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Background: Major societal guidelines recommend a 5-day stop interval before cardiac surgery for patients with acute coronary syndrome receiving clopidogrel. Yet, many such patients present with high acuity, generating surgeon inclination toward use of shorter stop intervals. Thus, this study aimed to determine the impact of the duration and timing of the interval of clopidogrel cessation on adverse bleeding events. Methods: Patients who underwent cardiac surgery between 2009 and 2016 at a tertiary-care centre were included in this retrospective cohort study. Multivariable logistic regression models adjusted for clopidogrel stop interval, age, urgency of procedure, and procedure type were used to quantify the effect of clinically relevant baseline demographic characteristics on incidence of massive transfusion as well as hemorrhagic complication outcomes. Results: A total of 5748 patients underwent cardiac surgery. In this cohort, 1743 patients (30.3%) received clopidogrel preoperatively, and 884 (50.7%) of these patients discontinued clopidogrel 5 days before presenting to the operating room. The administration of clopidogrel 1-2 days before surgery (odds ratio 1.97; 95% confidence interval: 1.18 to 3.29) was an independent predictor for massive transfusions and hemorrhagic complications (odds ratio 1.85; 95% confidence interval: 1.01 to 3.37). The 3-4 day group did not have an increased risk of major bleeding complications. The risk for both massive transfusions and hemorrhagic complications also increased with the urgency and complexity of surgery. Conclusion: A clopidogrel stop interval of 3-4 days preoperatively was not associated with an increased risk for major bleeding complications. Résumé: Introduction: Les grandes lignes directrices sociétales recommandent une interruption de cinq jours avant l’intervention chirurgicale du cœur des patients atteints d’un syndrome coronarien aigu qui prennent du clopidogrel. Toutefois, comme il s’agit pour plusieurs d’entre eux de patients de haute acuité, le chirurgien penche vers l’utilisation d’une interruption plus courte. Par conséquent, la présente étude avait pour objectif de déterminer les conséquences de la durée et du moment de la cessation du clopidogrel sur les événements hémorragiques indésirables. Méthodes: La présente étude de cohorte rétrospective portait sur les patients qui avaient subi une intervention chirurgicale au cœur entre 2009 et 2016 dans un centre de soins tertiaires. Nous avons utilisé les modèles multivariés de régression logistique ajustés à l’interruption du clopidogrel, à l’âge, à l’urgence de l’intervention chirurgicale et au type d’intervention chirurgicale pour quantifier les effets des caractéristiques démographiques initiales cliniquement pertinentes sur la fréquence des transfusions massives ainsi que sur les issues des complications hémorragiques. Résultats: Un total de 5 748 patients ont subi une intervention chirurgicale au cœur. Dans cette cohorte, parmi les 1 743 patients (30,3 %) qui avaient reçu du clopidogrel avant l’opération, 884 (50,7 %) avaient cessé le clopidogrel cinq jours avant leur admission à la salle d’opération. L’administration du clopidogrel un à deux jours avant l’intervention chirurgicale (ratio d’incidence approché 1,97; intervalle de confiance [IC] à 95 % : de 1,18 à 3,29) était un prédicteur indépendant des transfusions massives et des complications hémorragiques (ratio d’incidence approché 1,85; [IC] à 95 % : de 1,01 à 3,37). Le groupe de l’interruption de trois à quatre jours n’a pas montré de risque accru de complications hémorragiques graves. Le risque de transfusions massives et de complications hémorragiques a aussi contribué à l’augmentation de l’urgence et de la complexité de l’intervention chirurgicale. Conclusion: Une interruption du clopidogrel de trois à quatre jours avant l’opération n’a pas été associée à un risque accru de complications hémorragiques graves.

Aims Orthopaedic surgeries are complex, frequently performed procedures associated with significant haemorrhage and perioperative blood transfusion. Given refinements in surgical techniques and changes to transfusion practices, we aim to describe contemporary transfusion practices in orthopaedic surgery in order to inform perioperative planning and blood banking requirements. Methods We performed a retrospective cohort study of adult patients who underwent orthopaedic surgery at four Canadian hospitals between 2014 and 2016. We studied all patients admitted to hospital for nonarthroscopic joint surgeries, amputations, and fracture surgeries. For each surgery and surgical subgroup, we characterized the proportion of patients who received red blood cell (RBC) transfusion, the mean/median number of RBC units transfused, and exposure to platelets and plasma. Results Of the 14,584 included patients, the most commonly performed surgeries were knee arthroplasty (24.8%), hip arthroplasty (24.6%), and hip fracture surgery (17.4%). A total of 10.3% of patients received RBC transfusion; the proportion of patients receiving RBC transfusions varied widely based on the surgical subgroup (0.0% to 33.1%). Primary knee arthroplasty and hip arthroplasty, the two most common surgeries, were associated with in-hospital transfusion frequencies of 2.8% and 4.5%, respectively. RBC transfusion occurred in 25.0% of hip fracture surgeries, accounting for the greatest total number of RBC units transfused in our cohort (38.0% of all transfused RBC units). Platelet and plasma transfusions were uncommon. Conclusion Orthopaedic surgeries were associated with variable rates of transfusion. The rate of RBC transfusion is highly dependent on the surgery type. Identifying surgeries with the highest transfusion rates, and further evaluation of factors that contribute to transfusion in identified at-risk populations, can serve to inform perioperative planning and blood bank requirements, and facilitate pre-emptive transfusion mitigation strategies. Cite this article: Bone Jt Open 2021;2(10):850–857.

Objective Exercise is recommended for polycystic ovary syndrome (PCOS), but the most effective exercise prescription is unclear. This trial compared effects of high‐intensity interval training (HIIT), continuous aerobic exercise training (CAET) and no‐exercise control on reproductive, anthropometric and cardiometabolic outcomes in PCOS. Design Pilot randomized controlled trial. Participants Previously inactive women aged 18–40 years with PCOS. Measurements Feasibility outcomes included recruitment, retention, adherence to exercise and daily ovulation prediction kit (OPK) testing. Preliminary efficacy outcomes included reproductive, anthropometric and cardiometabolic health markers. Results Forty‐seven women were randomized to no‐exercise control (n = 17), HIIT (n = 16), or CAET (n = 14). Forty (85%) participants completed the trial. Median exercise adherence was 68% (IQR 53%, 86%). Median daily OPK‐testing adherence in the first half of the intervention was 87% (IQR 61%, 97%) compared with 65% (IQR 0%, 96%) in the second half. Body mass index decreased significantly in CAET compared with control (−1.0 kg/m2, p = .01) and HIIT (−0.9 kg/m2, p = .04). Mean waist circumference decreased in all groups (−7.3 cm, −6.9 cm, −4.5 cm in HIIT, CAET and control) with no significant between‐group differences. Mean LDL‐C was significantly reduced for HIIT compared to CAET (−0.33 mmol/L, p = .03). HDL‐C increased in HIIT compared with control (0.18 mmol/L, p = .04). Conclusions There were feasibility challenges with adherence to daily ovulation assessment limiting the ability to analyse the effect of the exercise interventions on ovulation. CAET and HIIT were both effective at improving anthropometrics and some cardiometabolic health markers. Further studies need to determine optimal and acceptable exercise prescriptions for this population.

OBJECTIVE To determine the predictors of postoperative acute kidney injury (AKI) following nonemergent cardiac surgery among patients with variable preoperative estimated glomerular filtration rate (eGFR) levels. METHODS A retrospective study of patients who underwent elective or in-hospital cardiac surgical procedures was performed between January 2006 and November 2015. The procedures included isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), or combined CABG and AVR. The primary outcome AKI (any stage) following nonemergent cardiac surgery utilizing the 2012 Kidney Disease-Improving Global Outcomes (KDIGO) criteria. Patients were categorized based on the following renal outcomes: mild AKI, severe AKI (KDIGO stage 2 or 3), and postoperative dialysis. Patients with G5 preoperative kidney function (including dialysis patients) were excluded. RESULTS A total of 6675 patients were included in our study. The mean age was 66.8 years (SD ± 10.4), with 76.3% being males. A total of 4487 patients had normal or mildly decreased eGFR (G1 or G2) preoperatively (67.2%), while 1960 patients were in the G3 category (29.4%). Only 228 patients (3.4%) had G4 renal function. A total of 1453 (21.7%) patients experienced postoperative AKI. The need for postoperative dialysis occurred in 3.2% of the AKI subgroup. In-hospital mortality was higher among the AKI subgroup (7.2% vs. 0.5%; p

BACKGROUND The Carpentier-Edwards Perimount valves have a proven track record in aortic valve replacement: good durability, hemodynamic performance, rates of survival, and low rates of valve-related complications and prosthesis-patient mismatch. The St. Jude Medical Trifecta is a newer valve that has shown comparable early and midterm outcomes. Studies show reoperation rates of Trifecta are comparable with Perimount valves, with a few recent studies bringing into focus early structural valve deterioration (SVD), and increased midterm SVD in younger patients. Given that midterm data for Trifecta is still sparse, we wanted to confirm the early low reoperation rates of Trifecta persist over time compared with Perimount. METHODS The Maritime Heart Centre Database was searched for AVR between 2011 and 2016, inclusive. The primary endpoint of the study was all-cause reoperation rate. RESULTS In total, 711 Perimount and 453 Trifecta implantations were included. The reoperation hazards were determined for age: 0.96 (0.92-0.99; p = .02), female (vs. male): 0.35 (0.08-1.53; p = .16), smoker (vs. nonsmoker): 2.44 (0.85-7.02; p = .1), and Trifecta (vs. Perimount): 2.68 (0.97-7.39; p = .06). Kaplan-Meier survival analysis in subgroups-age

Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM.We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: 1 cm, 1-1.9 cm, 2-2.9 cm, and 3 cm.A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89-5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p 0.001).Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM.

