (ASPIC).

Antimicrobial resistance and hospital infections have increased alarmingly in India. Antibiotic stewardship and hospital infection control are two broad strategies which have been employed globally to contain the problems of resistance and infections. For this to succeed, it is important to bring on board the various stakeholders in hospitals, especially the clinical pharmacologists. The discipline of clinical pharmacology needs to be involved in themes such as antimicrobial resistance and hospital infection which truly impact patient care. Clinical pharmacologists need to collaborate with faculty in other disciplines such as microbiology to achieve good outcomes for optimal patient care in the hospital setting. The ASPIC programme was initiated by the Indian Council of Medical Research (ICMR) in response to the above need and was designed to bring together faculty from clinical pharmacology, microbiology and other disciplines to collaborate on initiating and improving antibiotic stewardship and concurrently curbing hospital infections through feasible infection control practices. This programme involves the participation of 20 centres per year throughout the country which come together for a training workshop. Topics pertaining to the above areas are discussed in addition to planning a project which helps to improve antibiotic stewardship and infection control practices in the various centres. It is hoped that this programme would empower hospitals and institutions throughout the country to improve antibiotic stewardship and infection control and ultimately contain antimicrobial resistance.

Formulating a Community-Centric Indicator Framework to Quantify One Health Drivers of Antibiotic Resistance: A Preliminary Step towards Fostering 'Antibiotic-Smart Communities'.

Antibiotic resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through the 'One Health' approach is essential to complement top-down measures. However, the absence of objective criteria to measure the performance of ABR interventions in community settings makes it difficult to mobilize interest and investment for such interventions. An exercise was therefore carried out to develop an indicator framework for this purpose. A comprehensive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was carried out by global experts on ABR, looking at appropriateness, feasibility, and validity. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management, and Water Sanitation and Hygiene (WASH) domains. The indicator framework was piloted in the panchayat (located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating that the framework is sensitive to change. The indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use the framework with minimal training. It is hoped that, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community as part of National Action Plan on AMR.

Randomized Placebo-Controlled Trial of Topical Capsaicin for Delayed Chemotherapy-Induced Nausea and Vomiting.

PURPOSE: We examined the efficacy of topical capsaicin in reducing delayed chemotherapy-induced nausea and vomiting (CINV). METHODS: Adults on highly emetogenic chemotherapy regimens applied 2 g of capsaicin ointment (0.075%) or matching placebo four times a day to the abdomen for 5 days in addition to standard antiemetic regimen in this blinded randomized controlled trial. Patients were monitored for nausea and vomiting in the immediate (day 1), delayed (days 2-5), and extended phases (days 2-15). Self-reported incidence and daily episodes of CINV were compared between the groups. Onset, severity, need for rescue antiemetics, cumulative vomiting episodes, and safety were also compared. RESULTS: In total, 160 patients were enrolled. The final modified intention-to-treat population included 75 patients each in the capsaicin and placebo groups. Fewer patients experienced nausea (36.0% [n = 27] v 53.3% [n = 40]; P = .033) and vomiting (28.0% [n = 21] v 42.7% [n = 32]; P = .060) in the capsaicin arm during the delayed phase. During the extended phase, there was a significantly lower incidence of nausea (44% v 64.0%; P = .014) in the capsaicin arm. No difference in nausea (26.7% v 25.3%) or vomiting (22.7% v 18.7%) was evident in the immediate phase. The average daily episodes of nausea and vomiting were significantly fewer in the capsaicin arm during the delayed and extended phases. With capsaicin, no grade 3 nausea (9.3% v 0.0%; P = .007) was observed, and the time to first nausea and vomiting was significantly prolonged. There were no differences between the groups with respect to rescue antiemetics, unscheduled hospital visits, and adverse events. CONCLUSION: Topical capsaicin reduced the incidence of nausea and the average number of vomiting episodes during delayed and extended phases without increasing adverse effects.

Public perception and community-level impact of national action plans on antimicrobial resistance in Vietnam.

