Long-Term Safety Analysis of the BBV152 Coronavirus Vaccine in Adolescents and Adults: Findings from a 1-Year Prospective Study in North India.

BACKGROUND AND OBJECTIVE: Evidence on the long-term safety of COVID-19 vaccines is scarce. Here, in continuation of our previously published results on short-term safety, we provide data on the long-term safety of the BBV152 vaccine in adolescents and adults. METHODS: This was a prospective observational study conducted from January 2022 to August 2023. Adolescents and adults receiving the BBV152 vaccine were interviewed telephonically about long-term adverse events of special interest (AESIs) after 1 year of vaccination. Risk factors of AESIs and AESIs persistent for at least 1 month were identified. RESULTS: Out of 1024 individuals enrolled, 635 adolescents and 291 adults could be contacted during the 1-year follow-up. Viral upper respiratory tract infections were reported by 304 (47.9%) adolescents and 124 (42.6%) adults in this period. New-onset skin and subcutaneous disorders (10.5%), general disorders (10.2%), and nervous system disorders (4.7%) were the common AESIs in adolescents. General disorders (8.9%), musculoskeletal disorders (5.8%), and nervous system disorders (5.5%) were the common AESIs in adults. Menstrual abnormalities were noticed in 4.6% of female participants. Ocular abnormalities and hypothyroidism were observed in 2.7% and 0.6% of participants, respectively. Among serious AESIs (1%), stroke and Guillain-Barre syndrome were identified in 0.3% and 0.1% of participants, respectively. Among adolescents, female individuals, those with a history of allergy and post-vaccination typhoid were respectively at 1.6, 2.8, and 2.8 times higher risk of AESIs. The majority of the AESIs persisted at the 1-year follow-up. Female individuals, adolescents with pre-vaccination COVID-19, those with co-morbidities, and those with post-vaccination typhoid had respectively 1.6, 2, 2.7, and 3.2 times higher odds of persistent AESIs. Adults with co-morbidities had more than 2 times higher odds of AESIs and persistent AESIs. CONCLUSIONS: The patterns of AESIs developing after BBV152 differed from those reported with other COVID-19 vaccines as well as between adolescents and adults. With the majority of AESIs persisting for a significant period, extended surveillance of COVID-19-vaccinated individuals is warranted to understand the course and outcomes of late-onset AESIs. Serious AESIs might not be uncommon and necessitate enhanced awareness and larger studies to understand the incidence of immune-mediated phenomena post-COVID-19 vaccination. The relationship of AESIs with sex, co-morbidities, pre-vaccination COVID-19, and non-COVID illnesses should be explored in future studies.

A Scoping Review of Ayurveda Studies in Women with Polycystic Ovary Syndrome.

Introduction: Polycystic Ovary Syndrome (PCOS) is a complex disorder with diverse clinical presentations. Women with PCOS use traditional, complementary, and integrative medicines, including Ayurveda (traditional Indian medicine) to manage their symptoms. Therefore, it is important to understand the current evidence base and the potential areas that require further research. Objective: This novel study aimed at providing a description of the Ayurveda studies conducted on women with PCOS and identifying gaps for future research. Methods: This scoping review was undertaken using the Joanna Briggs Institute scoping review guidelines. Relevant electronic databases were searched for any peer-reviewed original research that examined the role of Ayurveda (interventions using single/compound formula of herbs or minerals or metals, Panchakarma procedures and other therapies, and Ayurveda-based diet and lifestyle) for managing symptoms of PCOS in women of reproductive age. Two reviewers independently screened the records, extracted the data on population, intervention, comparator, and outcome characteristics and descriptively summarized the data. Results: Of the 1820 records identified, 57 articles met the inclusion criteria; 32 case studies, 13 randomized controlled trials, 9 pre-post trials, 2 case series, and 1 non-randomized trial. Most studies were conducted in India and used either a compound formula or a complex intervention (e.g., panchakarma therapies and lifestyle modifications). The majority of the case studies/series used an Ayurvedic diagnostic approach that influenced the choice of Ayurveda intervention. Among the interventions, shatapushpa (dill seeds) and krishnatila (black sesame seeds) were the most used single herbs whereas kanchanara guggulu and rajapravartini vati were the most used compound formulas. Basti karma (therapeutic enema) was the most used complex intervention. Reproductive outcomes were the most studied; menstruation, PCOS-related infertility, and polycystic ovary morphology. Conclusions: There are a number of clinical studies on Ayurveda interventions for PCOS with a promising role in managing symptoms of PCOS. However, a few gaps were identified. Future research should aim at: (1) exploring a wider range of interventions, including Ayurvedic diet and lifestyle in different settings/locations; (2) exploring the effectiveness of Ayurveda treatments as an adjunct to biomedical treatments (3) a greater range of outcome measures such as obesity, type 2 diabetes, anxiety, depression, and quality of life needs to be further explored in women with PCOS; and (4) finally, safety and adverse event reporting needs to be undertaken rigorously and systematically.