The study's objective was to examine Canadian and Australian community pharmacists' experiences with people at risk of suicide.A survey was developed and administered online. Countries were compared by Fisher's exact and t tests. Multivariable logistic-regression analysis was used to identify variables associated with preparedness to help someone in a suicidal crisis.The survey was completed by 235 Canadian and 161 Australian pharmacists. Most (85%) interacted with someone at risk of suicide at least once, and 66% experienced voluntary patient disclosure of suicidal thoughts. More Australians than Canadians had mental health crisis training (p0.001). Preparedness to help in a suicidal crisis was negatively associated with being Canadian, having a patient who died by suicide, lacking training and confidence, and permissive attitudes toward suicide.Several perceived barriers impede pharmacists' abilities to help patients who voluntarily disclose suicidal thoughts. Gatekeeper and related suicide prevention strategy training for community pharmacists is warranted.

This study investigated the impact of exercise training on interindividual variability and response rates in body composition and cardiometabolic outcomes in adolescents with obesity. Postpubertal males and females (n = 143) were randomly assigned to 6 months of a diet-only control or aerobic, resistance, or combined exercise training. Body composition indices were percentages of body fat mass and lean body mass and waist circumference. Biomarkers of cardiometabolic health were systolic blood pressure and plasma fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Interindividual variability was examined by comparing the standard deviation of individual responses (SDIR) to a smallest robust change (SRC). The typical error of measurement was used to classify responses. SDIR exceeded the SRC for percent body fat mass in all exercise groups (SRC = 1.04%; aerobic SDIR = 1.50%; resistance SDIR = 1.22%; combined SDIR = 2.29%), percent lean body mass (SRC = 1.38%; SDIR = 3.2%,), systolic blood pressure (SRC = 2.06 mm Hg; SDIR = 4.92 mm Hg) in the resistance group, and waist circumference (SRC = 2.33 cm; SDIR = 4.09 cm), and fasting glucose (SRC = 0.08 mmol/L; SDIR = 0.28 mmol/L) in the combined group. However, half of the reported variables (11/21) did not have a positive SDIR. Importantly, adverse response rates were significantly lower in all 3 exercise groups compared with control for body composition. Although exercise had a small influence on interindividual variability for indices of body composition, the rate of adverse responses did not increase for any outcome. Novelty Interindividual variability and individual responses to exercise training have not been investigated in adolescents with obesity. Six months of exercise training does not increase interindividual variability in adolescents with obesity. Exercise created a positive, uniform shift in responses.

Vasovagal syncope (VVS) occurs in40% of individuals at least once in their lifetime. Sex-dependent differences in presentation and outcomes are not understood. We sought to determine differences in clinical presentation, treatment modalities, and outcomes of VVS between men and women.Data were collected as part of the Prevention of Syncope Trials (POST) I and II, 2 multicenter, placebo-controlled, randomized trials testing the effectiveness of metoprolol and fludrocortisone, respectively. Data regarding clinical presentation, outcomes, and time to first syncope event after randomization were compared.Of the 418 patients (280 women and 138 men), women were younger at the time of first syncope event (21 vs 26 years P = 0.002) and had a lower baseline systolic blood pressure (117 vs 124 mm Hg, P0.001). Response to heat as a trigger for syncope was more common in women (68% vs 48%, P = 0.011). Clinical presentation in women consisted more commonly of feeling warm, having seizures, and experiencing more postsyncope fatigue (68% vs 54%, P = 0.048; 10% vs 2.7%, P = 0.045; 75% vs 59%, P = 0.017, respectively). Women were more likely to experience recurrent syncope after adjustment for prerandomization syncope burden and randomization assignment (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P = 0.012).Clinical presentation and provocative factors of VVS differ between men and women, as do recurrent events. Recognition of these differences may help target therapy specifically in men and women.

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is functionally related to BDNF, and is associated with obesity and metabolic complications in adults, but limited research exists among adolescents. This study comparatively examined carriers and non-carriers of the BDNF Val66Met polymorphism on body composition, energy intake, and cardiometabolic profile among adolescents with obesity. The sample consisted of 187 adolescents with obesity; 99 were carriers of the homozygous Val (G/G) alleles and 88 were carriers of the Val/Met (G/A) or Met (A/A) alleles. Cardiometabolic profile and DNA were quantified from fasted blood samples. Body composition was assessed by magnetic resonance imaging (MRI). Compared to carriers of the homozygous Val (G/G) allele, carriers of the Val/Met (G/A) or Met/Met (A/A) variants exhibited significantly higher protein (p = 0.01) and fat (p = 0.05) intake, C-Reactive protein (p = 0.05), and a trend toward higher overall energy intake (p = 0.07), fat-free mass (p = 0.07), and lower HDL-C (p = 0.07) Results showed for the first time that among youth with obesity, carriers of the Val66Met BDNF Met-alleles exhibited significantly higher C-reactive protein and energy intake in the form of fat and protein compared to Val-allele carriers, thereby providing support for the possible role of BDNF in appetite, weight, and metabolic regulation during adolescence.Clinical Trial Registration:http://clinicaltrials.gov/, identifier NCT00195858.

Summary Introduction Despite efforts to improve adherence to physical activity interventions in youth with obesity, low adherence and attrition remain areas of great concern. Objective The study was designed to determine which physiological and/or psychological factors predicted low adherence in adolescents with obesity enrolled in a 6‐month exercise intervention study aimed to improve body composition. Methods Three hundred four adolescents with obesity aged 14–18 years who volunteered for the HEARTY (Healthy Eating Aerobic and Resistance Training in Youth) randomized controlled trial completed physiological (body mass index, waist circumference, per cent body fat, resting metabolic rate and aerobic fitness) and psychological (body image, mood, self‐esteem and self‐efficacy) measures. Results One hundred forty‐one out of 228 (62%) randomized to exercise groups had low adherence (completed

BACKGROUND Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital-wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations. STUDY DESIGN AND METHODS Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients. RESULTS Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p

Background: Prior studies have demonstrated an association between appropriate implantable cardioverter defibrillator (ICD) shocks and mortality in clinical trials. The effect of shock burden on heart failure and mortality has not been previously studied in a large population-based cohort. Methods: The cohort was derived using a comprehensive prospective ICD registry in the province of Nova Scotia with a mean follow-up of 4 ± 2.3 years. With the use of time-varying analysis, the relationship among shock burden, mortality, and heart failure hospitalization was determined. Results: A total of 776 patients (mean age of 64.8 years) were included in the study, of whom 37% received appropriate therapy during follow-up. A single ICD shock did not confer an increased mortality risk compared with no therapy (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.84-1.79; P = 0.3), but mortality risk was significantly increased with ≥ 2 shocks (HR, 3.23; 95% CI, 2.04-5.09; P < 0.0001). There was a significant increase in heart failure hospitalization associated with receiving 1 ICD shock (HR, 2.05; 95% CI, 1.46-2.89; P < 0.0001) or more than 1 ICD shock (HR, 4.36; CI, 2.53-7.52; P < 0.0001) compared with patients receiving no ICD therapy. Patients who received antitachycardia pacing alone showed no difference in heart failure hospitalization (HR, 0.93; CI, 0.67-1.29; P = 0.7) and improved survival (HR, 0.69; CI, 0.5-0.96; P = 0.03) compared with those receiving no ICD therapy. Conclusion: Ventricular arrhythmia treated with appropriate ICD shocks is associated with an increased risk of heart failure hospitalization, whereas recurrent episodes of ventricular arrhythmia requiring shocks are associated with both higher mortality and higher heart failure hospitalization rates. Résumé: Contexte: Des études menées antérieurement ont révélé l’existence d’un lien entre l’administration appropriée de décharges électriques au moyen d’un défibrillateur cardioverteur implantable (DCI) et la mortalité au cours des essais cliniques. L’effet de telles décharges sur l’insuffisance cardiaque et la mortalité n’avait encore jamais été étudié au sein d’une cohorte d’envergure représentative de la population. Méthodologie: La cohorte a été établie au moyen d’un registre prospectif exhaustif des DCI implantés chez des patients de la Nouvelle-Écosse ayant fait l’objet d’un suivi moyen de 4 ± 2,3 ans. La relation entre le fardeau imposé par les décharges, la mortalité et l’hospitalisation pour insuffisance cardiaque a été déterminée au moyen d’une analyse en fonction du temps. Résultats: Au total, 776 patients (âge moyen : 64,8 ans) ont été admis dans l’étude; 37 % d’entre eux avaient reçu un traitement approprié au cours de la période de suivi. Une seule décharge délivrée par un DCI n’augmentait pas le risque de mortalité par rapport à l’absence de traitement (rapport des risques instantanés [RRI] de 1,23; intervalle de confiance [IC] à 95 %, de 0,84 à 1,79; p = 0,3), mais le risque de mortalité était significativement accru chez les patients ayant reçu ≥ 2 décharges (RRI de 3,23; IC à 95 %, de 2,04 à 5,09; p < 0,0001). Le risque d’hospitalisation pour insuffisance cardiaque s’est révélé significativement supérieur chez les sujets ayant reçu 1 décharge par DCI (RRI de 2,05; IC à 95 %, de 1,46 à 2,89; p < 0,0001) ou plus de 1 décharge par DCI (RRI de 4,36; IC à 95 %, de 2,53-7,52; p < 0,0001), comparativement à ceux n’ayant reçu aucun traitement par DCI. On n’a observé aucune différence quant à l’hospitalisation pour insuffisance cardiaque (RRI de 0,93; IC à 95 %, de 0,67 à 1,29; p = 0,7) et à l’amélioration de la survie (RRI de 0,69; IC à 95 %, de 0,5 à 0,96; p = 0,03) chez les patients qui ont reçu uniquement une stimulation antitachycardie comparativement à ceux qui n’ont reçu aucun traitement par DCI. Conclusion: L’arythmie ventriculaire traitée de façon appropriée au moyen de décharges électriques délivrées par un DCI est associée à un risque accru d’hospitalisation pour insuffisance cardiaque, tandis que des épisodes récurrents d’arythmie ventriculaire exigeant un traitement par décharge électrique sont associés à des taux supérieurs de mortalité et d’hospitalisation pour insuffisance cardiaque.

