The effects of long COVID-19, its severity, and the need for immediate attention: Analysis of clinical trials and Twitter data.

Background: The coronavirus disease 2019 (COVID-19) has been declared a pandemic since March 2020 by the World Health Organization; identifying the disease progression, predicting patient outcomes early, the possibility of long-term adverse events through effective modeling, and the use of real-world data are of immense importance to effective treatment, resource allocation, and prevention of severe adverse events of grade 4 or 5. Methods: First, we raise awareness about the different clinical trials on long COVID-19. The trials were selected with the search term "long COVID-19" available in ClinicalTrials.gov. Second, we curated the recent tweets on long-haul COVID-19 and gave an overview of the sentiments of the people. The tweets obtained with the query term #long COVID-19 consisted of 8,436 tweets between 28 August 2022 and 06 September 2022. We utilized the National Research Council (NRC) Emotion Lexicon method for sentiment analysis. Finally, we analyze the retweet and favorite counts are associated with the sentiments of the tweeters via a negative binomial regression model. Results: Our results find that there are two types of clinical trials being conducted: observational and interventional. The retweet counts and favorite counts are associated with the sentiments and emotions, such as disgust, joy, sadness, surprise, trust, negative, and positive. Conclusion: We need resources and further research in the area of long COVID-19.

Energy- and protein-enriched formula improves weight gain in infants with malnutrition due to cardiac and noncardiac etiologies.

BACKGROUND: We aimed to assess safety, tolerability, and improvement in weight gain with an energy- and protein-enriched formula (EPEF) in infants with poor growth. METHODS: Infants aged 1-8 months with poor growth received EPEF for 16 weeks. Our primary objective was improvement in weight as measured by change in weight-for-age z-score (WAZ) and weight gain velocity (grams per day) ≥ median for age. Secondary objectives included improvement in other anthropometric z-scores, formula tolerance, and safety. RESULTS: Twenty-six patients with poor growth due to congenital heart disease (n = 15), other organic causes (n = 9), and nonorganic causes (n = 2) completed the study per protocol. Mean daily energy intake was 123 ± 32 kilocalories per kilogram of body weight, with >90% of energy coming from EPEF. Weight gain velocity exceeded the median for 83% (20 of 24) and 67% (16 of 24) of infants at ≥1 time point and for the overall study period, respectively. Mean ± SD WAZ improved from -2.92 ± 1.04 at baseline to -2.01 ± 1.12 at 16 weeks (P = 0.0001). Z-scores for weight-for-length and head circumference (P = 0.0001) and for length-for-age (P = 0.003) improved significantly at 16 weeks. Compared with baseline, stool consistency was different at 2, 4, and 16 weeks (P < 0.05). There were no significant differences in vomiting, fussiness, or daily number of stools while there was a decrease or no change in spit-up, flatulence, crying, or gassiness. CONCLUSION: EPEF is safe, well tolerated, and improves weight gain in infants with poor growth.

Coronavirus (COVID-19): A Systematic Review and Meta-analysis to Evaluate the Significance of Demographics and Comorbidities.

