Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

Introduction: Rapid diagnostic algorithms using high-sensitivity cardiac troponin can rapidly diagnose or exclude acute myocardial infarction (MI). However, multiple algorithms have been proposed and it is unclear if some outperform others. The objective of this study was to prospectively compare the diagnostic performance of 1- and 2-hour algorithms in clinical practice in a Canadian population. Methods: Emergency department patients with chest pain had high-sensitivity cardiac troponin-T (hs-cTnT) collected on presentation and 1- and 2-hours later at a single academic tertiary hospital and regional percutaneous coronary intervention site over a 2-year period. The primary outcome was index MI, the secondary outcome was 30-day major adverse cardiac events (MACE). All outcomes were 2 physician adjudicated. Results: We enrolled 1,167 patients with hs-cTnT collected on ED presentation. Of these, 350 had a valid 1-hour and 550 had a 2-hour hs-cTnT sample. Index MI prevalence was ~11%. Sensitivity of the 1- and 2-hour algorithms for index MI was 97.3% (95% CI 85.8-99.9%) and 100% (95% CI 91.6-100%) and for 30-day MACE was 80.9% (95% CI 66.7-90.9%) and 83.3% (95% CI 73.2-90.8%), respectively. The 1-hour algorithm was 96.3% specific for index MI (95% CI 93.8-98.2%) whereas specificity for the 2-hour algorithm was 97.9% (95% CI 96.3-100%). Both algorithms classified about one-quarter of patients in an indeterminate observational zone with an ~11% MI prevalence. Conclusion: Both the 1- and 2-hour algorithms were highly sensitive and specific for MI, but were less sensitive for 30-day MACE. However, the 2-hour algorithm trended toward better performance, likely because its larger delta cutoffs reduce the risk of misclassification owing to analytic variability. These findings suggest algorithms using larger delta cutoffs may provide a greater margin of safety. Further comparative evaluation of rapid diagnostic algorithms using different cutoffs and characterization of patients in the observational zone is warranted.

Introduction: Very low high-sensitivity troponin-T (hs-cTnT) concentrations on presentation can rule out acute myocardial infarction (AMI), but the ability to identify patients at low risk of 30-day major adverse cardiac events (MACE) is less clear. This study examines the sensitivity of low concentrations of hs-cTnT on presentation to rule out 30-day MACE. Methods: This prospective cohort study enrolled emergency department chest pain patients with non-ischemic ECGs who underwent AMI rule-out with an hs-cTnT assay. The primary outcome was 30-day MACE; secondary outcomes were individual MACE components. Because guidelines recommend using a single hs-cTnT strategy only for patients with more than 3-hours since symptom onset, a subgroup analysis was performed for this population. Outcomes were adjudicated based on review of medical records and telephone follow-up. Results: Of 1,167 patients enrolled, 125 (10.7%) experienced 30-day MACE and 97 (8.3%) suffered AMI on the index visit. More than one-third (35.6%) had presenting hs-cTnT concentrations below the limit of detection (5ng/L), which was 94.4% (95%CI 88.8-97.7%) sensitive for 30-day MACE and 99.0% (95%CI 94.5-100%) sensitive for index AMI. Of 292 (25.0%) patients with hs-cTnT < 5ng/L and at least 3-hours since symptom onset, only 3 experienced 30-day MACE (sensitivity 97.6%, 95%CI 93.2-100%) and none suffered AMI within 30-days (sensitivity 100%, 95%CI 96.3-100%). Conclusion: Among patients with non-ischemic ECGs and >3-hours since symptom onset, low hs-cTnT concentrations on presentation confer a very low risk of 30-day MACE. In the absence of a high risk clinical presentation, further risk stratification is likely to be low yield.