Background: Cardiac resynchronization therapy (CRT) is effective in treating advanced heart failure (HF), but data describing benefits and long-term outcomes for upgrades from a preexisting device are limited. This study sought to compare long-term outcomes in de novo CRT implants with those eligible for CRT with a prior device. Methods: This is a retrospective cohort study using data from a provincial registry (2002-2015). Patients were included if they had mild-moderate HF, left ventricular ejection fraction ≤ 35%, and QRS duration ≥ 130 ms. Patients were classified as de novo CRT or upgraded to CRT from a prior device. Outcomes were mortality and composite mortality and HF hospitalization. Results: There were 342 patients included in the study. In a multivariate model, patients in the upgraded cohort (n = 233) had a higher 5-year mortality rate (adjusted hazard ratio, 2.86; 95% confidence interval, 1.59-5.15; P = 0.0005) compared with the de novo cohort (n = 109) and higher composite mortality and HF hospitalization (adjusted hazard ratio, 2.60; 95% confidence interval, 1.54-4.37; P = 0.0003). Conclusions: Implantation of de novo CRTs was associated with lower mortality and HF hospitalization compared with upgraded CRTs from preexisting devices. It is unknown whether these differences are due to the timing of CRT implementation or other clinical factors. Further work in this area may be helpful to determine how to improve outcomes for these patients. Résumé: Contexte: La thérapie de resynchronisation cardiaque (TRC) est efficace pour traiter l’insuffisance cardiaque avancée, mais les données décrivant les bienfaits et les résultats à long terme de la mise à niveau d’un implant déjà en place sont limitées. La présente étude visait à comparer les résultats à long terme chez les patients recevant un implant de TRC de novo et chez ceux ayant déjà un implant qui sont admissibles à une TRC. Méthodologie: Il s’agit d’une étude de cohorte rétrospective reposant sur les données issues d’un registre provincial (2002-2015). Les patients ont été inclus dans l’étude s’ils présentaient une insuffisance cardiaque légère ou modérée, une fraction d’éjection ventriculaire gauche ≤ 35 % et un intervalle QRS ≥ 130 ms. Les patients ont été classés dans le groupe TRC de novo ou dans le groupe TRC remplaçant un implant antérieur. Les paramètres d’évaluation étaient la mortalité et le critère regroupant la mortalité et l’hospitalisation pour insuffisance cardiaque. Résultats: En tout, 342 patients ont été inclus dans l’étude. Après analyse selon un modèle multivarié, le taux de mortalité à 5 ans était plus élevé (rapport des risques instantanés [RRI] corrigé de 2,86; intervalle de confiance [IC] à 95 % de 1,59 à 5,15], p = 0,0005) dans la cohorte TRC remplaçant un implant antérieur (n = 233) que dans la cohorte TRC de novo (n = 109), tout comme le taux pour le critère regroupant la mortalité et l’hospitalisation pour insuffisance cardiaque (RRI corrigé de 2,60; IC à 95 % de 1,54 à 4,37], p = 0,0003). Conclusions: L’implantation d’une TRC de novo était associée à un taux de mortalité et d’hospitalisation pour insuffisance cardiaque inférieur comparativement à l’implantation d’une TRC chez des patients ayant déjà un implant. On ne sait pas si ces différences sont attribuables au moment choisi pour l’implantation de la TRC ou à d’autres facteurs cliniques. D’autres études sur cette question pourraient être utiles afin de déterminer comment améliorer les résultats chez ces patients.

Background Comparisons between frailty assessment tools for waitlist candidates are a recognized priority area for kidney transplantation. We compared the prevalence of frailty using three established tools in a cohort of waitlist candidates. Methods Waitlist candidates were prospectively enrolled from 2016 to 2020 across five centers. Frailty was measured using the Frailty Phenotype (FP), a 37-variable frailty index (FI), and the Clinical Frailty Scale (CFS). The FI and CFS were dichotomized using established cutoffs. Agreement was compared using κ coefficients. Area under the receiver operating characteristic (ROC) curves were generated to compare the FI and CFS (treated as continuous measures) with the FP. Unadjusted associations between each frailty measure and time to death or waitlist withdrawal were determined using an unadjusted Cox proportional hazards model. Results Of 542 enrolled patients, 64% were male, 80% were White, and the mean age was 54±14 years. The prevalence of frailty by the FP was 16%. The mean FI score was 0.23±0.14, and the prevalence of frailty was 38% (score of ≥0.25). The median CFS score was three (IQR, 2–3), and the prevalence was 15% (score of ≥4). The κ values comparing the FP with the FI (0.44) and CFS (0.27) showed fair to moderate agreement. The area under the ROC curves for the FP and FI/CFS were 0.86 (good) and 0.69 (poor), respectively. Frailty by the CFS (HR, 2.10; 95% CI, 1.04 to 4.24) and FI (HR, 1.79; 95% CI, 1.00 to 3.21) was associated with death or permanent withdrawal. The association between frailty by the FP and death/withdrawal was not statistically significant (HR, 1.78; 95% CI, 0.79 to 3.71). Conclusion Frailty prevalence varies by the measurement tool used, and agreement between these measurements is fair to moderate. This has implications for determining the optimal frailty screening tool for use in those being evaluated for kidney transplant.

Background: Remote monitoring is used to supplement in-clinic follow-up for patients with cardiac implantable electronic devices (CIEDs) every 6-12 months. There is a need to optimize remote management for CIEDs because of the consistent increases in CIED implants over the past decade. The objective of this study was to investigate real and perceived barriers to the use of remote patient management strategies in Canada and to better understand how remote models of care can be optimized. Methods: We surveyed 512 CIED patients and practitioners in 22 device clinics in Canada. Results: Device clinic surveys highlighted significant variation and inconsistency in follow-up care for in-clinic and remote visits across and within clinics. This survey showed that funding policies and management of additional workflow are barriers to optimal use and uptake. Despite this, device clinics perceive remote follow-up as a valuable resource and an efficient way to manage patient follow-up. Patients were broadly satisfied with their CIED follow-up care but identified barriers related to coordination of care, visit logistics, and information needs. Views varied as a function of clinical or sociodemographic characteristics. Most patients (n = 228; 91%) expressed a desire to receive a phone call from their device clinic after a remote transmission has been received. Conclusions: Lack of a unified, guideline-supported approach to follow-up after CIED implant, and discrepant funding policies across jurisdictions, are significant barriers to the use of remote patient management strategies in Canada. Efforts to increase or expand use of remote follow-up must recognize these barriers and the needs of specific subgroups of patients. Résumé: Introduction: La télésurveillance sert de complément à la consultation en clinique des patients porteurs d’un dispositif cardiaque électronique implantable (DCEI) tous les 6 à 12 mois. Il est nécessaire d’optimiser la prise en charge à distance des patients porteurs de DCEI en raison de la constante augmentation des implantations de DCEI au cours de la dernière décennie. L’objectif de la présente étude était d’examiner les obstacles réels et perçus à l’utilisation des stratégies de prise en charge à distance des patients du Canada et de mieux comprendre la façon d’optimiser les modèles de soins à distance. Méthodes: Nous avons interrogé 512 patients porteurs de DCEI et praticiens de 22 cliniques spécialisées en DCEI du Canada. Résultats: Les enquêtes des cliniques spécialisées en DCEI ont fait ressortir la variation importante et le manque d’uniformité dans les soins de suivi lors des consultations en clinique et à distance au sein de toutes les cliniques et entre elles. Cette enquête a montré que les politiques de financement et la gestion du flux de travail supplémentaire sont les obstacles qui empêchent l’utilisation optimale et l’adoption. Malgré cela, les cliniques spécialisées en DCEI perçoivent le suivi à distance comme une ressource très utile et un moyen efficace de prendre en charge le suivi du patient. Les patients étaient dans l’ensemble satisfaits de leurs soins de suivi relatifs à leur DCEI, mais relevaient des obstacles liés à la coordination des soins, à la logistique des consultations et à leurs besoins d’information. Les points de vue variaient en fonction des caractéristiques cliniques et sociodémographiques. La plupart des patients (n = 228 ; 91 %) ont fait part de leur souhait de recevoir un appel téléphonique de leur clinique spécialisée en DCEI après la réception de la transmission à distance. Conclusions: L’absence d’une approche unifiée et fondée sur les lignes directrices qui porte sur le suivi après l’implantation de DCEI, et la divergence des politiques de financement des provinces et territoires sont des obstacles importants à l’utilisation de stratégies de prise en charge à distance des patients au Canada. Les efforts visant à accroître ou à étendre l’utilisation du suivi à distance doivent tenir compte de ces obstacles et des besoins des sous-groupes particuliers de patients.

