Identification of Emerging Novel Psychoactive Substances by Retrospective Analysis of Population-Scale Mass Spectrometry Data Sets.

Over the last two decades, hundreds of new psychoactive substances (NPSs), also known as "designer drugs", have emerged on the illicit drug market. The toxic and potentially fatal effects of these compounds oblige laboratories around the world to screen for NPS in seized materials and biological samples, commonly using high-resolution mass spectrometry. However, unambiguous identification of a NPS by mass spectrometry requires comparison to data from analytical reference materials, acquired on the same instrument. The sheer number of NPSs that are available on the illicit market, and the pace at which new compounds are introduced, means that forensic laboratories must make difficult decisions about which reference materials to acquire. Here, we asked whether retrospective suspect screening of population-scale mass spectrometry data could provide a data-driven platform to prioritize emerging NPSs for assay development. We curated a suspect database of precursor and diagnostic fragment ion masses for 83 emerging NPSs and used this database to retrospectively screen mass spectrometry data from 12,727 urine drug screens from one Canadian province. We developed integrative computational strategies to prioritize the most reliable identifications and tracked the frequency of these identifications over a 3 year study period between August 2019 and August 2022. The resulting data were used to guide the acquisition of new reference materials, which were in turn used to validate a subset of the retrospective identifications. Last, we took advantage of matching clinical reports for all 12,727 samples to systematically benchmark the accuracy of our retrospective data analysis approach. Our work opens up new avenues to enable the rapid detection of emerging illicit drugs through large-scale reanalysis of mass spectrometry data.

Qualitative Exploration of Emergency Department Care Experiences Among People With Opioid Use Disorder.

STUDY OBJECTIVE: We described the experiences and preferences of people with opioid use disorder who access emergency department (ED) services regarding ED care and ED-based interventions. METHODS: Between June and September 2020, we conducted phone or in-person semistructured qualitative interviews with patients recently discharged from 2 urban EDs in Vancouver, BC, Canada, to explore experiences and preferences of ED care and ED-based opioid use disorder interventions. We recruited participants from a cohort of adults with opioid use disorder who were participating in an ED-initiated outreach program. We transcribed audio recordings verbatim. We iteratively developed a thematic coding structure, with interim analyses to assess for thematic saturation. Two team members with lived experience of opioid use provided feedback on content, wording, and analysis throughout the study. RESULTS: We interviewed 19 participants. Participants felt discriminated against for their drug use, which led to poorer perceived health care and downstream ED avoidance. Participants desired to be treated like ED patients who do not use drugs and to be more involved in their ED care. Participants nevertheless felt comfortable discussing their substance use with ED staff and valued continuous ED operating hours. Regarding opioid use disorder treatment, participants supported ED-based buprenorphine/naloxone programs but also suggested additional options (eg, different initiation regimens and settings and other opioid agonist therapies) to facilitate further treatment uptake. CONCLUSION: Based on participant experiences, we recommend addressing potentially stigmatizing practices, increasing patient involvement in their care during ED visits, and increasing access to various opioid use disorder-related treatments and community support.

Concordance between 8-1-1 HealthLink BC Emergency iDoctor-in-assistance (HEiDi) virtual physician advice and subsequent health service utilization for callers to a nurse-managed provincial health information telephone service.

BACKGROUND: British Columbia 8-1-1 callers who are advised by a nurse to seek urgent medical care can be referred to virtual physicians (VPs) for supplemental assessment and advice. Prior research indicates callers' subsequent health service use may diverge from VP advice. We sought to 1) estimate concordance between VP advice and subsequent health service use, and 2) identify factors associated with concordance to understand potential drivers of discordant cases. METHODS: We linked relevant provincial administrative databases to obtain inpatient, outpatient, and emergency service use by callers. We developed operational definitions of concordance collaboratively with researcher, patient, VP, and management perspectives. We used Kaplan-Meier curves to describe health service use post-VP consultation and Cox regression to estimate the association of caller factors (rurality, demography, attachment to primary care) and call factors (reason, triage level, time of day) with concordance as hazard ratios. RESULTS: We analyzed 17,188 calls from November 16, 2020 to April 30, 2021. Callers advised to attend an emergency department (ED) immediately were the most concordant (73%) while concordance was lowest for those advised to seek Family Physician (FP) care either immediately (41%) or within 7 days (47%). Callers unattached to FPs were less likely to schedule an FP visit (hazard ratio = 0.76 [95%CI: 0.68-0.85]). Rural callers were less likely to attend an ED within 48 h when advised to go immediately (0.53 [95%CI:0.46-0.61]) compared to urban callers. Rural callers advised to see an FP, either immediately (1.28 [95%CI:1.01-1.62]) or within 7 days (1.23 [95%CI: 1.11-1.37]), were more likely to do so than urban callers. INTERPRETATION: Concordance between VP advice and subsequent caller health service use varies substantially by category of advice and caller rurality. Concordance with advice to "Go to ED" is high overall but to access primary care is below 50%, suggesting potential issues with timely access to FP care. Future research from a patient/caller centered perspective may reveal additional barriers and facilitators to concordance.

