The association of extreme environmental heat with incidence and outcomes of out-of-hospital cardiac arrest in British Columbia: A time series analysis.

Background: The impact of extreme heat on out-of-hospital cardiac arrest (OHCA) incidence and outcomes is under-studied. We investigated OHCA incidence and outcomes over increasing temperatures. Methods: We included non-traumatic EMS (Emergency Medical Services)-assessed OHCAs in British Columbia during the warm seasons of 2020-2021. We fit a time-series quasi-Poisson generalized linear model to estimate the association between temperature and incidence of both EMS-assessed, EMS-treated, and EMS-untreated OHCAs. Second, we employed a logistic regression model to estimate the association between "heatwave" periods (defined as a daily mean temperature > 99th percentile for ≥ 2 consecutive days, plus 3 lag days) with survival and favourable neurological outcomes (cerebral performance category ≤ 2) at hospital discharge. Results: Of 5478 EMS-assessed OHCAs, 2833 were EMS-treated. OHCA incidence increased with increasing temperatures, especially exceeding a daily mean temperature of 25 °C Compared to the median daily mean temperature (16.9 °C), the risk of EMS-assessed (relative risk [RR] 3.7; 95%CI 3.0-4.6), EMS-treated (RR 2.9; 95%CI 2.2-3.9), and EMS-untreated (RR 4.3; 95%CI 3.2-5.7) OHCA incidence were higher during days with a temperature over the 99th percentile. Of EMS-treated OHCAs, during the heatwave (n = 179) and non-heatwave (n = 2654) periods, 4 (2.2%) and 270 (10%) survived and 4 (2.2%) and 241 (9.2%) had favourable neurological outcomes, respectively. Heatwave period OHCAs had decreased odds of survival (adjusted OR 0.28; 95%CI 0.10-0.79) and favourable neurological outcome (adjusted OR 0.31; 95%CI 0.11-0.89) at hospital discharge, compared to other periods. Conclusion: Extreme heat was associated with a higher incidence of OHCA, and lower odds of survival and favourable neurological status at hospital discharge.

Non-prescription drug-associated out-of-hospital cardiac arrest: Changes in incidence over time and the odds of receiving resuscitation.

BACKGROUND: Multiple jurisdictions reported a significant increase in out-of-hospital cardiac arrest (OHCA) incidence over the past decade, however the reasons for this remain unclear. We investigated how drug-associated OHCA (DA-OHCA) contributed to overall OHCA incidence, and whether the likelihood of treatment by emergency medical services (EMS) was associated with DA-OHCA classification. METHODS: Using a large provincial cardiac arrest registry, we included consecutive, non-traumatic adult OHCA from 2016-2022. We classified as drug-associated if there were historical accounts of non-prescription drug use within the preceding 24 hours or evidence of paraphernalia at the scene. We examined year-by-year trends in OHCA and DA-OHCA incidence. We also investigated the association between DA-OHCA and odds of EMS treatment using an adjusted logistic regression model. RESULTS: Of 33,365 EMS-assessed cases, 1,985/18,591 (11%) of EMS-treated OHCA and 887/9,200 (9.6%) of EMS-untreated OHCA were DA-OHCA. Of EMS-treated DA-OHCA, the median age was 40 years (IQR 31-51), 1,059 (53%) had a known history of non-prescription drug use, and 570 (29%) were public-location. From 2016 to 2022, EMS-treated OHCA incidence increased from 60 to 79 per 100,000 person-years; EMS-treated DA-OHCA incidence increased from 3.7 to 9.1 per 100,000 person-years. The proportion of overall OHCA classified as DA-OHCA increased from 6.1% to 11.5%. DA-OHCA was associated with greater odds of EMS treatment (AOR 1.34; 95%CI 1.13-1.58). CONCLUSION: Although EMS-treated DA-OHCA incidence increased by nearly three-fold, it comprised a minority of the overall OHCA increase during the study period. DA-OHCA was associated with an increased likelihood of EMS treatment.

The association of tibial vs. humeral intraosseous vascular access with patient outcomes in adult out-of-hospital cardiac arrests.

