Surveying the Indian research ethics committee response to the COVID-19 pandemic.

Research ethics committees (RECs) have played a crucial role in expediting the review of research protocols amidst the COVID-19 pandemic. To improve their performance and identify areas of enhancement, a multicentric study was conducted in India by the Forum for Ethical Review Committees in the Asian and Western Pacific Region (FERCAP). The study aimed to evaluate the preparedness of Indian RECs during the COVID-19 outbreak while conducting protocol reviews and comprehend the challenges they encountered. After obtaining ethics committee approval, a cross-sectional observational study was conducted using two validated questionnaires, one for REC member secretaries/chairpersons and another for REC members. The questionnaires consisted of 13 multiple-choice questions, 10 yes or no questions, and 2 open-ended questions each. The study was distributed to multiple RECs. A total of 109/200 participants, including 13 REC member secretaries, 12 chairpersons and 84 REC members from a total of 34 REC's, consented to participate in the study. During the COVID-19 pandemic, 23/25 (92%) of the RECs conducted online meetings. The most common challenges faced by RECs included risk-benefit analysis (12/25 RECs), review of informed consent (12/25 RECs), and protocols involving vulnerable populations (10/25 RECs). 65% of the REC members reported the need for ethics review training, and 66/84 REC members agreed or strongly agreed that RECs require training in COVID-19 protocol review. Additionally, 62/84 REC members agreed or strongly agreed that central/joint RECs should review multicenter COVID-19 protocols. RECs in India encountered difficulties while reviewing risk-benefit analyses, informed consent documents (ICDs), and COVID-19 protocols and they suggested providing training on these topics.

Evaluation of the Effects of Caesalpinia crista on Letrozole-Induced Models of Polycystic Ovarian Syndrome.

Background Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, affecting reproductive, endocrine, and metabolic functions. This study was designed to validate the claims in Ayurveda regarding the efficacy of Caesalpinia crista (Latakaranj) to treat PCOS. Its seeds are uterine stimulants and ovulation inducers and improve menstrual cycle irregularities. Objectives The present study aimed to evaluate the effects of Caesalpinia crista on reproductive abnormalities, reproductive hormones, and glycemic changes in a letrozole-induced model of PCOS. Material and methods The study was performed in rats with six groups having six rats in each group. The control group was given the vehicle carboxymethylcellulose (CMC) for 21 days orally, followed by normal saline (0.9% NaCl) orally for 15 days. The inducing agent, letrozole, was given to the disease control group and the four treatment groups for 21 days, followed by a treatment period of 15 days with either clomiphene citrate (1.8 mg/kg) orally in the clomiphene group, low-dose (100 mg/kg) Caesalpinia crista, medium-dose (300 mg/kg) Caesalpinia crista, or high-dose (500 mg/kg) Caesalpinia crista. The variables assessed were daily vaginal smears to check for estrous cyclicity, body weight, blood glucose, serum testosterone (T), serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and the number of oocytes from each oviduct. Histopathology of ovaries was also done. Result There was no significant difference between the different groups for body weight and blood glucose. There was a significant difference between the regularity of the estrous cycle of the disease control group and the high-dose Caesalpinia crista (500 mg/kg) group (p<0.01). Hormonal levels of luteinizing hormone (LH) (p<0.05) and follicle-stimulating hormone (FSH) (p<0.05) were significantly raised in the high-dose Caesalpinia crista group, and that of testosterone was significantly decreased (p<0.05) in the high-dose Caesalpinia crista group compared to the disease control group. The number of ova was significantly high in the high-dose Caesalpinia crista group compared to the disease control group (p<0.05). Decreased number of atretic follicles was seen in the high-dose and medium-dose Caesalpinia crista group on histopathology, with an increased number of corpus lutea (p<0.05). Conclusion Treatment with Caesalpinia crista in high dose, i.e., 500 mg/kg, significantly improved the reproductive abnormalities (ovulation and menstrual irregularities) and histopathological changes associated with PCOS. It also restored reproductive hormone levels (testosterone, FSH, and LH), which are elevated in PCOS, and normalized the LH/FSH ratio, which is deranged in PCOS.

A prospective, single centre, open label, single arm pilot study to evaluate the efficacy and safety of Amlapitta Mishran Suspension in participants with endoscopic gastritis.

