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There is substantial regional variation in out-of-hospital cardiac arrest (OHCA) survival. We investigated whether regional emergency medical services (EMS) intra-arrest transport (IAT) practices are associated with patient outcomes.We performed a secondary analysis of a multi-center North American clinical trial dataset, which enrolled EMS-treated adult OHCA cases from 49 regional population-based clusters. The exposure of interest was regional-level intra-arrest transport (IAT), calculated as the proportion of cases in each cluster transported to hospital prior to return of spontaneous circulation, examined as quartiles and as a continuous variable. Multilevel mixed-effects logistic regression modeling estimated the association between regional IAT with survival to hospital discharge and favorable neurologic status (modified Rankin Scale ≤ 3) at hospital discharge.Of 26,148 subjects (median age 68 years; 36% female; 23% shockable initial rhythm) 2424 (9.3%), survived to hospital discharge and 1993 (7.6%) had favourable neurological outcomes. Across regional clusters, IAT ranged from 0.84% to 75% (quartiles6.2%, 6.2-19.6%, 19.6-30.4%, and ≥30.4%). For each quartile, 13.3%, 7.9%, 7.4%, and 4.8% survived, and 10.4%, 7.8%, 7.4%, and 4.8% had favourable neurological status. Regional IAT (per 10% change) was associated with decreased probability of survival (AOR 0.86, 95% CI 0.82-0.91) and favorable neurological outcome (AOR 0.80, 95% CI 0.76-0.85).Treatment within a region that utilizes IAT less frequently was associated with improved clinical outcomes at hospital discharge. These findings may account for some of the known regional variation in OHCA outcomes.

Introduction In pediatric out-of-hospital cardiac arrest (OHCA) the effect of intraosseous (IO) or intravenous (IV) access on outcomes is unclear. Methods We analyzed prospectively collected data of non-traumatic OHCA in the Resuscitation Outcomes Consortium registry from 2011 to 2015. We included EMS-treated patients ≤17 years of age, classified patients based on vascular access routes, and calculated success rates of IO and IV attempts. After excluding patients with obvious non-cardiac etiologies and those with unsuccessful vascular access or multiple routes, we fit a logistic regression model to evaluate the association of IO vascular access (reference IV access) with the primary outcome of survival, using multiple imputation to address missing data. We analyzed a subgroup of patients at least 2 years of age. Results There were 1549 non-traumatic OHCA: 895 (57.8%) patients had an IO line attempted with 822 (91.8%) successful; 488 (31.5%) had an IV line attempted with 345 (70.7%) successful (difference 21%, 95% CI 17 to 26%). Of the 761 patients included in our logistic regression, 601 received IO (30 [5.2%] survived) and 160 received IV (40 [25%] survived) vascular access. Intraosseous access was associated with a decreased probability of survival (adjusted OR 0.46; 95% CI 0.21–0.98). Patients at least 2 years of age showed a similar association (adjusted OR 0.36; CI 0.15–0.86). Conclusions Intraosseous access was associated with decreased survival among pediatric non-traumatic OHCA. These results are exploratory and support the need for further study to evaluate the effect of intravascular access method on outcomes.

Background Rapid emergency medical service (EMS) response after out-of-hospital cardiac arrest (OHCA) is a major determinant of survival, however this is typically measured until EMS vehicle arrival. We sought to investigate whether the interval from EMS vehicle arrival to patient attendance (curb-to-care interval [CTC]) was associated with patient outcomes. Methods We performed a secondary analysis of the “CCC Trial” dataset, which includes EMS-treated adult non-traumatic OHCA. We fit an adjusted logistic regression model to estimate the association between CTC interval (divided into quartiles) and the primary outcome (survival with favourable neurologic status at hospital discharge; mRS ≤ 3). We described the CTC interval distribution among enrolling clusters. Results We included 24,685 patients: median age was 68 (IQR 56–81), 23% had initial shockable rhythms, and 7.6% survived with favourable neurological status. Compared to the first quartile (≤62 seconds), longer CTC quartiles (63 to 115, 116 to 180, and ≥181 seconds) demonstrated the following associations with survival with favourable neurological status: adjusted odds ratios 0.95, 95% CI 0.83 to 1.09; 0.77, 95% CI 0.66 to 0.89; 0.66, 95% CI 0.56 to 0.77, respectively. Of the 49 study clusters, median CTC intervals ranged from 86 (IQR 58–130) to 179 seconds (IQR 112–256). Conclusion A lower CTC interval was associated with improved patient outcomes. These results demonstrate a wide range of access metrics within North America, and provide a rationale to create protocols to mitigate access obstacles. A two-minute CTC threshold may represent an appropriate target for quality improvement.

Background: There is substantial regional variation in out-of-hospital cardiac arrest (OHCA) outcomes. We investigated whether regional-level intra-arrest transport practices were associated with patient outcomes. Methods: We performed a secondary analysis of the “CCC Trial” dataset, which included EMS-treated adult non-traumatic OHCA enrolled from 49 regional clusters. The exposure of interest was regional-level intra-arrest transport practices (RIATP), calculated as the proportion of cases within the enrolling cluster transported prior to return of spontaneous circulation (“intra-arrest transport”), divided into quartiles. We fit a multilevel mixed-effects logistic regression model to estimate the association of RIATP quartile and both survival and favorable neurologic status (mRS ≤ 3) at hospital discharge, adjusted for patient-level Utstein variables. Results: We included all 26,148 CCC-enrolled patients, 36% of whom were female, 97% were treated with prehospital ALS, and 23% had shockable initial rhythms. The median RIATP of the 49 clusters was 20% (IQR 6.2 - 30%). The figure shows outcomes stratified by RIATP quartile. Compared to the first quartile ( Conclusion: Treatment within a region that utilizes intra-arrest transport less frequently was associated with improved patient survival. These results may, in part, explain differences between regional OHCA survival outcomes.

