Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. OBJECTIVE, DESIGN, AND PATIENTS: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. METHODS: VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. RESULTS: TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6-13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6-19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. CONCLUSIONS: VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.

Multidimensional frailty in elderly emergency department patients: unveiling the prevalence and significance of social frailty.

PURPOSE: This study aimed to assess the prevalence and factors of physical, psychological, and social frailty among older adults in the emergency department, comparing these data with community population to understand emergency setting manifestations. METHODS: Conducted at the Emergency Department of National Taiwan University BioMedical Park Hospital, this prospective observational cohort study enrolled older adult patients over a three-month period. Frailty assessments included the Study of Osteoporotic Fractures scale for physical frailty, the Tilburg Frailty Indicator for psychological frailty, and the Makizako Social Frailty Index for social frailty. Data analysis involved a multivariable logistic model to determine the risk factors associated with each frailty type. RESULTS: Out of 991 older adult individuals seeking medical care, 207 participated in the study. The study found high prevalence rates of frailty: 46.38% for physical, 41.06% for psychological, and 48.79% for social frailty. Risk factors for frailty included older age and a history of falls. Interestingly, the prevalence of social frailty was notably higher than physical and psychological frailty. Gender and polypharmacy showed no significant association with any frailty type. CONCLUSION: This research reveals high physical, psychological, and social frailty among older ED patients, especially noting social frailty's prevalence. It highlights the importance for emergency care to adopt holistic care strategies that address older adults' multifaceted health challenges, suggesting a paradigm shift in current healthcare practices to better cater to the multifaceted needs of this vulnerable population.

RéSUMé: OBJECTIFS: Cette étude visait à évaluer la prévalence et les facteurs de la fragilité physique, psychologique et sociale chez les personnes âgées au service des urgences, en comparant ces données avec la population communautaire pour comprendre les manifestations en situation d'urgence. MéTHODES: Menée au service des urgences de l'hôpital BioMedical Park de l'Université nationale de Taiwan, cette étude prospective de cohorte observationnelle a recruté des patients adultes âgés sur une période de trois mois. Les évaluations de la fragilité comprenaient l'échelle de l'étude des fractures ostéoporotiques pour la fragilité physique, l'indicateur de la fragilité psychologique de Tilburg et l'indice de fragilité sociale de Makizako pour la fragilité sociale. L'analyse des données comportait un modèle logistique multivarié pour déterminer les facteurs de risque associés à chaque type de fragilité. RéSULTATS: Sur 991 personnes âgées ayant besoin de soins médicaux, 207 ont participé à l'étude. L'étude a révélé des taux de prévalence élevés de la fragilité : 46,38% pour le physique, 41,06% pour le psychologique et 48,79% pour la fragilité sociale. Les facteurs de risque de fragilité comprenaient un âge avancé et des antécédents de chute. Fait intéressant, la prévalence de la fragilité sociale était nettement plus élevée que la fragilité physique et psychologique. Le genre et la polypharmacie n'ont montré aucune association significative avec aucun type de fragilité. CONCLUSION: Cette recherche révèle une grande fragilité physique, psychologique et sociale chez les patients âgés aux urgences, en particulier la prévalence de la fragilité sociale. Il souligne l'importance pour les soins d'urgence d'adopter des stratégies de soins holistiques qui répondent aux défis de santé multiformes des personnes âgées, suggérant un changement de paradigme dans les pratiques de soins de santé actuelles pour mieux répondre aux besoins multiformes de cette population vulnérable.

Chief complaints and computed tomography results in the emergency department: a three-year retrospective cohort study.

BACKGROUND: Computed tomography (CT) is frequently performed in the patients who admitted to the emergency department (ED), discharged but returned to ED within 72 h. It is unknown whether the main complaints of patients assist physicians to use CT effectively. This study aimed to find the association between chief complaints and the CT results. METHODS: This three-year retrospective cohort study was conducted in the ED of a tertiary medical center. Adult patients who returned to the ED after the index visit were included from 2019 to 2021. Demographics, pre-existing diseases, chief complaints, and CT region were recorded by independent ED physicians. A logistic regression model with an odds ratio (OR) and 95% confidence interval (CI) was used to determine the relationship between chief complaints and positive CT results. RESULTS: In total, 7,699 patients revisited ED after the index visit; 1,202 (15.6%) received CT. The top chief complaints in patients who received CT were abdominal pain, dizziness, and muscle weakness. Patients with abdominal pain or gastrointestinal symptoms had a significantly higher rate of positive abdominopelvic CT than those without it (OR 2.83, 95% CI 1.98-4.05, p < 0.001), while the central nervous system and cardiopulmonary chief complaints were not associated (or negatively associated) with new positive CT findings. CONCLUSION: Chief complaints of patients on revisit to the ED are associated with different yields of new findings when CT scans of the chest, abdomen and head are performed. Physicians should consider these differential likelihoods of new positive findings based on these data.