Exploring how to enhance care and pathways between the emergency department and integrated youth services for young people with mental health and substance use concerns.

BACKGROUND: Integrated youth services (IYS) provide multidisciplinary care (including mental, physical, and social) prioritizing the needs of young people and their families. Despite a significant rise in emergency department (ED) visits by young Canadians with mental health and substance use (MHSU) concerns over the last decade, there remains a profound disconnect between EDs and MHSU integrated youth services. The first objective of this study was to better understand the assessment, treatment, and referral of young people (ages 12-24 years) presenting to the ED with MHSU concerns. The second objective was to explore how to improve the transition from the ED to IYS for young people with MHSU concerns. METHODS: We conducted semi-structured one-on-one video and phone interviews with stakeholders in British Columbia, Canada in the summer of 2020. Snowball sampling was utilized, and participants (n = 26) were reached, including ED physicians (n = 6), social workers (n = 4), nurses (n = 2), an occupational therapist (n = 1); a counselor (n = 1); staff/leadership in IYS organizations (n = 4); mental health/family workers (n = 3); peer support workers (n = 2), and parents (n = 3). A thematic analysis (TA) was conducted using a deductive and inductive approach conceptually guided by the Social Ecological Model. RESULTS: We identified three overarching themes, and factors to consider at all levels of the Social Ecological Model. At the interpersonal level inadequate communication between ED staff and young people affected overall care and contributed to negative experiences. At the organizational level, we identified considerations for assessments and the ED and the hospital (wait times, staffing issues, and the physical space). At the community level, the environment of IYS and other community services were important including wait times and hours of operation. Policy level factors identified include inadequate communication between services (e.g., different charting systems and documentation). CONCLUSIONS: This study provides insight into important long-term systemic issues and more immediate factors that need to be addressed to improve the delivery of care for young people with MHSU challenges. This research supports intervention development and implementation in the ED for young people with MHSU concerns.

Which Patients Should Have Early Surgical Intervention for Acute Ureteral Colic?

PURPOSE: Early surgical intervention is an attractive option for acute ureteral colic but existing evidence does not clarify which patients benefit. We compared treatment failure rates in patients receiving early intervention and patients offered spontaneous passage to identify subgroups that benefit from early intervention. MATERIALS AND METHODS: We used administrative data and structured chart review to study consecutive patients attending 9 emergency departments in 2 Canadian provinces with confirmed 2.0 to 9.9 mm ureteral stones. We described patient, stone and treatment characteristics, and performed multivariable regression to identify factors associated with treatment failure, defined as intervention or hospitalization within 60 days. Our secondary outcome was emergency department revisit rate. RESULTS: Overall 1,168 of 3,081 patients underwent early intervention. Those with stones smaller than 5 mm experienced more treatment failures (31.5% vs 9.9%, difference 21.6%, 95% CI 16.9 to 21.2) and emergency department revisits (38.5% vs 19.7%, difference 18.8%, 95% CI 13.8 to 23.8) with early intervention than with spontaneous passage. Patients with stones 7.0 mm or larger experienced fewer treatment failures (34.7% vs 58.6%, risk difference 23.9%, 95% CI 11.3 to 36.6) and similar emergency department revisit rates with early intervention. Patients with 5.0 to 6.9 mm stones had fewer treatment failures with intervention (37.4% vs 55.5%, risk difference 18.1%, 95% CI 7.1 to 28.9) if stones were in the proximal or middle ureter. CONCLUSIONS: Early intervention improves outcomes for patients with large (greater than 7 mm) ureteral stones or 5 to 7 mm proximal or mid ureteral stones. Early intervention may increase morbidity for patients with stones smaller than 5 mm. These findings could help inform future guidelines.