Overlooked contributions of Ayurveda literature to the history of physiology of digestion and metabolism.

Ayurveda is a traditional system of healthcare that is native to India and has a rich documented literature of its own. Most of the historians agree that the documentation of core Ayurveda literature took place approximately in between 400 BCE and 200 CE, while acknowledging that the roots of its theoretical framework can be traced back to a much earlier period. For multiple reasons many significant contributions of Ayurveda literature to various streams of biological and medical sciences have remained under-recognized while recounting the historical milestones of development. This is true in the context of the physiology of digestion and metabolism too. In this communication we try to reconstruct a picture of the processes of digestion and metabolism as had been understood by ancient Ayurveda scholars. Though this understanding was primitive and insufficient in many ways, we argue that this deserves to be documented and acknowledged. To help with grasping the importance of these contributions, we juxtapose them with the corresponding insights pertaining to this subject reported by prominent western scientists. The major contributions of Ayurveda that have been recounted in this paper are those related to the description of three distinct phases of digestion (Avasthapaka), multiple sets of transformative entities acting at different levels of metabolism (Agni), and the roles ascribed to various internal and external factors in executing these physiological functions.

Effects of two Ayurvedic formulations, Dhanwantaram Kashaya and Saraswatarishta on life history parameters and toxic aggregates in Drosophila models of Huntington's and Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurveda, the traditional healthcare system native to India, employs dosage forms containing multiple herbs in treating various clinical conditions. Dhanwantaram Kashaya (DK) and Saraswatarishta (SA) are two such formulations containing multiple herbs in varied proportions. Kashaya is a liquid decoction while Arishta is fermented liquid with permissible quantity of self-generated alcohol in it. Both the formulations have been reported to have clinical efficacy in age-related memory impairment. Other mental disorders having clinical presentations similar to psychoses are the other indications for these tested formulations. AIM OF THE STUDY: The present study was performed to evaluate the efficacy of two Rasayana formulations i.e., DK and SA, used by clinicians in different neurodegenerative conditions. We tested these formulations in Alzheimer's (AD) and Huntington's disease (HD) models of Drosophila melanogaster. MATERIALS AND METHOD: Initial experiments looking for life-history parameters in wild-type larvae were carried out in three sets with hundred larvae in each set. These parameters were also studied in diseased models in four sets with eighty larvae in each set. Aß plaques and polyQ aggregates were looked at with the help of immunostaining technique and images were captured using confocal microscopy. RESULTS: The results revealed that 0.25% concentration of both the formulations improve longevity in wild-type flies. Larval development and adult lifespan in Eye-GAL4>Aß42 (AD) and GMR-GAL4>127Q (HD) larvae/flies reared on 0.25% & 0.50% DK and 0.25% & 1.00% SA improved substantially. Reduced Aß plaques and polyQ aggregates indicate disease suppression. CONCLUSION: DK and SA enhanced longevity in Drosophila melanogaster. Suppression of disease aggregates suggests their potential utility in treating AD and HD. Further clinical and pharmaceutical studies are required to confirm these results, however, this is a workable model to test multi-herbal formulations of Ayurveda in the forms they are clinically used.

