Burnout among Japanese emergency medicine physicians: A multicentric questionnaire study.

Objective: Burnout negatively affects the wellness and performance of emergency physicians (EPs). This study aimed to clarify the actual prevalence of burnout and its associated factors among Japanese EPs. Methods: We conducted a cross-sectional questionnaire study of selected 27 Japanese emergency departments (EDs). We examined the Maslach Burnout Inventory-Human Services Survey score and its associations with ED-level- and EP-level factors in a multivariable analysis. Results: A total of 267 EPs (81.9%) completed survey. Of these, 43 EPs (16.1%) scored severe emotional exhaustion (EE), 53 (19.8%) scored severe depersonalization (DP), and 179 (67.0%) scored severe personal accomplishment (PA), and 24 (8.9%) scored severely in all three domains. In our multivariable analysis, emergency medical service centers were associated with severe PA scores (odds ratio [OR], 10.56; 95% confidence interval [CI], 1.78-62.66; p = 0.009). A 3 to 6 hour-sleep period was associated with severe EE scores (OR, 2.04; 95% CI, 1.04-3.98; p = 0.036), and EPs in their 20s were associated with severe DP scores (OR, 7.37; 95% CI, 1.41-38.38; p = 0.018). Conclusion: Our results suggest that 8.9% of Japanese EPs are in higher degrees of burnout. In particular, Japanese EPs scored more severely on PA. To avoid burnout in Japanese EPs, it is important to improve the working environment by ensuring more than 6 h of sleep, providing more support for young EPs, and taking effective action to combat low EP self-esteem.

Exposure to PM2.5 and Lung Function Growth in Pre- and Early-Adolescent Schoolchildren: A Longitudinal Study Involving Repeated Lung Function Measurements in Japan.

Rationale: Epidemiological evidence indicates that ambient exposure to particulate matter ⩽2.5 µm in aerodynamic diameter (PM2.5) has adverse effects on lung function growth in children, but it is not actually clear whether exposure to low-level PM2.5 results in long-term decrements in lung function growth in pre- to early-adolescent schoolchildren. Objectives: To examine long-term effects of PM2.5 within the 4-year average concentration range of 10-19 µg/m3 on lung function growth with repeated measurements of lung function tests. Methods: Longitudinal analysis of 6,233 lung function measurements in 1,466 participants aged 8-12 years from 16 school communities in 10 cities around Japan, covering a broad area of the country to represent concentration ranges of PM2.5, was done with a multilevel linear regression model. Forced expiratory volume in 1 second, forced vital capacity (FVC), and maximal expiratory flow at 50% of FVC were used as lung function indicators to examine the effects of 10-µg/m3 increases in the PM2.5 concentration on relative growth per each 10-cm increase in height. Results: The overall annual mean PM2.5 level was 13.5 µg/m3 (range, 10.4-19.0 µg/m3). We found no association between any of the lung function growth indicators and increases in PM2.5 levels in children of either sex, even after controlling for potential confounders. Analysis with two-pollutant models with O3 or NO2 did not change the null results. Conclusions: This nationwide longitudinal study suggests that concurrent, long-term exposure to PM2.5 at concentrations ranging from 10.4 to 19.0 µg/m3 has little effect on lung function growth in preadolescent boys or pre- to early-adolescent girls.

Methylxanthine use for acute asthma in the emergency department in Japan: a multicenter observational study.