Objective: To determine the predictors of postoperative AKI following non-emergent cardiac surgery among patients with variable preoperative eGFR levels. Methods: Retrospective study of patients who underwent elective or in-hospital cardiac surgical procedures performed between January 2006 and November 2015. The procedures included isolated CABG, isolated AVR or combined CABG and AVR. The primary outcome AKI (any stage) following non-emergent cardiac surgery utilizing the 2012 KDIGO criteria. Patients were categorized based the following renal outcomes: mild AKI, severe AKI (KDIGO stage 2 or 3) and post-operative dialysis.. Results: A total of 6713 patients were included in our study. The mean age was 66.8 years (SD ± 10.3), with 76.2% being males. A total of 4487 patients had normal or mildly decreased eGFR (G1 or G2) preoperatively (66.8%), while 1960 patients were in the G3 category (29.1%). Only 266 patients (3.9%) had G4 or worse renal function. A total of 1489 (28.5%) patients experienced post-operative AKI. The need for postoperative dialysis occurred in 4.2% of the AKI subgroup. In-hospital mortality was higher among the AKI subgroup (7.3% vs 0.5%, p

Understanding how frailty affects patients listed for transplantation has been identified as a priority research need. Frailty may be associated with a high risk of death or wait-list withdrawal, but this has not been evaluated in a large multicenter cohort of Canadian wait-listed patients.The primary objective is to evaluate whether frailty is associated with death or permanent withdrawal from the transplant wait list. Secondary objectives include assessing whether frailty is associated with hospitalization, quality of life, and the probability of being accepted to the wait list.Prospective cohort study.Seven sites with established renal transplant programs that evaluate patients for the kidney transplant wait list.Individuals who are being considered for the kidney transplant wait list.We will assess frailty using the Fried Phenotype, a frailty index, the Short Physical Performance Battery, and the Clinical Frailty Scale at the time of listing for transplantation. We will also assess frailty at the time of referral to the wait list and annually after listing in a subgroup of patients.The primary outcome of the composite of time to death or permanent wait-list withdrawal will be compared between patients who are frail and those who are not frail and will account for the competing risks of deceased and live donor transplantation. Secondary outcomes will include number of hospitalizations and length of stay, and in a subset, changes in frailty severity over time, change in quality of life, and the probability of being listed. Recruitment of 1165 patients will provide80% power to identify a relative hazard of ≥1.7 comparing patients who are frail to those who are not frail for the primary outcome (2-sided α = .05), whereas a more conservative recruitment target of 624 patients will provide80% power to identify a relative hazard of ≥2.0.Through December 2019, 665 assessments of frailty (inclusive of those for the primary outcome and all secondary outcomes including repeated measures) have been completed.There may be variation across sites in the processes of referral and listing for transplantation that will require consideration in the analysis and results.This study will provide a detailed understanding of the association between frailty and outcomes for wait-listed patients. Understanding this association is necessary before routinely measuring frailty as part of the wait-list eligibility assessment and prior to ascertaining the need for interventions that may modify frailty.Not applicable as this is a protocol for a prospective observational study.La compréhension de l’incidence de la fragilité sur les patients en attente d’une greffe rénale a été désignée comme un besoin prioritaire de recherche. La fragilité pourrait être associée à un risque élevé de mortalité ou de se voir retiré de la liste d’attente pour une transplantation, mais elle n’a jamais été évaluée dans une vaste cohorte multicentrique de patients canadiens en attente d’une greffe.Le principal objectif consiste à déterminer si la fragilité d’un patient l’expose à un plus grand risque de décès ou de retrait permanent de la liste d’attente pour une greffe. Nous souhaitons également vérifier s’il existe un lien entre la fragilité et le nombre d’hospitalisations, la qualité de vie et la probabilité d’être accepté sur la liste d’attente.Étude de cohorte prospective.Sept sites disposant d’un programme de transplantation rénale évaluant les patients en vue de leur inscription sur la liste d’attente pour une greffe.Des candidats à la liste d’attente pour une transplantation rénale.La fragilité sera évaluée à l’aide du Phénotype de Fried (un indice de la fragilité), du test SPPB (Le résultat principal, soit un composite du délai avant le décès ou le retrait permanent de la liste, sera comparé entre les patients fragiles et non fragiles, et tiendra compte des risques concurrents découlant de la transplantation selon que l’organe provient d’un donneur vivant ou décédé. Les résultats secondaires comprendront le nombre d’hospitalisations et leur durée, les variations de la fragilité et de la qualité de vie au fil du temps (pour un sous-groupe de patients), de même que les probabilités d’être inscrit sur la liste d’attente. Le recrutement de 1 165 patients nous permettrait d’obtenir un risque relatif d’au moins 1,7 dans plus de 80 % des cas lors de la comparaison des patients fragiles à ceux qui ne le sont pas pour le résultat principal (double erreur alpha = 0,05), alors que ce risque relatif serait de 2,0 avec un objectif de recrutement plus conservateur de 624 patients.Un total de 665 évaluations de la fragilité (tant pour le résultat primaire que pour les résultats secondaires, y compris les mesures répétitives) a été complété en décembre 2019.Les résultats et leur analyse devront tenir compte des possibles variations entre les différents sites en ce qui concerne les processus d’aiguillage et d’inscription sur les listes d’attente pour une greffe.Cette étude fournira une compréhension détaillée de l’association entre la fragilité et les résultats cliniques pour les patients en attente d’une greffe. La compréhension de cette association est nécessaire avant d’inclure systématiquement la mesure de la fragilité au processus d’évaluation de l’admissibilité à la liste d’attente et avant d’établir le besoin de procéder à des interventions susceptibles de modifier la fragilité du patient.

Exercise may improve cardiometabolic, reproductive and psychological outcomes in women with Polycystic Ovary Syndrome (PCOS). Clinical Practice Guidelines recommend exercise to treat PCOS, but the most effective exercise prescription is unclear. The aim of this randomized controlled trial was to evaluate the effects of six months of thrice weekly high-intensity interval training (HIIT) and continuous aerobic exercise training (CAET) programs compared with no exercise in previously-inactive women aged 18–40 years with PCOS. The primary outcome was change in ovulation rate. Ovulation was assessed with daily at home ovulation prediction kits, and confirmed with serum progesterone levels. Fisher’s exact test was used to compare groups. Secondary outcomes included change in BMI, waist circumference, blood pressure, A1C, fasting glucose, fasting insulin, and lipids and were analyzed using repeated measures mixed models. 47 women were randomly assigned to no exercise control (n=17), HIIT (n=16), or CAET (n=14). 22/33 (66.7%) women ovulated during the intervention period: no exercise: 8/12 (66.7%), HIIT: 8/11 (72.7%), and CAET: 6/10 (60%); NS between groups. BMI decreased significantly in the CAET group compared with control (-1 kg/m2, p=0.01) and compared with HIIT (-0.9 kg/m2, p=0.04). Mean waist circumference decreased significantly in all groups with no significant difference between groups. There were no significant within- or between- group changes for body weight. No within- or between group differences were identified for mean blood pressure, A1C, fasting glucose, fasting insulin, or triglycerides. Mean LDL-C was significantly different between the HIIT and CAET groups (-0.33 mmol/L, p=0.03), as LDL-C decreased in the HIIT group but not in the CAET group. HDL-C increased in the HIIT group compared with the no exercise group (0.18 mmol/L, p=0.04), with no significant difference between the CAET and no exercise groups (p=0.47). In conclusion, CAET and HIIT interventions in women with PCOS did not affect ovulation rates. CAET and HIIT both were effective at improving anthropometrics and some cardiometabolic health markers in women with PCOS. Further studies are needed to determine optimal exercise prescriptions for reproductive, anthropometric and cardiometabolic outcomes in women with PCOS.

Introduction The Diabetes Aerobic and Resistance Exercise trial found that aerobic training and resistance training alone each reduced hemoglobin A1c (HbA1c) compared with nonexercising controls, and combined aerobic and resistance training caused greater HbA1c reduction than either training type alone. Our objective was to determine whether a dose-response relationship existed between frequency of exercise training and HbA1c change, and whether this varied by exercise modality or participant characteristics. Methods Post hoc analysis of data from 185 Diabetes Aerobic and Resistance Exercise trial participants with type 2 diabetes randomized to aerobic, resistance or combined training thrice weekly. Dose-response relationships between adherence (percent of prescribed training sessions completed) and HbA1c change were assessed with linear regression. Results Median overall adherence was 84.9% (interquartile range, 74.4%-93.6%). Higher exercise adherence was associated with greater HbA1c reduction; a 20% increase in adherence (e.g., an additional two sessions per month) was associated with a 0.15% (2 mmol·mol) decrease in HbA1c (β = -0.0076, R = -0.170, P = 0.021). Significant dose-response relationships were identified for aerobic (β = -0.0142, R = -0.313, P = 0.016) and combined training (β = -0.0109, R = -0.259, P = 0.041), but not resistance training (β = 0.0068, R = 0.153, P = 0.233). Dose-response relationships in all training groups combined were significant in subgroups younger than 55 yr (β = -0.0113, R = -0.286, P = 0.005), males (β = -0.0123, R = -0.234, P = 0.010), and baseline HbA1c ≥7.5% (58 mmol·mol) (β = -0.013, R = -0.263, P = 0.011). Conclusions There was a dose-response relationship between adherence to prescribed exercise and HbA1c reduction suggesting that glycemic control is improved more in individuals with type 2 diabetes with a higher training volume. Dose-response relationships existed for aerobic and combined training but not resistance training. These findings support aerobic and combined exercise prescriptions outlined in clinical practice guidelines.