Self-correction is essential to science: Author's response.

I thank R Srivatsan [1] and Shailaja Chandra [2] for commenting on my reflective article [3]. While it is true that the scientific establishment has, on many occasions, betrayed the public trust because of the power and money associated with it, the same cannot be said of "science" as such. Science is an idea that places evidence-based thinking above everything else while understanding a phenomenon. The results of this endeavour often depend on how well people apply it in different situations. Thalidomide and Rofecoxib could be taken as two examples where the biomedical sciences have disappointed the public [4]. However, one must remember that science cannot be blamed for causing these disasters; instead, it is the "science establishment" that must take the blame. After all, was it not because of science that these mistakes were exposed? By "establishment" I mean the entire mechanism that plans and regulates drug development, safety testing, marketing approvals, post marketing pharmacovigilance, journal editing, publications, etc.

Confessions of an Ayurveda professor.

In this essay, I narrate my experiences of teaching Ayurveda physiology through an approach that involved laborious re-interpretation of ancient literature using the recent advances in the field of medical physiology. Though this approach made the ancient concepts and theories appear modern and relevant, it did not contribute much except for apparently reducing cognitive dissonance among students. I cite examples describing the processes of formation of shukra (semen) and rakta (blood) to show how we often overinterpret Ayurveda concepts to make them sound rational by proposing ad hoc conjectures. I illustrate why my previous writings were faulty by applying the falsification principle proposed by Karl Popper. I further explain how this approach made these concepts only verifiable but not refutable, and hence, non-falsifiable. I argue that instead of using such re-interpretation to prove obsolete concepts, they can be dropped altogether from the curricula of Ayurveda programmes. There is a need to develop a reliable method to identify such outdated content.

A case for testing and modifying theory in Ayurveda: Author's response.

This is my response to several recent criticisms that have challenged my views expressed in the article 'Confessions of an Ayurveda Professor' in this journal [1]. Some of these criticisms, such as the one by Karthik and Shajin, are directly expressed [2], while others, such as the one by Tubaki and Prasad, are indirect [3]. The criticism by Tubaki and Prasad is particularly significant because it is the only feedback I have received from the Ayush establishment thus far; and lists the President of the Board of Ayurveda, National Commission for Indian System of Medicine (NCISM), as an author. Additionally, there have been many reactions published on IJME's website. I also address them in this response since many of them share a similar line of thinking.

A Prospective Observational Study on BBV152 Coronavirus Vaccine Use in Adolescents and Comparison with Adults: Interim Results of the First Real-World Safety Analysis.

INTRODUCTION: The BBV152 coronavirus disease 2019 (COVID-19) vaccine (COVAXIN) has recently been approved for adolescents. OBJECTIVE: We provide the first real-world safety data of COVAXIN use in adolescents and compare with adults. METHODS: A prospective observational study was initiated in January 2022. Enrolled adolescents and adults were contacted by telephone after 14 days of receiving the BBV152 vaccine. The primary outcome was vaccine safety assessed as rate of adverse events following immunization (AEFIs). Severity grading of AEFIs was done using the Food and Drug Administration (FDA) scale. Interim results are presented. RESULTS: A total of 698 adolescents and 326 adults were enrolled. AEFIs after the first dose developed in 243 out of 670 adolescents (36.3%), with 21% reporting only local AEFIs and 15.2% reporting systemic AEFIs. Among 340 adolescents who had received the second dose of vaccine, 129 (37.9%) developed AEFIs, with only local involvement in 20.3% and systemic involvement in 17.6%. Injection site pain and fever were the common AEFIs. The majority of AEFIs were mild-moderate. Nearly 0.9% of adolescents receiving the first dose reported severe AEFIs. Atypical AEFIs were observed in 0.6-0.9% of adolescents. The majority of the AEFIs resolved in 1-2 days. AEFIs were persistent in > 2% of adolescents at day 14 after the second dose, and also in 3.7% of adults overall at follow-up. No difference was observed in AEFI incidence and patterns between adolescents and adults. Regression analysis showed females and those with a history of allergy to be, respectively, at 1.6 times and 3 times increased risk of AEFIs among adolescents. CONCLUSIONS: COVAXIN carries an overall favorable short-term safety profile in adolescents. The observed AEFI rates in adolescents are much lower than that reported with mRNA vaccines, but head-head comparisons in the same population are required to generate relative vaccine safety data. Female adolescents and those with a history of allergy need watchfulness for severe and persistent AEFIs. With some AEFIs persisting at 14 days, a longer follow-up is recommended to strengthen the safety data of COVAXIN.

