Effect of mulmina mango as an adjunct to standard of care treatment on COVID-19 positive subjects undergoing treatment for COVID-19 in hospital quarantine (Dedicated Covid Health Centre)

There are no approved drugs to treat COVID-19, and the vaccine is likely to be ready by early 2021. Many clinical studies are ongoing around the globe to find a cure or prevention of the disease. The objective of the proposed study is to determine the efficacy and safety profile of Mulmina Mango as an adjunct to standard of care treatment on COVID-19 positive subjects undergoing treatment for COVID-19 in Hospital Quarantine. Settings and Design: The enrolled subjects were randomized into either of the two treatment arms in the ratio of 1:1. The freshly diagnosed (24-48 hrs.) COVID-19 positive Male or Female is aged 20 to 65 years (both inclusive) hospitalized patients were approached and checked for their eligibility. They were recruited after signing the written informed consent form. The number of patients included in the study is 48. In efficacy, both the treatment arms and the reduction in clinical symptom scale value and ordinal scale value are seen on day 7. On the ordinal scale, 41.7% of subjects in Treatment arm A showed a reduction of 2 points on the day, and 16.7% of subjects show 2 points reduction in Treatment arm B. In Safety results, there was no clinically significant finding in safety parameters in Treatment arm B. Mulmina Mango showed encouraging results concerning RTPCR, CRP, Dopamine, IgG, CD4, and CD8 parameters. The properties of Mulmina Mango are highlighted below, along with the parameters for each property. Mulmina Mango, COVID-19, Treatment Arm A, Treatment Arm B, MoHFW (Ministry of Health and Family Welfare)

An integrative approach to clinical recovery for COVID-19 patients using an Ayurvedic formulation: A multicentric double-blind randomized control trial.

BackgroundTraditional medicine systems such as Ayurveda contain a vast repository of naturally occurring herbs with strong antimicrobial potency. A multitude of complementary therapies have been explored for their therapeutic role to treat COVID-19 during the pandemic. There have been promising results reported from in silico, in vitro and in vivo studies that need to be further explored in humans.ObjectiveThe present randomized placebo control trial evaluates the clinical efficacy of an integrated approach including Ayurvedic polyherbal formulation, NOQ19 in the improvement of mild to moderate category of COVID-19 infected patients.Patients and methodsA multicentric, randomized, placebo control design was adopted for the study. A total of 76 patients with positive COVID-19 RT-PCR test were enrolled in the study; 39 in the NOQ19 arm and 37 in the placebo arm. Patients were randomized and blinded to their respective intervention, which was provided along with the standard of care treatment. Rate of recovery assessment was done on Day 3, 5 and 7 via RT-PCR test to measure the rate of recovery. Blood markers were analysed on Day 0 and Day 7.OutcomesThe patients were assessed for rate of recovery via RT-PCR and improvement in blood biomarkers. They were also monitored for any adverse events or side effects of the drug.ResultsThe present study demonstrated a significant early recovery in the patients who took the NOQ19 formulation. Patients who received NOQ19 with the standard care of treatment showed clinical improvement in terms of oxygen requirement, breathlessness and SpO2, though the difference was not statistically significant. Moreover, no side effects were observed with the use of NOQ19.ConclusionAn overall integrated approach of standard of care treatment with Ayurvedic formulation (NOQ19) results in early clinical outcome in the management of mild to moderate cases of COVID-19.