Objectives: Vietnam was the first country from the WHO Western Pacific Region to adopt a national action plan (NAP) on antimicrobial resistance (AMR) in 2013. The multilayered nature of AMR requires coordination across 'One Health' sectors, dedicated financing, multistakeholder involvement, and widespread community engagement to implement the action plans. This study explores the perceived impact of NAP implementation at the community level. Methods: Key informant interviews (KIIs) were used for data collection during 2021. An interview tool was used for the KIIs and purposive sampling was used to identify study participants from Vietnam. The study participants were those engaged with a substantial scale of antimicrobial usage, diagnosis of infections or concerned with antimicrobial content in effluents in their professional life. Twelve KIIs were conducted with participants from human health, animal health and the environmental sector. The data were entered into Microsoft Excel, and manifest and latent content analysis was done. Results: The analysis highlighted themes such as limited public awareness of AMR, ongoing capacity building and quality assurance initiatives, implementation of guidelines and regulations for AMR containment, sustained investment in improving infrastructure, and challenges relating to accountability whilst prescribing and selling antibiotics. Conclusions: There were many positive critical developments during the NAP implementation period in Vietnam towards AMR mitigation. For better impact, there is a need to revitalize the implementation machinery of NAPs by improving the enforcement capacity of regulations, cross-sectoral collaboration and promoting community ownership.

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.

Patterns of antibiotic use in the community and challenges of antibiotic surveillance in a lower-middle-income country setting: a repeated cross-sectional study in Vellore, South India.

OBJECTIVES: There is considerable evidence linking antibiotic usage to bacterial resistance. Intervention strategies are needed to contain antibiotic use and thereby resistance. To plan appropriate strategies, it is imperative to undertake surveillance in the community to monitor antibiotic encounters and drivers of specific antibiotic misuse. Such surveillance is rarely in place in lower-middle-income countries (LMICs). This study describes antibiotic patterns and challenges faced while developing such surveillance systems in an LMIC. PATIENTS AND METHODS: Surveillance of antibiotic encounters (prescriptions and dispensations) was carried out using a repeated cross-sectional design for 2 years in Vellore, south India. Every month, patients attending 30 health facilities (small hospitals, general practitioner clinics and pharmacy shops) were observed until 30 antibiotic encounters were attained in each. Antibiotic use was expressed as the percentage of encounters containing specific antibiotics and defined daily doses (DDDs)/100 patients. Bulk antibiotic sales data were also collected. RESULTS: Over 2 years, a total of 52,788 patients were observed and 21,600 antibiotic encounters (40.9%) were accrued. Fluoroquinolones and penicillins were widely used. Rural hospitals used co-trimoxazole more often and urban private hospitals used cephalosporins more often; 41.1% of antibiotic prescriptions were for respiratory infections. The main challenges in surveillance included issues regarding sampling, data collection, denominator calculation and sustainability. CONCLUSIONS: Patterns of antibiotic use varied across health facilities, suggesting that interventions should involve all types of health facilities. Although challenges were encountered, our study shows that it is possible to develop surveillance systems in LMICs and the data generated may be used to plan feasible interventions, assess impact and thereby contain resistance.

Effectiveness of teaching medical ethics to medical students on an online platform: An analysis of students' perceptions and feedback.

Medical ethics education along with attitude and communication training has been incorporated into the regular MBBS curriculum in India from 2019, so as to encourage a caring and communicative approach by doctors towards patients. It would be important to understand the relevance of the educational module in the form of cases to ensure an optimal learning process for future students and doctors in the making. We selected three cases and conducted online debates among small groups of second year MBBS students. Students submitted narratives and their reflections after discussing each case and gave overall feedback. Our findings suggested that the students recognised the complexity of taking decisions when presented with ethical dilemmas and appreciated the opportunity to voice opposing views. The online platform was effective and may be considered in the future as a medium to help integrate discussions on medical ethics alongside clinical work.

Oral Faropenem Sodium - Implications for Antimicrobial Resistance and Treatment Effectiveness.

Rising antimicrobial resistance (AMR) is causing therapeutic failures with antibiotics. Inappropriate use is a contributing factor. One such antibiotic on the radar is faropenem, a broad spectrum antibiotic approved in 2005 in India. Recently, faropenem sodium suspension was approved for use in children. There is a potential danger of overuse due to the convenience of oral administration. Other carbapenems such as meropenem are used parenterally. Overuse of faropenem may promote cross-resistance with other carbapenems making them ineffective.