Background: The unprecedented outbreak of a contagious respiratory disease caused by a novel coronavirus has led to a pandemic since December 2019, claiming millions of lives. The study systematically reviews and summarizes COVID-19's impact based on symptoms, demographics, comorbidities, and demonstrates the association of demographics in cases and mortality in the United States. Methods: PubMed and Google Scholar were searched from December 2019- August 2020, and articles restricted to the English language were collected following PRISMA guidelines. US CDC data was used for establishing statistical significance of age, sex, and race. Results: Among 3745 patients in China, mean age is 50.63 (95% CI: 36.84, 64.42) years, and 55.7 % (95% CI: 52.2, 59.2) were males. Symptoms included fever 86.5% (82.7, 90.0), fatigue 41.9% (32.7, 51.4), dyspnea 29.0% (21.2, 37.5), cough 66.0% (61.3, 70.6), mucus 66% (61.3, 70.6), lymphopenia 18.9% (5.2, 38.0). Prevalent comorbidities were hypertension 16.4% (12.5, 20.8), diabetes 8.9% (7.0, 11.1), CVD 10.9% (6.1, 16.7), ARDS 14.6% (4.9, 27.8), malignancy 1.5 (0.05, 2.8), 1.3% (0.08, 1.9), COPD 1.3 (0.08, 1.9). 63.5 % (33.5, 88.7) received oxygen therapy, 20.8% (8.9, 35.7) were in ventilation, 23.5% (5.9, 47.8) were at the ICU. 86.5% (76.8, 94) had antiviral, 73.9% (55.3, 89.0) had antibiotics, 30% (20.6, 40.2) corticosteroids treatment.In the US, the odds ratio of infection in males to females is 0.873 (CI: 0.052,14.791), while the odds of dying from infection is 1.378 (CI: 0.081, 23.528) for males. The prevalence of infection is higher in females; case and death rates are higher in whites and Hispanics than other races; the death rate is higher in males irrespective of race and age; death rate per 100,000 population increases monotonically with age. Conclusion: Results showed that metabolic diseases comprising CVD, diabetes, hypertension, and respiratory diseases, including COPD, ARDS, are the most common comorbidities to severe condition and poor prognosis in covid-19 patients. Following the recent FDA's guidance for designing Covid-19 vaccine trials, stratification factors of age, race, sex, and comorbidities need consideration in allocation. This study aimed to provide clinical researchers, health policy planners a detailed insight into the coronavirus disease.

Statistical design of Phase II/III clinical trials for testing therapeutic interventions in COVID-19 patients.

BACKGROUND: Because of unknown features of the COVID-19 and the complexity of the population affected, standard clinical trial designs on treatments may not be optimal in such patients. We propose two independent clinical trials designs based on careful grouping of patient and outcome measures. METHODS: Using the World Health Organization ordinal scale on patient status, we classify treatable patients (Stages 3-7) into two risk groups. Patients in Stages 3, 4 and 5 are categorized as the intermediate-risk group, while patients in Stages 6 and 7 are categorized as the high-risk group. To ensure that an intervention, if deemed efficacious, is promptly made available to vulnerable patients, we propose a group sequential design incorporating four factors stratification, two interim analyses, and a toxicity monitoring rule for the intermediate-risk group. The primary response variable (binary variable) is based on the proportion of patients discharged from hospital by the 15th day. The goal is to detect a significant improvement in this response rate. For the high-risk group, we propose a group sequential design incorporating three factors stratification, and two interim analyses, with no toxicity monitoring. The primary response variable for this design is 30 day mortality, with the goal of detecting a meaningful reduction in mortality rate. RESULTS: Required sample size and toxicity boundaries are calculated for each scenario. Sample size requirements for designs with interim analyses are marginally greater than ones without. In addition, for both the intermediate-risk group and the high-risk group, the required sample size with two interim analyses is almost identical to analyses with just one interim analysis. CONCLUSIONS: We recommend using a binary outcome with composite endpoints for patients in Stage 3, 4 or 5 with a power of 90% to detect an improvement of 20% in the response rate, and a 30 day mortality rate outcome for those in Stage 6 or 7 with a power of 90% to detect 15% (effect size) reduction in mortality rate. For the intermediate-risk group, two interim analyses for efficacy evaluation along with toxicity monitoring are encouraged. For the high-risk group, two interim analyses without toxicity monitoring is advised.

A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants.

A multicenter, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of intravenous (IV) ibuprofen (L-lysine) for the early closure of nonsymptomatic patent ductus arteriosus (PDA) within 72 hours of birth in extremely low-birth-weight (ELBW) infants with evidence of ductal shunting by echocardiogram. Eleven sites enrolled 136 infants with nonsymptomatic early PDA (gestational age < 30 weeks; body weight 500 to 1000 g) to receive a 3-day course (10 mg/kg, 5 mg/kg, and 5 mg/kg) of IV ibuprofen ( N = 68) or placebo ( N = 68). Cardiac echocardiogram was performed on study days 1 and 14, and with rescue. Infants were followed to 36 weeks postconceptional age. Patient demographics, mean (standard deviation), were similar between ibuprofen and placebo: birth weight: 798.5 g (128.7) versus 797.3 g (132.8); gestational age: 26.1 weeks (1.3) versus 26.2 weeks (1.4); and age at first dose: 1.5 days (0.7). The intent-to-treat analysis of the primary endpoint, subjects rescued, died, or dropped through study day 14, was 21/68 (30.9%) with ibuprofen and 36/68 (52.9%) for placebo ( P = 0.005). Death, intraventricular hemorrhage, necrotizing enterocolitis, daily fluid intake/output, liver function, bronchopulmonary dysplasia, and retinopathy of prematurity did not differ. A trend toward decreased periventricular leukomalacia by ibuprofen was noted. IV ibuprofen was effective and safe in the early closure of PDA in preterm neonates.

