Evidence-Based Management of Acute Heart Failure.

Acute heart failure (AHF) is a complex, heterogeneous, clinical syndrome with high morbidity and mortality, incurring significant health care costs. Patients transition from home to the emergency department, the hospital, and home again and require decisions surrounding diagnosis, treatment, and prognosis at each step of the way. The purpose of this review is to examine the epidemiology, etiology, and classifications of AHF and specifically focus on practical information relevant to the clinician. We examine the mechanisms of decompensation relevant to clinical presentations-including precipitating factors, neuroendocrine interactions, and inflammation-along with how consideration of these factors may help select therapies for an individual patient. The prevalence and significance of end-organ manifestations such as renal, gastrointestinal, respiratory, and neurologic manifestations are discussed. We also highlight how the development of renal dysfunction relates to the choice of a variety of diuretics that may be useful in specific circumstances and review guideline-directed medical therapy. We discuss the practical use (and pitfalls) of a variety of evidence-based clinical scoring criteria available to risk stratify patients with AHF. Finally, evidence-based management of AHF is discussed, including both pharmacologic and nonpharmacologic therapies, including the lack of evidence for using old and new vasodilators and the recent evidence regarding initiation of newer therapies in hospital. Overall, we suggest that clinicians consider implementing the newer data in AHF and subject existing practice patterns and treatments to the same rigour as new therapies.

Ambulance Use, Health Outcomes, and Costs for Emergency Department Visits for Primary Diagnosis of Syncope in Canada.

BACKGROUND: Syncope is a common presentation to the emergency department (ED), yet little is known regarding patient mode of arrival. METHODS: We identified patients ≥20 years old who presented to the ED with a primary diagnosis of syncope in Alberta and Ontario, Canada, between 2010 and 2016. Outcomes included 30-day in-hospital mortality, ED revisits, and rehospitalizations according to mode of arrival and discharge status. The estimated cost for ambulance use was calculated based on the provincial rates (Alberta CAD$385 and Ontario $240). RESULTS: A total of 271,601 syncope presentations to the ED were identified and 60.7% arrived by ambulance. A total of 76.3% (n = 125,793) of ambulance users and 87.0% of self-presenters (n = 92,845) were discharged from the ED. Regardless of mode of arrival, discharged patients were younger with fewer comorbidities. Compared with ambulance users admitted, those discharged had lower in-hospital mortality (0.2% vs 3.5%, P < 0.001), ED revisits (4.4% vs 10.4%, P < 0.001), and rehospitalizations (3.6% vs 10.7%, P < 0.001). Discharged self-presenters also had significantly lower outcomes (P < 0.001, for each outcome) compared with admitted self-presenters. The estimated cost for ambulance use among patients discharged from the ED was $33,137,735. CONCLUSION: A majority of syncope patients arrived to the ED by ambulance, and over 3 quarters were directly discharged home. Although discharged patients had a favourable short-term prognosis, they incurred high transportation costs. Strategies aimed at preventing unnecessary ambulance use are needed.

CONTEXTE: La syncope est une manifestation courante chez les patients qui se présentent au service des urgences; pourtant, on en sait peu sur la façon dont ces patients arrivent à l'hôpital. MÉTHODOLOGIE: Nous avons examiné les dossiers de patients âgés de 20 ans ou plus qui se sont présentés au service des urgences d'hôpitaux de l'Alberta et de l'Ontario, au Canada, et qui ont reçu un diagnostic de syncope entre 2010 et 2016. Les issues évaluées comprenaient la mortalité hospitalière à 30 jours, les nouvelles visites au service des urgences et les réadmissions à l'hôpital en fonction du mode d'arrivée et du statut au moment de la sortie de l'hôpital. Le coût estimatif des services d'ambulance a été calculé à partir des tarifs provinciaux (385 $ en Alberta et 240 $ en Ontario). RÉSULTATS: En tout, 271 601 cas de syncope ont été recensés dans les services des urgences; dans 60,7 % des cas, le patient est arrivé en ambulance. Au total, 76,3 % (n = 125 793) des patients arrivés en ambulance et 87,0 % des patients qui se sont présentés d'eux-mêmes (n = 92 845) ont reçu leur congé du service des urgences. Quel que soit leur mode d'arrivée, les patients qui ont reçu leur congé étaient plus jeunes et présentaient moins d'affections concomitantes. Chez les patients arrivés en ambulance, ceux qui ont reçu leur congé ont affiché des résultats inférieurs à ceux qui ont été admis à l'hôpital quant à la mortalité hospitalière (0,2 % vs 3,5 %, p < 0,001), aux nouvelles visites au service des urgences (4,4 % vs 10,4 %, p < 0,001) et aux réadmissions à l'hôpital (3,6 % vs 10,7 %, p < 0,001). Dans le cas des patients qui se sont présentés d'eux-mêmes, l'incidence des issues évaluées était aussi plus faible chez ceux qui ont reçu leur congé (p < 0,001 pour chaque issue) que chez ceux qui ont été admis à l'hôpital. Le coût estimatif du recours aux services d'ambulance par les patients qui ont reçu leur congé du service des urgences se chiffrait à 33 137 735 $. CONCLUSION: La majorité des patients subissant une syncope sont arrivés au service des urgences en ambulance, et plus des trois quarts ont reçu directement leur congé à la maison. Bien que le pronostic à court terme des patients ayant reçu leur congé du service des urgences ait été favorable, ces patients ont dû payer des frais de transport élevés. Des stratégies visant à prévenir le recours inutile aux services d'ambulance s'imposent.