AIM: Methylxanthines are no longer recommended for emergency department (ED) patients with acute asthma according to international guidelines. We aimed to describe the current methylxanthine use for acute asthma and to determine factors related to its use in the ED. METHODS: We undertook a multicenter retrospective study in 23 EDs across Japan. From each participating hospital, we randomly identified 60 ED patients aged 18-54 years with acute asthma from 2009 through 2011. We examined the associations of ED and patient characteristics with methylxanthine use by constructing a multivariable logistic regression model adjusting for a predefined set of ED- and patient-level factors. RESULTS: Among 1,380 patients, methylxanthines were used for 79 patients (5.7%, 95% confidence interval [CI], 4.6-7.0%). The proportion of methylxanthine treatment varied substantially among EDs, ranging from 0% to 26.1%. In the multivariable analysis, the number of annual ED patients with acute asthma (odds ratio [OR] per 100 increase in annual asthma patients, 0.12; 95% CI, 0.04-0.34; P < 0.001) and having a protocol for asthma treatment (OR 2.91; 95% CI, 1.06-8.00; P = 0.04) at the ED level, and systemic corticosteroid use (OR 6.39; 95% CI, 3.34-12.22; P < 0.001) at the patient level were associated with likelihood of methylxanthine use. CONCLUSIONS: In this multicenter study, approximately 6% of ED patients with acute asthma were treated with methylxanthines, with a wide variation across EDs. The number of annual ED patients with acute asthma was significantly associated with a lower likelihood of methylxanthine use, whereas having an ED asthma treatment protocol and systemic corticosteroid use in the ED were associated with a higher likelihood of methylxanthine treatment.

Bacterial Memory of Persisters: Bacterial Persister Cells Can Retain Their Phenotype for Days or Weeks After Withdrawal From Colony-Biofilm Culture.

Persister cells, or persisters, are a specific subpopulation of bacterial cells that have acquired temporary antibiotic-resistant phenotypes. In this study, we showed that Escherichia coli produces many more persister cells in colony-biofilm culture than in the usual liquid culture and that these persisters can be maintained in higher numbers than those from liquid culture for up to 4 weeks at 37°C in a fresh, nutrient-rich, antibiotic-containing medium, even after complete withdrawal from the colony-biofilm culture. This suggests the presence of a long-retention effect, or "memory effect", in the persister cell state of E. coli cells. We also discovered that such increases in persisters during colony-biofilm culture and their memory effects are common, to a greater or lesser degree, in other bacterial species. This is true not only for gram-negative bacteria (Acinetobacter and Salmonella) but also for gram-positive bacteria (Staphylococcus and Bacillus). This is the first report to suggest the presence of a common memory mechanism for the persister cell state, which is inscribed during colony-biofilm culture, in a wide variety of bacteria.

[A CASE OF ANAPHYLAXIS IN THE PEDIATRIC PATIENT WITH MILK ALLERGY DUE TO TRACES OF MILK PROTEIN IN THE LACTOSE USED AS AN EXCIPIENT OF INAVIR INHALATION].

The patient was a 6-year-old female with milk allergy and persistent asthma. She experienced anaphylactic reactions just after the inhalation of Inavir (Laninamivir Octanoate Hydrate) to treat flu infection. A skin-prick test showed positive reactions for Inavir inhaler powder and lactose used as an excipient but negative for Laninamivir. Same results were obtained in a drug-stimulated basophil activation test. The lactose excipient in Inavir inhaler powder was supposed to contain milk proteins, which caused anaphylactic reactions. To test this possibility, we examined the contamination of allergic milk proteins in the lactose excipient and found the smear band by silver staining, which was identified as ß-lactoglobulin (ß-LG) by Western blotting using specific monoclonal antibody and patient's sera. The ß-LG in Inavir was supposed to be glycosylated with lactose because the molecular weight was slightly higher than ß-LG standard reference as seen in mobility. In fact, the incubation with lactose in vitro tended to increase molecular weight. Following these results, we herein report that the trace amounts of ß-LG contaminated in the lactose excipient of Inavir could cause immediate allergic reactions. The risk that the lactose-containing dry powder inhalers cause allergic reactions for patients with cow's milk allergy need to be reminded. In particular, the use for flu patients should be paid careful attention because of increased airway hypersensitivity in those patients.

Utility of blood lactate level in triage.

