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BackgroundHeart failure is a major cause of death globally and earlier initiation of treatment could mitigate disease progression. Multiple efforts have been made using genome-wide association studies (GWAS) or electronic health records (EHR) to identify individuals at high risk of heart failure (HF). However, integrating both sources using novel natural language processing (NLP) techniques and large scale global genetic predictors into heart failure prediction models has not been evaluated.ObjectivesThe study aimed to improve the accuracy of HF prediction by integrating GWAS- and EHR-derived risk scores.MethodsWe previously performed the largest HF GWAS to date within the Global Biobank Meta-analysis Initiative, which includes 974,174 samples (51,274 cases; 5%) from 9 biobanks across the world, to create a polygenic risk score (PRS). Next, to extract information from the Michigan Medicine high-dimensional EHR (N=61,849 subjects), we treated diagnosis codes as ‘words’ and applied NLP on the data. NLP was used to learn code co-occurrence patterns and extract 350 latent phenotypes (low-dimensional features) representing 29,346 EHR codes. Next, we regressed HF on the latent phenotypes in an independent cohort and the coefficients were used as the weights to calculate a clinical risk score (ClinRS). Model performances were compared between baseline (age and sex) model and three models with risk scores added: 1) PRS, 2) ClinRS, and 3) PRS+ClinRS, using 10-fold cross validated Area Under the Receiver Operating Characteristic Curve (AUC).ResultsOur results show that PRS and ClinRS are each, separately, able to predict HF outcomes significantly better than the baseline model, up to eight years prior to HF diagnosis. Higher AUC (95% CI) were observed in the PRS model (0.76 [0.74-0.78]) and ClinRS model (0.77 [0.74-0.79]), compared to the baseline model (0.71 [0.68-0.73]). Moreover, by including both PRS and ClinRS in the model, we achieved superior performance in predicting HF up to ten years prior to HF diagnosis (AUC: 0.79 [0.77-0.82]), 2-3 years earlier than using either single risk predictor alone.ConclusionsWe demonstrate the additive power of integrating GWAS- and EHR-derived risk scores to predict HF cases prior to diagnosis. Clinical application of this approach may allow identification of patients with higher susceptibility to HF and enable preventive therapies to be initiated at an earlier stage.

SUMMARYGenome wide association study (GWAS) results for Venous Thromboembolism (VTE) across 9 international cohorts of the Global Biobank Meta-analysis Initiative (GBMI), with representation across six ancestry groups (cases=27,987, controls=1,035,290), were combined using inverse-variance weighted meta-analysis. This multi-ancestry GWAS resulted in 38 genome-wide significant loci, 9 of which are potentially novel. For each autosomal locus we performed gene prioritization using seven independent, yet converging, lines of evidence. Through prioritization we identified genes known for VTE (e.g., F5, F11, VWF), genes known to modify blood coagulation (e.g., STAB2), and genes without known coagulation mechanisms from functional studies (e.g., PLCG2, TC2N). We evaluated the function of six prioritized genes, including F7 as a positive control, using laser mediated endothelial injury to induce thrombosis in zebrafish. We used CRISPR/Cas9 to knock down these potentially causal genes and measured time to occlusion after laser injury. From this assay we have supportive evidence for a role of RASIP1 and TC2N in the modification of human VTE, and suggestive evidence for STAB2 and TSPAN15. This study expands the currently identified genomic architecture of VTE through biobank-based multi-ancestry GWAS, in silico candidate gene predictions, and in vivo functional follow-up of novel candidate genes.

Background Elevated serum lactate is associated with higher mortality in sepsis, whereas liver dysfunction is associated with higher serum lactate levels. We assessed the predictive ability of serum lactate in patients with liver cirrhosis and sepsis. Methods This retrospective study included 12,281 cases of suspected infection with initial serum blood lactate drawn during January 2007-December 2013. Results Using one-to-two propensity score matching analysis, 1,053 and 2,106 septic patients with and without underlying liver cirrhosis, respectively, were successfully matched. Lactate levels of survivors and non-survivors were 2.58 and 5.93 mmol/L, respectively, in patients without liver cirrhosis (WLC), 2.96 and 7.29 mmol/L, respectively, in patients with non-decompensated liver cirrhosis (NDLC), and 4.08 and 7.1 6 mmol/L, respectively, in patients with decompensated liver cirrhosis (DLC). Adjusted odds ratios of an initial serum lactate level >2 mmol/L in 28-day in-hospital mortality were 4.99, 4.74, and 3.33 in the WLC, NDLC, and DLC groups, respectively. In receiver operating characteristic curve analysis, the sensitivity and specificity for predicting mortality were 0.81 and 0.55, respectively, in the WLC group, 0.85 and 0.45, respectively, in the NDLC group, and 0.86 and 0.33, respectively, in the DLC group, using serum lactate levels >2.0 mmol/L. Conclusions Serum lactate level can be used to predict the severity of sepsis in patients with liver cirrhosis; however, its specificity would be lower at a cutoff of 2.0 mmol/L.