Aim While public access automated external defibrillator (AED) programs appear to improve outcomes in out-of-hospital cardiac arrest (OHCA) it is unclear if men and women benefit equally. We examined gender-based differences in OHCA location to determine what proportion were potentially eligible for public access AED application, and if patient gender was associated with AED utilization. Methods We analyzed data from the Resuscitation Outcomes Consortium registry (2011–2015). We compared differences in OHCA locations by gender. We fit multivariate logistic regression models, restricted to public location OHCAs and public-location cases with bystander intervention, to calculate the association between gender and public access AED application. Results Among 61 473 cases, 34% were female and 50% had bystander resuscitation. The incidence of public OHCA was 8.8% for women and 18% for men (risk difference 9.2%, 95% CI 8.7–9.7%). Women had significantly fewer OHCAs on roadways, in public buildings, places of recreation, and farms, but more in homes, non-acute healthcare facilities, and residential institutions. Female gender was associated with a lower odds of AED application in public OHCA (adjusted OR 0.76, 95% CI 0.64–0.90) and public-location cases with bystander interventions (adjusted OR 0.83, 95% CI 0.71–0.99). Conclusion Women had fewer OHCA in public locations that may have public access AEDs. Even among public location OHCA with bystander interventions, women were less likely to have public access AED applied. Initiatives to optimize AED locations and to engage the public with gender-specific resuscitation training may improve outcomes in women with OHCA.

Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial.Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study.Multicenter study across North America.Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015.Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation).The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort.Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study.

Introduction: The benefits of early CPR are evident, however the relationship between the no-flow interval and neurological outcomes may assist clinicians with resuscitation management. Methods: We examined emergency medical system-treated non-traumatic out-of-hospital cardiac arrests from two clinical trials (PRIMED and CCC; 2006-2015), including only bystander witnessed cases without bystander resuscitation. We created a subgroup to simulate ECPR-treated cases (witnessed, age ≤65, non-asystole initial rhythm, and ROSC >30 minutes). We fit an adjusted logistic regression model to estimate the relationship between the “no-flow” interval (911 call-to-initiation of CPR) and favorable neurological outcome (MRS ≤3) at hospital discharge, and created a cubic spline curve. Results: Of 43,593 trial cases, 7299 were included; 616 (8.4%; 95% CI 7.8-9.1%) favourable neurological outcomes. The no-flow interval (per minute) was associated favorable neurological outcomes (adjusted OR 0.88, 95% CI 0.85-0.91). The adjusted probability of a favorable neurological outcome decreased by 0.52% (95% CI 0.39-0.65) per no-flow minute. No patients (0%; 1-sided 97.5% CI 0-0.051%) had both a no-flow duration >20 minutes and a favorable neurological outcome. In the ECPR group, 15 (9.9%; 95% CI 5.1-15%) had favourable neurological outcomes; 0/152 (0%; 1-sided 97.5% CI 0-2.4%) had both a no-flow interval >10 minutes and a favourable neurological outcome. Conclusions: The odds of a favorable neurological outcome decrease as the no-flow interval increases, highlighting the urgency of rescuer response. We found no favorable outcomes among cases with >20 minutes of no-flow duration, which may assist providers with decisions of starting or terminating resuscitation. Among ECPR-eligible cases with prolonged resuscitative efforts there were no favourable neurological outcomes among those with a no flow-interval >10 minutes, which may assist with ECPR candidacy assessment.

Introduction: It is unclear if the benefits of public access defibrillator (PAD) programs are similar between men and women. We investigated the location of out-of-hospital cardiac arrests (OHCA) stratified by sex to determine what proportion was eligible for PAD application. Second, we sought to determine if patient sex was associated with PAD utilization. Methods: We analyzed prospectively collected data from the North American Resuscitation Outcomes Consortium (ROC) Epistry dataset (2011 - 2015), excluding emergency medical services (EMS)-witnessed cases, those not treated by EMS, and children aged less than 10. We compared sex-based differences in public vs private location, and location type (street or highway, public building, place of recreation, industrial place, home residence, farm or ranch, healthcare facility, residential institution, other public property, or other private location). Among public location OHCAs with bystander interventions, we fit an adjusted logistic regression model to estimate the association between sex and PAD application. Results: Among the 61,473 cases, 20,933 (34%) were female, 30,353 had resuscitation attempted by bystander, and 13,597 had initial shockable rhythms. The OHCA incidence in a public location for women and men was 8.8% and 18%, respectively (95% CI for difference 8.7 - 9.7). Women had a significantly lower proportion of OHCAs on the street/highway, in public buildings, places of recreation, and farms, but a significantly higher proportion in the home, healthcare facilities, and residential institutions. Among public location OHCAs with bystander interventions, female sex was associated with a lower odds of bystander PAD application (adjusted OR 0.83, 95% CI 0.70-0.99). Conclusion: Women had fewer OHCAs in public locations eligible for PAD application. Further, among public OHCAs with bystander interventions, women were less likely to have PADs applied.

Study objective We seek to determine the effect of intraosseous over intravenous vascular access on outcomes after out-of-hospital cardiac arrest. Methods This secondary analysis of the Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed (PRIMED) study included adult patients with nontraumatic out-of-hospital cardiac arrests treated during 2007 to 2009, excluding those with any unsuccessful attempt or more than one access site. The primary exposure was intraosseous versus intravenous vascular access. The primary outcome was favorable neurologic outcome on hospital discharge (modified Rankin Scale score ≤3). We determined the association between vascular access route and out-of-hospital cardiac arrest outcome with multivariable logistic regression, adjusting for age, sex, initial emergency medical services–recorded rhythm (shockable or nonshockable), witness status, bystander cardiopulmonary resuscitation, use of public automated external defibrillator, episode location (public or not), and time from call to paramedic scene arrival. We confirmed the results with multiple imputation, propensity score matching, and generalized estimating equations, with study enrolling region as a clustering variable. Results Of 13,155 included out-of-hospital cardiac arrests, 660 (5.0%) received intraosseous vascular access. In the intraosseous group, 10 of 660 patients (1.5%) had favorable neurologic outcome compared with 945 of 12,495 (7.6%) in the intravenous group. On multivariable regression, intraosseous access was associated with poorer out-of-hospital cardiac arrest survival (adjusted odds ratio 0.24; 95% confidence interval 0.12 to 0.46). Sensitivity analyses revealed similar results. Conclusion In adult out-of-hospital cardiac arrest patients, intraosseous vascular access was associated with poorer neurologic outcomes than intravenous access.