Trends in the Explanatory or Pragmatic Nature of Cardiovascular Clinical Trials Over 2 Decades.

Importance: Pragmatic trials test interventions using designs that produce results that may be more applicable to the population in which the intervention will be eventually applied. Objective: To investigate how pragmatic or explanatory cardiovascular (CV) randomized clinical trials (RCT) are, and if this has changed over time. Data Source: Six major medical and CV journals, including New England Journal of Medicine, Lancet, JAMA, Circulation, European Heart Journal, and Journal of the American College of Cardiology. Study Selection: All CV-related RCTs published during 2000, 2005, 2010, and 2015 were identified and included. Data Extraction and Synthesis: Included RCTs were assessed by 2 independent adjudicators with expertise in RCT and CV medicine. Main Outcomes and Measures: The outcome measure was the level of pragmatism evaluated using the Pragmatic Explanatory Continuum Index Summary (PRECIS)-2 tool, which uses a 5-point ordinal scale (ranging from very pragmatic to very explanatory) across 9 domains of trial design, including eligibility, recruitment, setting, organization, intervention delivery, intervention adherence, follow-up, primary outcome, and analysis. Results: Of 616 RCTs, the mean (SD) PRECIS-2 score was 3.26 (0.70). The level of pragmatism increased over time from a mean (SD) score of 3.07 (0.74) in 2000 to 3.46 (0.67) in 2015 (P < .001 for trend; Cohen d relative effect size, 0.56). The increase occurred mainly in the domains of eligibility, setting, intervention delivery, and primary end point. PRECIS-2 score was higher for neutral trials than those with positive results (P < .001) and in phase III/IV trials compared with phase I/II trials (P < .001) but similar between different sources of funding (public, industry, or both; P = .38). More pragmatic trials had more sites, larger sample sizes, longer follow-ups, and mortality as the primary end point. Conclusions and Relevance: The level of pragmatism increased moderately over 2 decades of CV trials. Understanding the domains of current and future clinical trials will aid in the design and delivery of CV trials with broader application.

Twelve-Year Temporal Trends in Ambulance Use for Patients Hospitalized With a Primary Diagnosis of Syncope in Canada.

BACKGROUND: Ambulance use is a costly mode of transportation to the emergency department (ED). Syncope is a frequent presentation to the ED; however, no data exist regarding the proportion of hospitalized patients with syncope arriving by ambulance and their outcomes compared with self-presenters. METHODS: The Canadian Institute for Health Information database was used to identify patients aged > 20 years hospitalized with a primary diagnosis of syncope (International Classification of Diseases 10th Revision code R55) in Canada, except Quebec, between April 2004 and March 2016. Logistic regression models (odds ratio and 95% confidence interval) were used to identify demographics, clinical factors, and province associated with ambulance use and whether ambulance use was associated with in-hospital mortality. RESULTS: Among 108,967 syncope hospitalizations, 64% of patients arrived by ambulance, and use increased from 58.8% to 66.1% over 12 years (P for trend < 0.01). Significant variations existed in ambulance use across provinces (P < 0.01). Predictors associated with higher odds of ambulance use were increasing age, male sex, urban residence, residing in areas with lower annual household income, and higher comorbidity burden. In multivariable-adjusted analysis, ambulance use was associated with a 1.7-fold higher odds of in-hospital mortality. CONCLUSIONS: Approximately two-thirds of patients hospitalized for syncope presented by ambulance, and use has increased over time. Hospitalized patients in syncope who are transported by ambulance have a worse prognosis. Further research on emergency medical services' risk stratification of patients who are transported by ambulance may help to identify a low-risk population who may obviate the need for transport.