Rapid Agitation Control With Ketamine in the Emergency Department: A Blinded, Randomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. METHODS: We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events. RESULTS: Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]). CONCLUSION: In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.

Impact of Atrial Fibrillation Case Volume in the Emergency Department on Early and Late Outcomes of Patients With New Atrial Fibrillation.

STUDY OBJECTIVE: To define the association between atrial fibrillation case volume in the emergency department and death or all-cause hospitalization at 30 days and 1 year in patients with new atrial fibrillation. Secondary objectives examined repeat ED visits and the management of atrial fibrillation within 90 days. METHODS: We identified all adults presenting to an ED in Alberta, Canada, with a new primary diagnosis of atrial fibrillation/flutter between 2009 and 2015 using International Classification of Diseases, 10th Revision code I48. Volume was classified in tertiles weighted by annual ED number of atrial fibrillation cases. The association between volume and outcomes was evaluated using generalized linear mixed models, adjusting for prognostically important covariates as fixed effects and ED as a random effect to account for potential clustering within EDs. RESULTS: The tertiles consisted of 4 high, 9 medium, and 68 low atrial fibrillation volume EDs, with 4,217, 4,193, and 4,112 patients, respectively. Volume was not independently associated with the primary outcome or individual components. However, medium- and high-volume EDs had fewer repeat ED visits at 30 days (respective adjusted odds ratio [aOR] 0.75 [95% confidence interval {CI} 0.66 to 0.87] and 0.64 [0.52 to 0.79]) and 1 year (respective aOR 0.77 [95% CI 0.67 to 0.90] and 0.71 [0.56 to 0.90]). Fewer patients were admitted from medium- (37.1%) and high- (32.0%) compared with low-volume (39.5%) EDs. Patients attending medium- and high-volume EDs were more likely to be cardioverted (aOR 3.28 [95% CI 1.94 to 5.53] and 3.81 [1.39 to 10.48] for medium- and high-volume EDs, respectively). CONCLUSION: Treatment in higher volume EDs was associated with significantly lower admission rates and repeat ED visits but no difference in survival.

Can plain film radiography improve the emergency department detection of clinically important urinary stones?

OBJECTIVE: Physicians frequently use ultrasound to assess hydronephrosis in patients with suspected renal colic, but ultrasound has limited diagnostic sensitivity and rarely clarifies stone size or location. Consequently, up to 80% of emergency department (ED) renal colic patients undergo confirmatory CT imaging. Our goal was to estimate x-ray sensitivity for urinary stones and determine whether x-ray substantially improves stone detection (sensitivity) compared to hydronephrosis assessment alone. METHODS: We reviewed imaging reports from all renal colic patients who underwent x-ray and CT at four EDs. For each patient, we documented stone size, location and hydronephrosis severity on CT and whether stones were identified on x-ray. We considered moderate and severe hydronephrosis (MS-Hydro) as significant positive findings, then calculated the sensitivity (detection rate) of MS-Hydro and x-ray for large stones ≥5 mm and for stones likely to require intervention (all ureteral stones >7 mm and proximal or middle stones >5 mm). We then tested a diagnostic algorithm adding x-ray to hydronephrosis assessment. RESULTS: Among 1026 patients with 1527 stones, MS-Hydro sensitivity was 39% for large stones and 60% for interventional stones. X-ray sensitivity was 46% for large stones and 52% for interventional stones. Adding x-ray to hydronephrosis assessment increased sensitivity in all stone categories, specifically from 39% to 68% for large stones (gain = 29%; 95%CI, 23% to 35%) and from 60% to 82% for interventional stones (gain = 22%; 95%CI, 13% to 30%). Because CT and ultrasound show strong agreement for MS-Hydro identification, physicians who depend on ultrasound-based hydronephrosis assessment could achieve similar gains by adding x-ray. CONCLUSIONS: Adding x-ray to hydronephrosis assessment substantially improves diagnostic sensitivity, enabling the detection of nearly 70% of large stones and over 80% of interventional stones. This level of sensitivity may be sufficient to reassure physicians about a renal colic diagnosis without CT imaging for many patients.

High-Sensitivity Cardiac Troponin-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial.

Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. METHODS/DESIGN: CODE-MI (hs-cTn-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. CONCLUSIONS: This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.

Preventable adverse drug events: Descriptive epidemiology.

AIM: Our objective was to identify preventable adverse drug events and factors contributing to their development. METHODS: We performed a retrospective chart review combining data from three prospective multicentre observational studies that assessed emergency department patients for adverse drug events. A clinical pharmacist and physician independently reviewed the charts, extracted data and rated the preventability of each adverse drug event. A third reviewer adjudicated all discordant or uncertain cases. We calculated the proportion of adverse drug events that were deemed preventable, performed multivariable logistic regression to explore the characteristics of patients with preventable events, and identified contributing factors. RESULTS: We reviewed the records of 1 356 adverse drug events in 1 234 patients. Raters considered 869 (64.1%) of adverse drug events probably or definitely preventable. Patients with mental health diagnoses (OR 1.8; 95% CI 1.3-2.5) and diabetes (OR 1.7; 95% CI 1.2-2.4) were more likely to present with preventable events. The medications most commonly implicated in preventable events were warfarin (9.4%), hydrochlorothiazide (4.5%), furosemide (4.0%), insulin (3.9%) and acetylsalicylic acid (2.7%). Common contributing factors included inadequate patient instructions, monitoring and follow-up, and reassessments after medication changes had been made. CONCLUSIONS: Our study suggests that patients with mental health conditions and diabetes require close monitoring. Efforts to address the identified contributing factors are needed.

Impact of cardiology follow-up care on treatment and outcomes of patients with new atrial fibrillation discharged from the emergency department.

AIMS: The first presentation of atrial fibrillation (AF) is often to an emergency department (ED). We evaluated the association of subsequent specialist care with morbidity and mortality. METHODS AND RESULTS: Retrospective cohort study of all adults in Alberta, Canada, with a new primary diagnosis of AF treated and released during an index ED visit between 2009 and 2015. Types of physician follow-up within 3 months of ED visit was analysed using Cox proportional hazards models with time-varying covariates. Outcomes were evaluated at 1 year. Of 7986 patients, 476 (6.0%) had no physician follow-up within 3 months, whereas 2730 (34.2%) attended a non-specialist only, 1277 (16.0%) an internal medicine specialist, and 3503 (43.9%) cardiology. An increasing gradient of cardiac investigations occurred across these groups. Cardiology compared with non-cardiologist care was associated with approximately two-fold greater electrophysiology interventions and revascularization, and increased use of beta-blockers (48.9% vs. 43.0%, P < 0.0001), statins (31.4% vs. 26.7%, P < 0.0001), and oral anticoagulation in patients with CHADS2 scores ≥1 (53.7% vs. 43.6%, P < 0.0001). In the subsequent year, cardiology care was associated with fewer deaths [adjusted hazard ratio (aHR) 0.72, 95% confidence interval (CI) 0.55-0.93], strokes (aHR 0.60, 95% CI 0.37-0.96), or major bleeds (aHR 0.69, 95% CI 0.53-0.89). No differences in the risk of hospitalization or ED visits were associated with cardiology care. CONCLUSION: Cardiology care after an ED visit for symptomatic new-onset AF is associated with better prognosis. The benefit may be mediated through more intensive investigation, identification, and treatment of cardiovascular risk factors and disease.

Lorazepam Versus Diazepam in the Management of Emergency Department Patients With Alcohol Withdrawal.