Introduction: Chest pain is one of the most common presenting complaints to emergency departments (EDs) across the world, and the exclusion of acute myocardial infarction (AMI) using troponin testing is central to the care of many of these patients. While testing strategies using conventional troponin assays require repeat testing over many hours to avoid missed diagnoses, high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in a large proportion of patients with a single result at presentation. This objective of this study is to validate the ability of very low concentrations of hs-cTn at presentation to exclude AMI in ED chest pain patients. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at presentation. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. This study was REB approved. Results: A total of 1,167 patients were enrolled from August 2014 September 2016, of which 191 (16.3%) patients had an initial troponin below the limit of blank (LoB, <3 ng/L) and 416 (32.8%) were below the limit of detection (LoD, <5 ng/L). The sensitivity of a single troponin below the LoB (<3 ng/L) for index AMI was 100% (95% CI 96.2%-100%) and for 30-day AMI was 100% (95% CI 96.4-100%). The sensitivity of a troponin below the LoD (<5 ng/L) for index AMI was 97.9% (95% CI 92.7%-99.8%) and for 30-day AMI was 98.0% (95% CI 93.0-99.8%). Sensitivity for 30-day MACE at both cutoffs was lower: 98.4% (95% CI 94.3-99.8%) for <3 ng/L, and 94.4% (95% CI 88.8-97.7%) for <5 ng/L, respectively; however, negative predictive values remained high at both cutoffs: <3 ng/L, 99.0% (95% CI 96.3-99.9%) and <5 ng/L, 98.3% (95% CI 96.6-99.3%). Conclusion: A high sensitivity troponin T result below the LoB (<3 ng/L) is highly sensitive for excluding AMI and identifies patients at low risk of 30-day MACE. A result below the LoB (<5 ng/L) will identify a larger population of patients as low risk but has a greater risk of missed AMI and MACE.

Introduction: Utilization of CT pulmonary angiography (CTPA) to rule out pulmonary embolism (PE) has risen dramatically but diagnostic yield has fallen over the past several decades, suggesting that lower risk patients are being tested. Given little evidence to suggest improved patient outcomes with higher CTPA utilization, and increasing evidence of harm, evidence-based guidelines have been developed to reduce unnecessary CTPA use. The objective of this study was to assess the impact of an electronic clinical decision support (CDS) intervention to reduce unnecessary CTPA utilization for emergency department (ED) patients with suspected PE. Methods: This was a cluster-randomized, controlled trial with physicians as the unit of randomization. All emergency physicians (EPs) at 4 urban adult EDs and 1 urgent care center were randomly assigned to receive either evidence-based imaging CDS for patients with suspected PE (intervention) or no CDS (control) over a 1-year study period. CDS was launched in an external web browser whenever an intervention EP ordered a CTPA from the computerized physician order entry software for ED patients CTAS 2-5; however, physician interaction with CDS was voluntary. The CDS tool enabled calculation of patient-specific information, including the patients Wells score, PERC score, and age-adjusted D-dimer, as well as prediction of each patients pre-test risk of PE along with an imaging/no imaging recommendation. CDS recommendations could be printed for the medical record as could educational patient handouts to support physician decision-making. The primary outcome was CTPA utilization for patients with CEDIS chief complaints of shortness of breath or chest pain on the index visit. Secondary outcomes included index visit length of stay (LOS), and CTPA use or VTE diagnosis within 90-days. This study was REB approved. Results: Demographics were similar among intervention and control EPs; however, during a 2-year pre-intervention period control EPs had a higher baseline CTPA rate (8.5% vs 7.7%, p<0.001). In the first 8-months following CDS implementation, 94 intervention EPs saw 9,609 patients and voluntarily interacted with the CDS tool on 43.2% of eligible encounters while 91 control EPs saw 9,498 patients. CTPA utilization was higher among intervention EPs than control (9.6% vs 8.3%, p<0.001) as was ED LOS (302 vs 287 minutes, p<0.001). There was no difference in 90-day CTPA use or VTE diagnoses. Conclusion: In one of the largest RCTs of CDS to date, exposure to CDS was associated with higher rates of CTPA utilization and longer ED LOS on the index visit, and no difference in 90-day CT use or VTE diagnoses. These results differ from a concurrent study of CDS for patients with mild traumatic brain injury in the same physician population and may relate to the implementation of the CDS intervention and/or complexity of the underlying evidence-based algorithms.