British Columbia (BC) Emergency Health Services implemented a strategy to improve outcomes for out-of-hospital cardiac arrest (OHCA), focusing on paramedic-led high-quality on-scene resuscitation. We measured changes in care metrics and survival trends.This was a post-hoc study of prospectively identified consecutive non-traumatic ambulance-treated adult OHCAs from 2006 to 2016 within BC's four metropolitan areas. The primary outcome was survival to hospital discharge; we also described available favourable neurological outcomes (mRS ≤3). We tested the significance of year-by-year trends in baseline characteristics, and calculated risk-adjusted survival rates using multivariable Poisson regression.We included 15 145 patients. In univariate analyses there were significant increases in bystander CPR, chest compression fraction, advanced life support attendance, duration of resuscitation until advanced airway placement, duration of resuscitation until termination, and overall scene time. There was a significant decrease in initial shockable rhythms, bystander witnessed arrests, and transports initiated prior to ROSC. Survival and the proportion of survivors with favourable neurological outcomes increased significantly. In adjusted analyses, there was an improvement in return of spontaneous circulation (risk-adjusted rate 41% in 2006 to 51% in 2016; adjusted rate ratio per year 1.02, 95% CI 1.01-1.02, p 0.01 for trend) and survival at hospital discharge (risk-adjusted rate 8.6% in 2006 to 16% in 2016; adjusted rate ratio per year 1.05, 95% CI 1.04-1.06, p 0.01 for trend).From 2006 to 2016 BC's provincial ambulance system prioritized paramedic-led on-scene resuscitation, during which time there were significant improvements in patient outcomes. Our data may assist other systems, providing a model for prehospital resuscitation quality improvement.

Introduction Ipragliflozin is a novel antidiabetic drug that inhibits renal tubular sodium-glucose cotransporter-2 (SGLT2). The aim of this study was to evaluate the effects of ipragliflozin on glucose, insulin, glucagon, and gastrointestinal peptide responses to a meal tolerance test, as well as to investigate the glucose-lowering mechanisms of ipragliflozin. Methods Nine Japanese patients with obesity and type 2 diabetes mellitus were treated with ipragliflozin (50 mg/day) for 12 weeks. The postprandial profiles of glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose-dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were measured before and 12 weeks after ipragliflozin treatment. Results Body weight, body fat mass, systolic blood pressure, and HbA1c and serum uric acid levels were significantly decreased after the treatment. Postprandial glucose and insulin levels were also significantly decreased. Postprandial glucagon increased both before and after ipragliflozin treatment; however, the increment tended to be smaller after treatment. Active GLP-1, active GIP, ghrelin, and des-acyl ghrelin did not change after treatment. Conclusion Ipragliflozin improved glycemic control by reducing body weight, postprandial inappropriate glucagon secretion, and the postprandial insulin requirement. Although this was a short-term study with a small sample size, ipragliflozin may offer benefits for patients with obesity and type 2 diabetes mellitus. Trial Registration University Hospital Medical Information Network (UMIN No. 000017195).

Prognostication bias, in which a clinician predicts a negative outcome and terminates resuscitation (TR) thereby ensuring a poor outcome, is a rarely identified limitation of out-of-hospital cardiac arrest (OHCA) research. We sought to estimate the number of deaths due to intra-arrest prognostication in a cohort of OHCA's, and use this data to estimate the incremental benefit of continuing resuscitation.This study examined a cohort of consecutive non-traumatic EMS-treated OHCAs from a provincial ambulance service, between 2007 and 2011 inclusive. We used Cox and logistic regression modeling, adjusting for Utstein covariates, to estimate the probability of ROSC, survival, and favorable neurological outcomes as a function of resuscitation time, and applied these models to estimate the number of missed survivors in those who had TR (prior to 20, 30, or 40 minutes). We determined the time juncture at which (1) the likelihood of survival fell below 1%, and (2) the proportion of survivors who had achieved ROSC exceeded 99%.Of 5674 adult EMS-treated cases, 46% achieved ROSC, and 12% survived. The median time of TR was 27.0 minutes (IQR 19.0-35.0). Continuing resuscitation until 40 minutes yielded an estimated 17 additional survivors (95% CI 13-21), 10 (95% CI 7-13) with favorable neurological outcomes. The probability of survival of those in refractory arrest decreased below 1% at 28 minutes (95% CI 24-30 minutes). At 36 minutes (95% CI 34-38 minutes)99% of survivors had achieved ROSC.We identified possible deaths due to intra-arrest prognostication. Resuscitation should be continued for a minimum of 30 minutes in all patients, however for those with initial shockable rhythms 40 minutes appears to be warranted. Interventional trials and observational studies should standardize or adjust for duration of resuscitation prior to TR.