Ayurveda and Management of COVID-19 in Rural Indian Population: A pilot, double blind, randomized control trial

Background The SARS-CoV-2 virus responsible for the COVID-19 pandemic is a highly contagious and rapidly mutating virus. The COVID-19 pandemic has affected millions globally over the last 18 months and continues to overwhelm the healthcare system in several countries to date. The healthcare and scientific community has been vigorously searching for ways to manage the disease. Several solutions based on traditional systems of medicine like Ayurveda are also being explored for their effectiveness in managing COVID-19. The study explored the efficacy of a 19 ingredient Ayurvedic polyherbal formulation called NOQ19, on the recovery of mild, RT-PCR positive COVID-19 patients. Methods This was a prospective, double blind, randomized control trial that included 92 patients with a RT-PCR positive mild case of COVID-19. The patients were enrolled from rural areas of Karnataka, a state in India. The patients were randomized between the NF2 and placebo arms, in a 1:1 ratio, and were provided their respective intervention, along with the standard of care treatment (SOC). The trial took place at the Community Care Center, Konnanuru, Hassan, Karnataka. The study duration was around 2 months and the follow-up period for an individual patient was 14 days. RT-PCR analysis was done at baseline, Day 3, 7 and 10. Blood markers to track inflammation were assessed at baseline, Day 3 and 7. Result A statistically significant difference was observed between the two groups with regards to the percentage of population who turned RT-PCR negative on Day 3 and Day 10. On all three assessment time points (Day 3, 7 and 10), the NF2+SOC arm showed a greater percentage of population who were RT-PCR negative compared to the placebo+SOC arm: Day 3 (NF2 -19%, Placebo - 0%) ; Day 7 (NF2- 41%, Placebo - 19%) ; Day 10 (NF2-73%, Placebo 44%). No significant changes were observed in blood markers for both the groups. Conclusion NF2 administered along with standard of care treatment aided early recovery from COVID-19 as demonstrated by a higher percentage of population who were RT-PCR negative on Day 3, 7 and 10. No side effects were observed during the entire study duration. Early recovery of patients is essential for rational usage of limited healthcare resources in a pandemic.

Evaluation of an Ayurvedic formulation in clinical recovery of COVID-19 patients: A placebo controlled pilot study among moderate-severe patients

Introduction: The COVID-19 pandemic is a global health crisis that has affected millions of people worldwide. Apart from measures taken to reduce the transmission of virus and provide symptomatic relief to patients, a potent drug targeted against the virus is required to manage the disease. Traditional medicines with an array of phytochemicals and potent anti-viral properties, can provide alternate solution in the therapeutic cure of COVID-19.Objective: The present study investigates the efficacy of an Ayurvedic formulation, NOQ19, on the rate of recovery and clinical improvement among moderate-severe COVID-19 infected patients who were not on a ventilator or in intensive care unit.Methods: A placebo controlled randomized study design, with 1:1 ratio between the intervention and placebo arms was adopted. The participants were provided their respective intervention along with the standard of care treatment. A follow up was conducted on Day 7 and Day 10 to assess the rate of recovery and clinical improvement. Rate of recovery was the primary outcome measured and was determined by a negative result on the RT-PCR test. The secondary outcomes included clinical improvement among patients and were measured using blood biomarkers.Results: The NOQ19 arm had a higher percentage of population who turned RT-PCR negative on Day 7 (23%) when compared to the placebo arm (11%). Further subgroup analysis demonstrated that for both moderate and severe patients, there were a greater percentage of population who were RT-PCR negative in the NOQ19 arm compared to the placebo arm at Day 7: (NOQ-19: 22.22%, Placebo: 14.29% for moderate patients), (NOQ19: 23.08% Placebo: 0% for severe patients). By Day 10, both populations depicted an almost similar percentage of the population who were RT- PCR negative. Both the groups demonstrated an improvement in blood biomarkers, although the improvement was greater in the NOQ19 arm. None of the patients in the intervention arm reported any adverse events.Conclusion: The results of this pilot RCT indicates that NOQ19 along with standard of care treatment can be considered as an effective therapy for COVID-19 and aid early recovery from the disease.