Persistent Health Issues, Adverse Events, and Effectiveness of Vaccines during the Second Wave of COVID-19: A Cohort Study from a Tertiary Hospital in North India.

Background There is paucity of real-world data on COVID-19 vaccine effectiveness from cohort designs. Variable vaccine performance has been observed in test-negative case-control designs. There is also scarce real-world data of health issues in individuals receiving vaccines after prior COVID-19, and of adverse events of significant concern (AESCs) in the vaccinated. Methods: A cohort study was conducted from July 2021 to December 2021 in a tertiary hospital of North India. The primary outcome was vaccine effectiveness against COVID-19 during the second wave in India. Secondary outcomes were AESCs, and persistent health issues in those receiving COVID-19 vaccines. Regression analyses were performed to determine risk factors of COVID-19 outcomes and persistent health issues. Results: Of the 2760 health care workers included, 2544 had received COVID-19 vaccines, with COVISHIELD (rChAdOx1-nCoV-19 vaccine) received by 2476 (97.3%) and COVAXIN (inactivated SARS-CoV-2 vaccine) by 64 (2.5%). A total of 2691 HCWs were included in the vaccine effectiveness analysis, and 973 COVID-19 events were reported during the period of analysis. Maximum effectiveness of two doses of vaccine in preventing COVID-19 occurrence was 17% across three different strategies of analysis adopted for robustness of data. One-dose recipients were at 1.27-times increased risk of COVID-19. Prior SARS-CoV-2 infection was a strong independent protective factor against COVID-19 (aOR 0.66). Full vaccination reduced moderate-severe COVID-19 by 57%. Those with lung disease were at 2.54-times increased risk of moderate-severe COVID-19, independent of vaccination status. AESCs were observed in 33/2544 (1.3%) vaccinees, including one case each of myocarditis and severe hypersensitivity. Individuals with hypothyroidism were at 5-times higher risk and those receiving a vaccine after recovery from COVID-19 were at 3-times higher risk of persistent health issues. Conclusions: COVID-19 vaccination reduced COVID-19 severity but offered marginal protection against occurrence. The possible relationship of asthma and hypothyroidism with COVID-19 outcomes necessitates focused research. With independent protection of SARS-CoV-2 infection, and high-risk of persistent health issues in individuals receiving vaccine after recovery from SARS-CoV-2 infection, the recommendation of vaccinating those with prior SARS-CoV-2 infection needs reconsideration.

Patterns of Physical Activity Among University Students and Their Perceptions About the Curricular Content Concerned With Health: Cross-sectional Study.

BACKGROUND: University students are at risk of losing their focus on maintaining healthy levels of physical activity because of their engagements with curricular and cocurricular activities. In India, the physical activity levels of the adult population have been reported to be declining in the recent years. However, studies focusing on university students pertaining to their physical activity are lacking in the Indian context. Moreover, a question that has not been properly addressed is the following: "do the curricula in higher education promote physical activity?" OBJECTIVE: Our paper aims at describing the physical activity levels of the students in a large public-funded central university located in northern India. The study also aims at capturing the student perceptions about the emphasis they receive on leading a physically active lifestyle during their routine curricular activities. METHODS: This is a cross-sectional descriptive study and uses International Physical Activity Questionnaire-Long Form to record physical activity among 4586 students. Stratified sampling method was used to enroll the students from each stream (faculty). Out of 30,667 students, about 15% were included from each faculty. The study was conducted between 2016 and 2019. To capture the student perceptions, we used a newly developed 5-item scale. RESULTS: From a total of 4586 participants in the study, 2828 (61.7%) were male and 1758 (38.3%) were female students. The mean age of our sample was 22.34 (SD 3.12) years. Our results indicate that about 14.5% (n=666) of all students in the study fall under the "Inactive" category. Furthermore, the perception about the curricular content pertaining to physical activity varied widely between the students of different streams. CONCLUSIONS: Our sample reported a better physical activity pattern in comparison to the reported overall physical activity levels of the adult population of India. Our results also suggest that health-related topics are inadequately represented in many of the streams of higher education in the university.