CONTEXTE: L'ambulance est un moyen de transport coûteux pour se rendre à l'urgence. La syncope est un symptôme fréquent chez les patients se présentant à l'urgence; toutefois, on ignore quelle est la proportion des patients hospitalisés pour une syncope qui sont arrivés en ambulance et quelle est l'issue de leur séjour à l'hôpital par rapport à ceux qui sont arrivés à l'urgence par leurs propres moyens. MÉTHODOLOGIE: Nous avons utilisé la base de données de l'Institut canadien d'information sur la santé pour recenser les patients âgés de plus de 20 ans hospitalisés avec un diagnostic primaire de syncope (Classification internationale des maladies, 10e révision, code R55) au Canada, à l'exception du Québec, entre avril 2004 et mars 2016. Des modèles de régression logistique (rapport de cotes et intervalle de confiance à 95 %) ont été utilisés pour déterminer quelles caractéristiques démographiques, quels facteurs cliniques et quelles provinces sont associés au recours à l'ambulance et s'il existe une association entre ce moyen de transport et la mortalité en cours d'hospitalisation. RÉSULTATS: Sur 108 967 hospitalisations pour une syncope, 64 % des patients étaient arrivés en ambulance, et le recours à ce moyen de transport a augmenté de 58,8 % à 66,1 % sur une période de 12 ans (p pour la tendance < 0,01). Des variations importantes concernant le recours à l'ambulance ont été observées d'une province à l'autre (p < 0,01). Les facteurs prédictifs associés à une probabilité plus élevée d'utilisation de l'ambulance étaient l'augmentation de l'âge, le sexe masculin, la résidence en zone urbaine, la résidence dans une région où le revenu annuel moyen des ménages est plus bas, ainsi qu'un fardeau de comorbidité plus lourd. Une analyse après ajustement multivarié a mis en évidence une multiplication par 1,7 de la probabilité de décès à l'hôpital associée au recours à l'ambulance. CONCLUSIONS: Environ deux tiers des patients hospitalisés pour une syncope sont arrivés à l'hôpital en ambulance, et le recours à ce moyen de transport a augmenté au fil du temps. Le pronostic est plus défavorable chez les patients hospitalisés en état de syncope qui ont été transportés en ambulance. Des recherches plus poussées sur la stratification des risques liés aux services médicaux d'urgence pour les patients transportés en ambulance pourraient aider à repérer les individus à faible risque n'ayant pas besoin d'un tel transport.

Ethnic and sex differences in ambulance activation among hospitalized patients with acute coronary syndromes: Insights from the Alberta contemporary acute coronary syndrome patients invasive treatment strategies (COAPT) study.

BACKGROUND: With acute coronary syndromes (ACS), activation of emergency medical services (EMS) ensures early treatment. However, EMS activation remains under-utilized. We examined whether ground EMS use varied by sex or ethnicity among a population-based cohort of ACS patients. METHODS: We used linked administrative health datasets to identify patients who were hospitalized with an ACS (April 1, 2002-March 31, 2016). Validated naming algorithms were used to categorize patients according to ethnicity (Caucasian, South Asian, Chinese). RESULTS: Of the 60,717 patients with an ACS (male: 41,175; female: 19,542), 42.3% presented to hospital via ground ambulance. Compared to males, females were more likely to activate EMS (38.9% vs. 49.3%, p < 0.001). Compared to the Caucasians (n = 58,666), EMS activation was significantly higher among Chinese (n = 793) (42.1% vs. 49.8%; p = 0.0007) and slightly higher in South Asians (n = 1258) (42.1% vs. 44.7%; p = 0.45). The relatively higher EMS use among females was maintained across the ethnic groups. In multivariable adjusted analyses, females were more likely to use EMS compared to males (OR: 1.31; 95% CI: 1.26-1.36). Compared to the Caucasians, a weaker trend towards South Asian and Chinese EMS activation was observed (OR: 1.08; 95% CI 0.96-1.21; OR: 1.10; 95% CI 0.95-1.28, respectively). In the male cohort only, South Asians and Chinese tended to activate EMS more often than the Caucasians (Males: South Asian OR: 1.14; 95% CI 1.00-1.31, Chinese OR: 1.15; 95% CI 0.96-1.38; Females: South Asian OR: 0.93; 95% CI 0.75-1.15, Chinese OR: 1.01; 95% CI 0.77-1.30). CONCLUSION: EMS use was sub-optimal and differed based on sex and ethnicity. Our results reinforce the need for targeted public health efforts to enhance ambulance activation.

Empirical likelihood based detection procedure for change point in mean residual life functions under random censorship.