Particulate matter (PM) and other air pollutants are reportedly associated with both lung and systemic inflammation; however, an association between air pollutants and pneumonia outcomes has not been well established. Therefore, we evaluated the effect of air pollutants on the short-term outcomes of emergency department patients with pneumonia. We collected data on PM2.5 (aerodynamic diameter 17 years who had visited the emergency department with a principal diagnosis of pneumonia. In-hospital mortality and the association of air pollutant exposure with the need for invasive respiratory and/or vasopressor support (IRVS) within 72 h were evaluated. Interquartile range (IQR) increments of PM2.5 and PM10 were associated with an increased IRVS risk with odds ratios (ORs) of 1.211 (95% confidence interval [CI], 1.031–1.419) and 1.194 (95% CI, 1.020–1.394) on lag 1, respectively, and per-IQR increments of NO2 were associated with an increased IRVS risk with an OR of 1.146 (95% CI, 1.004–1.308) on lag 2. IQR increments of PM2.5 and NO2 were associated with an increased in-hospital mortality risk with ORs of 1.202 (95% CI, 1.100–1.429) and 1.175 (95% CI, 1.014–1.360), respectively. During the warm season, IQR increments of PM2.5, PM10, and NO2 corresponded with an increased IRVS risk, with ORs of 1.333 (95% CI, 1.078–1.644), 1.348 (95% CI, 1.090–1.665), and 1.321 (95% CI, 1.101–1.585), respectively. For patients with pneumonia, PM2.5, PM10, and NO2 exposures were risk factors for a poor prognosis. Exposure effects appeared to be greater during the warm season. Regulations focused on PM2.5, PM10, and NO2 levels should be considered to improve patient outcomes.

SummaryCerebrovascular accident (stroke) is the second leading cause of death and disability worldwide. Stroke prevalence varies by sex and ancestry, which could be due to genetic heterogeneity between subgroups. We performed a genome-wide meta-analysis of 16 biobanks across multiple ancestries to study the genetic contributions underlying ischemic stroke (60,176 cases, 1,310,725 controls) as part of the Global Biobank Meta-analysis Initiative (GBMI). Two novel loci associated ischemic stroke with plausible candidate genes, FGF5 and CENPQ/MUT, were identified after replication in four additional datasets. One locus showed significant ancestry heterogeneity (PDE3A) and two loci showed significant sex-heterogeneity (SH3PXD2A and ALDH2). The ALDH2 locus had a male-specific association for stroke in GBMI (P-value males = 1.67e-24, P-value females = 0.126). To test whether we would see a difference in the predictive power of sex-specific polygenic risk scores (PRSs), we compared the C-indexes for sex-specific and sex-combined PRSs in HUNT dataset. A sex-combined PRS was more successful at predicting stroke cases than a sex-specific PRS, most likely due to more stable effect estimates from the sex-combined summary-statistics. These approaches can be applied to further unravel the genetic underpinnings of stroke and other complex diseases.

The prognosis of out-of-hospital cardiac arrest (OHCA) is very poor. Although several pre-hospital factors are associated with survival, the different association of pre-hospital factors with OHCA outcomes in pediatric and adult groups remain unclear. To assess the association of pre-hospital factors with OHCA outcomes among pediatric and adult groups, a retrospective observational study was conducted using the emergency medical service (EMS) database in Kaohsiung from January 2015 to December 2019. Pre-hospital factors, underlying diseases, and OHCA outcomes were collected for the pediatric (Age ≤ 20) and adult groups. Kaplan-Meier type plots and multivariable logistic regression were used to analyze the association between pre-hospital factors and outcomes. In total, 7,461 OHCAs were analyzed. After adjusting for EMS response time, bystander CPR, attended by EMT-P, witness, and pre-hospital defibrillation, we found that age [odds ratio (OR) = 0.877, 95% confidence interval (CI): 0.764–0.990, p = 0.033], public location (OR = 7.681, 95% CI: 1.975–33.428, p = 0.003), and advanced airway management (AAM) (OR = 8.952; 95% CI, 1.414–66.081; p = 0.02) were significantly associated with survival till hospital discharge in pediatric OHCAs. The results of Kaplan-Meier type plots with log-rank test showed a significant difference between the pediatric and adult groups in survival for 2 h (p < 0.001), 24 h (p < 0.001), hospital discharge (p < 0.001), and favorable neurologic outcome (p < 0.001). AAM was associated with improved survival for 2 h (p = 0.015), 24 h (p = 0.023), and neurologic outcome (p = 0.018) only in the pediatric group. There were variations in prognostic factors between pediatric and adult patients with OHCA. The prognosis of the pediatric group was better than that of the adult group. Furthermore, AAM was independently associated with outcomes in pediatric patients, but not in adult patients. Age and public location of OHCA were independently associated with survival till hospital discharge in both pediatric and adult patients.