Introduction: Certain adult conditions treated by paramedics, such as myocardial infarction or stroke, have better outcomes if transported to a specialty centre, bypassing local generalist facilities when necessary. Little evidence exists to inform guidelines to identify pediatric patients who would benefit from direct transport to a pediatric centre. This study describes the characteristics of children brought to community emergency departments (ED) who subsequently required transfer to pediatric specialty care. Methods: A retrospective observational cohort study was performed in a metropolitan area with one tertiary pediatric specialty centre and four community EDs. The patient care record database was queried for patients under 16 years old transported by paramedics to a community ED during a five-year period. Secondary transfer to the pediatric specialty centre within 24 hours was identified. The primary outcome was percentage of transfers to specialty care. Descriptive statistics were used to characterize the whole group as well as stratified by age category, chief complaint and Canadian Triage Acuity Scale (CTAS). Results: A total of 872 pediatric patients were transported to community EDs with 95 (10.9%) requiring secondary transfer to the pediatric specialty centre. CTAS 1 and 2 were associated with increased secondary transfer (p

The literature suggests that p63 expression in Merkel cell carcinoma (MCC) is associated with a poor prognosis. p63 immunohistochemistry marks the 2 main isoforms of this transcriptional protein: TAp63 (tumor suppressor-like properties) and ∆Np63 (oncogenic properties). Little information about the isoform of relevance in MCC exists. p40 immunohistochemistry specifically marks ∆Np63, and using comparative, semiquantitative expression of p63 and p40, we sought to clarify the issue. Our cohort of 53 cases (28 men and 25 women, median age 79 years, interquartile range 71-88) was stratified by morphology and viral status. Immunohistochemistry (p63, p40, and cytokeratin 5/6) was performed, H-scores for nuclear expression of p63 and p40 were derived (2 observers; positivity ≥ 10), and interobserver agreement was evaluated. Clinical, pathological, and outcome data were documented. The results were analyzed statistically. Mortality amounted to 57% (median follow-up 686 days, interquartile range 292-1599). Positivity for Merkel cell polyomavirus was observed in 29 (55%) of cases. Expression of p63 and p40 was present in 36 (69%) and 4 (8%) of cases, respectively. Increased age (P = .0241), negative Merkel cell polyomavirus status (P = .0185), and p63 positivity (P = .0012) were significantly associated with mortality. The latter 2 variables were highly correlated (P = .004). The interclass correlation between the 2 sets of H-scores was 0.95. Our findings support an association between p63 expression and reduced overall survival in MCC and show consistency in scoring this prognostic parameter. TAp63 is the dominant isoform of the protein involved. The paradoxical tumor suppressor-like activity of this isoform in p63-positive MCCs with reduced overall survival requires further study.

Background The combined effect of a low-carbohydrate, high-protein (LCHP) diet and omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on patients with type 2 diabetes (T2D) is not known. Objective The aim of this study was to evaluate the effect of an LCHP diet combined with ω-3 (LCHP+ω-3) on glycemic control in patients with T2D. Design In this randomized, double-blind, parallel-controlled trial, 122 newly diagnosed participants with T2D were randomly assigned to receive a high-carbohydrate, low-protein diet with low ω-3 PUFAs [control (CON)], an LCHP, ω-3, or LCHP+ω-3 diet for 12 wk. The ratio of carbohydrate to protein was 42:28 in the LCHP and LCHP+ω-3 diet and 54:17 in the CON and ω-3 diet. The participants were given 6 g fish oil/d (containing 3.65 g docosahexaenoic acid, eicosapentaenoic acid, and docosapentaenoic acid/d) in the ω-3 and LCHP+ω-3 diet groups or 6 g corn oil/d (placebo) in the CON and LCHP diet groups. Results Compared with the CON diet group, greater decreases in glycated hemoglobin (HbA1c) and fasting glucose were observed in all of the other 3 diet groups at 12 wk. Of note, HbA1c reduction in the LCHP+ω-3 diet group (-0.51%; 95% CI: -0.64%, -0.37%) was greater than that in the LCHP (P = 0.03) and ω-3 (P = 0.01) diet groups at 12 wk. In terms of fasting glucose, only the LCHP+ω-3 diet group showed a significant decrease at 4 wk (P = 0.03 compared with CON). Moreover, the reduction in fasting glucose in the LCHP+ω-3 diet group (-1.32 mmol/L; 95% CI: -1.72, -0.93 mmol/L) was greater than that in the LCHP (P = 0.04) and ω-3 (P = 0.03) diet groups at 12 wk. Conclusions The LCHP+ω-3 diet provided greater effects on HbA1c and fasting glucose and faster effects on fasting glucose than both the LCHP and ω-3 diets, indicating the potential necessity of combining an LCHP diet with ω-3 PUFAs in T2D control. This trial was registered at chictr.org.cn/ as ChiCTR-TRC-14004704.

Brain derived neurotrophic factor (BDNF) is a protein that plays a critical role in modulating cognition in animals and humans. Aerobic exercise often increases BDNF in adults, but effects of this exercise modality and others among adolescents remain uncertain. This study examined the effects of aerobic training, resistance training, and combined training on resting serum BDNF levels in adolescents with overweight and obesity. After a 4-week pre-randomization treatment, 304 post-pubertal, adolescents with overweight or obesity (70% females) aged 14–18 years were randomized to one of four groups for 22 weeks: aerobic training (N = 75), resistance training (N = 78), combined aerobic and resistance training (N = 75), or non-exercising control (N = 76). All participants received dietary counseling targeting a daily energy deficit of 250 kcal. The exercise prescription was 4 times per week, progressing to 45 min/session for the aerobic and resistance groups and 90 min/session for the combined group. Resting serum BDNF levels were measured at baseline and 6-months. Results showed that in both intention-to-treat (ITT) and per protocol (≥70% adherence to prescribed sessions) analyses, there were no significant within- or between-group changes in BDNF. Findings indicate that aerobic training, resistance training or their combination did change serum BDNF levels in adolescents with overweight and obesity. Trial Registration: ClinicalTrials.Gov NCT00195858 http://clinicaltrials.gov/show/NCT00195858, September 12, 2005 (Funded by the Canadian Institutes of Health Research).

Objectives This study sought to evaluate the predictive value of noninducibility on long-term outcomes. Background The traditional endpoint for catheter ablation of ventricular tachycardia (VT) is noninducibility of VT by programmed stimulation; however, the definition of inducibility remains variable and its prognostic value limited by nonstandardized periprocedural antiarrhythmic drug therapy and implantable cardioverter-defibrillator programming in prior observational studies. The VANISH trial randomized patients with prior myocardial infarction and VT to ablation (with an endpoint of noninducibility of VT ≥300 ms after ablation) versus antiarrhythmic drug escalation. Methods Patients enrolled in the VANISH study randomized to catheter ablation were included. The relationship between post-ablation inducibility and the primary composite endpoint (death, VT storm >30 days, or appropriate implantable cardioverter-defibrillator shock >30 days) was assessed using a time-to-event analysis, adjusting for other clinical and procedural characteristics. Results A total of 129 patients from the ablation arm were included in the primary analysis, of which 51 were noninducible post-ablation compared with 78 who had inducible VT or in whom inducibility testing was not performed. There were no significant baseline characteristic or procedural differences except for increased implantable cardioverter-defibrillator shocks before randomization in the noninducible group. In multivariate analysis, inducibility significantly increased the risk of death, appropriate shock, or VT storm after 30 days (HR: 1.87; p = 0.017). Conclusions Inducibility of any VT post-ablation was associated with an increased risk of the composite endpoint in the VANISH trial. A randomized trial is required to confirm whether more aggressive ablation targeting faster induced VTs (

Contact force-sensing technology has become a widely used addition to catheter ablation procedures. Neither the optimal contact force required to achieve adequate lesion formation in the ventricle, nor the impact of left ventricular access route on contact force has been fully clarified. Consecutive patients (n = 24) with ischemic cardiomyopathy who underwent ablation for scar-related ventricular tachycardia were included in the study. All ablations (n = 25) were performed using irrigated contact force-sensing catheters (Smart Touch, Biosense Webster). Effective lesion formation was defined as electrical unexcitability post ablation at sites which were electrically excitable prior to ablation (unipolar pacing at 10 mA, 2 ms pulse width). We explored the contact force which achieved effective lesion formation and the impact of left ventricular access route (retrograde aortic or transseptal) on the contact force achieved in various segments of the left ventricle. Scar zone was defined as bipolar signal amplitude

BACKGROUND Patients with ventricular tachycardia (VT) postmyocardial infarction (MI) are a higher risk group with significant morbidity and mortality. We examined the impact of prior coronary revascularization on clinical outcomes in patients with ischemic cardiomyopathy and VT. METHODS The VANISH trial randomized 259 patients with prior MI and antiarrhythmic drug-refractory VT to receive escalated medical therapy or catheter ablation. Clinical outcomes were compared according to whether patients have undergone prior revascularization procedures. The primary outcome was a composite of death, appropriate implantable cardiac defibrillator (ICD) shock, or VT storm. The secondary outcomes included elements of the primary outcome, hospitalization, and any ventricular arrhythmia. RESULTS 190 patients (73%) had prior coronary revascularization. Revascularization group had more men (97% vs 83%; P = 0.0003) and patients in that group were older (mean age 69.3 ± 7.6 vs 66.7 ± 9.2; P = 0.04), had more renal insufficiency (22.6% vs 8.7%; P = 0.01), and were more likely to have an implanted cardiac resynchronization device (23% vs 10%, P = 0.03) as compared with the nonrevascularized patients. There were no significant differences in baseline medication use. There was a trend toward fewer hospitalizations in the revascularization group (64% vs 77%; P = 0.07); there were no differences in the individual outcomes of mortality, VT storm, ICD shocks, recurrent MI, or cardiac failure. CONCLUSIONS In this cohort of patients with an ischemic cause for VT, a history of prior coronary revascularization was not associated with a reduction in ventricular arrhythmia or mortality.

