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Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial.
Bruen, C, Al-Saadi, M, Michelson, EA, Tanios, M, Mendoza-Ayala, R, Miller, J, Zhang, J, Stauderman, K, Hebbar, S, Hou, PC
Critical care (London, England). 2022;(1):101
Abstract
BACKGROUND Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. METHODS CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio > 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early. RESULTS The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia. CONCLUSIONS Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614.
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Impact on aerosol generation during upper endoscopy of mouthpiece designed to reduce COVID-19 droplet spread: single-center randomized controlled trial.
Huang, IH, Sinonquel, P, Verbeure, W, Camps, C, Devriese, H, Holvoet, L, Verstockt, B, Willekens, H, Mori, H, Bisschops, R, et al
Endoscopy. 2022;(1):81-83
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A randomized, controlled, blinded, parallel group, clinical trial to study the role of Ayurcov (AyurCoro3), one day regimen as an adjuvant therapy for COVID-19 disease management, at dedicated Covid Hospital (DCH) in India.
Sankhe, AP, Memane, NS, Gawali, VP, Memane, SN, Ramakrishnan, G, Kundu, T, Bagul, MN, Kumar, A, Bansal, V, Tiwari, R
Complementary therapies in medicine. 2022;:102824
Abstract
INTRODUCTION Limited treatment options exist for COVID-19 infections; thus, attempts from complementary and alternative systems (CAM) of medicine are being explored as possible therapeutic options. Ayurcov is a formulation made of ingredients mentioned in Ayurveda. These constituents have proven antiviral, detoxifying, immune-modulating, and bio-enhancing properties. The present study was carried out to evaluate the therapeutic effect and safety of Ayurcov in patients with various severity states of COVID-19 infections. METHODS A randomized, single blinded, controlled trial was carried out in adults diagnosed with mild-to-moderate, and severe COVID-19 infections confirmed by real time reverse transcriptase polymerase chain reaction (rRTPCR) test. The interventional group received three doses of 'Ayurcov'. It is constituted of Haridra Churna (Curcuma longa), Go ark (Bos Indicus Distilled Urine), Sphatika (Alum), Sita (Rock Candy), Godugdham (Bos Indicus Milk) milk, Goghritam (Bos Indicus ghee) on Day 1, as an adjuvant to the standard of care, and the control group received only the standard of care. Key outcomes included: proportion of patients and time taken for symptom resolution, reduction in the rRT-PCR Ct values, safety, and functional status until 42 days after discharge. RESULTS Ninety patients with mild-to-moderate and 30 patients with severe COVID-19 disease were recruited. It was observed that significantly more proportions of patients receiving Ayurcov had symptom relief much earlier than control group. Additionally, the interventional group showed significantly lower rRT-PCR Ct values. However, a shorter time of resolution of symptoms was observed with the interventional group in the mild to moderate category but not with those having severe symptoms. Similarly, a significantly better functional status was observed with interventional group on days 7 and 28 after discharge. Ayurcov was not observed with higher risks of any adverse/serious adverse events. CONCLUSIONS Ayurcov as adjuvant with standard of care was associated with significantly earlier resolution of COVID-19 related symptoms than standard of care alone.
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Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.
Tandon, N, Gupta, Y, Kapoor, D, Lakshmi, JK, Praveen, D, Bhattacharya, A, Billot, L, Naheed, A, de Silva, A, Gupta, I, et al
JAMA network open. 2022;(3):e220773
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IMPORTANCE Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. OBJECTIVE To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. DESIGN, SETTING, AND PARTICIPANTS This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. INTERVENTIONS A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. MAIN OUTCOMES AND MEASURES The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. RESULTS A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. CONCLUSIONS AND RELEVANCE This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. TRIAL REGISTRATION Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.
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The effect of l-arginine supplementation on amelioration of oxygen support in severe COVID-19 pneumonia.