Iron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron binding capacity) in the Trøndelag Health Study (HUNT), the Michigan Genomics Initiative (MGI) and the SardiNIA study, followed by their meta-analysis with publicly available summary statistics, analyzing up to 257 953 individuals. We identify 127 genetic loci associated with iron traits. Among 19 novel protein-altering variants, we observe a rare missense variant (rs367731784) in HUNT, which suggests a role for DNAJC13 in transferrin recycling. We further validate the latest genetic risk scores for each biomarker in HUNT (6% variance in serum iron explained) and present linear and non-linear Mendelian randomization analyses of the traits on all-cause mortality. We find evidence of a harmful effect of increased serum iron and transferrin saturation in linear analyses that estimate population-averaged effects. However, there was weak evidence of a protective effect of increasing serum iron at the very low end of its distribution. Our findings contribute to our understanding of the genes affecting iron status and its consequences on human health.

Iron is essential for many biological processes, but iron levels must be tightly regulated to avoid harmful effects of both iron deficiency and overload. Here, we perform genome-wide association studies on four iron-related biomarkers (serum iron, serum ferritin, transferrin saturation, total iron-binding capacity) in the Trøndelag Health Study (HUNT), the Michigan Genomics Initiative (MGI), and the SardiNIA study, followed by their meta-analysis with publicly available summary statistics, analyzing up to 257,953 individuals. We identify 123 genetic loci associated with iron traits. Among 19 novel protein-altering variants, we observe a rare missense variant (rs367731784) in HUNT, which suggests a role for DNAJC13 in transferrin recycling. We further validate recently published results using genetic risk scores for each biomarker in HUNT (6% variance in serum iron explained) and present linear and non-linear Mendelian randomization analyses of the traits on all-cause mortality. We find evidence of a harmful effect of increased serum iron and transferrin saturation in linear analyses that estimate population-averaged effects. However, there was weak evidence of a protective effect of increasing serum iron at the very low end of its distribution. Our findings contribute to our understanding of the genes affecting iron status and its consequences on human health.

Background A feasible and accurate risk prediction systems for emergency department (ED) patients is urgently required. The Modified Early Warning Score (MEWS) is a wide-used tool to predict clinical outcomes in ED. Literatures showed that machine learning (ML) had better predictability in specific patient population than traditional scoring system. By analyzing a large multicenter dataset, we aim to develop a ML model to predict in-hospital morality of the adult non traumatic ED patients for different time stages, and comparing performance with other ML models and MEWS. Methods A retrospective observational cohort study was conducted in five Taiwan EDs including two tertiary medical centers and three regional hospitals. All consecutively adult (>17 years old) non-traumatic patients admit to ED during a 9-year period (January first, 2008 to December 31th, 2016) were included. Exclusion criteria including patients with (1) out-of-hospital cardiac arrest and (2) discharge against medical advice and transferred to other hospital (3) missing collect variables. The primary outcome was in-hospital mortality and were categorized into 6, 24, 72, 168 hours mortality. MEWS was calculated by systolic blood pressure, pulse rate, respiratory rate, body temperature, and level of consciousness. An ensemble supervised stacking ML model was developed and compared to sensitive and unsensitive Xgboost, Random Forest, and Adaboost. We conducted a performance test and examine both the area under the receiver operating characteristic (AUROC) and the area under the precision and recall curve (AUPRC) as the comparative measures. Result After excluding 182,001 visits (7.46%), study group was consisted of 24,37,326 ED visits. The dataset was split into 67% training data and 33% test data for ML model development. There was no statistically difference found in the characteristics between two groups. For the prediction of 6, 24, 72, 168 hours in-hospital mortality, the AUROC of MEW and ML mode was 0.897, 0.865, 0.841, 0.816 and 0.939, 0.928, 0.913, 0.902 respectively. The stacking ML model outperform other ML model as well. For the prediction of in-hospital mortality over 48-hours, AUPRC performance of MEWS drop below 0.1, while the AUPRC of ML mode was 0.317 in 6 hours and 0.2150 in 168 hours. For each time frame, ML model achieved statistically significant higher AUROC and AUPRC than MEWS (all P P 3, >4, and >5) were determined as baselines for comparison, ML mode consistently showed improved or equally performance in sensitivity, PPV, NPV, but not in specific. Conclusion Stacking ML methods improve predicted in-hospital mortality than MEWS in adult non-traumatic ED patients, especially in the prediction of delayed mortality.

Microenvironmental factors including physical and chemical cues can regulate stem cells as well as terminally differentiated cells to modulate their biological function and differentiation. However, one of the physical cues, the substrate's dimensionality, has not been studied extensively. In this study, the flow-focusing method with a microfluidic device was used to generate gelatin bubbles to fabricate highly ordered three-dimensional (3D) scaffolds. Rat H9c2 myoblasts were seeded into the 3D gelatin bubble-based scaffolds and compared to those grown on 2D gelatin-coating substrates to demonstrate the influences of spatial cues on cell behaviors. Relative to cells on the 2D substrates, the H9c2 myoblasts were featured by a good survival and normal mitochondrial activity but slower cell proliferation within the 3D scaffolds. The cortical actin filaments of H9c2 cells were localized close to the cell membrane when cultured on the 2D substrates, while the F-actins distributed uniformly and occupied most of the cell cytoplasm within the 3D scaffolds. H9c2 myoblasts fused as multinuclear myotubes within the 3D scaffolds without any induction but cells cultured on the 2D substrates had a relatively lower fusion index even differentiation medium was provided. Although there was no difference in actin α 1 and myosin heavy chain 1, H9c2 cells had a higher myogenin messenger RNA level in the 3D scaffolds than those of on the 2D substrates. This study reveals that the dimensionality influences differentiation and fusion of myoblasts.