The role of Schedule H1 and Red Line campaign in improving antibiotic use in India.

Purpose: Over-the-counter (OTC) sale of antibiotics have contributed to the growing threat of antibiotic resistance. The Government of India has instituted regulatory measures, such as Schedule H1 and public campaigns such as Red Line Campaign, to limit such sales. This study was conducted to assess the perceptions of stakeholders regarding their effectiveness. Methods: To assess Schedule H1, pharmacists who own retail pharmacies in the state of Kerala, India, were interviewed using a pre-prepared question guide. In the next phase, healthcare professionals and patients in a hospital were shown the Red Line on an antibiotic blister pack and asked about its significance. Finally, 100 patients were shown a blister pack of Amoxicillin, and asked to identify the medicine or its use. Results: It was observed that there is poor awareness about antibiotic regulations and a perception of laxity in enforcement. Regarding the Red Line, only 7% of healthcare professionals could describe its significance and none among patients. Among the 100 patients who were shown Amoxicillin, only 42 could identify it as an antibiotic or describe its use. Conclusions: There is a general perception that regulations are poorly enforced and all are not aware of the Red Line campaign including healthcare professionals. Greater awareness at all levels about appropriate antibiotic use through prescriptions followed by greater efforts towards regulatory implementation and compliance should form parts of a multi-modal strategy to contain OTC sales of antibiotics. This will greatly help to aid physicians in improving overall healthcare through safe and effective prescribing.

Global access to existing and future antimicrobials and diagnostics: antimicrobial subscription and pooled procurement.

The COVID-19 pandemic has underlined the importance of an efficient and equitable supply of and access to essential health products. These factors are equally pertinent to the antimicrobial resistance pandemic, in which access to a portfolio of existing and pipeline antimicrobials plus complementary diagnostics is crucial. This Viewpoint focuses on market shaping in low-income and middle-income countries (LMICs), where the need for effective antimicrobials and complementary diagnostics is most acute. We propose the creation of a subscription and pooled procurement model that consolidates the growing demand for a portfolio of antimicrobials and diagnostics in LMICs. Anchored by regional market leaders, these pooling mechanisms would guarantee consistent private-sector and public-sector access in participating countries, while creating conditions for long-term best practice in stewardship. Supported by data from South Africa and India, this proposal sets out an innovative approach to tackle the antimicrobial resistance crisis in LMICs.

Equitable Access to Antibiotics: A Core Element and Shared Global Responsibility for Pandemic Preparedness and Response.

Securing equitable antibiotic access as an essential component for health system resilience and pandemic preparedness requires a systems perspective. This article discusses key components that need to be coordinated and paired with adequate financing and resources to ensure antibiotic effectiveness as a global public good, which should be central while discussing a new global agreement.

Use of drugs not listed in the National List of Essential Medicines: Findings from a prescription analysis by the Indian Council of Medical Research-Rational Use of Medicines Centres Network in tertiary care hospitals across India.

BACKGROUND: The concept of listing essential medicines can lead to improved supply and access, more rational prescribing, and lower costs of drugs. However, these benefits hinge on the prescription of drugs from an Essential Medicines List (EML). Several studies have highlighted the problem of underutilization of EMLs by prescribers. Therefore, as part of prescription research by the Indian Council of Medical Research-Rational Use of Medicines Centres Network, we evaluated the extent of prescription of drugs not listed in the National List of Essential Medicines (NLEM). MATERIALS AND METHODS: Prescriptions of outpatients from participating centers were included after obtaining verbal/written informed consent as approved by the Ethics Committee, and evaluated for prescription of drugs from the NLEM 2015. RESULTS: Analysis of 4838 prescriptions from 13 tertiary health-care institutes revealed that 2677 (55.33%) prescriptions had at least one non-NLEM drug prescribed. In all, 5215 (31.12%) of the total 16,758 drugs prescribed were not in NLEM. Of these, 2722 (16.24%) were single drugs and 2493 (14.88%) were fixed-dose combinations (FDCs). These comprised 700 different drug products - 346 single drugs and 354 FDCs. The average number of non-NLEM drugs prescribed per prescription was 1.08, while the average number of all drugs prescribed was 3.35 per prescription. It was also found that some of the non-NLEM drugs prescribed had the potential to result in increased cost (for example, levocetirizine), increased adverse effects (dextromethorphan), and less effectiveness (losartan) when compared to their NLEM counterparts. Nonavailability of an essential drug (oral hydroxocobalamin) was another important finding of our study. CONCLUSION: This study highlights the extent and pattern of drugs prescribed from outside the NLEM at the tertiary health-care level and the need for training and enhanced awareness among prescribers for greater utilization of the NLEM.