Aim: Simple Triage and Rapid Treatment (START) is commonly used at disaster scenes. The Canadian Emergency Department Triage and Acuity Scale (CTAS) is used in urban and rural emergency departments (ED). However, triage is not always accurate or appropriate. The blood lactate level (BLL) is a major biomarker of physical status. We measured BLL using the Lactate Pro-1710 Test Meter in all patients transported to our ED and assessed their correlation with the triage level determined using START and the CTAS. Methods: This retrospective study included 510 patients admitted to our ED between January 2011 and July 2012 whose BLL was measured. The patients were classified into triage divisions (green, yellow, red, and black) according to vital signs and chief complaints, and correlations among BLL, triage level, and prognosis were assessed in all groups. Results: Of the total, 62 patients had cardiopulmonary arrest (CPA), 262 had internal pathologies, and 186 had external pathologies. Significant correlations were observed between BLL and both START and CTAS triage. Also BLL was significantly higher in severe patients categorized with START and CTAS (P < 0.0001), especially in the death group when the patients were divided into two groups according to prognosis (P < 0.0001). Two patients categorized yellow with START died during the hospitalization, however BLL of these two patients were high on admission at the ED. Conclusion: BLL could be used to correct the triage level, and decide the priority of treatment and transportation even within the same triage level, thereby avoiding under-triage.

[A MULTICENTER STUDY ON CHILDHOOD ALLERGIC RHINITIS TREATMENT IN THE TOHOKU REGION].

BACKGROUND: We performed a multicenter study in order to clarify the present conditions of the childhood allergic rhinitis treatment in many departments of otorhinolaryngology and pediatrics/internal medicine in the Tohoku region, northern Japan. METHODS: We performed a questionnaire survey about patient backgrounds, nasal symptoms, QOL disturbance, and treatment agents, for childhood allergic rhinitis patients under age 12. RESULTS: The total number of cases was 814, the mean age of the patients seen in pediatrics/internal medicine departments was significantly lower than that in otorhinolaryngology. The merger rate of bronchial asthma of the patients seen in pediatrics/internal medicine was significantly higher, and nasal symptoms and QOL disturbance of the patients seen in otorhinolaryngology were significantly more severe. For therapeutic agents, antihistamines were most prescribed, and the combination of LT receptor antagonist and intranasal steroids was used for the cases in which nasal symptoms were severe. The nasal symptoms in the combination group were significantly improved compared with the antihistamine monotherapy group. CONCLUSION: It was indicated that the combination therapy was useful in the severe cases of childhood allergic rhinitis.

Benefit profile of recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.

INTRODUCTION: The safety and efficacy of recombinant human soluble thrombomodulin (rhTM) have been demonstrated, with promising evidence suggestive of efficacy for patients with severe sepsis involving coagulopathy in a phase IIb randomized controlled trial. However, the benefit profiles of rhTM have not been elucidated. The purpose of this study was to explore whether patients with greater disease severity, determined according to the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores, would experience treatment benefit from rhTM administration. METHODS: This was a post hoc, subgroup analysis of a multicenter retrospective cohort study conducted in three Japanese tertiary referral hospitals. Patients with sepsis-induced disseminated intravascular coagulation (DIC) who required ventilator management were included. We stratified patients into several strata according to disease severity, determined by APACHE II and SOFA scores, using classification and regression trees for survival data. Intervention effects, expressed as hazard ratios (HR), were analyzed using Cox regression analysis adjusted for a propensity model to detect subgroup heterogeneity of the effects of rhTM on in-hospital mortality. RESULTS: Participants were 162 patients with sepsis-induced DIC; 68 of these patients received rhTM and 94 did not. After adjusting for imbalances, rhTM administration was significantly associated with reduced mortality in high-risk patients (APACHE II: 24 to 29; HR: 0.281; 95% confidence interval (CI): 0.093 to 0.850; P = 0.025). A similar nonsignificant tendency was observed in the very high-risk subset (APACHE II: ≥30; HR: 0.529; 95% CI: 0.202 to 1.387; P = 0.195) but was not evident in the moderate-risk subset of patients (APACHE II: <24; HR: 0.814; 95% CI: 0.351 to 1.884; P = 0.630). A similar tendency was observed in analysis of SOFA scores (moderate-risk subset (SOFA: <11), P = 0.368; high-risk subset (SOFA: ≥11), P = 0.042). CONCLUSIONS: Survival benefit was observed with rhTM treatment in sepsis-induced DIC and high risk of death according to baseline APACHE II and SOFA scores.