Introduction In patients with ischemic heart disease and ventricular tachycardia (VT) refractory to high dose amiodarone, the two most common therapeutic options are adjunctive mexiletine therapy or catheter ablation. There are little existing data on the efficacy of these strategies. We examined the relative efficacy of adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH trial. Methods All subjects enrolled in the VANISH trial who had VT refractory to high dose (≥ 300 mg daily) amiodarone at baseline were included. Per protocol, subjects randomized to escalated drug therapy received adjunctive mexiletine. Results Nineteen of the 259 patients were receiving high-dose amiodarone at baseline and 11 were randomized to escalated therapy with mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate of the primary composite outcome (death, VT storm, or appropriate shock) in comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients in the adjunctive mexiletine/group experienced a primary endpoint during a median 9.2 months' follow-up. There was no difference in the rate of adverse events between the two groups. Conclusions Mexiletine has limited efficacy in the treatment of recurrent VT despite high-dose amiodarone therapy, in patients with ischemic heart disease. Catheter ablation is a superior strategy in this population.

Background/objective We compared health-related quality of life (HRQoL) in patients randomized to escalated therapy and those randomized to ablation for ventricular tachycardia in the VANISH trial. Methods HRQoL was assessed among VANISH patients at baseline and 3-, 6-, and 12-month follow-up visits. Four validated instruments were used: the SF-36, the implanted cardioverter defibrillator (ICD) Concerns questionnaire (ICDC), the Hospital Anxiety and Depression Scale (HADS), and the EuroQol five dimensions questionnaire (EQ-5D). Linear mixed-effects modeling was used for repeated measures with SF-36, HADS, ICDC, and EQ-5D as dependent variables. In a second model, treatment was subdivided by amiodarone use prior to enrollment. Results HRQoL did not differ significantly between those randomized to ablation or escalated therapy. On subgroup analysis, improvement in SF-36 measures was seen at 6 months in the ablation group for social functioning (63.5-69.3, P = 0.03) and energy/fatigue (43.0-47.9, P = 0.01). ICDC measures showed a reduction in ICD concern in the ablation group at 6 months (10.4-8.7, P = 0.01) and a reduction in ICD concern in the escalated therapy group at 6 months (10.9-9.4, P = 0.04). EQ-5D measures showed a significant improvement in overall health in ablation patients at 6 months (63.4-67.3, P = 0.04). Conclusion Patients in the VANISH study randomized to ablation did not have a significant change in quality of life outcomes compared to those randomized to escalated therapy. Some subgroup findings were significant, as those randomized to ablation showed persistent improvement in SF-36 energy/fatigue and ICD concern, and transient improvement in SF-36 social functioning and EQ-5D overall health.

Objectives This study investigated the benefit of an implantable cardioverter-defibrillator (ICD) generator replacement in patients who did not have an ongoing theoretical indication for ICD therapy at time of replacement. Background Primary prevention ICD therapy is known to reduce mortality in patients with cardiomyopathy and reduced left ventricular systolic function. The data describing outcomes after generator replacement are limited. Methods This was a retrospective cohort study following patients implanted with primary prevention ICD therapy from 2002 until 2015 who subsequently received a generator replacement. Patients with an ongoing theoretical indication for ICD therapy were defined as either left ventricular ejection fraction ≤35% or having had prior appropriate ICD therapy. Outcomes were mortality, appropriate ICD therapy and shock, inappropriate shock, and device and lead complications. Results A total of 614 patients were identified; 173 (28.2%) underwent a generator replacement and were followed for a mean of 2.9 years after replacement; 144 (83.2%) had an ongoing theoretical indication. Patients with no ongoing theoretical indication (n = 29, 16.7%) had lower mortality (hazard ratio [HR]: 0.39, 95% confidence interval [CI]: 0.15-1.00, p = 0.0495), appropriate shock rate (HR: 0.29, 95% CI: 0.09 to 0.96, p = 0.04), and appropriate ICD therapy rate (HR: 0.30, 95% CI: 0.12 to 0.77, p = 0.012) when compared with patients with ongoing theoretical indication. In the entire cohort, there were low rates of inappropriate shock (4.0%), device complication (5.1%), and lead complication (2.3%). Conclusions In patients with primary prevention ICD therapy who underwent generator replacement, improved left ventricular ejection fraction and lack of prior appropriate ICD therapy at time of replacement were associated with a lower risk of mortality and incident ventricular arrhythmia.

Post-hoc analyses of clinical trials and population-based studies have shown no difference in mortality between men and women, but often show that men are more likely to receive appropriate ICD therapy. We utilized a population-based registry to investigate the interaction of sex and age and the occurrence of ventricular arrhythmia in an ICD population.A total of 776 consecutive patients receiving an ICD for primary or secondary prevention in a provincial ICD registry were studied. No significant mortality difference was found between men and women (27.5% versus 23.7%, p=0.39). Overall, men were more likely to receive appropriate ICD therapy compared to women (39.3% versus 26.7%, p=0.006). The hazard ratio for appropriate therapy in men vs. women60years of age was 3.22, CI 95% (1.56-6.65), p=0.002, and the same comparison in men vs. women over the age of 60 showed no significant difference (HR 1.11, CI 95% [0.74-1.65], p=0.61). This interaction between age and sex remained significant when adjusted for New York Heart Associated Class, ejection fraction, coronary artery disease and indication for ICD (p=0.02).This study demonstrates that the risk of appropriate ICD therapy increases as women are older, reaching similar risk as men in that age group. Further study of the mechanism of the interaction of age and sex as they modulate the occurrence of ventricular arrhythmia may be warranted.

This study examined the effects of aerobic and resistance training, and their combination on health-related quality of life (HRQoL) in adolescents with overweight or obesity. After a 4-week run-in period, 304 (91 males, 213 females) post-pubertal adolescents aged 14–18 years, were randomized to 4 groups for 22 weeks of: aerobic training (n = 75), resistance training (n = 78), combined aerobic and resistance training (n = 75), or nonexercising control (n = 76). All participants received dietary counseling with a daily energy deficit of 250 kcal. Indicators of HRQoL such as overall HRQoL, and physical and psychosocial (an aggregate of emotional, social, and school functioning) HRQoL at baseline and 6 months postintervention were measured by the Pediatric Quality of Life questionnaire. The trial began in March 2005 and was completed in June 2011. In the intention-to-treat analyses, all groups showed significant improvements at 6 months on all HRQoL indicators. The aerobic group showed greater improvements than controls on physical HRQoL (mean differences of 5.5; 95% CI; 1.4–9.6, p = 0.009). In participants with ≥70% adherence, combined training produced greater improvements than control on overall HRQoL (mean differences of 4.8, 95% CI; 0.7–9.0, p = 0.02), physical HRQoL (mean differences of 5.8; 95% CI: 0.6–10.7; p = 0.03), social HRQoL (mean differences of 7.6; 95% CI: 1.0–14.2; p = 0.02), and school-based HRQoL (mean differences of 7.6; 95% CI: 1.0–14.2; p = 0.02). These findings highlight the potential importance of including resistance exercise into traditional aerobic exercise programs to maximize HRQoL in adolescents with obesity.

We evaluated the hypothesis that resistance exercise training performed alone or in combination with aerobic exercise training would increase resting metabolic rate (RMR) relative to aerobic-only and nonexercising control groups. Postpubertal adolescents (N = 304) aged 14–18 years with obesity (body mass index (BMI) ≥ 95th percentile) or overweight (BMI ≥ 85th percentile + additional diabetes risk factor(s)) were randomized to 4 groups for 22 weeks: Aerobic exercise training, Resistance exercise training, Combined aerobic and resistance exercise training, or Control. All participants received dietary counselling targeting a daily energy deficit of 250 kcal. RMR was measured by indirect calorimetry and body composition by magnetic resonance imaging. There was no significant change in RMR in any group, in spite of significant within-group increases in fat-free mass in the Aerobic, Resistance, and Combined exercise training groups. RMR at baseline and 6 months were Aerobic: 1972 ± 38 and 1990 ± 41; Resistance: 2024 ± 37 and 1992 ± 41; Combined: 2023 ± 38 and 1995 ± 38; Control: 2075 ± 38 and 2073 ± 39 kcal/day (p > 0.05). There were no between-group differences in RMR after adjustment for total body weight or fat-free mass between groups over time. Per-protocol analyses including only participants with ≥70% adherence, and analyses stratified by sex, also showed no within- or between-group differences in RMR. In conclusion, despite an increase in fat-free mass in all exercise groups, 6 months of aerobic, resistance, or combined training with modest dietary restriction did not increase RMR compared with diet only in adolescents with obesity.

Introduction: With the shift to competency-based training, surgical skills lab training (SSLT) may become a mandatory part of Canadian urology residency programs (CURPs). This study aims to identify: 1) the status of SSLT in CURP; 2) stakeholder perspectives on the utility of SSLT; 3) barriers to developing and implementing SSLT; and 4) how to address these barriers. Methods: Surveys were developed and issued to three groups of stakeholders: 1) SSLT directors at all 13 CURPs (response rate 100%); 2) teaching faculty (response rate 33%); and 3) urology residents (response rate 24%). Surveys 2 and 3 were sent to ten English CURP. Results were collected through email and SurveyMonkey®. Results: Nine of 13 CURPs have a dedicated SSLT; 46% of CURP have 1–3 sessions per year, 8% have 5–7, and 30% >7. Most residents have independent lab access, but 80% do so less than once monthly. Over 90% of stakeholders find SSLT useful, of which high-fidelity models are most preferred (faculty rated 3.66/4, residents 3.18/4). Program directors (PDs) identified lack of protected faculty time, funding, and infrastructure as the top three barriers to SSLT implementation. Residents found lack of faculty time, protected academic time, and infrastructure as barriers. PDs viewed protecting faculty time and more funding as potential solutions, while residents suggested protected faculty and academic time, and after-hours lab access. Conclusions: Residents, faculty, and PDs in CURPs view SSLT as useful. Most CURPs have defined SSLT; programs without this have labs for resident use but are underused. To continue to develop and progress SSLT, more time, participation, and funding must be made available.

