Summary Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant ...hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial. Methods Healthy adults aged 16–65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov , number NCT01014845. Findings 11 165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100·0% (95% CI 72·1–100·0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted. Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16–65 years. Funding Chinese National High-tech R&D Programme (863 programme), Chinese National Key Technologies R&D Programme, Chinese National Science Fund for Distinguished Young Scholars, Fujian Provincial Department of Sciences and Technology, Xiamen Science and Technology Bureau, and Fujian Provincial Science Fund for Distinguished Young Scholars.
Background and Aims Confocal laser endomicroscopy can dynamically assess intestinal mucosal barrier defects and increased intestinal permeability (IP). These are functional features that do not have ...corresponding appearance on histopathology. As such, previous pathology training may not be beneficial in learning these dynamic features. This study aims to evaluate the diagnostic accuracy, learning curve, inter- and intraobserver agreement for identifying features of increased IP in experienced and inexperienced analysts and pathologists. Methods A total of 180 endoscopic confocal laser endomicroscopy (Pentax EC-3870FK; Pentax, Tokyo, Japan) images of the terminal ileum, subdivided into 6 sets of 30 were evaluated by 6 experienced analysts, 13 inexperienced analysts, and 2 pathologists, after a 30-minute teaching session. Cell-junction enhancement, fluorescein leak, and cell dropout were used to represent increased IP and were either present or absent in each image. For each image, the diagnostic accuracy, confidence, and quality were assessed. Results Diagnostic accuracy was significantly higher for experienced analysts compared with inexperienced analysts from the first set (96.7% vs 83.1%, P < .001) to the third set (95% vs 89.7, P = .127). No differences in accuracy were noted between inexperienced analysts and pathologists. Confidence (odds ratio, 8.71; 95% confidence interval, 5.58-13.57) and good image quality (odds ratio, 1.58; 95% confidence interval, 1.22-2.03) were associated with improved interpretation. Interobserver agreement κ values were high and improved with experience (experienced analysts, 0.83; inexperienced analysts, 0.73; and pathologists, 0.62). Intraobserver agreement was >0.86 for experienced observers. Conclusion Features representative of increased IP can be rapidly learned with high inter- and intraobserver agreement. Confidence and image quality were significant predictors of accurate interpretation. Previous pathology training did not have an effect on learning.
IMPORTANCE: Taiwan is one of the few countries with initial success in COVID-19 control without strict lockdown or school closure. The reasons remain to be fully elucidated. OBJECTIVE: To compare and ...evaluate the effectiveness of case-based (including contact tracing and quarantine) and population-based (including social distancing and facial masking) interventions for COVID-19 in Taiwan. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study used a stochastic branching process model using COVID-19 epidemic datafrom Taiwan, an island nation of 23.6 million people, with no locally acquired cases of COVID-19 reported for 253 days between April and December 2020. MAIN OUTCOMES AND MEASURES: Effective reproduction number of COVID-19 cases (the number of secondary cases generated by 1 primary case) and the probability of outbreak extinction (0 new cases within 20 generations). For model development and calibration, an estimation of the incubation period (interval from exposure to symptom onset), serial interval (time between symptom onset in an infector-infectee pair), and the statistical distribution of the number of any subsequent infections generated by 1 primary case was calculated. RESULTS: This study analyzed data from 158 confirmed COVID-19 cases (median age, 45 years; interquartile range, 25-55 years; 84 men 53%). An estimated 55% (95% credible interval CrI, 41%-68%) of transmission events occurred during the presymptomatic stage. In our estimated analysis, case detection, contact tracing, and 14-day quarantine of close contacts (regardless of symptoms) was estimated to decrease the reproduction number from the counterfactual value of 2.50 to 1.53 (95% CrI, 1.50-1.57), which would not be sufficient for epidemic control, which requires a value of less than 1. In our estimated analysis, voluntary population-based interventions, if used alone, were estimated to have reduced the reproduction number to 1.30 (95% CrI, 1.03-1.58). Combined case-based and population-based interventions were estimated to reduce the reproduction number to below unity (0.85; 95% CrI, 0.78-0.89). Results were similar for additional analyses with influenza data and sensitivity analyses. CONCLUSIONS AND RELEVANCE: In this comparative effectiveness research study, the combination of case-based and population-based interventions (with wide adherence) may explain the success of COVID-19 control in Taiwan in 2020. Either category of interventions alone would have been insufficient, even in a country with an effective public health system and comprehensive contact tracing program. Mitigating the COVID-19 pandemic requires the collaborative effort of public health professionals and the general public.
Abstract Objectives This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD). Background Although current clinical models help ...to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy. Methods Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort. Results The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval CI: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points. Conclusions We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy.
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