Prediction of high-risk emergency department revisits from a machine-learning algorithm: a proof-of-concept study.

BACKGROUND: High-risk emergency department (ED) revisit is considered an important quality indicator that may reflect an increase in complications and medical burden. However, because of its multidimensional and highly complex nature, this factor has not been comprehensively investigated. This study aimed to predict high-risk ED revisit with a machine-learning (ML) approach. METHODS: This 3-year retrospective cohort study assessed adult patients between January 2019 and December 2021 from National Taiwan University Hospital Hsin-Chu Branch with high-risk ED revisit, defined as hospital or intensive care unit admission after ED return within 72 hours. A total of 150 features were preliminarily screened, and 79 were used in the prediction model. Deep learning, random forest, extreme gradient boosting (XGBoost) and stacked ensemble algorithm were used. The stacked ensemble model combined multiple ML models and performed model stacking as a meta-level algorithm. Confusion matrix, accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUROC) were used to evaluate performance. RESULTS: Analysis was performed for 6282 eligible adult patients: 5025 (80.0%) in the training set and 1257 (20.0%) in the testing set. High-risk ED revisit occurred for 971 (19.3%) of training set patients vs 252 (20.1%) in the testing set. Leading predictors of high-risk ED revisit were age, systolic blood pressure and heart rate. The stacked ensemble model showed more favourable prediction performance (AUROC 0.82) than the other models: deep learning (0.69), random forest (0.78) and XGBoost (0.79). Also, the stacked ensemble model achieved favourable accuracy and specificity. CONCLUSION: The stacked ensemble algorithm exhibited better prediction performance in which the predictions were generated from different ML algorithms to optimally maximise the final set of results. Patients with older age and abnormal systolic blood pressure and heart rate at the index ED visit were vulnerable to high-risk ED revisit. Further studies should be conducted to externally validate the model.

Discovery of CMX990: A Potent SARS-CoV-2 3CL Protease Inhibitor Bearing a Novel Warhead.

There remains a need to develop novel SARS-CoV-2 therapeutic options that improve upon existing therapies by an increased robustness of response, fewer safety liabilities, and global-ready accessibility. Functionally critical viral main protease (Mpro, 3CLpro) of SARS-CoV-2 is an attractive target due to its homology within the coronaviral family, and lack thereof toward human proteases. In this disclosure, we outline the advent of a novel SARS-CoV-2 3CLpro inhibitor, CMX990, bearing an unprecedented trifluoromethoxymethyl ketone warhead. Compared with the marketed drug nirmatrelvir (combination with ritonavir = Paxlovid), CMX990 has distinctly differentiated potency (∼5× more potent in primary cells) and human in vitro clearance (>4× better microsomal clearance and >10× better hepatocyte clearance), with good in vitro-to-in vivo correlation. Based on its compelling preclinical profile and projected once or twice a day dosing supporting unboosted oral therapy in humans, CMX990 advanced to a Phase 1 clinical trial as an oral drug candidate for SARS-CoV-2.

The interaction of sex and age on outcomes in emergency medical services-treated out-of-hospital cardiac arrest: A 5-year multicenter retrospective analysis.