STUDY OBJECTIVE: Alcohol withdrawal is a common emergency department (ED) presentation. Although benzodiazepines reduce symptoms of withdrawal, there is little ED-based evidence to assist clinicians in selecting appropriate pharmacotherapy. We compare lorazepam with diazepam for the management of alcohol withdrawal to assess 1-week ED and hospital-related outcomes. METHODS: From January 1, 2015, to December 31, 2018, at 3 urban EDs in Vancouver, Canada, we studied patients with a discharge diagnosis of alcohol withdrawal. We excluded individuals presenting with a seizure or an acute concurrent illness. We performed a structured chart review to ascertain demographics, ED treatments, and outcomes. Patients were stratified according to initial management with lorazepam versus diazepam. The primary outcome was hospital admission, and secondary outcomes included in-ED seizures and 1-week return visits for discharged patients. RESULTS: Of 1,055 patients who presented with acute alcohol withdrawal, 898 were treated with benzodiazepines. Median age was 47 years (interquartile range 37 to 56 years) and 73% were men. Baseline characteristics were similar in the 2 groups. Overall, 69 of 394 patients (17.5%) receiving lorazepam were admitted to the hospital compared with 94 of 504 patients receiving diazepam (18.7%), a difference of 1.2% (95% confidence interval -4.2% to 6.3%). Seven patients (0.7%; 95% confidence interval 0.3% to 1.4%) had an in-ED seizure, but all seizures occurred before receipt of benzodiazepines. Among patients discharged home, 1-week return visits occurred for 78 of 325 (24.0%) who received lorazepam and 94 of 410 (23.2%) who received diazepam, a difference of 0.8% (95% confidence interval -5.3% to 7.1%). CONCLUSION: In our sample of ED patients with acute alcohol withdrawal, patients receiving lorazepam had an admission rate similar to that of those receiving diazepam. The few in-ED seizures occurred before medication administration. For discharged patients, the 1-week ED return visit rate of nearly 25% could warrant enhanced follow-up and community support.

Time to Epinephrine Administration and Survival From Nonshockable Out-of-Hospital Cardiac Arrest Among Children and Adults.

BACKGROUND: Previous studies have demonstrated that earlier epinephrine administration is associated with improved survival from out-of-hospital cardiac arrest (OHCA) with shockable initial rhythms. However, the effect of epinephrine timing on patients with nonshockable initial rhythms is unclear. The objective of this study was to measure the association between time to epinephrine administration and survival in adults and children with emergency medical services (EMS)-treated OHCA with nonshockable initial rhythms. METHODS: We performed a secondary analysis of OHCAs prospectively identified by the Resuscitation Outcomes Consortium network from June 4, 2011, to June 30, 2015. We included patients of all ages with an EMS-treated OHCA and an initial nonshockable rhythm. We excluded those with return of spontaneous circulation in <10 minutes. We conducted a subgroup analysis involving patients <18 years of age. The primary exposure was time (minutes) from arrival of the first EMS agency to the first dose of epinephrine. Secondary exposure was time to epinephrine dichotomized as early (<10 minutes) or late (≥10 minutes). The primary outcome was survival to hospital discharge. We adjusted for Utstein covariates and Resuscitation Outcomes Consortium study site. RESULTS: From 55 568 EMS-treated OHCAs, 32 101 patients with initial nonshockable rhythms were included. There were 12 238 in the early group, 14 517 in the late group, and 5346 not treated with epinephrine. After adjusting for potential confounders, each minute from EMS arrival to epinephrine administration was associated with a 4% decrease in odds of survival for adults, odds ratio=0.96 (95% confidence interval, 0.95-0.98). A subgroup analysis (n=13 290) examining neurological outcomes showed a similar association (adjusted odds ratio, 0.94 per minute; 95% confidence interval, 0.89-0.98). When epinephrine was given late in comparison with early, odds of survival were 18% lower (odds ratio, 0.82; 95% confidence interval, 0.68-0.98). In a pediatric analysis (n=595), odds of survival were 9% lower (odds ratio, 0.91; 95% confidence interval, 0.81-1.01) for each minute delay in epinephrine. CONCLUSIONS: Among OHCAs with nonshockable initial rhythms, the majority of patients were administered epinephrine >10 minutes after EMS arrival. Each minute delay in epinephrine administration was associated with decreased survival and unfavorable neurological outcomes. EMS agencies should consider strategies to reduce epinephrine administration times in patients with initial nonshockable rhythms.

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.

Safety of a Modified Community Trailer to Manage Patients with Presumed Fentanyl Overdose.

Opioid overdoses (OD) cause substantial morbidity and mortality globally, and current emergency management is typically limited to supportive care, with variable emphasis on harm reduction and addictions treatment. Our urban setting has a high concentration of patients with presumed fentanyl OD, which places a burden on both pre-hospital and emergency department (ED) resources. From December 13, 2016, to March 1, 2017, we placed a modified trailer away from an ED but near the center of the expected area of high OD and accepted low-risk patients with presumed fentanyl OD. We provided OD treatment as well as on-site harm reduction, addictions care, and community resources. The primary outcome was the proportion of patients requiring transfer to an ED for clinical deterioration, while secondary outcomes were the proportion of patients initiated on opioid agonists and provided take-home naloxone kits. We treated 269 patients with opioid OD, transferred three (1.1%) to a local ED, started 43 (16.0%) on opioid agonists, and provided 220 (81.7%) with THN. Our program appears to be safe and may serve as a model for other settings dealing with a large numbers of opioid OD.