This study sought to examine the adverse prognosis associated with ventricular arrhythmia clusters that falls outside the current electrical storm definition.Electrical storm is most frequently defined as a cluster of ≥3 episodes of ventricular arrhythmia (VA) in a 24-h period. This definition has been associated with adverse cardiovascular outcomes and mortality, but the effect of lesser and greater clustering of arrhythmias has not been described.Among all patients in the Resynchronization in Ambulatory Heart Failure trial, 14,515 implantable cardioverter-defibrillator-detected events with data available were rigorously adjudicated in blinded fashion. Arrhythmia incidence was examined for clustering, defined as 2 or more VA events occurring within 3 months. The prognostic importance of clustering was analyzed by varying the cluster length and number of events used to define a cluster. Mortality rates of groups with clustered arrhythmias were compared to patients with no arrhythmia or with unclustered arrhythmia.The trial included 1,764 patients, among whom 465 patients had two or more VA episodes within 3 months, whereas 406 had unclustered arrhythmias. Compared to patients with no arrhythmia, patients experiencing unclustered VA had increased risk of death (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.09 to 1.93; p = 0.011), whereas the risk was even higher in patients with clustered arrhythmia (HR: 2.68; 95% CI: 2.13 to 3.36; p 0.0001). Mortality risk increased with higher VA burden (number of VAs in a cluster) and shorter cluster length. This was observed in all groups tested, including the cluster with the least VA burden in the longest cluster length tested (2 VA episodes occurring within 3 months) (mortality HR: 2.85; 95% CI: 1.95 to 4.17; p 0.0001). Although clustered arrhythmias terminated with antitachycardia pacing were associated with increased mortality, clusters terminated with implantable cardioverter-defibrillator shocks were associated with still higher mortality risk.Significant adverse prognostic association of clustered VAs is observable with even 2 VA events within 3 months and increases with higher cluster density.

Background: There is limited information available regarding community pharmacists’ stigma of suicide. Pharmacists regularly interact with people at risk of suicide and stigmatizing attitudes may impact care. Objective: To measure community pharmacists’ stigma of suicide. Method: Pharmacists in Canada and Australia completed an online survey with the Stigma of Suicide Scale–Short Form. Data were analysed descriptively and with univariate and multivariate analyses. Results: Three hundred and ninety-six pharmacists returned completed surveys (Canada n = 235; Australia n = 161; female 70%; mean age = 38.6 ± 12.7 years). The rate of endorsement of stigmatizing terms was low overall. Canadian and Australian pharmacists differed (p Conclusion: Community pharmacists frequently interact with people at risk of suicide and generally have low agreement of stigmatizing terms for people who die by suicide. Research should focus on whether approaches such as contact-based education can minimize existing stigma.

There has been renewed interest in examining the relationship between specific components of energy expenditure and the overall influence on energy intake (EI). The purpose of this cross-sectional analysis was to determine the strongest metabolic and anthropometric predictors of EI. It was hypothesized that resting metabolic rate (RMR) and skeletal muscle mass would be the strongest predictors of EI in a sample of overweight and obese adolescents. 304 post-pubertal adolescents (91 boys, 213 girls) aged 16.1 (±1.4) years with body mass index at or above the 95th percentile for age and sex OR at or above the 85th percentile plus an additional diabetes risk factor were measured for body weight, RMR (kcal/day) by indirect calorimetry, body composition by magnetic resonance imaging (fat free mass (FFM), skeletal muscle mass, fat mass (FM), and percentage body fat), and EI (kcal/day) using 3 day food records. Body weight, RMR, FFM, skeletal muscle mass, and FM were all significantly correlated with EI (p < 0.005). After adjusting the model for age, sex, height, and physical activity, only FFM (β = 21.9, p = 0.007) and skeletal muscle mass (β = 25.8, p = 0.02) remained as significant predictors of EI. FFM and skeletal muscle mass also predicted dietary protein and fat intake (p < 0.05), but not carbohydrate intake. In conclusion, with skeletal muscle mass being the best predictor of EI, our results support the hypothesis that the magnitude of the body’s lean tissue is related to absolute levels of EI in a sample of inactive adolescents with obesity.

The purpose of this study was to examine the effects of aerobic, resistance, and combined exercise training on cardiorespiratory and musculoskeletal fitness in postpubertal adolescents with obesity. After a 4-week supervised moderate-intensity exercise run-in, 304 adolescents aged 14–18 years with body mass index ≥85th percentile were randomized to 4 groups for 22 weeks of aerobic training, resistance training, combined training, or a nonexercising control. All participants received dietary counselling with a maximum daily energy deficit of 250 kcal. Cardiorespiratory fitness (peak oxygen consumption) was measured by indirect calorimetry using a graded treadmill exercise test. Musculoskeletal fitness was measured using the 2003 Canadian Physical Activity Fitness and Lifestyle Appraisal tests (hand grip, push-ups, partial curl-ups, sit and reach, and vertical jump). Muscular strength was assessed using an 8-repetition maximum test on the bench press, seated row, and leg press machines. A greater increase in peak oxygen consumption in the aerobic exercise group (30.6 ± 0.6 to 33.4 ± 0.7 mLO2/kg/min) was measured relative to the control group (30.6 ± 0.5 to 30.9 ± 0.7 mLO2/kg/min) (p = 0.002). Similarly, the number of partial curl-ups increased in the aerobic group (19 ± 1 to 23 ± 1) while no differences were measured in the control group (19 ± 1 to 20 ± 1) (p = 0.015). Increases in muscular strength and number of push-ups were greatest in the resistance group versus the control and combined groups versus the aerobic group (p < 0.05). In conclusion, aerobic training had the strongest effect on cardiorespiratory fitness, while resistance and combined training improved both muscular strength and endurance more than control and aerobic training alone, respectively, in adolescents with obesity.

Background: In Canada, septic shock accounts for approximately 30,000 hospitalizations annually and is associated with a mortality rate of 30%. Thrombocytopenia in septic shock is associated with a poor prognosis including increased length of stay, longer duration of organ support, increased major bleeding events and mortality. The trajectory of the platelet count over time in patients with septic shock has not been well-studied. We hypothesized that the platelet count trajectory in septic shock can identify distinct clinical groups and is an independent predictor of 30-day mortality. Objectives: 1) To identify groups of patients with distinct platelet count trajectories; 2) To evaluate patient and illness factors associated with platelet count trajectories; and 3) To estimate the association of platelet count trajectory with mortality patients with septic shock. Methods: We performed a retrospective cohort study of adult patients admitted with septic shock to an intensive care unit (ICU) in Winnipeg, Canada between 2006-2014. We used group-based trajectory analysis to analyze the trend of platelet count over the first seven days of ICU admission to group patients with similar platelet trajectories. Group-based trajectory analysis is a statistical method that analyzes the pattern of a variable over time and allows distinct groups with similar trajectories to arise from the data. We utilized both the Bayesian Information Criterion (BIC) and clinical validity characteristics to choose the most suitable trajectory model. We developed a multinomial logistic regression model to associate patient characteristics with platelet count trajectories. We created a multivariable Cox proportional hazard model adjusted for age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II score, comorbidities, site or source of infection, and time to first appropriate antimicrobial to examine the association between platelet count trajectory and 30-day mortality. Results: Our study cohort included 913 patients with septic shock. The favoured trajectory model identified six distinct trajectories (Figure 1) using the platelet count over the first 7 days of ICU admission. We found that the number of organ failures on day 1was independently associated with platelet count trajectory, while other characteristics were not. The 30-day mortality of the entire cohort was 26.2% and ranged from 16.4% in group 1 (rising platelet count) to 44.4% in group 6 (high platelet count throughout). In the multivariable Cox proportional hazard model, compared with group 2 (thrombocytopenia), group 4 (high normal platelet count) was independently associated with a reduced risk of death at 30 days (Hazard Ratio (HR) 0.33, p = 0.002). The trajectory group with thrombocytosis (group 6) was associated with an increased risk of death at 30 days (HR 3.24, p=0.48) however the small number in this group limits the generalizability of this finding. Conclusion: We identified 6 distinct and clinically relevant platelet count trajectories in critically ill patients with septic shock. Platelet count trajectory was associated with the number of organ failures on day 1. Our study confirms that thrombocytopenia is associated with a worse prognosis as other trajectories with higher platelet count were associated with a lower risk of death. While it is well recognized that thrombocytopenia is associated with adverse outcomes in patients with septic shock, it is not known whether other patterns of the platelet trajectory such as thrombocytosis are similarly clinically important. Further studies are needed to fully characterize the impact platelet count trajectory on outcomes in patients with septic shock. The interplay between platelet count trajectory and other parameters (such as the white blood cell count trajectory, or INR trajectory) may have a more predictive role in evaluating prognosis in sepsis. Disclosures No relevant conflicts of interest to declare.