Background: Intensive care unit (ICU) admission following a short-term emergency department (ED) revisit has been considered a particularly undesirable outcome among return-visit patients, although their in-hospital prognosis has not been discussed. We aimed to compare clinical outcomes between adult patients admitted to the ICU after unscheduled ED revisits and those admitted during index ED visits. Method: This retrospective study was conducted at two tertiary medical centers in Taiwan from 1 January 2016 to 31 December 2017. All adult non-trauma patients admitted to the ICU directly via the ED during the study period were included and divided into two comparison groups: patients admitted to the ICU during index ED visits and those admitted to the ICU during return ED visits. The outcomes of interest included in-hospital mortality, mechanical ventilation (MV) support, profound shock, hospital length of stay (HLOS), and total medical cost. Results: Altogether, 12,075 patients with a mean (standard deviation) age of 64.6 (15.7) years were included. Among these, 5.3% were admitted to the ICU following a return ED visit within 14 days and 3.1% were admitted following a return ED visit within 7 days. After adjusting for confounding factors for multivariate regression analysis, ICU admission following an ED revisit within 14 days was not associated with an increased mortality rate (adjusted odds ratio (aOR): 1.08, 95% confidence interval (CI): 0.89 to 1.32), MV support (aOR: 1.06, 95% CI: 0.89 to 1.26), profound shock (aOR: 0.99, 95% CI: 0.84 to 1.18), prolonged HLOS (difference: 0.04 days, 95% CI: −1.02 to 1.09), and increased total medical cost (difference: USD 361, 95% CI: −303 to 1025). Similar results were observed after the regression analysis in patients that had a 7-day return visit. Conclusion: ICU admission following a return ED visit was not associated with major in-hospital outcomes including mortality, MV support, shock, increased HLOS, or medical cost. Although ICU admissions following ED revisits are considered serious adverse events, they may not indicate poor prognosis in ED practice.

The outbreak of the new coronavirus disease 2019 (COVID-19) has notably affected the medical system worldwide and influenced the health-seeking behavior of people while depleting medical resources, causing a delay in ST-elevation myocardial infarction (STEMI) management In this single-center, retrospective cohort study, we compared the clinical pictures of nontransfer patients who presented to the emergency department directly and received primary percutaneous cardiovascular intervention (PPCI) from February 1 to April 30, 2020 (group 2, N = 28), with patients who received PPCI from February 1 to April 30, 2016–2019 (group 1, N = 130) A total of 158 patients with STEMI who received PPCI were included in the study A decrease in the percentage of patients with door-to-balloon time

In human bodies, cartilage tissue lacks the ability to heal when it encounters trauma or lesions. This inability of cartilage tissue to self-repair motivates all sorts of studies on autologous chondrocyte transplantation; however, the drawback of high chondrocyte concentration is hard to overcome due to the loss of differentiated chondrocyte phenotype during cell culture. The differentiation of stem cells into chondrocytes is a possible solution to provide a large number of differentiated chondrocytes. In this study, human adipose-derived stem cells (hASCs) have been chosen as a model for further differentiation into chondrocytes. Studies on the influence of porous biomaterials on cell behavior have been performed to determine the best conditions for stem cell differentiation. Among these conditions, bubble or pore size is a factor that is commonly discussed. In our study, we fabricated four gelatin microbubble scaffolds with different pore sizes, but uniform spherical shapes by microfluidic techniques. Then, we compared the influence of pore size on cell growth and differentiation. Previously, we have examined adipogenesis and osteogenesis of hASCs in this scaffold. In this study, we focused on the influence of pore size on chondrogenesis. According to the experimental results of immunofluorescence staining, GAG content, and qPCR, the largest pore size, which is 200 μm in diameter, shows the best chondrogenesis result.