Muralidharan, J, Kashyap, S, S, P, Jacob, M, Ollapally, A, Idiculla, J, Raj, JM, Thomas, T, Kurpad, AV
Clinical nutrition ESPEN. 2022;:431-435
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BACKGROUND & AIMS l-Arginine (l-Arg) has been shown to help reduce respiratory support requirements in coronavirus disease 2019 (COVID-19), in an Italian study. We investigated the effect of l-Arg supplementation on the reduction in respiratory support for patients with severe COVID-19 pneumonia in an Indian population. METHODS A parallel-group, triple-blinded, randomized controlled trial (RCT) was conducted on patients with severe COVID-19 pneumonia on oxygen (O2) support. Patients received either 3 g of oral l-Arg or placebo, daily under supervision, until they were off O2 support, or for a maximum of 10 days, whichever was earlier. The primary outcome was cessation in O2 support. Other outcomes were time to cessation of O2 support, duration of hospitalization, and incidence of adverse thrombotic events. RESULTS We did an intention-to-treat analysis on 74 patients who were randomized into l-Arg (n = 38) or placebo group (n = 36). There were no significant differences between the two groups in the outcomes. At end of the study, 28 patients (73.6%) in l-Arg and 26 patients (72.2%) in the placebo group were weaned off oxygen support. The median number of days to the cessation of O2 support estimated using Kaplan Meir survival analysis, was 3 days in the l-Arg group (95% confidence interval [CI]: 1.2, 4.7) and 5 days in the placebo group (95% CI, 4.1,5.8); P = 0.27. CONCLUSION In this group of patients with severe COVID-19 pneumonia, l-Arg supplementation did not show any significant difference in outcomes when compared to placebo supplementation.
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Global Self-Esteem, Physical Activity, and Body Composition Changes Following a 12-Week Dietary and Physical Activity Intervention in Older Women.
Grajek, M, Gdańska, A, Krupa-Kotara, K, Głogowska-Ligus, J, Kobza, J
International journal of environmental research and public health. 2022;(20)
Abstract
UNLABELLED Older adults show lower physical activity. These changes altogether promote the development of overweight, obesity, and other chronic diseases. These factors substantially influence the quality of life and self-esteem of older adults. This phenomenon is especially visible after the lockdown caused by the COVID-19 pandemic. OBJECTIVES Our study aimed to evaluate the effect of a 12-week reductive diet and a 12-week physical activity plan for older adults on the global self-esteem of lifestyle in 60-70-year-old women. MATERIALS AND METHODS Our participants were 600 women with increased body mass (BMI > 25 kg/m2) aged 60-70 years. After the initial evaluation, the participants were randomly divided into three groups: CG-control group (n =200); DI-dietary group (n =200) that committed to a 12-week reductive diet; PA-physical activity group (n =200) that committed to a 12-week physical activity plan. The global self-esteem score (using the SES Rosenberg scale) and the anthropometric measurements were collected before and after the 12-week study. In the statistical analysis of data, the significance level was assumed to be 0.05. RESULTS The global self-esteem score for all groups before the study started was 30-31 points, which corresponded to average self-esteem. After a 12-week dietary or physical activity intervention, the score in the DI group was 33, which corresponded with high self-esteem. In the CG group, the self-esteem score remained unchanged (30 points). The average body mass loss was 0.5 kg/m2 for CG, 1.92 kg/m2 for DI, and 1.10 kg/m2 for the PA group. The average waist-hip ratio (WHR) change for CG, DI, and PA was 1 cm, 1 cm, and 2 cm, respectively. A decrease in body mass and body composition indicators (BMI and WHR) corresponded to participants' global self-esteem increase (p <0.05); the greater the decrease noted for BMI and WHR, the greater the global self-esteem score that was achieved. In the CG group, a negative correlation between global self-esteem and BMI value (p <0.05) was observed. CONCLUSIONS A 12-week reductive diet and a 12-week regular physical activity plan lowered participants' body mass. Adipose tissue content was reflected by decreased BMI and WHR indicators of participants from the DI and PA groups and was accompanied by higher global self-esteem scores.
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Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID).