Rationalizing antibiotic use to limit antibiotic resistance in India.

Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics.

A One Health Review of Community-Acquired Antimicrobial-Resistant Escherichia coli in India.

Antimicrobial resistance (AMR) threatens to undermine nearly a century of progress since the first use of antimicrobial compounds. There is an increasing recognition of the links between antimicrobial use and AMR in humans, animals, and the environment (i.e., One Health) and the spread of AMR between these domains and around the globe. This systematic review applies a One Health approach-including humans, animals, and the environment-to characterize AMR in Escherichia coli in India. E. coli is an ideal species because it is readily shared between humans and animals, its transmission can be tracked more easily than anaerobes, it can survive and grow outside of the host environment, and it can mobilize AMR genes more easily than other intestinal bacteria. This review synthesized evidence from 38 studies examining antimicrobial-resistant E. coli (AR-E) across India. Studies of AR-E came from 18 states, isolated from different sample sources: Humans (n = 7), animals (n = 7), the environment (n = 20), and combinations of these categories, defined as interdisciplinary (n = 4). Several studies measured the prevalence of AMR in relation to last-line antimicrobials, including carbapenems (n = 11), third-generation cephalosporins (n = 18), and colistin (n = 4). Most studies included only one dimension of the One Health framework, highlighting the need for more studies that aim to characterize the relationship of AMR across different reservoirs of E. coli.

Collateral effects and ethical challenges in healthcare due to COVID-19 - A dire need to support healthcare workers and systems.

COVID-19 has affected the daily activities of people across the globe. The effects of the pandemic have not just been medical, but also societal and economical. The responses of government and the public have varied in different countries. Measures have ranged from improving hygiene, information dissemination, and social distancing to more radical measures such as social isolation, quarantine and lockdown. The disease and human responses have had consequences on the way we live, work, eat and rest. Life and livelihoods have been affected. This article highlights how the response to the pandemic has affected various aspects of healthcare and ethical dilemmas this has raised. As the pandemic progresses, awareness and evaluation of the unintended consequences of the pandemic and responses on our health and healthcare systems are needed. Discussing these points and being aware of the ethical issues may help countries and policy makers plan suitable strategies to mitigate these collateral effects, especially as the pandemic continues. It is hoped that this article will support healthcare workers, especially those in primary and secondary healthcare, as they overcome various challenges to treat patients with existing and prior diseases, and encourage them to advocate for robust and sustainable healthcare systems for public health. This would then help effectively combat future epidemics. Most importantly, it can mitigate the adverse collateral effects on healthcare that the public are experiencing and the treatment dilemmas that family and primary care physicians are facing.

Resetting the agenda for antibiotic resistance through a health systems perspective.

Although the individual and societal consequences of antibiotic resistance spiral upwards, coordinated action has not kept pace on a global scale. The COVID-19 pandemic has highlighted the need for resilient health systems and has resulted in an unprecedented rate of collaboration in scientific, medical, social, and political dimensions. The pandemic has also created a renewed awareness of the importance of infectious diseases and is a substantial entry point for reigniting the momentum towards containing the silent pandemic of antibiotic resistance. In this Viewpoint, we discuss the limitations in the current narrative on antibiotic resistance and how it could be improved, including concerted efforts to close essential data gaps. We discuss the need for capacity building and coordination at the national and global levels to strengthen the understanding of the importance of sustainable access to effective antibiotics for all health systems that could generate tangible links to current processes for global health and development.