Objectives The genetics of binge-eating disorder (BED) is an emerging topic and one candidate pathway, namely the fat mass and obesity-associated (FTO) gene, may be implicated because of its role in food reward sensitivity and self-regulation of eating. The aims of this study were to examine the independent effects of variants of FTO on binge frequency in women with and without BED and to examine the moderating role of interpersonal attachment in this association. Methods Secondary data analysis was conducted on a cross-sectional comparison of three groups of women in a trial of group treatment for BED: BED with obesity (n = 73), BED without obesity (n = 55), and normal weight without BED (n = 50). Women were genotyped for five of the most common FTO single-nucleotide polymorphisms, rs9939609, rs8050136, rs3751812, rs1421085, and rs1121980, which have been related to body mass index and energy intake. Binge frequency (Eating Disorder Examination), body composition (bioelectric impedance), and attachment (Attachment Style Questionnaire) were assessed. Results There were no significant between-group differences for frequencies of FTO alleles, nor were there any significant anthropometric associations. The FTO × attachment interaction was significant whereby, relative to a low-risk FTO genotype, individuals with a high-risk genotype for the SNP rs1421085 and high-avoidant attachment had higher mean binge frequency than those with high genetic risk but low-avoidant attachment (β = –7.96; t = –2.07; P = 0.042). Conclusions FTO genotypes associated with risk for obesity and loss of control of eating, specifically rs1421085, may interact with insecure attachment in a way that may exacerbate binge eating among women with BED.

Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge.We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome).A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43).Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Obesity in youth increases the risk of type 2 diabetes (T2D), and both are risk factors for neurocognitive deficits. Exercise attenuates the risk of obesity and T2D while improving cognitive function. In adults, these benefits are associated with the actions of the brain-derived neurotrophic factor (BDNF), a protein critical in modulating neuroplasticity, glucose regulation, fat oxidation, and appetite regulation in adults. However, little research exists in youth. This study examined the associations between changes in diabetes risk factors and changes in BDNF levels after 6 months of exercise training in adolescents with obesity. The sample consisted of 202 postpubertal adolescents with obesity (70% females) aged 14–18 years who were randomized to 6 months of aerobic and/or resistance training or nonexercise control. All participants received a healthy eating plan designed to induce a 250/kcal deficit per day. Resting serum BDNF levels and diabetes risk factors, such as fasting glucose, insulin, homeostasis model assessment (HOMA-B—beta cell insulin secretory capacity) and (HOMA-IS—insulin sensitivity), and hemoglobin A1c (HbA1c), were measured after an overnight fast at baseline and 6 months. There were no significant intergroup differences on changes in BDNF or diabetes risk factors. In the exercise group, increases in BDNF were associated with reductions in fasting glucose (β = −6.57, SE = 3.37, p=0.05) and increases in HOMA-B (β = 0.093, SE = 0.03, p=0.004) after controlling for confounders. No associations were found between changes in diabetes risk factors and BDNF in controls. In conclusion, exercise-induced reductions in some diabetes risk factors were associated with increases in BDNF in adolescents with obesity, suggesting that exercise training may be an effective strategy to promote metabolic health and increases in BDNF, a protein favoring neuroplasticity. This trial is registered with ClinicalTrials.gov NCT00195858, September 12, 2005 (funded by the Canadian Institutes of Health Research).

Background The VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease) compared the effectiveness of escalated antiarrhythmic drug therapy to catheter ablation in patients with prior myocardial infarction, an implanted defibrillator, and ventricular tachycardia (VT). The effectiveness of these interventions in patients on sotalol versus amiodarone was compared. Methods and Results Analysis was conducted based on whether patients had recurrent VT, despite amiodarone (amio-refractory) or nonamiodarone drugs (sotalol-refractory). Outcomes included death, VT storm, appropriate implantable cardioverter defibrillator shock, and any ventricular arrhythmia. At baseline, 169 (65.2%) were amio-refractory, and 90 (34.7%) were sotalol-refractory (1 patient on procainamide rather than sotalol). Amio-refractory patients had more renal insufficiency (23.7% versus 10%; P =0.0008), worse New York Heart Association class (82.3% II/III versus 65.5%; P =0.0003), and lower ejection fraction (29±9.7% versus 35.2±11%; P P =0.020). Sotalol-refractory patients had trends toward higher mortality and VT storm with ablation, with no effect on implantable cardioverter defibrillator shocks. Within the escalated drug therapy arm, amio-refractory patients had a higher rate of the composite outcome (hazard ratio, 1.94; 95% confidence interval, 1.14–3.29; P =0.0144) and a trend to higher mortality (hazard ratio, 2.40; 95% confidence interval, 0.93–6.22; P =0.07), whereas mortality was not different between amio- and sotalol-refractory patients within the ablation treatment group. Conclusions Patients with amio-refractory VT have a higher rate of ventricular arrhythmia and mortality than those with sotalol-refractory VT and derive greater benefit of catheter ablation than for patients with sotalol-refractory VT who are switched to amiodarone. CLINICAL TRIAL REGISTRATION URL: https://clinicaltrials.gov . Unique identifier: NCT00905853.

Background Despite widespread use of the 250-mcg Cosyntropin test (ACTH test) for the diagnosis of adrenal insufficiency (AI), the effect of time of day and the utility of performing both 30- and 60-min serum cortisol values remains unclear. Methods We conducted a retrospective cohort study of all ACTH testing at the Halifax Neuropituitary Program, Nova Scotia, Canada between January 2006 and April 2016. Data were collected on age, gender, medication history, serum cortisol levels at 0, 30 and 60 min after ACTH administration, as well as time of and indication for testing. Results There were 336 tests performed, divided by time of day (0800–1000 h, 1001–1200 h, and after 1200 h). There were no differences in mean cortisol levels at 30 (574.5, 559, 534 nmol/L, respectively; p = 0.25) and 60 min (642, 623, 619 nmol/L, respectively; p = 0.63) between groups. When comparing 30- vs. 60-min values using a cut-off of ≥500 nmol/L, 45 patients (13.4%) failed to reach the cut-off at 30 min but met the cut-off at 60 min. Conversely, only 2 patients (0.6%) who met the cut-off at 30 min failed to reach it at 60 min. Conclusion We found that outcomes from ACTH testing are not affected by time of day. Furthermore, using a 30-min cortisol level in isolation results in more than one in seven patients having a false positive diagnosis of AI; a 60-min value of ≥500 nmol/L alone may be sufficient to diagnose AI in >99% of cases.

Background: Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. Aim: To determine the epidemiology of SM in the province of Nova Scotia, Canada. Methods: Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. Results: A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke’s cyst (6.5%; 0.5), growth hormone–secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone–secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at Conclusions: This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.

Purpose To determine the incidence of postintubation hypotension (PIH) and associated outcomes in critically ill patients requiring endotracheal intubation. Materials and Methods Medical records were reviewed for 479 consecutive critically ill adult patients who required intubation by an intensive care unit (ICU) service at 1 of 4 academic tertiary care hospitals. The primary outcome measure was the incidence of PIH. Secondary outcome measures included mortality, ICU length of stay, requirement for renal replacement therapy, and a composite end point consisting of overall mortality, ICU length of stay greater than 14 days, duration of mechanical ventilation longer than 7 days, and renal replacement therapy requirement. Results Overall, the incidence of PIH among ICU patients requiring intubation was 46% (218/479 patients). On univariate analysis, patients who developed PIH had increased ICU mortality (37% PIH vs 28% no PIH, P = .049) and overall mortality (39% PIH vs 30% no PIH, P = .045). After adjusting for important risk factors, development of PIH was associated with the composite end point of major morbidity and mortality (odds ratio, 2.00; 95% confidence interval, 1.30-3.07; P = .0017). Conclusions The development of PIH is common in ICU patients requiring emergency airway control and is associated with poor patient outcomes.

To investigate the effects of aerobic training, resistance training, or both on abdominal subcutaneous fat (subcutaneous adipose tissue (SAT)) (deep and superficial), visceral fat (visceral adipose tissue (VAT)), apolipoproteins A-1 and B (ApoA-1, ApoB), ApoB/ApoA-1 ratio and high-sensitivity C-reactive protein (HSCRP) in post-pubertal adolescents with obesity.After a 4-week supervised moderate-intensity exercise run-in period, 304 postpubertal adolescents with overweight (body mass index (BMI) ⩾85th percentile for age and sex+diabetes risk factor) or obesity (⩾95th BMI percentile) aged 14-18 years were randomized to four groups for 22 weeks (5 months): aerobic training, resistance training, combined training or a non-exercising control.This study used a randomized controlled design. All groups received dietary counseling designed to promote healthy eating with a maximum daily energy deficit of 250 kcal. Abdominal fat (SAT and VAT) at the level of the fourth and fifth lumbar vertebrae (L4-L5) was measured by magnetic resonance imaging and ApoA-1, ApoB and HSCRP were measured after a 12-h fast at baseline and after 6 months.Changes in SAT at L4-L5 were -16.2 cm(2) in aerobic (P=0.04 vs control), -22.7 cm(2) in resistance (P=0.009 vs control) and -18.7 cm(2) in combined (P=0.02 vs control). Combined training reduced ApoB levels from 0.81±0.02 to 0.78±0.02 g l(-1) (P=0.04 vs control) and ApoB/ApoA-1 ratio from 0.67±0.02 to 0.64±0.02 (P=0.02 vs control and P=0.04 vs aerobic). There were no significant differences in VAT, ApoA-1 or HSCRP levels between groups.Aerobic and resistance training and their combination decreased abdominal SAT in adolescents with obesity. Combined training caused greater improvements in ApoB/ApoA-1 ratio compared with aerobic training alone.