Methods for evaluating adverse drug event preventability in emergency department patients.

BACKGROUND: There is a high degree of variability in assessing the preventability of adverse drug events, limiting the ability to compare rates of preventable adverse drug events across different studies. We compared three methods for determining preventability of adverse drug events in emergency department patients and explored their strengths and weaknesses. METHODS: This mixed-methods study enrolled emergency department patients diagnosed with at least one adverse drug event from three prior prospective studies. A clinical pharmacist and physician reviewed the medical and research records of all patients, and independently rated each event's preventability using a "best practice-based" approach, an "error-based" approach, and an "algorithm-based" approach. Raters discussed discordant ratings until reaching consensus. We assessed the inter-rater agreement between clinicians using the same assessment method, and between different assessment methods using Cohen's kappa with 95% confidence intervals (95% CI). Qualitative researchers observed discussions, took field notes, and reviewed free text comments made by clinicians in a "comment" box in the data collection form. We developed a coding structure and iteratively analyzed qualitative data for emerging themes regarding the application of each preventability assessment method using NVivo. RESULTS: Among 1356 adverse drug events, a best practice-based approach rated 64.1% (95% CI: 61.5-66.6%) of events as preventable, an error-based approach rated 64.3% (95% CI: 61.8-66.9%) of events as preventable, and an algorithm-based approach rated 68.8% (95% CI: 66.1-71.1%) of events as preventable. When applying the same method, the inter-rater agreement between clinicians was 0.53 (95% CI: 0.48-0.59), 0.55 (95%CI: 0.50-0.60) and 0.55 (95% CI: 0.49-0.55) for the best practice-, error-, and algorithm-based approaches, respectively. The inter-rater agreement between different assessment methods using consensus ratings for each ranged between 0.88 (95% CI 0.85-0.91) and 0.99 (95% CI 0.98-1.00). Compared to a best practice-based assessment, clinicians believed the algorithm-based assessment was too rigid. It did not account for the complexities of and variations in clinical practice, and frequently was too definitive when assigning preventability ratings. CONCLUSION: There was good agreement between all three methods of determining the preventability of adverse drug events. However, clinicians found the algorithmic approach constraining, and preferred a best practice-based assessment method.

Safety of a Brief Emergency Department Observation Protocol for Patients With Presumed Fentanyl Overdose.

STUDY OBJECTIVE: Fentanyl overdoses are increasing and few data guide emergency department (ED) management. We evaluate the safety of an ED protocol for patients with presumed fentanyl overdose. METHODS: At an urban ED, we used administrative data and explicit chart review to identify and describe consecutive patients with uncomplicated presumed fentanyl overdose (no concurrent acute medical issues) from September to December 2016. We linked regional ED and provincial vital statistics databases to ascertain admissions, revisits, and mortality. Primary outcome was a composite of admission and death within 24 hours. Other outcomes included treatment with additional ED naloxone, development of a new medical issue while in the ED, and length of stay. A prespecified subgroup analysis assessed low-risk patients with normal triage vital signs. RESULTS: There were 1,009 uncomplicated presumed fentanyl overdose, mainly by injection. Median age was 34 years, 85% were men, and 82% received out-of-hospital naloxone. One patient was hospitalized and one discharged patient died within 24 hours (combined outcome 0.2%; 95% confidence interval [CI] 0.04% to 0.8%). Sixteen patients received additional ED naloxone (1.6%; 95% CI 1.0% to 2.6%), none developed a new medical issue (0%; 95% CI 0% to 0.5%), and median length of stay was 173 minutes (interquartile range 101 to 267). For 752 low-risk patients, no patients were admitted or developed a new issue, and one died postdischarge; 3 (0.4%; 95% CI 0.01% to 1.3%) received ED naloxone. CONCLUSION: In our cohort of ED patients with uncomplicated presumed fentanyl overdose-typically after injection-deterioration, admission, mortality, and postdischarge complications appear low; the majority can be discharged after brief observation. Patients with normal triage vital signs are unlikely to require ED naloxone.

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.