Objectives H1-antihistamines (H1a) can be used to treat ED patients with allergic reactions; however, this is inconsistently done, likely as there is no evidence that this therapy has an impact on serious outcomes. Among emergency department (ED) patients initially presenting with allergic reactions, we investigated whether H1a were associated with lower rates of progression to anaphylaxis. Methods This was a retrospective cohort study conducted at two urban Canadian EDs from April 1, 2007 to March 31, 2012. We included consecutive adult patients with allergic reactions while excluding those presenting with anaphylaxis, according to pre-specified criteria. The primary outcome was the proportion of patients who subsequently developed anaphylaxis during medical care, either by emergency medical services (EMS) or in the ED. A pre-specified subgroup analysis excluded patients who received H1a prior to EMS or ED contact. We compared those who received H1a and those who did not, and used multivariable regression and propensity score adjustment techniques to compare outcomes. Results Of 2,376 overall patients included, 1,880 (79.1%) were managed with H1a. Of the latter group, 36 / 1,880 (1.9%) developed anaphylaxis, compared to 17 / 496 (3.4%) in the non-H1a-treated group (adjusted odds ratio [AOR] 0.34, 95% CI 0.17 to 0.70; number needed to treat [NNT] to benefit 44.74, 95% CI 35.36 to 99.67). In the subgroup analysis of 1,717 patients who did not receive H1a prior to EMS or ED contact, a similar association was observed (AOR 0.26, 95% CI 0.10 to 0.50; NNT to benefit 38.20, 95% CI 32.58 to 55.24). Conclusions Among ED patient with allergic reactions, H1a administration was associated with a lower likelihood of progression to anaphylaxis. These data indicate that early H1a treatment in the ED or prehospital setting may decrease progression to anaphylaxis. This article is protected by copyright. All rights reserved.

Background Targeted temperature management (TTM) is a recommended treatment modality to improve neurological outcomes in patients with out‐of‐hospital cardiac arrest. The impact of the duration from hospital admission to TTM initiation (door‐to‐TTM; DTT) on clinical outcomes has not been well elucidated. We hypothesized that shorter DTT initiation intervals would be associated with improved survival with favorable neurological outcome. Methods and Results We performed a post hoc analysis of nontraumatic paramedic‐treated out‐of‐hospital cardiac arrests. The primary outcome was favorable neurological status at hospital discharge, with a secondary outcome of survival to discharge. We fit a logistic regression analysis to determine the association of early compared with delayed DTT, dichotomized by the median DTT duration, and outcomes. Of 3805 patients enrolled in the CCC (Continuous Chest Compressions) Trial in British Columbia, 570 were included in this analysis. There was substantial variation in DTT among patients receiving TTM. The median DTT duration was 122 minutes (interquartile range 35‐218). Favorable neurological outcomes in the early and delayed DTT groups were 48% and 38%, respectively. Compared with delayed DTT (interquartile range 167‐319 minutes), early DTT (interquartile range 20‐81 minutes) was associated with survival (adjusted odds ratio 1.56, 95% CI 1.02‐2.38) but not with favorable neurological outcomes (adjusted odds ratio 1.45, 95% CI, 0.94‐2.22) at hospital discharge. Conclusions There was wide variability in the initiation of TTM among comatose out‐of‐hospital cardiac arrest survivors. Initiation of TTM within 122 minutes of hospital admission was associated with improved survival. These results support in‐hospital efforts to achieve early DTT among out‐of‐hospital cardiac arrest patients admitted to the hospital., See Editorial Schenone and Menon

Objective: There is conflicting data in studies investigating the effectiveness of advanced life support (ALS) for out-of-hospital cardiac arrest (OHCA). Within a tiered BLS-ALS system, we sought to determine if the ALS response interval was associated with patient outcomes. Methods: This secondary analysis examined prospectively identified consecutive non-traumatic adult OHCAs from 2006-2016 in British Columbia. We excluded EMS-witnessed arrests and those not treated by ALS. The primary and secondary outcomes were survival and favorable neurological outcomes (mRS ≤3) at hospital discharge. Using logistic regression we estimated the association of ALS response interval (9-1-1 call to ALS arrival) and outcomes, adjusting for treatment year, response interval of the first EMS unit, and other baseline characteristics. We drew spline curves to illustrate this relationship. Results: Of 12,722 included cases, survival was 12%. The median response interval for the first EMS unit was 6.4 minutes (IQR 5.2 - 8.3) and for ALS was 11.8 minutes (IQR 8.7 - 16.5).The adjusted odds of survival and favourable neurological outcome for each additional minute in ALS response interval were 0.98 (95 % CI 0.96-0.99) and 0.98, (95% CI 0.97-0.99) respectively. The spline curve demonstrated an initial decline in survival probability that moderated at approximately 11 minutes. Conclusion: Among ALS-treated subjects within our tiered EMS system, earlier ALS arrival was associated with improved survival and favorable neurological outcomes. The greatest yield of ALS care may be prior to 11 minutes. This may help inform the optimal deployment configuration of prehospital providers.

Background Certain subgroups of patients with out-of-hospital cardiac arrest (OHCA) may not benefit from treatment. Early identification of this cohort in the prehospital (EMS) setting prior to any resuscitative efforts would prevent futile medical therapy and more appropriately allocate EMS and hospital resources. We sought to validate a clinical criteria from Bokutoh, Japan that identified a subgroup of OHCAs for whom withholding resuscitation may be appropriate. Methods We performed a secondary analysis of the “Trial of Continuous or Interrupted Chest Compressions during CPR”, which enrolled EMS-treated adult non-traumatic OHCA. We classified patients as per the Bokutoh criteria (“Bokutoh Positive”: age ≥ 73, unwitnessed arrest, non-shockable initial rhythm) and calculated test performance for the primary outcome of favourable neurologic outcome (mRS ≤ 3) at hospital discharge. We calculated the number of EMS-hours and hospital days per patient with a favourable neurologic outcome. Results Of 26,148 patients in the parent trial, 5442 (21%) were “Bokutoh Positive”, among whom 0.51% (95% CI 0.35– 0.75%) had favourable neurologic outcomes, and 1.2% (95% CI 0.92–1.5%) survived. The positive predictive value was 0.995 (95% CI 0.992–0.997). EMS and hospital-based resource utilization per favourable neurological outcome was 91 h and 199 days for in the “Bokutok Positive” group, respectively, and 5.7 h and 33 hospital days in the “Bokutok Negative” group. Conclusion In this validation of the Bokutoh criteria in a large North American cohort of OHCA patients, 0.51% meeting criteria had favourable neurological outcomes. This may rapidly and reliably identify the one-fifth of OHCA who are very unlikely to benefit from resuscitation.