Surgical practice and Ayurveda: A realistic analysis of the current debate.

The recent notification issued by the Central Council of Indian Medicine making it compulsory for the postgraduate students of two streams of Ayurveda (Shalya Tantra and Shalakya Tantra) to be trained in different kinds of modern surgical procedures as a part of their curricula has led to a nation-wide debate. While practitioners from biomedical sciences are voicing their concerns against the decision, Ayurveda professionals are seen defending the same. In this article we try to look at this issue from a dispassionate and realistic point of view. We recount the historical milestones that paved way for the incorporation of the modern surgical practices in to Ayurveda curricula. Currently though there are many skilful Ayurveda surgeons who practice surgery in India, the standard of education in many Ayurveda colleges is very poor because of a low patient turn-out which is a matter of serious concern. We argue that, however, by citing these varying standards in education, imposing deliberate restrictions on Shalya-Shalakya students and not giving them access to treat patients too is unwarranted. Such a move can affect the research potential in these fields. We cite the history of the evolution of Kshara-Sutra therapy to justify our argument. Further, we delve into the issue of prospective and retrospective applicability of the said notification and suggest a few options that the Ministry of AYUSH may consider to resolve this issue. We conclude by saying that well-trained Ayurveda surgeons must be allowed to practice surgery, but at the same time, a blanket license to all Shalya-Shalakya postgraduate degree holders to practice surgery without ensuring their actual clinical training would be unreasonable.

Introducing Hybrid Problem-Based Learning Modules in Ayurveda Education: Results of an Exploratory Study.

Objectives: Problem-based learning (PBL) is a well-known student-centered instructional approach that is known to enhance problem-solving skills among the learners. Because teaching/learning methods in most of the Ayurveda colleges in India are still didactic and teacher centric, the effects of introducing PBL have not yet been evaluated. The primary objective of this study was to develop PBL modules for Kriya Sharira (Ayurveda Physiology) and their implementation in a hybrid format. In this method, PBL is used as an add-on component along with didactic lectures. The secondary objective of the study was to compare the learning outcomes achieved through hybrid problem-based learning (HPBL) with those achieved through conventional teaching. Design: This is a prospectively planned post-test-only, controlled interventional design with nonequivalent groups. However, the results have been analyzed in a retrospective manner. Subjects: Students enrolled in the first professional Bachelor of Ayurvedic Medicine and Surgery program during two consecutive academic sessions 2016-2017 and 2017-2018 at the Banaras Hindu University were included in the study. While the cohort from 2016 to 2017 session served as the control group, the one from 2017 to 2018 session served as the experimental group. Interventions: The instructional method commonly known as HPBL was introduced to the experimental group. Outcome measures: Five test papers containing mostly Multiple Choice Questions for five different topics were used as the tools for evaluating the learning outcomes in both the groups. Feedback forms regarding the experiences of undergoing HPBL were obtained from experimental group. Results: While the test results for three topics showed that the outcomes of HPBL were comparable with conventional teaching, the results on other two topics suggested that HPBL was slightly better. Feedback obtained showed that there is a considerable acceptance for HPBL over conventional method. Conclusions: The study shows that it is possible to implement HPBL method in a large classroom in the context of Ayurveda education. The findings also indicate that students find HPBL as an acceptable teaching method.