The use of an inflammation-modulating diet in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of outcome data.

BACKGROUND: This meta-analysis of clinical trials compares an inflammation-modulating diet enriched with eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA), and elevated antioxidants (EPA + GLA) vs a control diet to determine the effectiveness of this specialized diet on oxygenation and clinical outcomes in mechanically ventilated patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). METHODS: MEDLINE, EMBASE, Cochrane Clinical Trials Register, and the U.S. National Institute of Health Clinical Trials databases were searched. The outcome measures assessed were 28-day in-hospital mortality, 28-day ventilator-free and intensive care unit (ICU)-free days, and the development of new organ failures. An evaluation of oxygenation and ventilatory variables was also performed. Outcomes were analyzed using both fixed-effects and random-effects models. RESULTS: Three randomized controlled studies (n = 411 patients) were included in this meta-analysis. Among the most important findings of this evaluation is a significant reduction in the risk of mortality (odds ratio [OR] = 0.40; 95% confidence interval [CI] = 0.24-0.68; P = .001), with significant reductions in the risk of developing new organ failures (OR = 0.17; 95% CI = 0.08-0.34; P < .0001), time on mechanical ventilation (standardized mean difference [SMD] = 0.56; 95% CI = 0.32-0.79; P < .0001), and ICU stay (SMD = 0.51; 95% CI = 0.27-0.74; P < .0001) in patients who received EPA + GLA. CONCLUSIONS: The meta-analysis showed a significant reduction in the risk of mortality as well as relevant improvements in oxygenation and clinical outcomes of ventilated patients with ALI/ARDS given EPA + GLA.

Health effects of ultraviolet irradiation in asthmatic children's homes.

OBJECTIVE: Centrally installed ultraviolet (UV) irradiation units were investigated to determine the potential health benefits in mold-sensitized asthmatic children. METHODS: Nineteen mold-sensitized asthmatic children 5 to 17 years of age with home central ventilation systems were enrolled in a 28-week double-blinded placebo controlled cross-over trial. Clinical outcome measurements included morning and evening peak expiratory flow rates (PEFR), PEFR variability, change in forced expiratory volume in 1 second (FEV1), change in total rhinoconjunctivitis and asthma symptom scores, change in rhinoconjunctivitis and asthma quality-of-life scores, and total (rescue and controller) medication use from baseline and between time periods. Environmental outcomes included changes in temperature, relative humidity, dew point, and indoor airborne mold and bacterial counts from baseline and between time periods. Analysis of variance (ANOVA) and regression analysis and t test were used to evaluate relationships between environmental exposure(s) and clinical outcome measurements during each study period. RESULTS: Twelve male and seven female children, average age 10.6 years, were enrolled. A statistically significant improvement in PEFR variability in subjects receiving CREON2000 units followed by placebo units was observed (p < 0.05) across both treatment periods. Within group analysis during treatment period 1, a statistically significant improvement in reduction of asthma symptom scores, the number of days with asthma symptoms, total asthma medication use, and PEFR variability were observed in subjects receiving CREON2000 units versus placebo units (p < 0.05). No significant differences were observed between the CREON 2000 and placebo units for other clinical or environmental outcome measurements. CONCLUSIONS: Central UV irradiation was effective at reducing airway hyperresponsiveness manifested as PEFR variability and some clinical symptoms. A larger cohort controlled longitudinal study to validate the clinical health effects of UV irradiation as a primary indoor environmental intervention for allergic asthma is necessary to confirm this finding.