Objective Data demonstrating benefit of advanced life support (ALS) practitioners for out-of-hospital cardiac arrest (OHCA) is conflicting. In our tiered emergency medical services (EMS) system, we sought to determine if the ALS response interval was associated with patient outcomes. Methods We performed a secondary analysis of consecutive adult OHCAs (2006–2016) in British Columbia. Primary and secondary outcomes were survival and favorable neurological outcomes (mRS ≤ 3) at hospital discharge. Logistic regression estimated the association of ALS response interval (911 call-to-ALS arrival, continuous and categorical analyses) and outcomes, adjusting for first EMS response interval, and other clinical characteristics. We calculated the optimal time threshold to differentiate “early” vs “late” ALS response intervals for a binary comparison. Results Of 12,722 included cases, 12% survived to discharge. Median response interval was 6.4 min (IQR 5.2–8.3) for the first EMS unit and 11.8 min (IQR 8.7–16.5) for ALS. ALS response interval (per minute) was associated with decreased survival (adjusted OR 0.98, 95% CI 0.96–0.99) and favourable neurological outcome (0.98, 95% CI 0.97–0.99). ALS response ≤10 min (the optimal threshold) was associated with improved survival (adjusted OR 1.46; 95% CI 1.27–1.68) and favourable neurological outcomes (adjusted OR 1.41; 95% CI 1.18–1.68). Conclusion In our tiered EMS system, earlier ALS arrival was associated with improved survival and favorable neurological outcomes. ALS attendance within 10 min of the 9-1-1 call in tiered systems of prehospital care may improve patient outcomes and serve as a quality metric.

SUMMARYAlthough outbreaks of acute respiratory infection (ARI) at shelters are hypothesized to be associated with shelter crowding, no studies have examined this relationship. We conducted a retrospective study by reviewing medical records of evacuees presenting to one of the 37 clinics at the shelters in Ishinomaki city, Japan, during the 3-week period after the Great Eastern Japan Earthquake and tsunami in 2011. On the basis of a locally weighted scatter-plot smoothing technique, we categorized 37 shelters into crowded (mean space 2/per person) and non-crowded (⩾5·5 m2) shelters. Outcomes of interest were the cumulative and daily incidence rate of ARI/10 000 evacuees at each shelter. We found that the crowded shelters had a higher median cumulative incidence rate of ARI [5·4/10 000 person-days, interquartile range (IQR) 0–24·6,P= 0·04] compared to the non-crowded shelters (3·5/10 000 person-days, IQR 0–8·7) using Mann–WhitneyUtest. Similarly, the crowded shelters had an increased daily incidence rate of ARI of 19·1/10 000 person-days (95% confidence interval 5·9–32·4,P< 0·01) compared to the non-crowded shelters using quasi-least squares method. In sum, shelter crowding was associated with an increased incidence rate of ARI after the natural disaster.

Background Sodium bicarbonate (SB) is widely used for resuscitation in out-of- hospital cardiac arrest (OHCA); however, its effect on long term outcomes is unclear. Methods From 2005–2016, we prospectively conducted a province-wide population-based observational study including adult non-traumatic OHCA patients managed by paramedics. SB was administered by paramedics based on their clinical assessments. To examine the association of SB administration and survival and favorable neurological outcome to hospital discharge, defined as modified Rankin scale of 3 or less, we performed a multivariable logistic regression analysis: (1) within propensity score matched comparison groups, and; (2) within the full cohort with missing variables addressed by multiple imputation techniques. Results Of 15 601 OHCA patients, 13,865 were included in this study with 5165 (37.3%) managed with SB. In the SB treated group, 118 (2.3%) patients survived and 62 (1.2%) had favorable neurological outcomes to hospital discharge, compared to 1699 (19.8%) and 831 (10.6%) in the non-SB treated group, respectively. In the 1:1 propensity matched cohort including 5638 OHCA patients, SB was associated with decreased probability of outcomes (adjusted OR for survival: 0.64, 95% CI 0.45–0.91, and adjusted OR for favorable neurological outcome: 0.59, 95% CI 0.39–0.88, respectively). The association remained consistent in the multiply imputed cohort (adjusted OR 0.48, 95 CI 0.36–0.64, and adjusted OR 0.54, 95% CI 0.38–0.76, respectively). Conclusions In OHCA patients, prehospital SB administration was associated with worse survival rate and neurological outcomes to hospital discharge.

ObjectiveAfter the Great Eastern Japan Earthquake and tsunami, the World Health Organization cautioned that evacuees at shelters would be at increased risk of infectious disease transmission; however, the frequency that occurred in this population was not known.MethodsWe reviewed medical charts of evacuees who visited medical clinics at 6 shelters from March 19, to April 8, 2011. Excluded were patients who did not reside within the shelters or whose medical records lacked a name or date. We investigated the frequency of and cumulative incidences of acute respiratory infection [ARI], acute gastroenteritis, acute jaundice syndrome, scabies, measles, pertussis, and tetanus.ResultsOf 1364 patients who visited 6 shelter clinics, 1167 patients (86.1%) were eligible for the study. The median total number of evacuees was 2545 (interquartile range [IQR], 2277-3009). ARI was the most common infectious disease; the median number of patients with ARI was 168.8 per week per 1000 evacuees (IQR, 64.5-186.1). Acute gastroenteritis was the second most common; the median number of patients was 23.7 per week per 1000 evacuees (IQR, 5.1-24.3). No other infectious diseases were observed. The median cumulative incidence of ARI per 1000 evacuees in each shelter was 13.1 person-days (IQR, 8.5–18.8). The median cumulative incidence of gastroenteritis was 1.6 person-days (IQR, 0.3–3.4).ConclusionAfter the Great Eastern Japan Earthquake and tsunami, outbreaks of ARI and acute gastroenteritis occurred in evacuation shelters. (Disaster Med Public Health Preparedness. 2014;0:1-7)

IntroductionRecent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs.Methods and analysisIn total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation.Ethics and disseminationThe study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals.