Background: Studies have established that sex and age influence outcomes following out-of-hospital cardiac arrest (OHCA). However, a knowledge gap exists regarding their interaction. This study aimed to investigate the interaction of age and sex and how they cooperatively influence OHCA outcomes. Methods: This retrospective cohort study included adult, nontraumatic OHCA patients admitted to a university hospital and its affiliated hospitals in Taiwan from January 2017 to December 2021. Data including sex, age, body mass index, cardiac rhythm, and resuscitation information in the emergency department (ED) were collected from medical records. The study outcomes encompassed survival to intensive care unit (ICU) admission, survival to hospital discharge, and a favorable neurological outcome. Multivariable logistic regression was performed to estimate the influence of sex on study outcomes. Results: We analyzed a total of 2,826 eligible subjects categorized into three groups: young (18-44 years, 149 males and 57 females), middle-aged (45-64 years, 524 males and 188 females), and old (≥65 years, 1,049 males and 859 females). Analysis of the effects of sex according to age stratification showed that old males had higher odds for survival to ICU admission (OR: 1.49, 95% CI: 1.21-1.83) and favorable neurological outcomes (OR: 2.74, 95% CI: 1.58-4.76) than did old females. Analysis of the effects of age according to sex stratification revealed that old males had lower odds for survival to hospital discharge (OR: 0.33, 95% CI: 0.21-0.51) and favorable neurological outcomes (OR: 0.26, 95% CI: 0.16-0.43) than did young males. Old females also showed the same trend as males, with lower odds for survival to hospital discharge (OR: 0.37, 95% CI: 0.17-0.78) and favorable neurological outcomes (OR: 0.11, 95% CI: 0.05-0.25) than did young females. Conclusions: The interaction between sex and age in patients with OHCA results in diverse outcomes. Within the same sex, age demonstrated varying effects on distinct outcomes.

Development of validated sandwich ELISA for detecting peanut allergen Ara h 3 in food.

Peanut is an important food that can cause food allergies, often leading to moderate and severe allergic symptoms such as skin rashes, asthma, and even anaphylactic shock.Research indicates that Ara h 3 is one of the major peanut allergen. In order to establish a simple analytical method for detecting Ara h 3, we developed a sandwich enzyme-linked immunosorbent assay (ELISA) with antibodies that were induced from purified Ara h 3. The experimental results showed that the purified Ara h 3 had good purity, and we successfully prepared capture and detection antibodies. The method established in this study exhibited high specificity and did not cross-react with soybeans, cashew nuts, and sesame. For validation, including precision, recovery and sensitivity were in good condition. We also detected the Ara h 3 in peanut related foods. Overall, the ELISA developed in this study is a reliable method for Ara h 3 detection.

Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study.

BACKGROUND: Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care. METHODS: This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods. RESULTS: The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC. CONCLUSIONS: Routine EHR data can stratify the general population for GAC risk. IMPACT: Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Trends in Detection of Adenoma and Sessile Serrated Lesions Over a Decade in a Community-Based Healthcare System.

INTRODUCTION: Adenoma detection rate (ADR) is an accepted benchmark for screening colonoscopy. Factors driving ADR and its relationship with sessile serrated lesions detection rate (SSLDR) over time remain unclear. We aim to explore patient, physician, and procedural influences on ADR and SSLDR trends. METHODS: Using a large healthcare system in northern California from January 2010 to December 2020, a total of 146,818 screening colonoscopies performed by 33 endoscopists were included. ADR and SSLDR were calculated over time using natural language processing. Logistic regression was used to calculate the odd ratios of patient demographics, physician attributes, and procedural details over time. RESULTS: Between 2010 and 2020, ADR rose from 19.4% to 44.4%, whereas SSLDR increased from 1.6% to 11.6%. ADR increased by 2.7% per year (95% confidence interval 1.9%-3.4%), and SSLDR increased by 1.0% per year (95% confidence interval 0.8%-1.2%). Higher ADR was associated with older age, male sex, higher body mass index, current smoker, higher comorbidities, and high-risk colonoscopy. By contrast, SSLDR was associated with younger age, female sex, white race, and fewer comorbidities. Patient and procedure characteristics did not significantly change over time ( P -interaction >0.05). Longer years in practice and male physician were associated with lower ADR and SSLDR in 2010, but significantly attenuated over time ( P -interaction <0.05). DISCUSSION: Both ADR and SSLDR have increased over time. Patient and procedure factors did not significantly change over time. Male endoscopist and longer years in practice had lower initial ADR and SSLDR, but significantly lessened over time.

Comparison of on-scene Glasgow Coma Scale with GCS-motor for prediction of 30-day mortality and functional outcomes of patients with trauma in Asia.