Pediatric versus Adult Medulloblastoma: Towards a Definition That Goes beyond Age

Medulloblastoma is a rare malignant brain tumor that predominantly affects children but also occurs in adults. The incidence declines significantly after age 15, and distinct tumor molecular features are seen across the age spectrum. Standard of care treatment consists of maximal safe surgical resection followed by adjuvant radiation and/or chemotherapy. Adjuvant treatment decisions are based on individual patient risk factors and have been informed by decades of prospective clinical trials. These trials have historically relied on arbitrary age cutoffs for inclusion (age 16, 18, or 21, for example), while trials that include adult patients or stratify patients by molecular features of disease have been rare. The aim of this literature review is to review the history of clinical trials in medulloblastoma, with an emphasis on selection criteria, and argue in favor of rational and inclusive trials based on molecular features of disease as opposed to chronological age. We performed a scoping literature review for medulloblastoma and clinical trials and include a summary of those results. We also discuss some of the significant advances made in understanding the molecular biology of medulloblastoma within the past decade, most notably the identification of four distinct subgroups based on gene expression profiling. We will also cite the recent experiences of childhood leukemia and the emergence of tissue-agnostic therapies as examples of successes of rationally designed, inclusive trials translating to improved clinical outcomes for patients across the age spectrum. Despite the prior trial history and recent molecular advances outcomes remain poor for ~30% of medulloblastoma patients. We believe that defining patients by the specific molecular alterations their tumors harbor is the best way to ensure they can access potentially efficacious therapies on clinical trials.

Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma

Glioblastoma remains the deadliest form of brain cancer, largely because these tumors become resistant to standard of care treatment with radiation and chemotherapy. Intracellular production of reactive oxygen species (ROS) is necessary for chemo- and radiotherapy-induced cytotoxicity. Here, we assessed whether antioxidant catalase (CAT) affects glioma cell sensitivity to temozolomide and radiation. Using The Cancer Genome Atlas database, we found that CAT mRNA expression is upregulated in glioma tumor tissue compared with non-tumor tissue, and the level of expression negatively correlates with the overall survival of patients with high-grade glioma. In U251 glioma cells, CAT overexpression substantially decreased the basal level of hydrogen peroxide, enhanced anchorage-independent cell growth, and facilitated resistance to the chemotherapeutic drug temozolomide and ionizing radiation. Importantly, pharmacological inhibition of CAT activity reduced the proliferation of glioma cells isolated from patient biopsy samples. Moreover, U251 cells overexpressing CAT formed neurospheres in neurobasal medium, whereas control cells did not, suggesting that the radio- and chemoresistance conferred by CAT may be due in part to the enrichment of glioma stem cell populations. Finally, CAT overexpression significantly decreased survival in an orthotopic mouse model of glioma. These results demonstrate that CAT regulates chemo- and radioresistance in human glioma.

Retrospective study of patterns of vitamin D testing and status at a single institution paediatric orthopaedics and sports clinics

Objective(s)There has been a recent increase in awareness of the importance of bone health in children treated by paediatric orthopaedic and sports medicine providers. The purpose of this study was to assess our utilisation of 25 hydroxy vitamin D (25(OH)Vit D) testing in the past 10 years, and to evaluate the level of 25(OH)Vit D sufficiency in various populations of patients seen.DesignThis is a single site, retrospective medical record review study.SettingThe study took place at a single large, private, paediatric level 1 trauma teaching hospital in the Northeast USA.ParticipantsOur internal medical records query system identified all patients who have had 25(OH)Vit D testing in the past 10 years, from 1 January 2009 to 31 December 2018. All patients included were seen on an outpatient basis at our Orthopaedic clinics.InterventionsNo interventions for strict research, however, eligible patients have had 25(OH)Vit D testing during their standard of care treatment.Main outcome measure(s)The varying number of 25(OH)Vit D testing that occurred over the study time period within Orthopaedic groups, and by Vit D levels as sufficient, insufficient and deficient. 25(OH)Vit D sufficiency was ≥30 ng/mL, insufficiency <30 ng/mL and deficiency were <20 ng/mL. Patients were stratified and analysed.ResultsBetween 2009 and 2018, there were 4426 patients who had 25(OH)Vit D testing. Vitamin D testing increased significantly (p<0.001) in the past 10 years. 43% of patients had sufficient 25(OH)Vit D levels, 41% had insufficient levels and 15% had deficient levels.ConclusionMore frequent testing has led to an increased identification of patients with insufficient and deficient 25(OH)Vit D levels. We found over 50% of patients tested were found to have 25(OH)Vit D levels under 30 ng/mL. There should be an increased awareness of patients with orthopaedic problems who may present with 25(OH) insufficiency.

