Worldwide Trends in Registering Real-World Studies at ClinicalTrials.gov: A Cross-Sectional Analysis.

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice. Methods: A retrospective analysis of 944 studies was performed on February 28, 2023. Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions. Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.

Effectiveness of the Fiocruz recombinant ChadOx1-nCoV19 against variants of SARS-CoV-2 in the Municipality of Botucatu-SP.

Introduction: As the COVID-19 pandemic progresses, rapidly emerging variants of concern raise fears that currently licensed vaccines may have reduced effectiveness against these new strains. In the municipality of Botucatu, São Paulo State, Brazil, a mass vaccination campaign using ChadOx1-nCoV19 was initiated on 16th of May 2021, targeting people 18-60 years old. Two vaccine doses were offered 12 weeks apart, with the second delivered on 8th of August, 2021. This setting offered a unique opportunity to assess the effectiveness of two ChadOx1-nCoV19 doses in a real-life setting. Materials and methods: Data on testing, hospitalization, symptoms, demographics, and vaccination were obtained from the Hospital das Clínicas da Faculdade de Medicina de Botucatu. A test-negative study design was employed; whereby the odds of being vaccinated among cases vs controls were calculated to estimate vaccine effectiveness (VE; 1-OR). All individuals aged 18-60 who received a PCR test after the 16th of May and were unvaccinated prior to this date were included in the analysis until the study ended in mid-November 2021. Results: 77,683 citizens of Botucatu aged 18-60 received the first dose, and 74,051 received a second ChadOx1-nCoV19 dose 12 weeks later for a vaccination coverage of 84.2 and 80.2%, respectively. Of 7.958 eligible PCR tests, 2.109 were positive and 5.849 negative. The VE against any symptomatic infection was estimated at 39.2%, 21 days after dose 1, and 74.5%, 14 days after dose 2. There were no COVID-19-related hospitalizations or deaths among the 74,051 fully vaccinated individuals. The VE against severe disease was estimated at 70.8 and 100% after doses 1 and 2, respectively. 90.5% of all lineages sequenced between doses 1 and 2 (16th of May-7th of August) were of the Gamma variant, while 83.0% were of the Delta variant during the second period after dose 2 (8th of August-18th of November). Discussion: This observational study found the effectiveness of ChadOx1-nCoV19 to be 74.5% against COVID-19 disease of any severity, comparable to the efficacy observed in clinical trials (81.3% after dose 2), despite the dominance of the Gamma and Delta VoCs. No COVID-19-related hospitalizations or deaths in fully vaccinated individuals were reported.

A Comparison Between Clinical Guidelines and Real-World Treatment Data in Examining the Use of Session Summaries: Retrospective Study.

BACKGROUND: Although behavioral interventions have been found to be efficacious and effective in randomized clinical trials for most mental illnesses, the quality and efficacy of mental health care delivery remains inadequate in real-world settings, partly owing to suboptimal treatment fidelity. This "therapist drift" is an ongoing issue that ultimately reduces the effectiveness of treatments; however, until recently, there have been limited opportunities to assess adherence beyond large randomized controlled trials. OBJECTIVE: This study explored therapists' use of a standard component that is pertinent across most behavioral treatments-prompting clients to summarize their treatment session as a means for consolidating and augmenting their understanding of the session and the treatment plan. METHODS: The data set for this study comprised 17,607 behavioral treatment sessions administered by 322 therapists to 3519 patients in 37 behavioral health care programs across the United States. Sessions were captured by a therapy-specific artificial intelligence (AI) platform, and an automatic speech recognition system transcribed the treatment meeting and separated the data to the therapist and client utterances. A search for possible session summary prompts was then conducted, with 2 psychologists validating the text that emerged. RESULTS: We found that despite clinical recommendations, only 54 (0.30%) sessions included a summary. Exploratory analyses indicated that session summaries mostly addressed relationships (n=27), work (n=20), change (n=6), and alcohol (n=5). Sessions with meeting summaries were also characterized by greater therapist interventions and included greater use of validation, complex reflections, and proactive problem-solving techniques. CONCLUSIONS: To the best of our knowledge, this is the first study to assess a large, diverse data set of real-world treatment practices. Our findings provide evidence that fidelity with the core components of empirically designed psychological interventions is a challenge in real-world settings. The results of this study can inform the development of machine learning and AI algorithms and offer nuanced, timely feedback to providers, thereby improving the delivery of evidence-based practices and quality of mental health care services and facilitating better clinical outcomes in real-world settings.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern in real-world: a literature review and meta-analysis.