Objective. By analyzing closed criminal malpractice claims involving resident physicians, we aimed to clarify the characteristics of litigations and examine the litigious errors leading to guilty verdicts. Design. A retrospective descriptive study. Setting/Study Participants. The verdicts pertaining to physicians recorded on the national database of the Taiwan justice system were reviewed. Main Outcome Measures. The characteristics of litigations were documented. Negligence and guilty verdicts were further analyzed to identify litigious errors. Results. Between January 1, 2000, and December 31, 2014, from a total of 436 closed criminal malpractice cases, 40 included resident physicians. Five (12.5%) cases received guilty verdicts with mean imprisonment sentences of 5.4 ± 4.1 months. An average of 77.2 months was required for the final adjudication, and surgery residents were involved most frequently (38.9%). Attending physicians were codefendants in 82.5% of cases and were declared guilty in 60% of them. Sepsis (37.5%) was the most common disease in the 40 cases examined, followed by operation/procedure complications (25%). Performance errors (70%) were more than twice as common than diagnostic errors (30%), but the percentage of guilty verdicts in performance error cases was much lower (7.1% vs. 25%). Four negligence cases received nonguilty verdicts, which were mostly due to lack of causation. Conclusion. Closed criminal malpractice cases involving residents took on average 6.22 years to conclude. Performance errors accounted for 70% of cases, with treatment of sepsis and operation/procedure complications predominant. To reduce medicolegal risk, residents should learn experiences from analyzing malpractice cases to avoid similar litigious pitfalls.

In patients experiencing out-of-hospital cardiac arrest (OHCA), hypotension is common after return of spontaneous circulation (ROSC). Both dopamine and norepinephrine are recommended as inotropic therapeutic agents. This study aimed to determine the impact of the use of these two medications on hypotension. This is a multicenter retrospective cohort study. OHCA patients with ROSC were divided into three groups according to the post resuscitation inotropic agent used for treatment in the emergency department, namely, dopamine, norepinephrine, and dopamine and norepinephrine combined therapy. Thirty-day survival and favorable neurologic performance were analyzed among the three study groups. The 30-day survival and favorable neurologic performance rates in the three study groups were 12.5%, 13.0%, and 6.8% as well as 4.9%, 4.3%, and 1.2%, respectively. On controlling the potential confounding factors by logistic regression, there was no difference between dopamine and norepinephrine treatment in survival and neurologic performance (adjusted odds ratio (aOR): 1.0, 95% confidence interval (CI) 0.48–2.06; aOR: 0.8, 95% CI: 0.28–2.53). The dopamine and norepinephrine combined treatment group had worse outcome (aOR: 0.6, 95% CI: 0.35–1.18; aOR: 0.2, 95% CI: 0.05–0.89). In conclusion, there was no significant difference in post-ROSC hypotension treatment between dopamine and norepinephrine in 30-day survival and favorable neurologic performance rates.

This study aimed to clarify the association between the crowding and clinical practice in the emergency department (ED).This 1-year retrospective cohort study conducted in two EDs in Taiwan included 70,222 adult non-trauma visits during the day shift between July 1, 2011, and June 30, 2012. The ED occupancy status, determined by the number of patients staying during their time of visit, was used to measure crowding, grouped into four quartiles, and analyzed in reference to the clinical practice. The clinical practices included decision-making time, patient length of stay, patient disposition, and use of laboratory examinations and computed tomography (CT).The four quartiles of occupancy statuses determined by the number of patients staying during their time of visit were24, 24-39, 39-62, and62. Comparing62 and24 ED occupancy statuses, the physicians' decision-making time and patients' length of stay increased by 0.3h and 1.1h, respectively. The percentage of patients discharged from the ED decreased by 15.5% as the ED observation, general ward, and intensive care unit admissions increased by 10.9%, 4%, and 0.7%, respectively. CT and laboratory examination slightly increased in the fourth quartile of ED occupancy.Overcrowding in the ED might increase physicians' decision-making time and patients' length of stay, and more patients could be admitted to observation units or an inpatient department. The use of CT and laboratory examinations would also increase. All of these could lead more patients to stay in the ED.

Objective To examine the epidemiologic data, identify the pattern of dispute, and determine clinical litigious errors by analyzing closed malpractice claims involving myocardial infarction (MI) in Taiwanese courts. Methods A retrospective descriptive study was performed to analyze the verdicts pertaining to MI from the population-based database of the Taiwan judicial system between 2002 and 2013. The results of adjudication, involved specialists, primary dispute leading to lawsuits, and litigious errors were recorded. Results A total of 36 closed malpractice claims involving MI were included. The mean interval between the incident and litigation closure was 65.5 ± 28.3 months. Nearly 20% of the cases were judged against clinicians and the mean payment was $100639 ± 49617, while the mean imprisonment sentence was 4.3 ± 1.8 months. Cardiologists and emergency physicians were involved in 56.3% of cases, but won 92.6% of lawsuits, while other specialists lost nearly 25% of lawsuits. The most common dispute was misdiagnosis (38.9%), but this dispute had the lowest percentage of loss (7.1%). Disputes regarding delayed diagnosis were judged against the defendants in 50% of claims. Clinicians lost the lawsuit in the following conditions: 1) misdiagnosis of MI in patients with typical chest pain and known coronary artery risk factors; 2) failure to perform thoughtful evaluation and series investigations in patients suspicious of ischemic heart disease; 3) failure to perform indicated treatment to avoid disease progression. Conclusions Medical practitioners should keep a high index of MI suspicion, especially if the diagnosis and treatment of MI are beyond their daily practice. Prudent patient reevaluation, serial ECG and cardiac enzyme testing, and early consultation are suggested to reduce malpractice liability.