Introduction: Ruling out acute myocardial infarction (AMI) using serial troponin testing is central to the care of many emergency department (ED) patients with chest pain. While diagnostic strategies using conventional troponin assays require repeat sampling over many hours to avoid missed diagnoses, serial high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in most patients within 1 or 2 hours. However, many of the initial studies deriving and validating these rapid diagnostic algorithms had all hs-cTn samples analyzed in a central core lab likely representing optimal assay performance. This objective of this study is to validate a 1-hour rapid diagnostic algorithm to exclude AMI in ED chest pain patients using an hs-cTn assay in real world practice. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at ED presentation and 1-hour later. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and 30-day major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. The study was REB approved. Results: A total of 350 patients were enrolled from August 2014 September 2016 with 1-hour serial hs-cTnT results, of which 219 (62.6%) met the 1-hour rapid diagnostic algorithm low risk criteria (time 0h hs-cTnT <12ng/L and delta 1h <3ng/L). The sensitivity of the 1-hour low risk criteria for index AMI was 97.2% (95% CI 85.5%-99.9%) and for 30-day AMI was 97.3% (95% CI 85.8-99.9%). The sensitivity of the low risk criteria for 30-day MACE was lower 80.9% (95% CI 66.7-90.9%) but maintained a high negative predictive value, 95.9% (95% CI 92.3-98.1%). Conclusion: A 1-hour rapid diagnostic algorithm using an hs-cTnT assay was highly sensitive for AMI on the index visit and successfully identified patients at low risk of 30-day AMI; however, sensitivity for 30-day MACE was much lower. Of note, the 1-hour algorithm appears to be less sensitive for both AMI and 30-day MACE than a 2-hour algorithm validated in the same population.

Introduction: ex-specific diagnostic cutoffs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction. Sex-specific cutoffs for ruling in MI improve the sensitivity of the assay for MI among women, and improve the specificity of diagnosis among men. We hypothesized that the use of sex-specific high-sensitivity Troponin T (hsTnT) cutoffs for ruling out MI at the time of ED arrival would improve the classification efficiency of the assay by enabling more patients to have MI ruled out at the time of ED arrival while maintaining diagnostic sensitivity. The objective of this study was to quantify the test characteristics of sex-specific cutoffs of an hsTnT assay for acute myocardial infarction (AMI) when performed at ED arrival in patients with chest pain. Methods: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs were, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes was AMI at 7 days. Secondary outcomes included major adverse cardiac events (MACE: all-cause mortality, AMI and revascularization) and the individual MACE components. We quantified test characteristics (sensitivity, negative predictive value, likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific rule-out cutoffs. We calculated net reclassification improvement compared to universal rule-out cutoffs of 5ng/L (the assays limit of detection) and 6ng/L (the FDA-approved limit of quantitation for US laboratories). Results: 7130 patients, including 3931 men and 3199 women, were included. The 7-day incidence of AMI was 7.38% among men and 3.78% among women. Universal cutoffs of 5 and 6 ng/L ruled out AMI with 99.7% sensitivity in 33.6 and 42.2% of patients. The best-performing combination of sex-specific cutoffs (8g/L for men and 6ng/L for men) ruled out AMI with 98.7% sensitivity in 51.9% of patients. Conclusion: Sex-specific hsTnT cutoffs for ruling out AMI at ED arrival may achieve substantial improvement in classification performance, enabling more patients to be ruled out at ED arrival, while maintaining acceptable diagnostic sensitivity for AMI. Universal and sex-specific rule-out cutoffs differ by only small changes in hsTnT concentration. Therefore, these findings should be confirmed in other datasets.

Introduction: Ruling out acute myocardial infarction (AMI) using serial troponin testing is central to the care of many emergency department (ED) patients with chest pain. While diagnostic strategies using conventional troponin assays require repeat sampling over many hours to avoid missed diagnoses, serial high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in most patients within 1 or 2 hours. However, many of the initial studies deriving and validating these rapid diagnostic algorithms had all hs-cTn samples analyzed in a central core lab likely representing optimal assay performance. This objective of this study is to validate a 2-hour rapid diagnostic algorithm to exclude AMI in ED chest pain patients using an hs-cTn assay in real world practice. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at ED presentation and 2-hours later. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and 30-day major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. This study was REB approved. Results: A total of 549 patients were enrolled from August 2014 September 2016 with 2-hour serial hs-cTnT results, of which 349 (63.6%) met the 2-hour rapid diagnostic algorithm low risk criteria (time 0 h/2 h hs-cTnT <14 ng/L and delta 2 h <4 ng/L). The sensitivity of the 2-hour low risk criteria for index AMI was 98.4% (95% CI 91.3%-100%) and for 30-day AMI was 98.4% (95% CI 91.6-100%). The sensitivity for 30day MACE was lower 84.4% (95% CI 74.4-91.7%) but maintained a high negative predictive value, 96.6% (95% CI 94.1-98.2%). Conclusion: A 2-hour rapid diagnostic algorithm using an hs-cTnT assay was highly sensitive for AMI on the index visit and successfully identified patients at low risk of 30-day AMI. Sensitivity for MACE was lower, reminding us that while biomarker-only rapid diagnostic algorithms excel at ruling out AMI, careful clinical risk stratification is needed to avoid missed MACE events.