Knowing vaccine effectiveness (VE) against variants of concern (VOCs) in the real-world setting is essential for public health decision-making. A systematic landscape of the VE against a series of clinical outcomes caused by the VOCs in the real-world setting is needed. We systematically searched for studies that evaluated VE against VOCs in the real-world setting and collected individual data. We identified 113 studies meeting the eligibility criteria. We found full vaccination provided strong protection against each clinical outcome with summary VE ranging from 86.8% to 96.0% Alpha, moderate protection against infection caused by Beta, Gamma and Delta with summary VE ranging from 70.9% to 72.8%, strong protection against severe disease caused by Delta with summary VE ranging from 84.9% to 90.3%, limited protection with summary VE of 23.5% (95% CI, 17.0-29.5) against infection and moderate protection with summary VE ranging from 56.5% to 82.4% against severe diseases caused by Omicron. Booster vaccination can provide a substantial improvement in protection against Delta and Omicron, but not as much as the Delta. The meta-regression analysis showed that the VE against the Omicron wanned over time, and the VE against hospitalization declined relatively slowly, compared to against infection. Those findings supported the need for public health measures, increasing booster vaccination coverage in response to current and new infectious waves driven by variants and developing broadly protective vaccines to confront virus evolution.

A case-case study on the effect of primary and booster immunization with China-produced COVID-19 vaccines on prevention of pneumonia and viral load among vaccinated persons infected by Delta and Omicron variants.

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.

How to Reduce Inequity of Access to Cardiac Rehabilitation After Surgical Aortic Valve Replacement. Recommendations for the Post-COVID-19 Era From a Real-World, Population-Based Study.

PURPOSE: Cardiac rehabilitation (CR) is a class I recommendation after valvular surgery. Few data exist on the level of access to CR after surgical aortic valve replacement (SAVR), and the factors affecting the probability of timely access to CR after SAVR have never been empirically investigated. This study aims at estimating the proportion of SAVR patients who initiated timely CR and understanding to what extent timely access to CR for SAVR patients is influenced by specific characteristics of patients and hospitals. METHODS: We conducted a real-world, retrospective, population-based study by identifying from the Italian National Hospital Discharge Records all the discharged alive SAVR patients who accessed timely CR from 2009-2016. Two different cutoffs for timely access were considered, i.e. one and 21 days after discharge. A unique dataset was constructed by merging several data sources. Multiple logistic regressions were performed to identify the factors influencing the probability to access to timely CR. FINDINGS: 107,545 patients underwent SAVR in Italy from 2009-2016 and were discharged alive. Overall, 71,593 SAVR patients (66.6%) accessed timely CR, with an increasing trend over time. Additional 6,149 patients (5.7%) started CR from 2-21 days after discharge, slightly decreasing over time. The probability of timely CR (one-day cutoff) was significantly higher in older (OR=1.025, p<0.001) female patients (OR = 1.003, p<0.05) and patients with cardiovascular and cerebrovascular comorbidities. Presence of rehabilitation wards and number of rehabilitation beds in the index hospital significantly increased the probability of timely access to CR (OR = 1.105, p<0.001 and OR = 1.006, p<0.001 respectively). Patients hospitalized in private teaching hospitals had the highest predicted probability of timely CR after SAVR. A substantial variation in access to CR was found across Italian regions. Similar results were obtained with the alternative 21-days cutoff. IMPLICATIONS: Approximately one-third of SAVR patients did not benefit from CR in Italy, mainly due to shortness of rehabilitation facilities, with relevant disparities across the country. The cessation of CR services during the COVID-19 pandemic provides the opportunity to re-think and innovate CR, shifting from center-based to home-based models. Digital health technologies can supplement traditional health services and grant safe, effective, and equitable access to care, especially for countries with insufficient rehabilitation bed capacity. As CR is associated with better outcomes, we recommend decision-makers to use our results to plan adequate healthcare services, also investing in digital health, to ensure patients' access to cost-effective care.