Research orientation in Ayurveda educational institutions: Challenges and the way forward.

This paper examines the scenario of research orientation in Ayurveda educational institutions of India. We demonstrate through the data obtained by searching the SCOPUS that the actual research output by these institutions is not very significant in terms of number of publications. While a lack of research expertise and infrastructure is one contributing factor to this status, a lack of questioning attitude is more crucial one. Mushrooming of new colleges, laxity in regulations, corruption, lack of atmosphere for ethical and quality research make the problem more complex. We show, with the help of SCOPUS Data, that the recent trend of establishing stand-alone institutions of Ayurveda may not help in invigorating research activities since the research contributions from such institutions have always been very poor. Instead, we suggest that existing stand-alone institutions of Ayurveda be merged with other established Central/State universities or other Medical colleges. The data demonstrates that the research output has been always significant when an institution has many experts working in different streams of science within, than when the institutions have only Ayurveda experts. We also take up the question of designing the clinical trials that are suitable for Ayurveda and propose an algorithm that may be considered for research in educational institutions, at least at doctoral level. We further enlist a set of recommendations that could potentially change the scenario. Evidence-informed policy making, inducting clinicians into the education system, making the curricula more attractive by including recent advances, introducing efficient faculty training programs, and rigorous implementation of the existing regulations - are some of the key recommendations we have made.

Allopathic, AYUSH and informal medical practitioners in rural India - a prescription for change.

This paper looks at the treatment seeking behaviour of rural households and presents factors that discourage them from using public health facilities. It also brings out how Allopathic medical graduates as well as institutionally qualified AYUSH doctors predominantly offer services in cities and townships which results in lakhs of village households having to depend on unqualified medical practitioners as the first line of medical treatment; also how this situation will continue unless the approach to providing medical treatment is modified. Continued dependence on unqualified practitioners is fraught with dangers of incorrect diagnosis, irrational drug use, resulting in the spread of multi-drug resistance. The reality that surrounds Allopathic practice by AYUSH doctors has also been described along with the educational underpinnings of accepting this approach. We opine that existing state policies that legitimise Allopathic practice by non-Allopathic practitioners do not help the rural poor to access proper medical treatment for acute conditions. Also, it does not enhance the credibility of the indigenous systems of medicine among which Ayurveda is the dominant system. First, we position our views in the context of the recently introduced National Medical Commission (NMC) Bill 2017 and provisions which call for the assessment of the need for human resources for health and building a road map to achieve the same. Second, we advocate re-inventing the pre-independence system of trained medical auxiliaries enrolled on a new schedule of the respective state medical register, authorised to give immediate medical treatment and making informed referrals for further diagnosis or specialised treatment. Finally, we recommend reinforcing the AYUSH systems to tackle emerging non-communicable diseases which are affecting all population cohorts adversely and, in whose prevention and management, the AYUSH systems are reported to possess special skills and competence.

Ayurveda formulations: A roadmap to address the safety concerns.

It is a matter of serious concern that the number of case reports pointing at a possible association between the clinical toxicity and the use of Ayurveda formulations is increasing significantly over the years in scientific medical literature. Though most of these cases are connected with the presence of heavy metals such as lead, mercury and arsenic in these formulations, there are also reports suggesting toxicity due to the presence of toxic chemicals of herbal origin. In the year 2008, the Government of India took an initiative of establishing the National Pharmacovigilance Programme for Ayurveda, Siddha and Unani drugs in a structured way. However, due to lack of sustained support, this program has now become defunct. This issue is of vital importance and needs to be addressed effectively on a priority basis. In this communication, we propose the following crucial policy interventions to be introduced at different levels: a. Amendments to Drug and Cosmetic Act, b. Issuing consumer guidelines, c. Issuing prescription guidelines, d. Issuing clinical monitoring guidelines, e. Implementation of good manufacturing guidelines, f. Promoting documentation of clinical safety, g. Identifying the sources of contamination, and, h. Provision for stringent punishment. If these policy interventions are taken up and implemented, a significant positive change in the scenario can be expected in the near future.