In search for a panacea for coronavirus disease-19: Analysis of ongoing clinical trials for the management of coronavirus disease-19 pandemic in India.

OBJECTIVE: To analyze the clinical trials that are registered on the Clinical Trial Registry of India (CTRI) portal for a year, for the treatment, prevention, and supportive therapy of coronavirus disease-19 (COVID-19). MATERIALS AND METHODS: All the trials registered on CTRI (since January 2020 till January 2021) for therapeutic, preventive, and supportive interventions for COVID-19 were searched with the keywords "Coronavirus," "COVID-19," "SARS-COV-2," and "2019-nCoV". These registered studies were analyzed as follows: Trials under different systems of Medicine-Allopathy/Homeopathy/Ayurveda/Unani/Yoga/Naturopathy. The Allopathy trials were further analyzed in detail: Intervention, design, comparator, number of subjects, duration, and approvals taken. RESULTS: A total of 1597 records were found. After excluding the overlaps, behavioral and other studies conducted to understand the diagnosis, epidemiology, a total of 419 registered studies were included for further analysis. Out of these 419 studies, 166 (39.6%) were in Ayurveda, 154 (36.7%) in Allopathy, 33 (7.8%) in Homeopathy, 30 (7%) in Unani/Siddha, 18 (4.3%) in Yoga and Naturopathy and 18 (4.3%) in Nutraceuticals. A total of 264 interventions had been registered in 419 clinical trials. Sixty-seven interventions were being studied under allopathy in 154 studies. Same product was being evaluated in differently designed protocols with different endpoints. Maximum number of trials and subjects were for Hydroxychloroquine 25 (17,998), Ivermectin 11 (2820), Convalescent Plasma 11 (3982), Remdesivir 8 (3725), Tocilizumab 6 (884), and Azithromycin 6 (582). CONCLUSIONS: In response to the COVID-19 pandemic, Indian researchers came forward from all the systems of medicine to evaluate interventions for prophylaxis or treatment of the disease. The involvement of AYUSH systems of medicine was specifically more in this regard. A wide variation and heterogeneity in doses and outcomes were observed in trial designs which might make it difficult to generalize the study results when they are made available. Urgent analyses of studies involving interventions on the treatment advisory of the Government may help the healthcare providers take more informed decisions for managing COVID-19 patients in India.

Parent-Directed use of Over-the-Counter Medications and Complementary and Alternative Medicine Therapies among Pediatric Patients: A Cross-Sectional Study.

Objective: The use of over-the-counter (OTC) drugs and complementary and alternative medicines (CAM) as initial options by parents is common in the pediatric population. Despite the widespread use of parent-directed medication (PDM) among the pediatric population, we have scarce data in the Indian context. This study was done to assess the PDM practices and its determinants in the Indian population. Methods: It was a descriptive cross-sectional study assessing a representative sample of 284 parents of pediatric patients visiting the pediatrics department of a tertiary care hospital. Findings: Majority (64.08%; 182 out of 284) of the parents agreed to have used some form of PDM in the past 3 months. While higher socioeconomic status and having 2 or more children were associated with higher practice of PDM (P < 0.05), it was similar between educated or uneducated parents, rural or urban backgrounds, and nuclear or joint families (P > 0.05). CAM was the most commonly used option (58.12%; 161 out of 277), followed by OTC conventional allopathic medications (41.88%; 116 out of 277). Homeopathic medicines were the most preferred alternative therapy under the Alternative Medical System Category of National Centre for Complementary and Alternative Medicine. Majority of parents (71.43%; 130 out of 182) were confident that the treatment chosen could not harm the health of their children and they attributed time constraints or availability of prior prescriptions as reasons for such practice. Conclusion: PDM is a widespread phenomenon in the Indian pediatric population. The parents as well as the prescribers need to take a more balanced, practical, and judicious approach toward medications given to a child.

Is There a Rationale for Using Bacillus Calmette-Guerin Vaccine in Coronavirus Infection?