Introduction: Patients with acute atrial fibrillation or flutter (AAFF) are the most common acute arrhythmia cases requiring care in the ED. Our goal was to adapt the existing Canadian Cardiovascular Society (CCS) AF Management Guidelines into an emergency physician-friendly best practices checklist. Methods: We chose to adapt, for use by emergency physicians, existing high-quality clinical practice guidelines (CPG) previously developed by the CCS using the GRADE system. We used the Canadian CAN-IMPLEMENT© process adapted from the ADAPTE Collaboration. We created an Advisory Committee consisting of 14 academic and community emergency physicians, three cardiologists, one PhD methodologist, and two patients. The Advisory Committee communicated by a two-day face-to-face meeting, teleconferences, and email. The checklist was prepared and revised through a process of feedback and discussions through ten iterations until consensus was achieved. We then circulated the draft checklist for comment to approximately 300 emergency medicine and cardiology colleagues whose written feedback was further incorporated into the final approved version. Results: The final CAEP ED AAFF Guidelines are comprised of two algorithms and four sets of checklists, organized by 1) Assessment and Risk Stratification, 2) Rhythm and Rate Control, 3) Long-term Stroke Prevention with the CHADS-65 Algorithm, and 4) Disposition and Follow-up. The guidelines have been endorsed by CAEP and accepted for publication in the Canadian Journal of Emergency Medicine. During the consensus and feedback processes, we addressed a number of issues and concerns. We highlighted the issue that many unstable patients are actually suffering from underlying medical problems rather than a primary arrhythmia. One controversial recommendation is to consider rate control or transesophageal echocardiography guided cardioversion if the duration of symptoms is 24-48 hours and the patient has two or more CHADS-65 criteria. We emphasize the importance of evaluating long-term stroke risk by use of the CHADS-65 algorithm and encourage ED physicians to prescribe anticoagulants where indicated. Conclusion: We have created the CAEP AAFF Best Practices Checklist which we hope will standardize and improve care of AAFF patients in all EDs across Canada. We believe that most of these patients can be managed rapidly and safely with ED rhythm control, early discharge, and appropriate use of anticoagulants.

Introduction: Utilization of CT imaging has risen dramatically with increases in availability, but without corresponding improvements in patient outcomes for many clinical scenarios. Previous attempts to improve imaging appropriateness have met with limited success, with commonly cited barriers including a lack of confidence in patient outcomes, medicolegal risk, and patient expectations. The objective of this study was to assess the impact of an electronic clinical decision support (CDS) intervention to reduce CT utilization for emergency department (ED) patients with mild traumatic brain injury (MTBI). Methods: This was a cluster-randomized, controlled trial with physicians as the unit of randomization. All emergency physicians (EPs) at 4 urban adult EDs and 1 urgent care center were randomly assigned to receive evidence-based imaging CDS (intervention) or no CDS (control) for patients with MTBI over a 1-year study period. CDS was launched in an external web browser whenever an intervention EP ordered a non-enhanced head CT from the computerized physician order entry (CPOE) system for ED patients CTAS 2-5 with a CEDIS chief complaint of head injury; however, interaction with CDS was voluntary. The CDS tool provided detailed information to physicians about the Canadian CT Head Rule, including patient eligibility, exclusion criteria, risk factors and probability of serious injury, as well as an imaging recommendation (yes/no). CDS recommendations could be printed for the medical record as could educational patient handouts to support physician decision making. The primary outcome was CT utilization for patients with MTBI on the index visit. Secondary outcomes included ED length of stay (LOS), and return visits, CT use, hospital admission and traumatic head injury diagnoses over the next 30-days. This study was REB approved. Results: Physician demographics and baseline CT utilization for MTBI patients were similar among intervention and control EPs during a 2-year pre-intervention period. In the first 8-months following CDS implementation, 102 intervention EPs saw 2,189 eligible patients while 100 control EPs saw 1,707 patients. Intervention EPs voluntarily interacted with CDS on 36.2% of eligible encounters. Head CT utilization was lower among intervention EPs than controls (38.5% vs 45.1%, p<0.0001) as was ED LOS (201 vs 218.5 minutes, p<0.001). There was no difference in 30-day ED return visits, head CT utilization, hospital admission or traumatic head injury diagnoses. Conclusion: In one of the largest RCTs of CDS to date, exposure to CDS was associated with decreased head CT utilization and shorter LOS on the index visit, and no difference in 30-day head CT use, return ED visits or hospital admission. These results suggest that a comprehensive CDS implementation may be able to overcome several barriers to use of decision rules and may contribute to improved clinical decision making and decreased CT utilization.