AIM: Humeral and tibial intraosseous (IO) vascular access can deliver resuscitative medications for out-of-hospital cardiac arrest (OHCA), however the optimal site is unclear. We examined the association between IO tibia vs. humerus as the first-attempted vascular access site with OHCA outcomes. METHODS: We used prospectively-collected data from the British Columbia Cardiac Arrest registry, including adult OHCAs treated with IO humerus or IO tibia as the first-attempted intra-arrest vascular access. We fit logistic regression models on the full study cohort and a propensity-matched cohort, to estimate the association between IO site and both favorable neurological outcomes (Cerebral Performance Category 1-2) and survival at hospital discharge. RESULTS: We included 1041 (43%) and 1404 (57%) OHCAs for whom IO humerus and tibia, respectively, were the first-attempted intra-arrest vascular access. Among humerus and tibia cases, 1010 (97%) and 1369 (98%) had first-attempt success, and the median paramedic arrival-to-successful access interval was 6.7 minutes (IQR 4.4-9.4) and 6.1 minutes (IQR 4.1-8.9), respectively. In the propensity-matched cohort (n = 2052), 31 (3.0%) and 44 (4.3%) cases had favourable neurological outcomes in the IO humerus and IO tibia groups, respectively; compared to IO humerus, we did not detect an association between IO tibia with favorable neurological outcomes (OR 1.44; 95% CI 0.90-2.29) or survival to hospital discharge (OR 1.29; 95% CI 0.83-2.01). Results using the full cohort were similar. CONCLUSIONS: We did not detect an association between the first-attempted intra-arrest IO site (tibia vs. humerus) and clinical outcomes. Clinical trials are warranted to test differences between vascular access strategies.

Out-of-hospital cardiac arrests terminated without full resuscitation attempts: Characteristics and regional variability.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) investigations may elect to exclude cases with resuscitation terminated for reasons other than a full resuscitative attempt. We sought to examine characteristics of these cases and regional variability in classification. METHODS: Using the North American Resuscitation Outcomes Consortium Epistry, we included adult emergency medical services (EMS)-treated cases, examining the rationale ("futility", do-not resuscitate [DNR] order, "verbal directive", or "obvious death") and timing of resuscitation termination, and the timing of ROSC among hospital-discharge survivors. We tested regional variability in EMS patient arrival-to-termination intervals with one-way ANOVA. RESULTS: Of 63,554 included cases, 27,232 were declared dead in the prehospital setting: (1) 23,009 (36%) for futility (after a median of 24 minutes [IQR 19-31] of professional resuscitation); (2) 1622 (2.6%) for a DNR order (at 6.3 minutes [IQR 3.0-11]); (3) 1018 (1.6%) for a verbal directive (at 12 minutes [IQR 7.0-17]); and, (4) 1583 (2.5%) for obvious death (at 5.4 minutes [IQR 3.0-9.0]). The EMS patient arrival-to-ROSC interval among hospital-discharge survivors was 7.7 (3.8-13) minutes. Among regions, 0.20-12% and 0.20-5.3% were terminated to due to obvious death or verbal directives, respectively. There were significant regional differences in the EMS patient arrival-to-termination interval for futility (p < 0.010) and obvious death (p < 0.010). CONCLUSION: There is significant variation in the rationale and interval until termination of resuscitation between regions. Cases terminated due to obvious death or DNR orders/verbal directives are often treated with similar durations of resuscitation as survivors. These data highlight a considerable risk of bias in between-region comparisons or observational analyses.

Emergency medical services employing intra-arrest transport less frequently for out-of-hospital cardiac arrest have higher survival and favorable neurological outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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% (quartiles <6.2%, 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). CONCLUSION: 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.

The association of intraosseous vascular access and survival among pediatric patients with out-of-hospital cardiac arrest.

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.

The association of scene-access delay and survival with favourable neurological status in patients with out-of-hospital cardiac arrest.

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 s), longer CTC quartiles (63-115, 116-180, and ≥181 s) demonstrated the following associations with survival with favourable neurological status: adjusted odds ratios 0.95, 95% CI 0.83-1.09; 0.77, 95% CI 0.66-0.89; 0.66, 95% CI 0.56-0.77, respectively. Of the 49 study clusters, median CTC intervals ranged from 86 (IQR 58-130) to 179 s (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 2-min CTC threshold may represent an appropriate target for quality improvement.

The relationship between no-flow interval and survival with favourable neurological outcome in out-of-hospital cardiac arrest: Implications for outcomes and ECPR eligibility.