BACKGROUND AND IMPORTANCE: This study compared the on-scene Glasgow Coma Scale (GCS) and the GCS-motor (GCS-M) for predictive accuracy of mortality and severe disability using a large, multicenter population of trauma patients in Asian countries. OBJECTIVE: To compare the ability of the prehospital GCS and GCS-M to predict 30-day mortality and severe disability in trauma patients. DESIGN: We used the Pan-Asia Trauma Outcomes Study registry to enroll all trauma patients >18 years of age who presented to hospitals via emergency medical services from 1 January 2016 to November 30, 2018. SETTINGS AND PARTICIPANTS: A total of 16,218 patients were included in the analysis of 30-day mortality and 11 653 patients in the analysis of functional outcomes. OUTCOME MEASURES AND ANALYSIS: The primary outcome was 30-day mortality after injury, and the secondary outcome was severe disability at discharge defined as a Modified Rankin Scale (MRS) score ≥4. Areas under the receiver operating characteristic curve (AUROCs) were compared between GCS and GCS-M for these outcomes. Patients with and without traumatic brain injury (TBI) were analyzed separately. The predictive discrimination ability of logistic regression models for outcomes (30-day mortality and MRS) between GCS and GCS-M is illustrated using AUROCs. MAIN RESULTS: The primary outcome for 30-day mortality was 1.04% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.917 (0.887-0.946) vs. GCS-M:0.907 (0.875-0.938), P  = 0.155. The secondary outcome for poor functional outcome (MRS ≥ 4) was 12.4% and the AUROCs and 95% confidence intervals for prediction were GCS: 0.617 (0.597-0.637) vs. GCS-M: 0.613 (0.593-0.633), P  = 0.616. The subgroup analyses of patients with and without TBI demonstrated consistent discrimination ability between the GCS and GCS-M. The AUROC values of the GCS vs. GCS-M models for 30-day mortality and poor functional outcome were 0.92 (0.821-1.0) vs. 0.92 (0.824-1.0) ( P  = 0.64) and 0.75 (0.72-0.78) vs. 0.74 (0.717-0.758) ( P  = 0.21), respectively. CONCLUSION: In the prehospital setting, on-scene GCS-M was comparable to GCS in predicting 30-day mortality and poor functional outcomes among patients with trauma, whether or not there was a TBI.

The effect of papain hydrolysis on tropomyosin levels in shrimp.

Shrimp allergy is a serious public health problem. Epidemiological studies indicated the main cause of food allergy is the ingestion of shrimp and crab. Consequently, reducing the risk of shrimp and crab allergy is a major research focus. Few studies have demonstrated the effect of enzyme hydrolysis on reduction of shrimp allergens in food. In this study, we used papain, a commonly used enzyme in the food industry, as an ingredient to decrease levels of allergen tropomyosin in shrimp. 0-50U of papain was used to treat the shrimp meat, and then heated to measure the levels of tropomyosin, and determined the change of the protein secondary structure. The results showed that 20U of papain decrease the tropomyosin levels up to 80 %, which was further enhanced when combined with 3 min of heating. Furthermore, the result of Fourier-transform infrared spectroscopy (FTIR) showed alteration of secondary protein structure after the processing. The processing developed in this study may be an effective method used to change the levels and structure of tropomyosin.

Updated trends in the outcomes of out-of-hospital cardiac arrest from 2017-2021: Prior to and during the coronavirus disease (COVID-19) pandemic.

Objective: This study aims to describe out-of-hospital cardiac arrest (OHCA) characteristics and trends before and during the coronavirus disease-2019 (COVID-19) pandemic in Taiwan. Methods: We conducted a retrospective cohort study using a 5-year interrupted time series analysis. Eligible adults with non-traumatic OHCAs from January 2017 to December 2021 in 3 hospitals (university medical center, urban second-tier hospital, and rural second-tier hospital) were retrospectively enrolled. Variables were extracted from the emergency medical service reports and medical records. The years 2020 and 2021 were defined as the COVID-19 pandemic period. Outcomes included survival to admission after a sustained return of spontaneous circulation, survival to hospital discharge, and good neurological outcomes (cerebral performance category score 1 or 2). Results: We analyzed 2819 OHCA, including 1227 from a university medical center, 617 from an urban second-tier hospital, and 975 from a rural second-tier hospital. The mean age was 71 years old, and 60% of patients were males. During the COVID-19 pandemic period, video-assisted endotracheal tube intubation replaced the traditional direct laryngoscopy intubation. The trends of outcomes in the pre-pandemic and pandemic periods varied among different hospitals. Compared with the pre-pandemic period, the outcomes at the university medical center during the COVID-19 pandemic were significantly poorer in several respects. The survival rate on admission dropped from 44.6% to 39.4% (P = 0.037), and the survival rate to hospital discharge fell from 17.5% to 14.9% (P = 0.042). Additionally, there was a notable decrease in patients' good neurological outcomes, declining from 13.2% to 9.7% (P = 0.048). In contrast, the outcomes in urban and rural second-tier hospitals during the COVID-19 pandemic did not significantly differ from those in the pre-pandemic period. Conclusions: COVID-19 may alter some resuscitation management in OHCAs. There were no overall significant differences in outcomes before and during COVID-19 pandemic, but there were significant differences in outcomes when stratified by hospital types.