Introduction: Chest pain is one of the most common presenting complaints to emergency departments (EDs) across the world, and the exclusion of acute myocardial infarction (AMI) using troponin testing is central to the care of many of these patients. Testing strategies using conventional troponin assays require repeat testing over many hours to avoid missed diagnoses. This study aims to validate the ability of very low concentrations of troponin at presentation to exclude AMI in ED chest pain patients. Methods: This prospective cohort study was conducted at a single urban tertiary centre and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. High-sensitivity troponin-T (Roche Elecsys hs-cTnT) results were obtained in all patients at presentation. Relevant outcomes were obtained from administrative data. The primary outcome was AMI within 30-days of ED visit, the secondary outcome was 30-day major adverse cardiac events (MACE). The study was REB approved. Results: A total of 1,016 patients were enrolled from August 2014-September 2016, of which 174 (17.1%) patients had an initial troponin below the limit of blank (<3 ng/L) and 369 (36.3%) had a level below the limit of detection (<5 ng/L). The sensitivity and negative predictive value (NPV) of a troponin below limit of blank (<3 ng/L) for 30-day AMI were 100% (95% CI 89.3%-100%) and 100% (95% CI 97.8-100%), respectively. The sensitivity and NPV of a troponin below limit of detection (<5 ng/L) for 30-day AMI were 93.8% (95% CI 80.0-98.3%) and 99.5% (95% CI 98.1-99.9%) respectively. Sensitivity for 30-day MACE at both cutoffs was lower: 96.1% (95% CI 92.5-98.0%) for <3 ng/L, and 88.4% (95% CI 83.3-92.1%) for <5 ng/L, respectively. Conclusion: A high sensitivity troponin T result below the limit of blank is highly sensitive at excluding AMI and identifies patients at reasonably low risk of 30-day MACE. A result below the limit of detection will identify a larger population of patients as low risk but has a greater risk of missed AMI and MACE.

Introduction: The HEART score is a validated tool created to risk stratify emergency department (ED) chest pain patients using 5 simple criteria (History, ECG findings, Age, Risk factors, and Troponin). Several studies have demonstrated the superiority of HEART over other well known risk stratification tools in identifying low risk chest pain patients suitable for early discharge. All but one of these studies used conventional troponin assays, and most were conducted in European populations. This study aims to validate the HEART score using a high-sensitivity troponin T assay in a Canadian population. Methods: This prospective cohort study was conducted at a single urban tertiary centre and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were age 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. Clinical data were recorded by the emergency physician at the time of enrolment and outcomes were obtained from administrative data. High-sensitivity troponin-T (Roche Elecsys hs-cTnT) results were obtained in all patients at presentation. The primary outcome was AMI within 30-days of ED visit, the secondary outcome was 30-day major adverse cardiac events (MACE). Results: A total of 984 ED patients with complete HEART scores were enrolled from August 2014 to September 2016. The 30-day incidence of AMI and MACE in the overall population was 3.3% and 20.6%, respectively. HEART scores were predictive of 30-day AMI incidence: low risk (0-3): 0.77% (95%CI 0.0-1.5%), moderate risk (4-6): 4.3% (95%CI 2.3-6.2%) and high risk (7-10): 12.2% (95%CI 5.5-19.0%). HEART scores also predicted 30-day MACE: low risk (0-3): 5.0% (95%CI 3.1-6.9%), moderate risk (4-6): 31.8% (95%CI 27.2-36.4%) and high-risk (7-10): 61.4% (95%CI 51.2-71.5%). More than half of patients, 522 (53.0%) could be identified as low risk based on the HEART score using a single troponin result. Conclusion: Using a single high-sensitivity troponin result collected at ED presentation, the HEART score can rapidly and effectively identify more than half of ED chest pain patients as low risk for 30-day AMI, but is less sensitive for 30-day MACE.