Coronavirus disease 2019 (COVID-19) has become a global pandemic in 2020. The pathogen responsible for the COVID-19 has been found to be coronavirus (2019-nCoV) with human transmission through droplets, airway secretions, and even direct contact with host. Currently multiple drugs and their combinations are being tried for the treatment of the COVID-19 disease, but none approved. In absence of definitive and approved treatment, it is imperative that prevention of COVID-19 infection is of utmost importance. For the same, face masks, hand hygiene, isolation, and quarantine are being practiced all over the world. However much successful these methods be, they cannot be used for a very long time. Thus, it becomes necessary that a vaccine be developed for the disease so that the further spread could be halted. Some reports suggest the use of Bacillus Calmette-Guerin (BCG) vaccine as the prophylaxis for coronavirus. BCG vaccine is a live attenuated vaccine, used for prophylaxis of Mycobacterium tuberculosis and is present in the essential list of the World Health Organization as well as immunization programs of many countries. Immunostimulatory antiviral effects of BCG vaccine are well known. At present, there are no published evidence available to support the use of BCG vaccine for the prevention of coronavirus infection. However, there have been speculations on enhanced immunity with BCG vaccine, which might be useful in prevention of coronavirus infection. Results from the clinical studies of BCG vaccine in vulnerable population are required to confirm this hypothesis.

Interplay of neuronal and non-neuronal genes regulates intestinal DAF-16-mediated immune response during Fusarium infection of Caenorhabditis elegans.

Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood. Here, we show that F. oxysporum f. sp. ciceri causes neuronal stress and intestinal disintegration, ultimately leading to the death of Caenorhabditis elegans. To explore the regulatory framework of Fusarium-associated disease, we analysed the gene expression during infection, integrated temporal gene expression, and network analysis with genetic inactivation data in Caenorhabditis elegans. We identified 1024 genes showing significant changes in expression (corrected P-values <0.05) in response to Fusarium infection. Co-expression network analysis of our data identified prognostic genes related to disease progression. These genes were dynamically expressed in various neuronal and non-neuronal tissues exhibiting diverse biological functions, including cellular homeostasis, organ patterning, stress response, and lipid metabolism. The RNA-seq analysis further identified shared and unique signalling pathways regulated by DAF-16/FOXO and SIR-2.1 linking neuronal stress, which facilitates negative regulation of intestinal innate immunity. Genetic analysis revealed that GCY-5 in ASE functions upstream of DAF-16, whereas ASI-specific SRD-1 regulates behavioural immunity. Overall, our results indicate that a ubiquitous response occurs during Fusarium infection mediated by highly conserved regulatory components and pathways, which can be exploited further for the identification of disease-responsive genes conserved among animals and plants. Finally, this study provided a novel insight into cross-species immune signalling and may facilitate the discovery of cellular therapeutic targets for Fusarium-associated disease.

Idiopathic short stature: decision making in growth hormone use.

Short stature is a common concern in pediatrics. Several ambiguities and controversies persist, especially with regard to criteria, cost, medical necessity and outcomes of growth hormone (GH) therapy for idiopathic short stature (ISS). Due to these ambiguities and controversies, a series of decisions by primary care physicians (whether to refer the short child to a pediatric endocrinologist), pediatric endocrinologist (whether to recommend GH treatment), families (whether to raise concern about short stature and whether to agree to undertake treatment), and third party payers (whether to cover the costs of GH therapy) influence which individual short children will receive GH in the US. Together, these decisions determine overall GH use. Apart from child's growth characteristics, several non-physiological factors drive the critical decisions of these stakeholders. This article focuses on current ambiguities and controversies regarding GH therapy in ISS, discusses the decision-makers involved in GH therapy, and explores the factors influencing their decisions.

Structure prediction and functional characterization of secondary metabolite proteins of Ocimum.

Various species of Ocimum have acquired special attention due to their medicinal properties. Different parts of the plant (root, stem, flower, leaves) are used in the treatment of a wide range of disorders from centuries. Experimental structures (X-ray and NMR) of proteins from different Ocimum species, are not yet available in the Protein Databank (PDB). These proteins play a key role in various metabolic pathways in Ocimum. 3D structures of the proteins are essential to determine most of their functions. Homology modeling approach was employed in order to derive structures for these proteins. A program meant for comparative modeling- Modeller 9v7 was utilized for the purpose. The modeled proteins were further validated by Prochek and Verify-3d and Errat servers. Amino acid composition and polarity of these proteins was determined by CLC-Protein Workbench tool. Expasy's Prot-param server and Cys_rec tool were used for physico-chemical and functional characterization of these proteins. Studies of secondary structure of these proteins were carried out by computational program, Profunc. Swiss-pdb viewer was used to visualize and analyze these homology derived structures. The structures are finally submitted in Protein Model Database, PMDB so that they become accessible to other users for further studies.