Introduction The purpose of this study was to describe the demographic characteristics and prognosis of children admitted to the intensive care unit (ICU) after a pediatric emergency department (PED) return visit within 72 h. Method We conducted this retrospective study from 2010 to 2016 in the PED of a tertiary medical center in Taiwan and included patients under the age of 18 years old admitted to the ICU after a PED return visit within 72 h. Clinical characteristics were collected to perform demographic analysis. Pediatric patients who were admitted to the ICU on an initial visit were also enrolled as a comparison group for outcome analysis, including mortality, ventilator use, and length of hospital stay. Results We included a total of 136 patients in this study. Their mean age was 3.3 years old, 65.4% were male, and 36.0% had Chronic Health Condition (CHC). Disease-related return (73.5%) was by far the most common reason for return. Compared to those admitted on an initial PED visit, clinical characteristics, including vital signs at triage and laboratory tests on return visit with ICU admission, demonstrated no significant differences. Regarding prognosis, ICU admission on return visit has a higher likelihood of ventilator use (aOR:2.117, 95%CI 1.021~4.387), but was not associated with increased mortality (aOR:0.658, 95%CI 0.150~2.882) or LOHS (OR:-1.853, 95%CI -4.045~0.339). Conclusion Patients who were admitted to the ICU on return PED visits were associated with an increased risk of ventilator use but not mortality or LOHS compared to those admitted on an initial visit.

Background Feedback is an essential part of clinical teaching and learning, yet it is often perceived as unsatisfactory in busy clinical settings. Clinical teachers need to balance the competing demands of clinical duty and feedback provision. The influence of the clinical environment and the mutual relationship between feedback giving and seeking has been inadequately investigated. This study therefore aimed to quantify the adequacy, perceptions, and influential factors of feedback provision during resident training in emergency departments (EDs). Methods A multicenter online questionnaire study was undertaken. The respondents comprised ED residents and clinical teachers from four teaching hospitals in Taiwan. The questionnaire was developed via an expert panel, and a pilot study ensured validity. Ninety clinical teachers and 54 residents participated. Results The respondents reported that the majority of feedback, which usually lasted 1–5 min, was initiated by the clinical teachers. Feedback satisfaction was significantly lower for the clinical teachers than for the residents (clinical teachers M = 13.8, SD = 1.83; residents M = 15.3, SD = 2.14; p

This study aimed to examine the association between air pollution and out-of-hospital cardiac arrest (OHCA), and the effects of underlying diseases. Between January 2015 and December 2016, data on particulate matter (PM)2.5 and other air pollutants in Kaohsiung City were collected, and an emergency medical service database was used for information on patients who experienced OHCA. Overall, 3566 patients were analyzed and subgroup analyses by sex, age, and preexisting morbidities were performed. Interquartile increments in PM2.5, PM10, and O3 levels on lag 1 and NO2 level on lag 3 were associated with increments of 10.8%, 11.3%, 6.2%, and 1.7% in OHCA incidence, respectively. Subgroup analyses showed that patients with diabetes (1.363; interaction p = 0.009), heart disease (1.612; interaction p = 0.001), and advanced age (≥70 years, 1.297; interaction p = 0.003) were more susceptible to NO2 on lag 3. Moreover, patients were more susceptible to O3 during the cold season (1.194; interaction p = 0.001). We found that PM2.5, PM10, NO2, and O3 may play an important role in OHCA events, and the effects vary by underlying condition, age and season.

English translation of Questionnaire. (DOCX 44 kb)

Most medical malpractice in Taiwan leads to criminal prosecution. This study examined the epidemiologic factors and clinical errors that led to medical malpractice convictions in Taiwanese criminal prosecutions. A retrospective, 15-year population-based review of criminal Supreme Court judgments pertaining to medical malpractice against physicians and nurses was conducted. Eighty-four cases were reviewed, yielding data that included the number and specialty involved, accused hospitals, the diagnosis, the time interval between incidents to closure, result of adjudication, the origin of cases (private vs. public prosecution), the result of medical appraisal, and the primary error. Overall, the cases averaged 7.6years to achieve final adjudication. Seventy-five percent were settled in favor of the clinician; twenty-three physicians and three nurses were found guilty, but all of these avoided imprisonment via probation or replacement with forfeit. The single most risky specialty was emergency medicine (22.6% of the cases), with 36.8% of those resulting in guilty verdicts. The most common diagnosis groups were infectious diseases (23.8%), intracranial hemorrhages (10.7%), and acute coronary syndrome (9.5%). Public prosecutions had a 41.2% conviction rate; no guilty verdicts resulted from private prosecution. Nineteen (22.6%) cases were commuted, and 73.7% of those had a controversial appraisal result. The characteristics of criminal malpractice prosecution in Taiwan that could be improved to relieve the stress of frivolous lawsuits on the judicial process include lengthy jurisdiction process; low public-prosecution conviction rate; frequent commuted jurisdiction related to a controversial appraisal; and zero imprisonment rate for clinicians.