Although it has been suggested that the increase in older population contributes to overcrowding in emergency departments (EDs), there are limited data defining this relationship. This study examines whether patients' mean age per day affects length of ED stay.This cross-sectional analysis evaluated how patient age affects length of ED stay. The study was conducted at an ED attached to Fujisawa City Hospital, Japan, between 1 November 2009 and 31 October 2010. Patients scheduled to visit for childbirth and patients under age 15 were excluded. The primary outcome measure was the relationship between length of ED stay and patient age. The secondary outcome was the relationship between patient age and patient dispositions indicated by column chart and 100% staked column chart.Over the study period, there were 17 744 patient visits to the ED. The study included 15 840 (89.3%) patients. The mean (SD) age of these patients was 56.9 (21.5) years. In single and multiple linear regression analyses, mean patient age per day was an important factor in length of ED stay for the total number of patients visiting the ED (single linear regression analysis: regression coefficient=1.59 min/year, r(2)=0.005, p0.001; multiple linear regression analysis: regression coefficient=0.72 min/year, r(2)=0.24, p0.001). The ratio of admitted and transferred patients increased with patient age.The increase in older patients visiting the ED has a direct significant negative effect on overcrowding in the ED.

Objectives We determined whether crowding at emergency shelters is associated with a higher incidence of sleep disturbance among disaster evacuees and identified the minimum required personal space at shelters. Design Retrospective review of medical charts. Setting 30 shelter-based medical clinics in Ishinomaki, Japan, during the 46 days following the Great Eastern Japan Earthquake and Tsunami in 2011. Participants Shelter residents who visited eligible clinics. Outcome measures Based on the result of a locally weighted scatter-plot smoothing technique assessing the relationship between the mean space per evacuee and cumulative incidence of sleep disturbance at the shelter, eligible shelters were classified into crowded and non-crowded shelters. The cumulative incidence per 1000 evacuees was compared between groups, using a Mann-Whitney U test. To assess the association between shelter crowding and the daily incidence of sleep disturbance per 1000 evacuees, quasi–least squares method adjusting for potential confounders was used. Results The 30 shelters were categorised as crowded (mean space per evacuee 2 , 9 shelters) or non-crowded (≥5.0 m 2 , 21 shelters). The study included 9031 patients. Among the eligible patients, 1079 patients (11.9%) were diagnosed with sleep disturbance. Mean space per evacuee during the study period was 3.3 m 2 (SD, 0.8 m 2 ) at crowded shelters and 8.6 m 2 (SD, 4.3 m 2 ) at non-crowded shelters. The median cumulative incidence of sleep disturbance did not differ between the crowded shelters (2.3/1000 person-days (IQR, 1.6–5.4)) and non-crowded shelters (1.9/1000 person-days (IQR, 1.0–2.8); p=0.20). In contrast, after adjusting for potential confounders, crowded shelters had an increased daily incidence of sleep disturbance (2.6 per 1000 person-days; 95% CI 0.2 to 5.0/1000 person-days, p=0.03) compared to that at non-crowded shelters. Conclusions Crowding at shelters may exacerbate sleep disruptions in disaster evacuees; therefore, appropriate evacuation space requirements should be considered.

Adiponectin is an adipose-derived cytokine, and it is suggested that hypoadiponectinemia increases the prevalence of ischemic heart disease (IHD). The present study was undertaken to determine serum adiponectin levels in patients with arteriosclerosis obliterans (ASO) and IHD. Forty-nine patients with ASO and 49 age-, sex-, and body mass index-matched control subjects were examined. The diagnosis of ASO was derived from an ankle brachial index of less than 0.90 and stenotic or obstructive change in angiogram. Ischemic heart disease was diagnosed by ischemic or stenotic change in ECG, treadmill, or coronary angiogram. Serum adiponectin level was 8.6 +/- 0.9 microg/mL in the patients with ASO, a value significantly less than that of 12.4 +/- 1.0 microg/mL in the control subjects ( P < .01). Next, we subgrouped the subjects into 4 groups according to the presence of ASO and IHD. Serum adiponectin levels were 9.4 +/- 1.5 and 10.2 +/- 1.6 microg/mL in the subjects with ASO (n =23) and those with IHD (n = 13), respectively. It was further reduced to 7.9 +/- 1.2 microg/mL in the subjects having both ASO and IHD (n = 26), a value significantly less than that of 13.2 +/- 1.4 microg/mL in the control subjects (n = 36; P < .05). Serum high-density lipoprotein cholesterol was significantly less in the subjects with ASO than in the control subjects (42.1 +/- 1.7 vs 48.5 +/- 2.0 mg/dL; P < .05), but there were no differences in blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, and uric acid levels. The present results indicate that a reduction in serum adiponectin level is associated with the prevalence and magnitude of systemic atherosclerosis including IHD and ASO.