Clinical characteristics of coronavirus disease 2019 infected with Delta variant in Guangzhou:A real-world study

Objective To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment. Methods A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University. Results The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant (P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥ 39 °C);other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥ 39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases (P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases (OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively. © 2021 Chinese Medical Association. All rights reserved.

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary-the HUN-VE study.

OBJECTIVES: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals. METHODS: Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 - incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day. RESULTS: Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73-9.3/100 000 person-days and 0.04-0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%-70.1%) and 88.7% (95% CI 86.6%-90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%-89.4%) and 97.5% (95% CI 95.6%-98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16-44 years for all vaccines. CONCLUSIONS: Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.

Age and Gender Disparities in Adverse Events Following COVID-19 Vaccination: Real-World Evidence Based on Big Data for Risk Management.

Background: Two coronavirus disease 2019 (COVID-19) vaccines have received emergency use authorizations in the U.S. However, the safety of these vaccines in the real-world remains unknown. Methods: We reviewed adverse events (AEs) following COVID-19 vaccination among adults in the Vaccine Adverse Event Reporting System (VAERS) from December 14, 2020, through January 22, 2021. We compared the top 10 AEs, serious AEs, along with office and emergency room (ER) visits by age (18-64 years, ≥65 years) and gender (female, male). Results: There were age and gender disparities among adults with AEs following COVID-19 vaccination. Compared to younger adults aged between 18 and 64 years, older adults were more likely to report serious AEs, death, permanent disability, and hospitalization. Males were more likely to report serious AEs, death, and hospitalization compared to females. Conclusions: COVID-19 vaccines are generally safe but possible age and gender disparities in reported AEs may exist.

Pulmonary telerehabilitation and efficacy among discharged COVID-19 patients: Rational and design of a prospective real-world study.

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) could cause physical and psychological dysfunction in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. Pulmonary telerehabilitation is strongly recommended due to the contagious nature of the disease, but its efficacy and benefit need to be comprehensively evaluated. METHODS: An 8-week pulmonary telerehabilitation programme is designed in a real-world and prospective manner, aiming to assess the efficacy of remote rehabilitation among discharged patients with COVID-19 from three designated hospitals in the epicenter of China (Wuhan City). The telerehabilitation programme includes physicians and physiotherapists remotely guided training (online) for 2 weeks, and patient self-managed rehabilitation (offline) for 6 weeks with assistance of information technology and digital device. The main rehabilitation intervention includes breathing exercise, respiratory muscle training, aerobic exercise, and resistance training. The primary outcome is 6-min walk distance, and secondly pulmonary function, respiratory muscle strength, physical activity, symptom, psychological status and quality of life, etc. will also be assessed. Patients will be followed up periodically at week two, four, eight after enrolment and at month one, three, six and 12 after the rehabilitation accomplished, respectively. Current study has been approved by the ethics committee of China-Japan Friendship Hospital and three participating centers in Wuhan City. DISCUSSION: We anticipate that the health status of discharged patients with COVID-19 could be improved through this systemic pulmonary telerehabilitation programme. The interdisciplinary remote mode of rehabilitation could be an optimal way in management of emerging respiratory tract infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04368793.

Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.

OBJECTIVE: Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19). METHODS: In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022). RESULTS: The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures. CONCLUSION: Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.