Background Subarachnoid hemorrhage (SAH) is a serious cause of headaches. The Ottawa subarachnoid hemorrhage (OSAH) rule helps identify SAH in patients with acute nontraumatic headache with high sensitivity, but provides limited information for identifying other intracranial pathology (ICP). Objectives To assess the performance of the OSAH rule in emergency department (ED) headache patients and evaluate its impact on the diagnosis of intracranial hemorrhage (ICH) and other ICP. Method We conducted a retrospective cohort study from January 2016 to March 2017. Patients with acute headache with onset within 14 days of the ED visit, were included. We excluded patients with head trauma that occurred in the previous 7 days, new onset of abnormal neurologic findings, or consciousness disturbance. According to the OSAH rule, patients with any included predictors required further investigation. Results Of 913 patients were included, 15 of them were diagnosed with SAH. The OSAH rule had 100% (95% CI, 78.2%–100%) sensitivity and 37.0% (95% CI, 33.8–40.2%) specificity for identifying SAH. Twenty-two cases were identified as SAH or ICH with 100% sensitivity (95% CI, 84.6%–100%) and 37.3% (95% CI, 34.1%–40.5%) specificity. As for non-hemorrhagic ICP, both the sensitivity and negative predictive values (NPV) decreased to 75.0% (95% CI, 53.3%–90.2%) and 98.2% (95% CI, 96.1%–99.3%), respectively. Conclusions The OSAH rule had 100% sensitivity and NPV for diagnosing SAH and ICH with acute headache. The sensitivity and specificity were lower for non-hemorrhagic ICP. The OSAH rule may be an effective tool to exclude acute ICH and SAH in our setting.

Diabetes induces neurovascular dysfunction leading to peripheral neuropathy. MicroRNAs (miRNAs) affect many biological processes and the development of diabetic peripheral neuropathy. In the present study, we investigated whether thymosin-β4 (Tβ4) ameliorates diabetic peripheral neuropathy and whether miR-146a mediates the effect of Tβ4 on improved neurovascular function. Male Type II diabetic BKS. Cg-m+/+Leprdb/J (db/db) mice at age 20 weeks were treated with Tβ4 for 8 consecutive weeks, and db/db mice treated with saline were used as a control group. Compared to non-diabetic mice, diabetic mice exhibited substantially reduced miR-146a expression, and increased IL-1R-associated kinase-1 (IRAK1), tumor necrosis factor (TNFR)-associated factor 6 (TRAF6) levels and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) activity in sciatic nerve tissues. Treatment of diabetic mice with Tβ4 significantly elevated miR-146a levels and overcame the effect of diabetes on these proteins. Tβ4 treatment substantially improved motor and sensory conduction velocity of the sciatic nerve, which was associated with improvements in sensory function. Tβ4 treatment significantly increased intraepidermal nerve fiber density and augmented local blood flow and the density of fluorescein isothiocyanate (FITC)-dextran perfused vessels in the sciatic nerve tissue. In vitro, treatment of dorsal root ganglion (DRG) neurons and mouse dermal endothelial cells (MDEs) with Tβ4 significantly increased axonal outgrowth and capillary-like tube formation, whereas blocking miR-146a attenuated Tβ4-induced axonal outgrowth and capillary tube formation, respectively. Our data indicate that miR-146a may mediate Tβ4-induced neurovascular remodeling in diabetic mice, by suppressing pro-inflammatory signals.

Background The unpredictable nature of patient visits poses considerable challenges to the staffing of emergency department (ED) medical personnel. There is a lack of common physician usage parameters at present. Objective The aim of this study was to quantify the ED traffic intensity of patients and physicians using a queueing model approach. Methods A retrospective administrative electronic data analysis was conducted in a tertiary medical center. All patients who registered at the ED in 2013 were included. Precisely recorded patient waiting time, service time, and disposition time were obtained. An M/M/s (Markovian patient arrival, Markovian patient service, s servers) queueing model was used, while taking account of the actual physician number and number of patients managed simultaneously. Physician utilization and performance indicators were measured. Results A total of 148,581 patients were analyzed after exclusion. The overall mean waiting time, service time, and disposition time were 0.23 (standard deviation [SD] = 0.24), 2.31 (SD = 3.89), and 2.54 (SD = 3.90) hours, respectively. Hourly physician utilization (ρ), stratified by different patient entities, was ρ = 0.75 ± 0.17 for adult non-trauma, ρ = 0.75 ± 0.28 for pediatric, and ρ = 0.53 ± 0.18 for trauma (p = 0.0004). There was a surge of utility for pediatric non-trauma patients in the late evening (ρ = 1.4 at 11 pm ). The distribution of number of patients in the system was derived and compared by different patient entities and time points. Conclusions A queueing model was built to model traffic intensity of physicians and patients, the physician utility trend disclosed the fluctuation of manpower utility. The estimated parameters serve as important factors for developing tailored staffing policies for minimizing ED waiting and improving ED crowding.