Introduction: Most patients with acute renal colic are discharged from the ED after initial diagnosis and symptom control, but 20-30% require repeat ED visits for ongoing pain, and 15-25% require rescue intervention (ureteroscopic intervention or lithotripsy). If patients destined for failure of outpatient management could be identified based on information available during their ED visits, they could be prioritized early for intervention to reduce short term pain and disability. Our objective was to identify predictors of outpatient treatment failure, defined as the need for hospitalization or rescue intervention within 60 days of ED discharge. Methods: We collated prospectively gathered administrative data from all Calgary region patients with an ED diagnosis of renal colic over a one-year period. Demographics, arrival mode, triage category, vital signs, pain scores, analgesic use and ED disposition were recorded. Research assistants reviewed imaging reports and documented stone characteristics. These data were linked with regional hospital databases to identify ED revisits, hospital admissions, and surgical procedures. The primary outcome was hospitalization or rescue intervention within 60 days of ED discharge. Results: Of 3104 patients with first ED visit for acute renal colic, 1296 had CT or US imaging and were discharged without intervention. Median age was 50 years and 69% were male. 325 patients (25.1%) required an ED re-visit and 11.8% required admission or rescue intervention. Patients with small (<5mm), medium (5-7mm) and large (>7mm) stones failed in 9.0%, 14.4% and 9.9% of cases respectively. The only factor predictive of treatment failure in multivariable models was stone position in the proximal or mid-ureter. Age, sex, vital signs, pain score, WBC, creatinine, history of prior stone or intervention, stone side, stone size, presence of stranding and degree of hydronephrosis were not associated with outpatient failure. Conclusion: Outpatient treatment failure could not be predicted based on any of the predictors studied.

Introduction: In light of escalating health care costs, initiatives such as Choosing Wisely have been advocating the need to “reduce unnecessary or wasteful medical tests, treatments and procedures”. We have identified coagulation studies as one of those low cost, but frequently ordered items, where we can decrease unnecessary testing and costs by leveraging our Computerized Practitioner Order Entry (CPOE). Considerable evidence exists to suggest a low yield of doing coagulation studies (herein defined as PTT AND INR’s) in suspected cardiac chest pain patients (SCCP). Methods: Using administrative data merged with CPOE we extracted data 90 days pre- and 90 post-intervention (Pre-intervention: May 20, 2015 to August 19th 2015, Post-intervention: August 20th, 2015 to November 18th 2015). The setting for the study is a large urban center (4 adult ED’s with an annual census of over 320,000 visits per year). Our CPOE system is fully integrated into the ED patient care. The intervention involved modifying the nursing CPOE to remove the pre-selected coagulation studies in SCCP and providing education around appropriate usage of coagulation studies. Patients were included in the study if the bedside nurse or physician felt 1. the chest pain may be cardiac in nature and 2. Labs were ordered. The primary outcome was to compare the number of coagulation studies ordered pre and post-intervention. Results: Our analysis included 10,776 patients that were included in an SCCP pathway as determined by the CPOE database. Total number of visits in these two phases were similar (73,551 pre and 72, 769 post). In the pre-intervention phase, 5255 coagulation studies were done (4246 ordered by nursing staff and 1009 studies ordered by ED physicians). In the post-intervention phase, 1464 coagulation studies were ordered (1211 by nursing staff and 253 additional tests were ordered by ED physicians). With our intervention, we identified a net reduction of 3791 coagulation studies in our post-intervention phase for a reduction of 72.14% reduction (p=<0.0001) At a cost of 15.00$ (CDN$ at our center), we would realize an estimated cost -savings of 56,865$ for this intervention over a 90 day period. Conclusion: We have implemented a simple, sustainable, evidence based intervention that significantly minimizes the use of unnecessary coagulation studies in patients presenting with SCCP.