Study objective The Universal Termination of Resuscitation Rule (TOR Rule) was developed to identify out-of-hospital cardiac arrests eligible for field termination of resuscitation, avoiding futile transportation to the hospital. The validity of the rule in emergency medical services (EMS) systems that do not routinely transport out-of-hospital cardiac arrest patients to the hospital is unknown. We seek to validate the TOR Rule in British Columbia. Methods This study included consecutive, nontraumatic, adult, out-of-hospital cardiac arrests treated by EMS in British Columbia from April 2011 to September 2015. We excluded patients with active do-not-resuscitate orders and those with missing data. Following consensus guidelines, we examined the validity of the TOR Rule after 6 minutes of resuscitation (to approximate three 2-minute cycles of resuscitation). To ascertain rule performance at the different time junctures, we recalculated TOR Rule classification accuracy at subsequent 1-minute resuscitation increments. Results Of 6,994 consecutive, adult, EMS-treated, out-of-hospital cardiac arrests, overall survival was 15%. At 6 minutes of resuscitation, rule performance was sensitivity 0.72, specificity 0.91, positive predictive value 0.98, and negative predictive value 0.36. The TOR Rule recommended care termination for 4,367 patients (62%); of these, 92 survived to hospital discharge (false-positive rate 2.1%; 95% confidence interval 1.7% to 2.5%); however, this proportion steadily decreased with later application. The TOR Rule recommended continuation of resuscitation in 2,627 patients (38%); of these, 1,674 died (false-negative rate 64%; 95% confidence interval 62% to 66%). Compared with 6-minute application, test characteristics at 30 minutes demonstrated nearly perfect positive predictive value (1.0) and specificity (1.0) but a lower sensitivity (0.46) and negative predictive value (0.25). Conclusion In this cohort of adult out-of-hospital cardiac arrest patients, the TOR Rule applied at 6 minutes falsely recommended care termination for 2.1% of patients; however, this decreased with later application. Systems using the TOR Rule to cease resuscitation in the field should consider rule application at points later than 6 minutes.

Introduction: Sepsis protocols call for the acquisition of blood cultures in septic emergency department (ED) patients.However, the criteria for blood cultures are vague, they are costly, only positive 8-12% of the time, with up to half of these being false positives. The objective of this study was to establish if positive blood cultures could be excluded in low-risk sepsis patients with levels of CRP below 20 ml/L. Methods: This was a multicenter prospective cohort study of 765 ED patients at St Paul’s and Mount St Joseph’s hospitals in Vancouver with sepsis (2 or more SIRS criteria and infection) and none of: immuncompromised, injection drug use, indwelling vascular device or septic shock (SBPResults: 765 ED patients with sepsis met inclusion criteria. Mean age was 48.3 years and 57% were male. Blood cultures were positive in 99/765 (12.9%) subjects, of which 19 were false positive (19.2%). CRP was >20 mg/L in 595/765 (77.8%) of patients. Of 170 subjects with a CRPConclusion: In this cohort of low-risk sepsis patients, based on a CRP of

Background Although increasing staff numbers during shifts when emergency department (ED) crowding is severe can help meet patient demand, it remains unclear how different types of added staff, particularly junior residents, may affect crowding. Methods To identify associations between types of staff and ED crowding, we conducted a cross-sectional, single-center study in the ED of a large, teaching hospital in Japan between January and December 2012. Patients who visited the ED during the study period were enrolled. We excluded (1) patients previously scheduled to visit the ED, and (2) neonates transferred from other hospitals. During the study period, 27,970 patients were enrolled. Types of staff analyzed were junior (first and second year) residents, senior (third to fifth year) residents, attending (board-certified) physicians, and nurses. A generalized linear model was applied to length of ED stay for all patients as well as admitted and discharged patients to quantify an association with the additional staff. Results In the model, addition of one attending physician or senior resident was associated with decreased length of ED stay for total patients by 3.88 or 1.64 minutes, respectively (95% CI, 2.20–5.56 and 0.81–2.48 minutes); while additional nursing staff had no association. Surprisingly, however, one additional junior resident was associated with prolonged length of ED stay for total patients by 0.97 minutes (95% CI 0.37–1.57 minutes) and for discharged patients by 1.01 minutes (95% CI 0.45–1.59 minutes). Conclusion Staffing adjustments aimed at alleviating ED crowding should focus on adding more senior staff during peak-volume shifts.

Introduction: H1-antihistamines are often used to treat allergic reactions, however, the influence of H1-antihistamines on progression to anaphylaxis remains unclear. Among patients initially presenting with allergic reactions, we investigated whether H1-antihistamines were associated with a lower proportion of patients progressing to anaphylaxis during observation. Methods: This was a retrospective cohort study conducted at two urban EDs from 2007 to 2012. We included adult patients with allergy and excluded those who met criteria of anaphylaxis at first evaluation by medical professionals and/or received antihistamines before the evaluation. Primary outcomes of interest were the number of patients who developed anaphylaxis during observation at ED and/or transportation by EMS. Secondary outcomes were the number of biphasic reactions and severe anaphylaxis (defined as sBPResults: This study included 1717 patients with allergic reactions, of whom 1228 were treated with H1-antihistamines. In the H1-antihistamine group 1.0% and 0.2% developed anaphylaxis and severe anaphylaxis, respectively; in the non-H1-antihistamine group 2.6% and 0.6% developed anaphylaxis and severe anaphylaxis, respectively. There were no biphasic reactions (0%, 95% confidence interval [CI] 0 to 0.17%). Administration of H1-antihistamines was associated with a lower incidence of subsequent anaphylaxis (adjusted odds ratio [OR] 0.23, 95% CI 0.10 to 0.53; NNT to benefit 49.1, 95% CI 41.6 to 83.3). There were no significant associations between H1-histamines administration and secondary outcomes. Conclusion: Among ED patient with allergic reactions, H1-antihistamine administration was associated with a lower likelihood of progression to anaphylaxis. These findings suggest that H1-antihistamines should be administered early in the care of patients with allergic reactions.