Objective To examine the epidemiologic data of closed medical claims from Taiwanese civil courts against obstetric departments and identify high-risk diseases. Design A retrospective descriptive study. Setting/study participants The verdicts from the national database of the Taiwan judicial system that pertained to obstetric departments were reviewed. Between 2003 and 2012, a total of 79 closed medical claims were included. Main outcome measures The epidemiologic data of litigations including the results of adjudication and the disease and outcome of the alleged injury. Results A majority of the disputes (65.9%) were fetus-related. Four disease categories accounted for 78.5% of all claims including (i) perinatal maternal complications (25.3%); (ii) errors in antenatal screening or ultrasound diagnoses (21.5%); (iii) fetal hypoxemic-ischemia encephalopathy (16.5%); and (iv) brachial plexus injury (15.2%). Six cases (7.6%) resulted in an indemnity payment with a mean amount of $109 205. Fifty-one cases (64.6%) were closed in the district court. The mean incident-to-litigation closure time was 52.9 ± 29.3 months. All cases with indemnity payments were deemed negligent or were at least determined to be controversial by a medical appraisal, while all defendants whose care was judged as appropriate by a medical appraisal won their lawsuits. Conclusions Almost 93% of clinicians win their cases but spend 4.5 years waiting for final adjudication. The court ruled against the clinician only if there was no appropriate response during a complication or if there was no follow-up or further testing for potential critical diseases.

The purpose of this study was to investigate the prevalence of do-not-resuscitate (DNR) orders and to identify relevant factors influencing the DNR decision-making process by patients' surrogates in the emergency department (ED).A prospective, descriptive, and correlational research design was adopted. A total of 200 surrogates of cancer or non-cancer terminal patients, regardless of whether they signed a DNR order, were recruited as subjects after physicians of the emergency department explained the patient's conditions, advised on withholding medical treatment, and provided information on palliative care to all surrogates.Of the 200 surrogates, 23 % signed a DNR order for the patients. The demographic characteristics of patients and surrogates, the level of understanding of DNR orders, and factors of the DNR decision had no significant influence on the DNR decision. However, greater severity of disease (odds ratio (OR) = 1.38; 95 % confidence interval (CI) = 0.95-1.74), physician's initiative in discussing with the families (OR = 1.42; 95 % CI = 1.21-1.84), and longer length of hospital stay (OR = 1.06; 95 % CI = 1.03-1.08) were contributing factors affecting patient surrogates' DNR decisions.The findings of this study indicated that surrogates of patients who were more severe in disease condition, whose physicians initiated the discussion of palliative care, and who stayed longer in hospital were important factors affecting the surrogates' DNR decision-making. Therefore, early initiation of DNR discussions is suggested to improve end-of-life care.

Background Emergency Department (ED) overcrowding is a worldwide problem, and it might be caused by prolonged patient stay in the ED. This study tried to analyze if different practice models influence patient flow in the ED. Materials and methods A retrospective, 1-year cohort study was conducted across two EDs in the largest healthcare system in Taiwan. A total of 37,580 adult non-trauma patients were involved in the study. The clinical practice between two ED practice models was compared. In one model, urgent and non-urgent patients were treated by different emergency physicians (EPs) separately (separated model). In the other, EPs treated all patients assigned randomly (merged model). The ED length of stay (LOS), diagnostic tool use (including laboratory examinations and computed tomography scans), and patient dispositions (including discharge, general ward admission, intensive care unit (ICU) admissions, and ED mortality) were selected as outcome indicators. Result Patients discharged from ED had 0.4 h shorter ED LOS in the separated model than in merged model. After adjusting for the potential confounding factors through regression model, there was no difference of patient disposition of the two practice models. However, the separated model showed a slight decrease in laboratory examination use (adjusted odds ratio, 0.9; 95% confidence interval, 0.83–0.96) compared with the merged model. Conclusion The separated model had better patient flow than the merged model did. It decreased the ED LOS in ED discharge patients and laboratory examination use.

Background. This study evaluated the impact on clinical outcomes using a cloud computing system to reduce percutaneous coronary intervention hospital door-to-balloon (DTB) time for ST segment elevation myocardial infarction (STEMI). Methods. A total of 369 patients before and after implementation of the transfer protocol were enrolled. Of these patients, 262 were transferred through protocol while the other 107 patients were transferred through the traditional referral process. Results. There were no significant differences in DTB time, pain to door of STEMI receiving center arrival time, and pain to balloon time between the two groups. Pain to electrocardiography time in patients with Killip I/II and catheterization laboratory to balloon time in patients with Killip III/IV were significantly reduced in transferred through protocol group compared to in traditional referral process group (both p<0.05). There were also no remarkable differences in the complication rate and 30-day mortality between two groups. The multivariate analysis revealed that the independent predictors of 30-day mortality were elderly patients, advanced Killip score, and higher level of troponin-I. Conclusions. This study showed that patients transferred through our present protocol could reduce pain to electrocardiography and catheterization laboratory to balloon time in Killip I/II and III/IV patients separately. However, this study showed that using a cloud computing system in our present protocol did not reduce DTB time.