Risk stratification of patients with chest pain who have an unscheduled revisit to the emergency department.

AIMS: Acute cardiovascular (CV) emergencies are critical conditions that require urgent attention in the emergency department (ED). Failure to make a timely diagnosis may result in unscheduled ED revisits and severe outcomes. Therefore, this study aimed to investigate the risk factors associated with potentially missed acute CV emergencies. METHODS AND RESULTS: This retrospective study enrolled adult patients who presented with chest pain and returned to the ED within 72 h. Demographic information, pre-existing medical conditions, chief complaints, triage level and vital signs, electrocardiography (ECG) reports, and laboratory data were collected from medical charts by independent physicians. The primary outcome was the diagnosis of acute CV diseases, including ACS, pulmonary embolism, unstable arrhythmia, acute decompensated heart failure, and aortic dissection. Multivariable logistic regression was used to analyze the association between variables and acute CV emergencies. A total of 453 eligible patients were included, with 60 (13.2%) patients diagnosed as acute CV emergencies at the ED revisit. Risk factors for acute CV emergencies included male gender (adjusted odds ratio [aOR] = 2.71, 95% confidence interval [CI] = 1.17-6.25), abnormal ECG rhythm (aOR = 10.33, 95% CI = 4.68-22.83), and abnormal changes in high sensitivity Troponin-T (hs-cTnT) during sequential follow-up (aOR = 6.52, 95% CI = 2.19-19.45). CONCLUSIONS: Male gender, abnormal ECG rhythm, and a significant increase in sequential follow-up hs-cTnT levels were identified as significant risk factors for acute CV emergencies. ED physicians should recognize these high-risk patients with chest pain to prevent misdiagnosis and potential severe complications.

A simplified scoring model for predicting bacteremia in the unscheduled emergency department revisits: The SADFUL score.

BACKGROUND: Bacteremia is a severe complication of infectious disease. Patients with a high bacteremia risk in the emergency department (ED) but misidentified would lead to the unscheduled revisits. This study aimed to develop a simplified scoring model to predict bacteremia in patients with unscheduled ED revisits. METHODS: Adult patients with unscheduled ED revisits within 72 h with a final diagnosis of infectious disease were retrospectively included. The development cohort included patients visiting the ED from January 1, 2019 to December 31, 2021. Internal validation was performed in patients visiting the ED from January 1, 2022 to March 31, 2022. Variables including demographics, pre-comorbidities, triage levels, vital signs, chief complaints, and laboratory data in the index visit were analyzed. Bacteremia was the primary outcome determined by blood culture in either index visits or revisits. RESULTS: The SADFUL score for predicting bacteremia comprised the following predictors: "S"egmented neutrophil percentage (+3 points), "A"ge > 55 years (+1 point), "D"iabetes mellitus (+1 point), "F"ever (+2 points), "U"pper respiratory tract symptoms (-2 points), and "L"eukopenia (2 points). The area under receiver operating characteristic curve with 95% confidence interval in the development (1802 patients, 190 [11%] with bacteremia) and the validation cohort (134 patients, 17 [13%] with bacteremia) were 0.78 (0.74-0.81) and 0.79 (0.71-0.88), respectively. CONCLUSIONS: The SADFUL score is a simplified useful tool for predicting bacteremia in patients with unscheduled ED revisits. The scoring model could help ED physicians decrease misidentification of patients at a high risk for bacteremia and potential complications.

Differences in the characteristics and patterns of adult emergency department return visits before and after the coronavirus disease 2019 outbreak.