Leukocyte deformability is a novel biomarker to reflect sepsis-induced disseminated intravascular coagulation.

Aim: Sepsis-induced disseminated intravascular coagulopathy is associated with a high mortality rate. The function and deformability of polymorphonuclear leukocytes change in patients with sepsis. The goal of this study was to characterize the changes in polymorphonuclear leukocyte deformability in patients with sepsis-induced disseminated intravascular coagulopathy and to evaluate the relationship between the severity of disseminated intravascular coagulopathy and the deformability of polymorphonuclear leukocytes. Methods: Thirty-five patients with sepsis-induced disseminated intravascular coagulopathy at our department were enrolled in this study. These patients were diagnosed with severe sepsis and an acute disseminated intravascular coagulopathy score ≥ 4. Blood samples were obtained from these patients on days 1, 3, and 7. Polymorphonuclear leukocyte deformability was measured with a microchannel flow analyzer, and polymorphonuclear leukocyte activity, represented as CD11b, was measured by flow cytometry. In contrast, 14 patients who fulfilled with sepsis criteria but without complicated disseminated intravascular coagulopathy were also entered in this study. Results: In patients with sepsis-induced disseminated intravascular coagulopathy, there was a significant correlation between their Japanese Association for Acute Medicine disseminated intravascular coagulopathy score and polymorphonuclear leukocyte deformability, and CD11b expression. Polymorphonuclear leukocytes became more stiffened and CD11b expression was higher in patients with sepsis-induced disseminated intravascular coagulopathy compared to patients without the condition. Conclusion: Polymorphonuclear leukocyte deformability correlated with the severity of sepsis-induced disseminated intravascular coagulopathy and the response to treatment.

Oxidative stress and heart rate variability in patients with vertigo.

Aims: Peripheral vertigo has been reported to result from oxidative stress or autonomic nervous dysfunction. Recently, heart rate variability has been used to evaluate autonomic nervous activity. Parasympathetic nervous dysfunction is associated with peripheral vertigo; however, the relationships between vertigo, oxidative stress, and autonomic nervous activity have not been investigated. The aim of this study was to elucidate the changes in oxidative stress and autonomic nervous activity in vertigo patients compared with healthy volunteers. Methods: Oxidative stress was assessed by evaluating biological antioxidant potential and reactive oxygen metabolites, and heart rate variability was measured to evaluate autonomic nervous activity. Thirty-four patients who complained of peripheral vertigo and were treated in our emergency department between January and August 2011 were enrolled in study 1. Oxidative stress and heart rate variability were measured and compared with those of healthy volunteers (n = 23). In study 2, oxidative stress in 18 vertigo patients and heart rate variability in 41 vertigo patients were measured between January and August 2012 before and after conventional treatment of vertigo to evaluate the effect of the treatment on oxidative stress and autonomic nervous activity. Results: Reactive oxygen metabolites were higher in vertigo patients than in healthy volunteers. Parasympathetic nervous activity was lower and the sympathetic/parasympathetic nervous activity ratio (autonomic nervous activity ratio) was higher in vertigo patients than in healthy volunteers. After treatment of vertigo, reactive oxygen metabolites decreased significantly and the autonomic nervous activity ratio became similar to that observed in healthy volunteers. Conclusions: Bedside monitoring of oxidative stress and heart rate variability may be useful for the diagnosis of vertigo and evaluation of the effect of treatment.

Hospital disaster response using business impact analysis.