The preoviposition period of R. pomonella (Walsh) varied from 5 to 11 days at constant and 6 to 15 days at variable rearing conditions. Its duration was influenced by the source of the adults, cultivars for oviposition, and rearing conditions: ca. 3 days longer for adults from infested Wealthy apples than for adults from infested Gravensteins, ca. 2 days longer when the apples for oviposition were late season cultivars, and ca. 1 day longer at variable than at constant rearing conditions. Estimates of the preoviposition period of adults in two unsprayed orchards were 14 and 21 days in 1979 and 16 days in both orchards in 1980, and were 7–14 days longer than that for adults at constant rearing conditions.

The oviposition periods of adults were 40–74 days at constant and 25–55 days at variable rearing conditions in 1979, and were influenced by the source of the adults, cultivars for oviposition, and the rearing conditions. Females from infested Gravensteins laid 339.2 and 180.7 eggs/female at constant and variable conditions and those from infested Wealthy 178.4 and 68.8 eggs/female at constant and variable conditions. Females also laid fewer eggs in Red Delicious apples than in Gravenstein, McIntosh, or Cortland apples.

The first spray for control of apple maggot in Nova Scotia can be applied at least 14 days after first emergence or first capture as the preoviposition period in natural (orchard) conditions exceeded the recommended time of 7–10 days.

Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ß receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.

Two feeding trials were conducted with pigs to determine the effects of blueberry supplementation on plasma lipid levels and other indices of cardiovascular benefit. In the first trial, where basal diets contained a high level of plant-based components (70 % soya, oats and barley), supplementation with 1, 2 and 4 % blueberries resulted in a decrease in total, LDL- and HDL-cholesterol. The greatest reduction was observed in the 2 % blueberry-fed pigs, where total, LDL- and HDL-cholesterol were reduced 11·7, 15·1 and 8·3 %, respectively. In the second trial where basal diets contained only 20 % (w/w) of soya, oats and barley, the lipid-modulating effect of blueberries was attenuated, so that supplementation with 1·5 % blueberries reduced total cholesterol by 8 %, which occurred only in pigs whose diets had been supplemented with cholesterol (0·08 %), NaCl (0·11 %) and fructose (9 %). In the first feeding trial, blueberry supplementation had no effect on blood platelet activity. Blueberry supplementation also had no effect on the susceptibility of leucocyte DNA to oxidation in the first trial and no effect on the susceptibility of LDL to oxidation in the second trial. Results of these two feeding trials are discussed in relation to the effects of basal diet composition on lipid-modulating effects of blueberries.

Objective: Despite numerous clinical trials, it is unknown whether ethnicity affects treatment response to cognitive enhancers in Alzheimer's disease (AD). There is convincing evidence of ethnic and genetic variability in drug metabolism. This article reviews the available data on ethnicity in clinical trials for AD to answer two questions: (1) what are the challenges to diagnose and treat AD across different ethnic groups, and (2) are there differences in response to pharmacologic interventions for AD across these different ethnic groups?

Method: Available data from Alzheimer's Disease Cooperative Study (ADCS) randomized controlled clinical trials and from randomized controlled industry-sponsored trials for four cognitive enhancers (donepezil, galantamine, rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian participants.

Results: The participation of ethnic minority subjects in clinical trials for AD was dependent on the funding source, although Caucasian participants were over-represented and non-Caucasian participants were under-represented in the clinical trials. Because of the low participation rate of ethnic minorities, there were insufficient data to assess any differences in treatment outcome among different ethnic groups. Strategies to improve diversity in clinical trials are discussed.

Conclusion: Greater participation of ethnically diverse participants in clinical trials for AD would generate additional information on possible differences in metabolism, treatment response, adverse events to therapeutic agents, and could foster the investigation of genetic variability among ethnic groups.