BACKGROUND: Data about changes in the characteristics of ED return visits before and after the COVID-19 outbreak are limited. This study aimed to report the differences on utility in ED return visits after the COVID-19 outbreak. METHODS: This retrospective cohort study was conducted from 2019 to 2020. Adult patients with ED return visits were included in the analysis. Variables including demographic characteristics, pre-comorbidities, triage levels, vital signs, chief complaints, management, and diagnosis were recorded and confirmed via a manual assessment. RESULTS: The proportion of patients with ED visits decreased by 23%. Hence, that of patients with ED return visits also reduced from 2580 to 2020 patients (22%) after the COVID-19 outbreak. The average age (60-57.8 years) of patients with return visits was significantly younger, and the proportion of female patients decreased remarkably. Further, the proportion of patients with chronic pre-existing diseases at the return visit significantly differed after the COVID-19 outbreak. The proportion of patients with chief complaints including dizziness, dyspnea, cough, vomiting, diarrhea, and chills during the return visits significantly differed before and after the COVID-19 pandemic. In the multivariable logistic regression model, age, high triage level were significantly associated with unfavorable outcome return visit. CONCLUSION: The use of services in the ED has changed since the COVID-19 outbreak. Hence, the proportion of patients with unplanned return visits within 72 h decreased. After the COVID-19 outbreak, people are now cautious whether they should return to the ED, as in the pre-pandemic situation, or just treat conservatively at home.

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence. Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks. Design, Setting, and Participants: This phase 3, single-arm, open-label trial (ECOSPOR IV) was conducted at 72 US and Canadian outpatient sites from October 2017 to April 2022. Adults aged 18 years or older with recurrent CDI were enrolled in 2 cohorts: (1) rollover patients from the ECOSPOR III trial who had CDI recurrence diagnosed by toxin enzyme immunoassay (EIA) and (2) patients with at least 1 CDI recurrence (diagnosed by polymerase chain reaction [PCR] or toxin EIA), inclusive of their acute infection at study entry. Interventions: SER-109 given orally as 4 capsules daily for 3 days following symptom resolution after antibiotic treatment for CDI. Main Outcomes and Measures: The main outcomes were safety, measured as the rate of treatment-emergent adverse events (TEAEs) in all patients receiving any amount of SER-109, and cumulative rates of recurrent CDI (toxin-positive diarrhea requiring treatment) through week 24 in the intent-to-treat population. Results: Of 351 patients screened, 263 were enrolled (180 [68.4%] female; mean [SD] age, 64.0 [15.7] years); 29 were in cohort 1 and 234 in cohort 2. Seventy-seven patients (29.3%) were enrolled with their first CDI recurrence. Overall, 141 patients (53.6%) had TEAEs, which were mostly mild to moderate and gastrointestinal. There were 8 deaths (3.0%) and 33 patients (12.5%) with serious TEAEs; none were considered treatment related by the investigators. Overall, 23 patients (8.7%; 95% CI, 5.6%-12.8%) had recurrent CDI at week 8 (4 of 29 [13.8%; 95% CI, 3.9%-31.7%] in cohort 1 and 19 of 234 [8.1%; 95% CI, 5.0%-12.4%] in cohort 2), and recurrent CDI rates remained low through 24 weeks (36 patients [13.7%; 95% CI, 9.8%-18.4%]). At week 8, recurrent CDI rates in patients with a first recurrence were similarly low (5 of 77 [6.5%; 95% CI, 2.1%-14.5%]) as in patients with 2 or more recurrences (18 of 186 [9.7%; 95% CI, 5.8%-14.9%]). Analyses by select baseline characteristics showed consistently low recurrent CDI rates in patients younger than 65 years vs 65 years or older (5 of 126 [4.0%; 95% CI, 1.3%-9.0%] vs 18 of 137 [13.1%; 95% CI, 8.0%-20.0%]) and patients enrolled based on positive PCR results (3 of 69 [4.3%; 95% CI, 0.9%-12.2%]) vs those with positive toxin EIA results (20 of 192 [10.4%; 95% CI, 6.5%-15.6%]). Conclusions and Relevance: In this trial, oral SER-109 was well tolerated in a patient population with recurrent CDI and prevalent comorbidities. The rate of recurrent CDI was low regardless of the number of prior recurrences, demographics, or diagnostic approach, supporting the beneficial impact of SER-109 for patients with CDI. Trial Registration: ClinicalTrials.gov identifier: NCT03183141.