INTRODUCTION: The catastrophic Great East Japan Earthquake in 2011 created a crisis in a university-affiliated hospital by disrupting the water supply for 10 days. In response, this study was conducted to analyze water use and prioritize water consumption in each department of the hospital by applying a business impact analysis (BIA). Identifying the minimum amount of water necessary for continuing operations during a disaster was an additional goal. PROBLEM: Water is essential for many hospital operations and disaster-ready policies must be in place for the safety and continued care of patients. METHODS: A team of doctors, nurses, and office workers in the hospital devised a BIA questionnaire to examine all operations using water. The questionnaire included department name, operation name, suggested substitutes for water, and the estimated daily amount of water consumption. Operations were placed in one of three ranks (S, A, or B) depending on the impact on patients and the need for operational continuity. Recovery time objective (RTO), which is equivalent to the maximum tolerable period of disruption, was determined. Furthermore, the actual use of water and the efficiency of substitute methods, practiced during the water-disrupted periods, were verified in each operation. RESULTS: There were 24 activities using water in eight departments, and the estimated water consumption in the hospital was 326 (SD = 17) m³ per day: 64 (SD = 3) m³ for S (20%), 167 (SD = 8) m³ for A (51%), and 95 (SD = 5) m³ for B operations (29%). During the disruption, the hospital had about 520 m³ of available water. When the RTO was set to four days, the amount of water available would have been 130 m³ per day. During the crisis, 81% of the substitute methods were used for the S and A operations. CONCLUSION: This is the first study to identify and prioritize hospital operations necessary for the efficient continuation of medical treatment during suspension of the water supply by applying a BIA. Understanding the priority of operations and the minimum daily water requirement for each operation is important for a hospital in the event of an unexpected adverse situation, such as a major disaster.

Blunt cardiac injury with scintigraphic perfusion-metabolism mismatch.

PATIENT: A healthy 37-year-old man who bruised his chest with a steel frame developed ventricular fibrillation, pulseless ventricular tachycardia, and temporary torsade de pointes, and was resuscitated with emergency medical treatment. Thallium 201 scintigraphy 7 days later revealed a defect only in a small area of the apex, whereas 123 I-beta-methyl iodophenyl pentadecanoic acid scintigraphy showed defects in a larger area of the apex, ventricular septum, and inferior wall, indicating perfusion-metabolism mismatch. Follow-up dual myocardial scintigraphy on day 49 showed that the scintigraphic defects persisted only at a small area of the apex. CONCLUSION: Blunt external force appeared to have caused perfusion-metabolism mismatch and subsequent life-threatening arrhythmias in this patient.

Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis.

PURPOSE: Evidence of efficacy and safety of, and especially mortality related to, recombinant human thrombomodulin (rhTM) treatment for sepsis-induced disseminated intravascular coagulation (DIC) is limited. We hypothesized that patients with sepsis-induced DIC receiving treatment with rhTM would have improved mortality compared with those with similar acuity who did not. METHODS: This retrospective cohort study conducted in three tertiary referral hospitals in Japan between January 2006 and June 2011 included all patients with sepsis-induced DIC who required ventilator management. Primary endpoint was in-hospital mortality, with duration of intensive care unit treatment, changes in DIC scores and rate of bleeding complications as secondary endpoints. Regression technique was used to develop a propensity model adjusted for baseline imbalances between groups. RESULTS: Eligible were 162 patients with sepsis-induced DIC; 68 patients received rhTM and 94 did not. Patients receiving rhTM had higher severity of illness according to baseline characteristics. After adjusting for these imbalances by stratified propensity score analysis, treatment with rhTM was significantly associated with reduced in-hospital mortality (adjusted hazard ratio, 0.45; 95 % confidential interval, 0.26-0.77; p = 0.013). An association between rhTM treatment and higher numbers of intensive care unit-free days, ventilator-free days, and vasopressor-free days were observed. DIC scores were significantly decreased in the rhTM group compared with the control group in the early period after rhTM treatment, whereas the incidence of bleeding-related adverse events did not differ between the two groups. CONCLUSIONS: Therapy with rhTM may be associated with reduced in-hospital mortality in adult mechanically ventilated patients with sepsis-induced DIC.

The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene.