BACKGROUND: Endoscopic gastritis is associated with symptoms of gastritis, along with endoscopic findings. Amlapitta Mishran has multiple active components that act via various mechanisms in patients with gastritis symptoms. We planned to conduct this study to find out the efficacy and safety of Amlapitta Mishran in patients with endoscopic gastritis. OBJECTIVES: To find out efficacy of Amlapitta Mishran in patient with endoscopic gastritis. MATERIALS AND METHODS: This study was an open-label, prospective, single-center study. Thirty participants were recruited, and Amlapitta Mishran Suspension was given for 30 days. Blood investigations for safety were performed at baseline (Visit 1), on Visit 3 and Visit 4. Endoscopy was performed at baseline and Visit 4, and stomach erosion score was recorded. Amlapitta Symptom Rating Scale score, Postprandial Distress Syndrome (PPDS) score, and Epigastric Pain Syndrome (EPS) score were efficacy endpoints. RESULTS: Out of the 30 participants recruited, 28 participants completed the study. The median age of participants in the study was 26.50 years. A statistically significant (P<0.05) reduction was seen in endoscopy score at Visit 4 as compared to baseline (Visit 1) by Wilcoxon Signed Rank test. Amlapitta Symptom Rating Scale score, PPDS score, EPS score also exhibited significant reduction (P < 0.05) at Visit 3 and Visit 4 as compared to baseline by Friedman's test with post hoc analysis. No statistically significant reduction was seen in these scores from Visit 3 to Visit 4, except for the EPS score. At the end of Visit 4, 18 (64%) participants had an endoscopy score of 1 (no erosions). At the end of Visit 4, ≥ 50% improvement was seen in Amlapitta Symptom Rating Scale score in 27 (96%) participants, PPDS score improved by ≥ 50% in 25 (89%) participants, and EPS score improved by ≥ 50% in 26 (93%) participants. All safety variables including laboratory investigation were within the normal range in all visits. CONCLUSION: Amlapitta Mishran Suspension effectively reduced endoscopic gastritis scores in the participants and reduced the symptoms of gastritis measured by the Amlapitta Symptom Rating Scale, PPDS, and EPS scores with no adverse events.

Evaluation of Antidepressant Effect of Minocycline in Alcohol Abstinence-Induced Depression Model in Mice.

Introduction Depression is one of the common comorbidities seen in chronic alcohol use disorder. Also, alcohol withdrawal induces depression and anxiety, which is associated with relapse in alcohol consumption. Minocycline, a tetracycline derivative, has shown an antidepressant effect in preclinical models. However, their effect on alcohol withdrawal-induced depression has not been studied. Therefore, the current study has been undertaken to evaluate the effect of minocycline on alcohol abstinence-induced depression models in mice. Method We conducted the study in two models. C57bl/6 mice were given a two-bottle choice (alcohol + water) for 28 days. During alcohol abstinence of 14 days, mice were treated with 10 mg/kg, 30 mg/kg, and 50 mg/kg of minocycline and were evaluated for behavioral changes using the forced swim test (FST) and tail suspension test (TST). A sucrose preference test was carried out where mice were exposed to binge alcohol drinking protocol for 12 days, where a two-bottle choice (alcohol or water) was given. This was followed by exposing the mice to a two-bottle choice paradigm (alcohol + sucrose) and they were divided into groups - no treatment group, vehicle-treated, minocycline 30 mg/kg or minocycline 50 mg/kg treated - and consumption of sucrose was assessed. Result In the forced swim test, a significant decrease in immobility time (p<0.05) was observed in the high-dose minocycline group (82.75±19.09) as compared to the vehicle control group (128.12±35.44). In the tail suspension test also, a significant decrease in immobility time (p<0.05) was seen in the high-dose minocycline group (83.75±18.61) as compared to the vehicle control group (122.25±18.51). The water and alcohol intake were comparable among all groups. In the sucrose preference test, it was found that the minocycline 50 mg/kg group had the highest sucrose preference (55%) followed by the minocycline 30 mg/kg group (50%) as compared to 42% in the vehicle control group. Significant reduction in brain-derived neurotrophic factor (BDNF) levels was seen with minocycline 50 mg/kg (p<0.05) and minocycline 30 mg/kg group (p<0.05) in BDNF levels when compared to the normal control group. Conclusion Minocycline in a higher dose (50 mg/kg) has shown an effect in alcohol withdrawal-induced depression in the abstinence-induced two-bottle choice model in mice. Both doses of minocycline have shown an effect in the sucrose preference test in the alcohol withdrawal-induced depression model.

Evaluation of Issues Affecting Time Between Study Completion, Manuscript Submission, Acceptance, and Publication in Medical Journals.