Chronic cough: new insights and future prospects

Chronic cough is defined in adults as a cough that lasts for ≥8 weeks. When it proves intractable to standard-of-care treatment, it can be referred to as refractory chronic cough (RCC). Chronic cough is now understood to be a condition of neural dysregulation. Chronic cough and RCC result in a serious, often unrecognized, disease burden, which forms the focus of the current review.The estimated global prevalence of chronic cough is 2–18%. Patients with chronic cough and RCC report many physical and psychological effects, which impair their quality of life. Chronic cough also has a significant economic burden for the patient and healthcare systems. RCC diagnosis and treatment are often delayed for many years as potential treatable triggers must be excluded first and a stepwise empirical therapeutic regimen is recommended.Evidence supporting most currently recommended treatments is limited. Many treatments do not address the underlying pathology, are used off-label, have limited efficacy and produce significant side-effects. There is therefore a significant unmet need for alternative therapies for RCC that target the underlying disease mechanisms. Early clinical data suggest that antagonists of the purinergic P2X3 receptor, an important mediator of RCC, are promising, though more evidence is needed.

Rate of Recovery and Symptomatic Efficacy of a Polyherbal AYUSH Formulation in the Treatment of SARS CoV-2 disease: A Single-arm trial

Background The COVID-19 pandemic, caused by the human coronavirus SARS- CoV-2, has led to millions of deaths across the globe. Not only is the SARS-CoV-2 virus highly infectious, it also mutates very easily. This creates additional challenges for development of robust therapeutic solutions. Along with modern system of healthcare, there is a definite need for exploring natural plant based antiviral compounds directed against the SARS CoV-2 virus. Objective The present observational study investigates the efficacy of an Ayurvedic polyherbal formulation of 19 ingredients, NOQ19, in the management of COVID-19. Methodology: A single arm, single centric, open label study design was adopted for this feasibility study. 161 RT-PCR positive COVID-19 patients were enrolled. The enrolled participants were provided the Ayurvedic intervention, 2 tablets of NOQ19, thrice daily along with the standard of care treatment. Follow up COVID-19 RT- PCR tests were conducted on Day 5, Day 10 and Day 14, or until the patient turned negative. The time required for testing negative on the RT-PCR test or becoming asymptomatic was noted. Results A subjective analysis demonstrated that 74% of patients turned RT-PCR negative within 5 days of taking NOQ19. Additionally, 98% of the subjects turned RT-PCR Negative on Day 10 after taking NOQ19 in addition to the standard of care treatment of Vitamin C, Zinc and antipyretic (as necessary). None of the participants reported any adverse or side effects to the medication. Conclusion NOQ19 Ayurvedic polyherbal formulation can be an effective and safe option for the symptomatic management of COVID-19.

Advances in systemic therapy for non-small cell lung cancer

ABSTRACT Lung cancer remains a leading cause of cancer related mortality worldwide. Despite numerous advances in treatments over the past decade, non-small cell lung cancer (NSCLC) remains an incurable disease for most patients. The optimal treatment for all patients with locally advanced, but surgically resectable, NSCLC contains at least chemoradiation. Trimodality treatment with surgical resection has been a subject of debate for decades. For patients with unresectable or inoperable locally advanced disease, the incorporation of immunotherapy consolidation after chemoradiation has defined a new standard of care. For decades, the standard of care treatment for advanced stage NSCLC included only cytotoxic chemotherapy. However, with the introduction of targeted therapies and immunotherapy, the landscape of treatment has rapidly evolved. This review discusses the integration of these innovative therapies in the management of patients with newly diagnosed NSCLC.