Introduction: Emergency medical services (EMS) have the opportunity to treat allergic reactions anaphylactic reactions rapidly. However, the rate of recognition and treatment is unknown. Methods: This was a retrospective cohort study conducted at two urban emergency departments from 2007 to 2012 including adult patients with allergy and anaphylaxis, both of which were predefined by explicit criteria. The patients of interest were those attended by EMS and transported to hospital. The primary outcome was the proportion of patients who met anaphylaxis criteria in the prehospital setting, but who did not have epinephrine administered. The secondary outcome was the proportion of patients who did not meet anaphylaxis criteria, yet had epinephrine administered. Results: Of 2819 overall patients, 491 (17.4%) arrived by EMS. The median age was 38 (IQR 27 to 49) and 60.9% were female. For the 151 (30.8%) patients with anaphylaxis, 55 received ephinephrine, (36.4%, 95% CI 27.4 to 47.4%). For the 340 (69.2%) patients without anaphylaxis, 28 received ephinephrine (8.2%, 95% CI 5.5 to 11.9%). Conclusion: For patients with anaphylaxis and allergic reactions who are managed by EMS, there may be a mismatch between illness severity and treatment.

We experienced the first death case of the serotonin syndrome in Japan caused by fluvoxamine and tandospirone. A 15-year-old man was transported to our hospital for shock, muscle hypertonia and hyperthermia after cardiopulmonary arrest. His serum concentrations of fluvoxamine and tandospirone were 3,554 ng/mL and 698 ng/mL respectively after 24 hours from oral intake. He was dead in spite of intensive treatments. The progress of the serotonin syndrome is usually rapid. So, it should be monitored appropriately a patient with serotonin syndrome. If he has hyperthermia, immediate paralysis should be induced. We should aware of the serotonin syndrome a case of overdose on a serotonergic agent.

Introduction Deficiency of Von Willebrand factor (VWF)-cleaving protease (ADAMTS13) causes platelet thrombosis in the microcirculation. Intrarenal coagulation is thought to be associated with the development and progression of diabetic nephropathy. Our aim was to clarify the association between plasma ADAMTS13 antigen (ADAMTS13Ag) levels and diabetic nephropathy. Material and Methods We measured the plasma levels of VWF antigen (VWFAg) and ADAMTS13Ag, and calculated the VWF/ADAMTS13 ratio in 86 type 2 diabetic patients and 26 healthy volunteers, to investigate the relationship between these levels and renal function. With regard to diabetic macroangiopathy, the relationship between these levels and carotid intima-media thickness (IMT) was also investigated. Results and Conclusions A significant positive and negative correlation was noted between ADAMTS13Ag and the estimated glomerular filtration rate (eGFR), vWF/ADAMTS13 ratio and eGFR, respectively. The diabetic patients were divided into normoalbuminuria (n = 50), microalbuminuria (n = 8) and overt nephropathy (n = 28) groups. Compared among these three groups and the 26 healthy volunteers, ADAMTS13Ag was significantly lower only in the overt nephropathy group. The mean carotid IMT was measured in 69 patients and was significantly negatively correlated with ADAMTS13Ag and positively correlated with VWF/ADAMTS13 ratio. When these 69 patients were divided into four groups according to eGFR and ADAMTS13 levels (ADAMTS13/eGFR; low/low: n = 12; high/low: n = 7; low/high: n = 25; high/high: n = 25), the mean carotid IMT was increased in patients with a low ADAMTS13Ag in the same eGFR group. The present study suggests that reduced ADAMTS13 might be associated with diabetic nephropathy.

Objective The present study was undertaken to measure serum levels of adiponectin and CD146, an endothelial cell injury marker, and to clarify the property of adiponectin and CD146 in patients with diabetic nephropathy. Design A total of 280 diabetic patients, and 49 control subjects were enrolled. Serum levels of adiponectin and CD146 were measured by ELISA. Results Serum adiponectin levels were relatively low in the diabetic patients as compared to the control subjects. Inversely, serum adiponectin levels were significantly greater in those with stages IV and V of diabetic nephropathy than the control subjects. Serum CD146 levels were gradually increased according to the progression of diabetic nephropathy, and that in the stages IIIb–V was significantly greater than that in the control group. Serum adiponectin positively correlated with serum creatinine and negatively correlated with 1/creatinine. Similar results were obtained with serum CD146 levels. However, there was no relationship between serum adiponectin and CD146 levels. Conclusion These results indicate that serum adiponectin levels seem to reduce in the diabetic patients, and finally increase in end stage of diabetic nephropathy. In contrast, serum CD146 may closely associate with development of micro- and macrovascular complications in diabetic patients. Further study is required to elucidate the exact role of adiponectin and CD146 in the development of vascular complication in end stage of diabetic nephropathy.

The adrenal gland is one of the organs which tuberculosis infects. In most clinical settings bilateral adrenal tuberculosis has been clarified after adrenal insufficiency is overt. On the contrary, active adrenal tuberculosis is rarely detected during the survey of infectious disease. A 68-year-old man was admitted because of intermittent fever. The fever had continued for the last 3 months. The intermittent fever was accompanied with leukocytosis and elevation of C-reactive protein. Serum soluble interleukin-2 receptor was 1920 U/ml, and beta2-microglobulin was 4.0 mg/l. Bacterial cultures of blood, sputa, urine, bone marrow and cerebrospinal fluid did not show any particular bacteria. Mycobacterium tuberculosis was negative in culture of sputa, and there was no tuberculin reaction. Plasma ACTH and serum cortisol were 18.5 pmol/l and 527.0 nmol/l, respectively. Abdominal CT scan showed right adrenal mass with a size of 28 x 20 mm, which was low density and had a well-encapsulated homogenous appearance. After the adrenalectomy, histology verified active adrenal tuberculosis. The intermittent fever disappeared, and white blood cells and C-reactive protein normalized. These findings indicate an atypical, rare case of unilateral, active adrenal tuberculosis closely linked to intermittent fever, and without any other organ involvement.