INTRODUCTION: Difficulty in finding the appropriate journal, adherence to the formatting differences between various journals, publication fees, delay in acceptance/rejection, etc., are a few reasons due to which much research is not published or when published the data in the research may become outdated. There are no studies to find out the issues which affect the time delay between study completion, submission to the journal, acceptance by the journal, and publication. With this background, we conducted this study. METHODS: This study was exempted by the Ethics committee as it was based on online data. Journal Citation Reports (JCR) 2020 (Clarivate analytics), CiteScore, and Google Scholar were used to sort the high-, moderate-, and low-impact factor journals. Forty-five journals each from high-, medium- and low-impact factors (h-index median, Google Scholar Metrics h5-index) were selected. Similarly, 15 predatory scientific journals were chosen. Journals with medical science backgrounds were chosen by randomization. Only original research articles were included. From each journal, five articles were chosen randomly from the latest issue pre-pandemic. The search was performed from April 2021 to June 2021. Variables analyzed were indexing of the journal, publication fees, level of impact factor, specialty domain, number of editors, frequency per year, date of study completion, date of submission, date of acceptance, date of publication, and h-index median. Data were compiled in Microsoft Excel Workbook (Microsoft, Redmond, WA, USA) and analyzed using IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp. Variables of time were represented as median and interquartile range, and the number of journals and processing fees for publication were descriptively analyzed. RESULTS: Out of 60 journals selected, 300 original articles were analyzed. There were 26 specialty-wise journals; the commonest was multispecialty journals. The fastest time from study completion to submission, submission to acceptance, submission to publication, and acceptance to publication was 15.5, 30, 61, and 0 days, respectively, and the slowest duration was 1636, 452, 615, and 456 days, respectively. PubMed indexed journals had a higher number of editors, h5-index, and h5 median, and slower time for acceptance and publication compared to non-PubMed indexed journals (p<0.05). Predatory journals had a lower h5-index and h5 median along with faster time to acceptance and publication compared to high and moderate impact factor journals (p<0.05). Journal with faster acceptance had faster publication as well (r=0.85), but no impact of the number of editors, number of issues per year (frequency), and publication fees with time to acceptance and publication. CONCLUSION: Though PubMed indexed journals with a greater number of editors and high fees are slower to publish articles but they are a safe option for researchers. The impact factor does not effect the speed of publication for non-predatory journals. Paying high fees and choosing a journal with more issues per year does not ensure quick publication to the researchers.

An Evaluation of the Efficacy, Safety, and Tolerability of Abhraloha Compared With Oral Ferrous Ascorbate on Iron Deficiency Anemia in Women: A Randomized Controlled, Parallel-Group, Assessor-Blind Clinical Trial.

Background and objective Iron deficiency anemia (IDA) is a common condition in women for which ferrous ascorbate (FA) is often prescribed, which can lead to multiple side effects. Abhraloha is an Ayurvedic medicine that has been used for decades in India to treat IDA. In this study, we aimed to evaluate the efficacy and safety of Abhraloha with regard to change in hemoglobin (Hb) levels as compared to the standard treatment using FA in participants with IDA. Materials and methods We conducted a single-center, pragmatic, prospective, randomized, active-controlled, two-arm, parallel-group, assessor-blind study to evaluate the efficacy and safety of Abhraloha with regard to change in Hb levels as compared to the standard treatment using FA in participants suffering from IDA. The eligible participants were randomized and were advised to take either Abhraloha (two tablets twice a day) or FA (one tablet twice a day) for eight weeks; they were asked to follow up after 14 days for re-evaluation. On visit 1 and during the study period, the physician assessed the participants on the Pandurog scale and subjective variables. Descriptive statistics were used with unpaired T-test/Mann-Whitney U test for comparison between the groups. The Wilcoxon signed-rank test was used for within-group analysis, and the chi-square test/Fisher's exact test was employed for categorical data. Results Based on our findings, Abhraloha tablets significantly increased all the variables including the Pandurog scale after eight weeks of treatment. Abhraloha reduced total iron-binding capacity (TIBC) and peripheral smear lymphocyte (PSL), which is consistent with an improvement in IDA. There was a statistically significant increase in Hb, red blood cell (RBC) count, packed cell volume (PCV), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in the Abhraloha group as compared with the FA group at eight weeks. The Abhraloha group also exhibited a statistically significant improvement in all the subjective variables. Abhraloha was found to be safe and well-tolerated among the participants. Conclusions Abhraloha possesses hematinic activity and it improves all the blood indices. It is associated with significantly fewer adverse effects compared to oral iron therapy, which proves that it can be safely used for the treatment of IDA.

A systematic review of standard treatment guidelines in India.

