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.

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.

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.

Payment for participation in clinical research: Review of proposals submitted to the ethics committees.

OBJECTIVE: In view of dearth of information in national and international guidelines on payment practices in research, the present study was done to find out payments for participation allowed by 3 Ethics committees (ECs) and reasons for payment. METHOD: This was a retrospective observational study which analysed research proposals reviewed by 2 institutional and 1 non-institutional ECs over a period of 2 years. The permission of ECs was obtained and confidentiality of data was maintained. RESULTS: Of the 73 studies requiring payment, 89.04% were interventional and 10.96% observational. Reimbursement of travel expenses (60%) was the major reason for payment followed by inconvenience due to participation, loss of wages and time spent. The queries raised by EC in more than 50 % of studies were related to informing patients about the payment in the informed consent document. The investigators complied with the EC requirements regarding payment (15/21) and the remaining provided explanations. The median amount of payment in pharmaceutical sponsored studies was higher compared to investigator initiated studies. Higher payments were approved by ECs on case to case basis in a few studies. The ECs did not have any policy/ standard operating procedure for payment practices. CONCLUSION: The present study first of its kind in India, demonstrated that quantum of payment was not uniform for pharmaceutical sponsored and investigator initiated studies and payments were not considered for majority of observational studies. Travel reimbursement was the most common reason for payment. There is a need to develop guidelines for determining appropriate payment/incentives to participants for specific types of research related activities.

Serious Adverse Events Reports: Analysis and Outcome of Review by an Institutional Ethics Committee of a Tertiary Care Hospital in Mumbai, India.

The Indian regulations for clinical trials were amended in January 2013 regarding reporting time lines, relatedness, and compensation for Serious Adverse Events (SAEs). Our study assessed the extent of regulatory compliance in reporting SAEs to the Institutional Ethics Committee (IEC) over 4 years (January 2009-January 2013) before and 18 months after (February 2013-July 2014) the amended regulations. SAE reports were studied retrospectively for reporting time lines, relatedness, compensation, and IEC response before and after the law revision. Before 2013 had 89/160 (55.6%) SAEs reports submitted late while in the after period, only 2/11 reports were delayed (18%). In the before period, 26 SAE reports mentioned "relatedness" of which only 15 (57.6%) stated about compensation. After 2013, all the 9 non-death reports were complete. The IEC took median 17 days to respond before 2013, while after 2013 responded within 5 days. Thus, there was poor compliance in terms of SAE reporting time lines before the revision of the law.

Evaluation of the estrogenic activity of Indian medicinal plants in immature rats.

INTRODUCTION: The objective of the study was to evaluate the estrogenic activity of four Indian medicinal plants Saraca indica (Si), Symplocos racemosa (Sr), Cyperus rotundus (Cr), Terminalia arjuna (Ta), a marketed preparation of Si (Asokarista) and a combination of Si + Sr using an experimental model of estrogenicity. MATERIALS AND METHODS: After approval of the institutional animal ethics committee, 22 day old female rats (n = 54) were randomly allocated to 9 groups - Group 1 and Group 2: Vehicle controls, Group 3: Ethinyl estradiol, Group 4: Si (270 mg/kg), Group 5: Sr (270 mg/kg), Group 6: Cr (540 mg/kg), Group 7: Ta (270 mg/kg), Group 8: Ashokarishta (4 ml/kg), Group 9: Si + Sr (135 mg/kg). Variables studied were: Body weight, uterine weight, relative uterine weight, presence of vaginal opening, histomorphology of the uterus and total uterine glycogen content. Parametric data were analyzed using one-way ANOVA and the categorical data were analyzed using Chi-square test. RESULTS: All animals in the ethinyl estradiol group showed a significant change in all the variables. None of the individual test drugs, neither the marketed preparation produced change in any of the variables. The plant drug combination also did not produce a change in any of the variables studied except in histomorphology wherein it caused a slight increase in the height of the luminal epithelium of the uterus (P < 0.05 vs. Group 1). CONCLUSION: The plant drugs Si, Sr, Cr, Ta and Asokarista did not demonstrate estrogenic activity in the immature rat model. The plant drug combination Si + Sr showed questionable estrogenic activity which needs to be evaluated in further studies.

Introduction of case based teaching to impart rational pharmacotherapy skills in undergraduate medical students.

OBJECTIVE: The aim of this study is to assess the impact of case based teaching (CBT) on learning rational prescribing and to compare CBT with the traditional method of teaching (TRD). MATERIALS AND METHODS: Second year Bachelor of Medicine and Bachelor of Surgery (MBBS) students (n = 179) were administered a pre-test and randomly divided into groups to receive CBT (n = 96) and TRD (n = 83). CBT group was further sub-divided into CBT1 and CBT2. Both these groups were taught two topics each by CBT and TRD during tutorials; however, the topics were switched with respect to method of teaching. The post-test comprised of three therapeutic problems of which two were related, and one was not related to the tutorial topics. Marks obtained in the post-test were graded and analysed using Fischer's exact test. RESULTS: In the post-test, the therapeutic problems on diabetes mellitus and peptic ulcer were attempted by 85.41% students from CBT and 73.49% from TRD group. CBT group obtained more marks for these problems (4.23 ± 0.94; P < 0.001) than the TRD (3.32 ± 0.92) group. Also, more students in the CBT obtained grade 3 (P < 0.001) and fewer obtained grade 1 (P < 0.01), compared to the TRD group. When the grades of the two CBT groups were compared, it was found that fewer students in CBT 2 had obtained grade 1 and those scoring higher grades were comparable between the two groups. For the therapeutic problem on malaria, 7.29% students from CBT and 18.07% from TRD received 0 grade (P < 0.05). More students received ≥ 2 grade in CBT group (P < 0.05). CONCLUSION: Use of CBT during tutorials is better than TRD and facilitates learning of rational pharmacotherapy.