Absalón-Aguilar, A, Rull-Gabayet, M, Pérez-Fragoso, A, Mejía-Domínguez, NR, Núñez-Álvarez, C, Kershenobich-Stalnikowitz, D, Sifuentes-Osornio, J, Ponce-de-León, A, González-Lara, F, Martín-Nares, E, et al
Journal of general internal medicine. 2022;(1):4-14
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BACKGROUND Colchicine is an available, safe, and effective anti-inflammatory drug and has been suggested as a COVID-19 treatment, but its usefulness in hospitalized severe COVID-19 patients has not been thoroughly demonstrated. OBJECTIVE To address the safety and efficacy of colchicine in hospitalized patients with severe COVID-19. DESIGN We conducted a triple-blind parallel non-stratified placebo-controlled clinical trial. PARTICIPANTS We recruited 116 hospitalized patients with severe COVID-19 in Mexico. INTERVENTIONS Patients were randomized to receive 1.5 mg of colchicine or placebo at the time of the recruitment in the study (baseline) and 0.5 mg BID PO to complete 10 days of treatment. MAIN MEASURES The primary composite outcome was the progression to critical disease or death. Besides, we evaluated immunological features at baseline and after recovery or disease progression in 20 patients. KEY RESULTS Fifty-six patients were allocated to colchicine and 60 patients received placebo. The study was suspended after the second interim analysis demonstrated colchicine had no effect on the primary outcome (OR 0.83, 95%CI 0.35-1.93, P = 0.67), nor in the days of ICU and hospital stays. Adverse events were similar between groups (OR 1.63, 95% CI 0.66-3.88, P = 0.37). After colchicine treatment, patients had higher BUN and lower serum levels of IL-8, IL-12p70, and IL-17A. CONCLUSIONS Colchicine is safe but not effective in the treatment of severe COVID-19. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04367168.
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Efficacy and Safety of ELOM-080 as Add-On Therapy in COVID-19 Patients with Acute Respiratory Insufficiency: Exploratory Data from the Prospective Placebo-Controlled COVARI Trial.
Dreher, M, Grohè, C, Hartmann, NU, Kanzler, S, Kraft, K, Sarrazin, C, Doll, M, Spiesshöfer, J, Steiner, S, Wöhrle, J, et al
Advances in therapy. 2022;(6):3011-3018
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INTRODUCTION Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases. PATIENTS/METHODS This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency. RESULTS The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001). CONCLUSION These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.
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Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.
Creech, CB, Anderson, E, Berthaud, V, Yildirim, I, Atz, AM, Melendez Baez, I, Finkelstein, D, Pickrell, P, Kirstein, J, Yut, C, et al
The New England journal of medicine. 2022;(21):2011-2023
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BACKGROUND Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. METHODS Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. RESULTS In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. CONCLUSIONS Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).
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Clinical (BMI and MRI) and Biochemical (Adiponectin, Leptin, TNF-α, and IL-6) Effects of High-Intensity Aerobic Training with High-Protein Diet in Children with Obesity Following COVID-19 Infection.
Nambi, G, Alghadier, M, Elnegamy, TE, Basuodan, RM, Alwhaibi, RM, Vellaiyan, A, Nwihadh, NA, Aldhafian, OR, Verma, A, Pakkir Mohamed, SH, et al
International journal of environmental research and public health. 2022;(12)
Abstract
Objective: To find the clinical and biochemical effects of high-intensity aerobic training with a high-protein diet in children with obesity following COVID-19 infection. Methods: By using the block randomization method, the eligible participants were randomized into two groups. The first group received high-intensity aerobic training with a high-protein diet (Group A; n = 38) and the second group were allowed to do regular physical activities and eat a regular diet (Group B; n = 38) for 8 weeks. Clinical (basal metabolic index (BMI) and muscle-mass-cross-sectional area (CSA)) and biochemical (Adiponectin, leptin, TNF-α, and IL-6) measures were measured at baseline, on the 8th week, and at 6-months follow-up. Results: Baseline demographic and clinical attributes show homogenous presentation among the study groups (p > 0.05). After eight weeks of intervention, and at the end of 6-months follow-up, the basal metabolic index (BMI) (6.3) (CI 95% 4.71 to 7.88), mid-arm CSA (17) (CI 95% 14.70 to 19.29), mid-thigh CSA (13.10) (CI 95% 10.60 to 15.59), mid-calf CSA (11.3) (CI 95% 9.30 to 13.29), adiponectin (−1.9) (CI 95% −2.13 to −1.66), leptin (5.64) (CI 95% 5.50 to 5.77), TNF-α (0.5) (CI 95% 0.42 to 0.57), and IL-6 (0.21) (CI 95% 0.18 to 0.23) showed more improvement (p < 0.001) in Group A than Group B (p > 0.05). Conclusion: Overall, this trial found that high-intensity aerobic training with a high-protein diet decreased the BMI percentile and muscle mass (arm, thigh, and calf), and positively altered the biochemical variables in children with obesity.