The mean residual life (MRL) function is one of the basic parameters of interest in survival analysis that describes the expected remaining time of an individual after a certain age. The study of changes in the MRL function is practical and interesting because it may help us to identify some factors such as age and gender that may influence the remaining lifetimes of patients after receiving a certain surgery. In this paper, we propose a detection procedure based on the empirical likelihood for the changes in MRL functions with right censored data. Two real examples are also given: Veterans' administration lung cancer study and Stanford heart transplant to illustrate the detecting procedure. Copyright © 2016 John Wiley & Sons, Ltd.

Midterm results of endovascular stent grafts in the proximal aortic arch (zone 0): an imaging perspective.

BACKGROUND: Endovascular options to repair the arch and ascending aorta are rapidly evolving. Little is known about the durability of endovascular devices deployed at this location. This report describes a single-centre experience with the novel application of thoracic endovascular aortic repair (TEVAR) by examining clinical and radiological outcomes. METHODS: A retrospective review was performed for a cohort of patients undergoing TEVAR of the arch or ascending aorta, or both, at a single centre from November 2008-July 2012. RESULTS: Sixteen patients were included in the study, with mean imaging follow-up of 38 months (range, 15-72 months). Two complications at the proximal landing zone in the ascending aorta were identified: 1 endoleak and 1 infolding identified at 3 and 24 months postoperatively, respectively. Clinically, both these complications were attributed to the bird-beak configuration at the proximal landing zone site. At up to 72 months of follow-up, there were no cases of retrograde dissection of the native sinus of Valsalva. There were no cases of stent graft migration, graft fracture, open surgical reintervention for aortic pathologic conditions, or late mortality. CONCLUSIONS: Early outcomes suggest that the current generation of thoracic aortic endografts can be placed in the complex anatomy of the ascending aorta and aortic arch without a high incidence of early graft fracture or migration. Future endeavors will need to focus on techniques to achieve optimal apposition with the curves of the ascending aorta. These findings are important as indications for endovascular aortic therapies expand to address proximal aortic pathologic conditions.

Microwave-assisted radiosynthesis of the hypoxia marker 1-α-D-(5- deoxy-5-[18F]fluoroarabinofuranosyl)-2-nitroimidazole ([18F]FAZA).

UNLABELLED: The routine manufacture of most short-lived positron-emitting radiopharmaceuticals (PERs) involves conventional heating to accelerate the radiolabeling process. Nucleophilic radiofluorination reactions are generally slow at lower temperatures, and are accompanied by thermal decomposition of both precursor and product at higher temperatures. This necessitates HPLC purification and results in lower recovered radiochemical yields (rRCYs). [(18)F]FAZA, a PER for clinical imaging of focal tissue hypoxia, is routinely manufactured in-house in 3-12% rRCY using a Health Canada approved conventional heating procedure. The microwave-assisted (MW) radiosynthesis of [(18)F]FAZA is now reported. METHODS: Manual (MRDS) and automated (ASU) reagent delivery systems coupled to a commercial MW unit were built in-house. The MW unit controlled power, irradiation time and monitored reaction temperature (Tmax control), while the acetylAZA tosylate precursor and QMA Accel(TM) cartridge eluent reagents (K2CO3, K2.2.2) were dispensed by the MRDS or ASU. The radiofluorination yields (RFYs) and the chemical and radiochemical TLC profiles of the post-labeling reaction mixtures were compared to those obtained using the conventional heating production method and to those reported for optimized literature methods. RESULTS: MW RFYs for [(18)F]FAZA reached >76% (n=3) in 3 min. Post-labeling analysis of the MW-assisted reaction mixtures demonstrated cleaner UV and radiochemical TLC profiles than those obtained from conventional heating in routine production runs; the relatively clean MW reactions allowed rapid HPLC isolation of [(18)F]FAZA in overall rRCYs of 55±4%. CONCLUSIONS: In practical terms, the MW process provided only small gains in reaction time and RFY, but produced only a few secondary impurities, thereby improving the rRCY in comparison to conventional heating methods. These findings provide a rationale for adaptation of the MW-assisted method for the routine production of clinical [(18)F]FAZA.

Improved statistics for contrasting means of two samples under non-normality.

This paper presents the asymptotic expansions of the distributions of the two-sample t-statistic and the Welch statistic, for testing the equality of the means of two independent populations under non-normality. Unlike other approaches, we obtain the null distributions in terms of the distribution and density functions of the standard normal variable up to n(-1), where n is the pooled sample size. Based on these expansions, monotone transformations are employed to remove the higher-order cumulant effect. We show that the new statistics can improve the precision of statistical inference to the level of o (n(-1)). Numerical studies are carried out to demonstrate the performance of the improved statistics. Some general rules for practitioners are also recommended.