BACKGROUND: Bronchial asthma is a chronic airway disorder characterized by bronchial inflammation. Oxidative stress is a key component of inflammation. Glutathione S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferases (GSTs) in lung epithelium, plays a key role in cellular protection against oxidative stress. Several studies have shown that the GSTP1 geneis involved in the pathogenesis of asthma and a gene-gene interaction may occur within the GST gene superfamily. METHODS: We screened single-nucleotide polymorphisms (SNPs) at the GSTP1 locus and performed an association study in the Japanese population using two independent case-control groups (group 1: 391 pediatric patients with asthma, 462 adult patients with asthma, and 639 controls, and group 2: 115 pediatric patients with asthma and 184 controls). The effect of GSTM1 null/present genotype on the association between GSTP1 Ile105Val and asthma was also investigated. RESULTS: We identified 20 SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by four SNPs (tag SNPs). The association between the Ile105Val polymorphism in the GSTP1 gene and childhood asthma was significant in both groups (p = 0.047 in group 1, and p = 0.021 in group 2). This association was only significant in patients with GSTM1-positive genotype in both groups (group 1: GSTM1 present p = 0.013 and GSTM1 null p = 0.925, and group 2: GSTM1 present p = 0.015 and GSTM1 null p = 0.362). CONCLUSIONS: These findings suggest that the GSTP1 gene is a childhood asthma susceptible gene, and the GSTM1 gene is a modifier gene of GSTP1 for the risk of childhood asthma in the Japanese population.

A study of the factors responsible for the development of allergic diseases in early life.

In order to analyze the determinants involved in the development of allergic diseases early in infancy, we examined the environmental and genetic factors that might affect the induction of such diseases during infancy, using a questionnaire. Maternal pharyngitis during pregnancy was significantly related to the development of atopic dermatitis in their progeny. Moreover, the frequency of the maternal infection was associated with a significantly increased risk of allergy in their infants. The prevalence of post-delivery maternal allergy was positively linked to the allergic symptoms in their children while the likelihood of bearing allergic children was related to the numbers of allergic individuals within their family. These results suggested that pre- and post-natal maternal factors and any genetic predisposition might modify the development of allergy in infancy.

Fetal growth promotion in allergic children.

Several in vitro studies have suggested the presence of Th2-skewed immunity during pregnancy in infants with atopic diseases. Our study indicated that allergic infants showed a higher birth weight and shorter gestational period at birth than those of non-allergic peers. Moreover, allergic mothers gave birth to neonates whose birth weights and gestational ages were higher and shorter than those of the non-allergic mothers, respectively. Thus, our data clearly demonstrated the promotion of intrauterine growth, either in the allergic children, or allergic mothers. Such an intrauterine environment favorable for the fetal growth may also accelerate the development of allergic diseases in their offspring that are most probably caused by the Th2-oriented immunity.

Linkage and association of childhood asthma with the chromosome 12 genes.

Several studies have shown linkage of chromosome region 12q13-24 to bronchial asthma and related phenotypes in ethnically diverse populations. In the Japanese population, a genome-wide study failed to show strong evidence of linkage of this region. Chromosome 12 genes that showed association with the disease in at least one report include: the signal transducer and activator of transcription 6 gene ( STAT6), the nitrogen oxide synthetase 1 gene ( NOS1), the interferon gamma gene ( IFNG), and the activation-induced cytidine deaminase gene ( AICDA). To evaluate the linkage between chromosome 12 and childhood asthma in the Japanese population, we performed sib-pair linkage analysis on childhood asthma families using 18 microsatellite markers on chromosome 12. To investigate association between chromosome 12 candidate genes and asthma, distributions of alleles and genotypes of repeat polymorphisms of STAT6, NOS1, and IFNG were compared between controls and patients. Single nucleotide polymorphism of AICDA was also investigated. Chromosome region 12q24.23-q24.33 showed suggestive linkage to asthma. The NOS1 intron 2 GT repeat and STAT6 exon 1 GT repeat were associated with asthma. Neither the IFNG intron 1 CA repeat nor 465C/T of AICDA showed any association with asthma. Our results suggest that NOS1 and STAT6 are asthma-susceptibility genes and that chromosome region 12q24.23-q24.33 contains other susceptibility gene(s).