BACKGROUND: The "no flow" interval is the time from out-of-hospital cardiac arrest (OHCA) to cardiopulmonary resuscitation (CPR). Its prognostic value is important to define for prehospital resuscitation decisions, post-resuscitation care and prognostication, and extracorporeal cardiopulmonary resuscitation (ECPR) candidacy assessment. METHODS: We examined bystander-witnessed OHCAs without bystander CPR from two Resuscitation Outcomes Consortium datasets. We used modified Poisson regression to model the relationship between the no-flow interval (9-1-1 call to professional resuscitation) and favourable neurological outcome (Modified Rankin Score ≤ 3) at hospital discharge. Furthermore, we identified the no-flow interval beyond which no patients had a favourable outcome. We analysed a subgroup to simulate ECPR-treated patients (witnessed arrest, age < 65, non-asystole initial rhythm, and >30 min until return of circulation). RESULTS: Of 43,593 cases, we included 7299; 616 (8.4%) had favourable neurological outcomes. Increasing no-flow interval was inversely associated with favourable neurological outcomes (adjusted relative risk 0.87, 95% CI 0.85-0.90); the adjusted probability of a favourable neurological outcome decreased by 13% (95% CI 10-15%) per minute. No patients (0/7299, 0%; 1-sided 97.5% CI 0-0.051%) had both a no-flow interval >20 min and a favourable neurological outcome. In the hypothetical ECPR group, 0/152 (0%; 1-sided 97.5% CI 0-2.4%) had both a no-flow interval >10 min and a favourable neurological outcome. CONCLUSIONS: The probability of a favourable neurological outcome in OHCA decreases by 13% for every additional minute of no-flow time until high-quality CPR, with the possibility of favourable outcomes up to 20 min.

Public access defibrillators: Gender-based inequities in access and application.

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.

Relationship Between Duration of Targeted Temperature Management, Ischemic Interval, and Good Functional Outcome From Out-of-Hospital Cardiac Arrest.

OBJECTIVES: 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. DESIGN: Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study. SETTING: Multicenter study across North America. PATIENTS: 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. INTERVENTIONS: 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). MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments: protocol for a multicentre prospective cohort study.

INTRODUCTION: Recent 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 ANALYSIS: In 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 DISSEMINATION: The 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.

The Association of the Average Epinephrine Dosing Interval and Survival With Favorable Neurologic Status at Hospital Discharge in Out-of-Hospital Cardiac Arrest.

STUDY OBJECTIVE: For patients with out-of-hospital cardiac arrest, the recommended dosing interval of epinephrine is 3 to 5 minutes, but this recommendation is based on expert opinion without data to guide optimal management. We seek to evaluate the association between the average epinephrine dosing interval and patient outcomes. METHODS: In a secondary analysis of the Resuscitation Outcomes Consortium continuous chest compression trial, we identified consecutive patients treated with greater than or equal to 2 doses of epinephrine. We defined average epinephrine dosing interval as resuscitation duration after the first dose of epinephrine divided by the total administered epinephrine, and categorized the dosing interval in minutes as less than 3, 3 to less than 4, 4 to less than 5, and greater than or equal to 5. We fit a logistic regression model to estimate the association of the average epinephrine dosing interval category with survival with favorable neurologic status (modified Rankin Scale score ≤3) at hospital discharge. RESULTS: We included 15,909 patients (median age 68 years [interquartile range 56 to 80 years], 35% women, 13% public location, 46% bystander cardiopulmonary resuscitation, and 19% initial shockable rhythm). The median epinephrine dosing interval was 4.3 minutes (interquartile range 3.5 to 5.3 minutes). Survival with favorable neurologic status occurred in 4.7% of patients. Compared with the reference dosing interval of less than 3 minutes, longer epinephrine dosing intervals were associated with lower survival with favorable neurologic status: dosing interval 3 to less than 4 minutes, adjusted odds ratio 0.44 (95% confidence interval 0.32 to 0.60); 4 to less than 5 minutes, adjusted odds ratio 0.26 (95% confidence interval 0.18 to 0.36); and greater than or equal to 5 minutes, adjusted odds ratio 0.21 (95% confidence interval 0.15 to 0.30). CONCLUSION: In this out-of-hospital cardiac arrest series, a shorter average epinephrine dosing interval was associated with improved survival with favorable neurologic status.

Door-to-Targeted Temperature Management Initiation Time and Outcomes in Out-of-Hospital Cardiac Arrest: Insights From the Continuous Chest Compressions Trial.

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.

North American validation of the Bokutoh criteria for withholding professional resuscitation in non-traumatic out-of-hospital cardiac arrest.

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.

Early advanced life support attendance is associated with improved survival and neurologic outcomes after non-traumatic out-of-hospital cardiac arrest in a tiered prehospital response system.

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.

Trends in care processes and survival following prehospital resuscitation improvement initiatives for out-of-hospital cardiac arrest in British Columbia, 2006-2016.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Effects of Ipragliflozin on Postprandial Glucose Metabolism and Gut Peptides in Type 2 Diabetes: A Pilot Study.

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).

Intraosseous Vascular Access Is Associated With Lower Survival and Neurologic Recovery Among Patients With Out-of-Hospital Cardiac Arrest.

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.

Gains of Continuing Resuscitation in Refractory Out-of-hospital Cardiac Arrest: A Model-based Analysis to Identify Deaths Due to Intra-arrest Prognostication.

OBJECTIVE: 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. METHODS: 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%. RESULTS: 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. CONCLUSION: 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.