Background & objectives: Standard treatment guidelines (STGs) are the cornerstone to therapeutics. Multiple agencies in India develop STGs. This systematic review was conducted to find out STGs available in India, evaluate if these were as per World Health Organization (WHO) recommendations for STGs and compare these with National Institute for Health and Care Excellence (NICE) guidelines. Information on legal authority and responsibility for formulating STGs was also sought. Methods: PRISMA guidelines were followed. Publications from PubMed and Google Scholar were searched for STGs using terms 'Standard Treatment Guidelines AND India'. Data from STGs were compiled in excel as per the WHO and authors' criteria for STGs and compared with NICE guidelines. Results: PubMed and Google Scholar search provided 56 publications (out of 1695 search results) mentioning 27 STGs. Google search and replies from authors led us 36 STGs, totalling to 63 STGs. No STG mentioned any specific period of revision, eight STGs were not evidence-based, 55 had some Indian references, 48 STGs were for single disease and the remaining multi-disease, three STGs did not include diagnostic criteria, 16 STGs did not give prescribing information of recommended treatment and 16 STGs provide no referral criteria for patients. Fifty five STGs did not mention level of health care. While NICE is a single legal authority in England and guidelines are as per WHO recommendations for STGs, in India although Acts and rules do not vest authority, National Health Systems Resource Center is generally designated responsible for STGs. Interpretation & conclusions: In India, although there are multiple STGs developed by various authorities and professionals for the same conditions, these fulfil WHO recommendations only partially. Authority with statutory duty collaborating with professional organizations, a standard methodology for adopting international guidelines, Indian data for evidence base, attention to local needs will help in developing better STGs and their acceptance.

Prescription pattern & adverse drug reactions of prokinetics.

Background & objectives: Prokinetics are extensively prescribed leading to several adverse events (AEs). The aim of this study was to assess the prescription pattern in patients receiving prokinetics, and characteristics of adverse drug reactions (ADRs) in an outpatient department set up in a tertiary care hospital in western India. Methods: Patients attending outpatient departments of a tertiary care hospital and who had received prokinetic agent for at least seven days over the last one month were enrolled. Causality assessment of AEs was done and assessed for severity, preventability, seriousness and predictability. Results: A total of 304 patients [161 males (52.96%); 143 females (47.04%)] were enrolled. Most prescriptions (299/304, 98%) included domperidone, most commonly prescribed as fixed-dose combination (FDC) with pantoprazole (274/304, 90%). Prokinetic dose was not mentioned in 251/304 (83%) prescriptions, and 18/304 (6%) did not mention frequency. Of the 378 AEs reported from 179 patients (47.35%), 306 (81%) were mild, all non-serious; 272 (72%) not preventable and 291 (77%) predictable in nature. Decreased appetite (n=31, 8.2%) and fatigue (n=27,7.14%) were most commonly reported. Causality assessment by the World Health Organization-Uppsala Monitoring Centre scale showed that 180 AEs were related to suspected drug (17 probable and 163 possible ADRs). Significant correlation was observed for AEs with increasing number of drugs per prescription (Spearman's R=+0.8, P =0.05) and with increasing therapy duration (Spearman's R=+1.00, P <0.001). Interpretation & conclusions: Our findings showed that prokinetics were often prescribed as FDCs, with incomplete prescriptions. Domperidone was found to be associated with multiple AEs. It is suggested that regular prescription monitoring should be done in hospitals to encourage rational use of drugs.

Intra-articular injections of ketamine and 25% dextrose improve clinical and pathological outcomes in the monosodium iodoacetate model of osteoarthritis.

BACKGROUND: The study evaluated the effect of intra-articular injections of ketamine and 25% dextrose with triamcinolone acetate (TA) and hyaluronic acid (HA) on joint pathology and pain behavior in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) in experimental mice. METHODS: In phase I, the MIA-induced OA model was standardized. In phase II, mice were divided into three groups: disease controls (DC), ketamine 12 mg/kg (K12) and ketamine 24 mg/kg (K24) to select an effective dose of ketamine for phase III. In phase III, the groups were: DC, normal controls (NC), K24, 25% dextrose (D25) - 10 µL, TA 6 mg/kg, and HA - 3.5 mg/kg. The effect of ketamine was compared with the standard drugs - TA and HA. In phases II and III, after 7 days following the induction of OA, animals were subjected to weekly behavioral tests and biweekly drug administration from week 2 to week 4. Subsequently, after 4 weeks knee joint samples were collected and sent for histopathological evaluation to a veterinary pathologist. RESULTS: In phase I, the DC group showed significant OA changes as compared to NC on knee joint histopathology scoring. In phase II, all the behavioral tests and knee joint histopathology results demonstrated a significant improvement with K24 as compared to DC. In phase III, significant differences were found between DC vs. HA, DC vs. D25, DC vs. K24, K24 vs. TA, HA vs. TA for open field test and hot plate test (p<0.001), whereas HA and ketamine showed comparable results for these tests. There was a significant improvement in D25, TA and K24, HA groups as compared to DC in histopathology scores, (p<0.05). CONCLUSIONS: The NMDA antagonist effect of ketamine and the proliferative effect of 25% dextrose showed a reduction in pain and disease activity in the OA model.