Group counseling: A silver lining in the psychological management of disaster trauma.

Management of disaster effects, physical or psychological, has been the subject of considerable research. Though physical rehabilitation of the victims of any disaster, whether natural or man-made, receives immediate attention, the management of psychological trauma often remains a challenge for the disaster management machinery, in general, and mental health professionals, in particular. The magnitude of population affected, on the one hand, and lack of sufficient mental health professionals, on the other hand, often hinders the psychological rehabilitation of a cross section of the affected population. We attempt to present an overview of the literature to bring home the understanding of correlates of psychological effects in the mass disaster affected population in this article. It dwells on the efficacy of group counseling as the most appropriate paradigm of primary prevention to check the onset of severe psychological disorders. The article also presents an overview of two case studies: tsunami disaster (Nagapatanam, Tamil Nadu, India) and victims of bomb blast (Dhimajee, Assam, India) to highlight the silver lining in the psychological management of disaster traumas. It is proposed that group counseling can prove to be a most important mental rehabilitation program to further strengthen the efficacy of individual therapeutic interventions.

Pleiotropic effects of statins: benefit beyond cholesterol reduction? A meta-regression analysis.

OBJECTIVES: This study sought to determine whether statins reduce coronary heart disease (CHD) risk more than other interventions that also primarily lower low-density lipoprotein cholesterol (LDL-C). BACKGROUND: Statins have anti-inflammatory, immunomodulatory, antithrombotic, vascular, and other non-LDL-C-lowering effects. It is unclear whether these pleiotropic effects contribute to cardiovascular risk reduction beyond that expected from LDL-C reduction alone. METHODS: Trials published in English language journals were retrieved by searching Medline (1966 to October 2004), bibliographies, and the author's reference files. Randomized, placebo-controlled trials of interventions to primarily lower LDL-C of three or more years' duration in which clinical disease or death were primary outcomes were used. Information on sample size, treatment type and duration, participant characteristics at baseline, reduction in lipids, and outcome was independently abstracted by two authors (J.R. and N.M.) using a standardized protocol. Data from 5 diet, 3 bile acid sequestrant, 1 surgery, and 10 statin trials, with 81,859 participants, were included in the CHD meta-regression analysis. RESULTS: The regression lines for non-statin and statin trials were similar and consistent with a one-to-one relationship between LDL-C lowering and CHD and stroke reduction over five years of treatment. CONCLUSIONS: The pleiotropic effects of statins do not seem to contribute an additional cardiovascular risk reduction benefit beyond that expected from the degree of LDL-C lowering observed in other trials that primarily lowered LDL-C.

A "poly-portfolio" for secondary prevention: a strategy to reduce subsequent events by up to 97% over five years.

A "polypill" for the primary prevention of cardiovascular disease has been proposed. We estimated the projected benefit of a secondary prevention "poly-portfolio" strategy, including pharmacologic and lifestyle approaches for those with coronary heart disease (CHD) or stroke. Based on recent clinical trial results and clinical guidelines, combinations of a high-dose statin, low to standard doses of antihypertensive therapy, aspirin, omega-3 fish oil, cardiac rehabilitation, and diet were evaluated. Patients with CHD, post-myocardial infarction (MI), or stroke were projected to experience 84%, 91%, and 77% reductions, respectively, in CHD events from a pharmacologic approach. Numbers of those needed to treat (NNT) for 5 years were 9 to 11 to prevent 1 CHD event, and 21 to prevent 1 stroke. Post-MI patients were projected to experience a 93% reduction in the risk of CHD death (NNT 16) from a pharmacologic approach and a 97% reduction in the risk of CHD death (NNT 15) with the addition of lifestyle changes. A secondary prevention polyportfolio holds great promise for reducing the burden of cardiovascular disease in the highest risk patients.