Weight loss enhances cardiac energy metabolism and function in heart failure associated with obesity.

AIMS: Obesity is associated with high rates of cardiac fatty acid oxidation, low rates of glucose oxidation, cardiac hypertrophy and heart failure. Whether weight loss can lessen the severity of heart failure associated with obesity is not known. We therefore determined the effect of weight loss on cardiac energy metabolism and the severity of heart failure in obese mice with heart failure. MATERIALS AND METHODS: Obesity and heart failure were induced by feeding mice a high-fat (HF) diet and subjecting them to transverse aortic constriction (TAC). Obese mice with heart failure were then switched for 8 weeks to either a low-fat (LF) diet (HF TAC LF) or caloric restriction (CR) (40% caloric intake reduction, HF TAC CR) to induce weight loss. RESULTS: Weight loss improved cardiac function (%EF was 38 ± 6% and 36 ± 6% in HF TAC LF and HF TAC CR mice vs 25 ± 3% in HF TAC mice, P < 0.05) and it decreased cardiac hypertrophy post TAC (left ventricle mass was 168 ± 7 and 171 ± 10 mg in HF TAC LF and HF TAC CR mice, respectively, vs 210 ± 8 mg in HF TAC mice, P < 0.05). Weight loss enhanced cardiac insulin signalling, insulin-stimulated glucose oxidation rates (1.5 ± 0.1 and 1.5 ± 0.1 µmol/g dry wt/min in HF TAC LF and HF TAC CR mice, respectively, vs 0.2 ± 0.1 µmol/g dry wt/min in HF TAC mice, P < 0.05) and it decreased pyruvate dehydrogenase phosphorylation. Cardiac fatty acid oxidation rates, AMPKTyr172 /ACCSer79 signalling and the acetylation of ß-oxidation enzymes, were attenuated following weight loss. CONCLUSIONS: Weight loss is an effective intervention to improve cardiac function and energy metabolism in heart failure associated with obesity.

Impact of frailty on outcomes after discharge in older surgical patients: a prospective cohort study.

BACKGROUND: Frailty is a state of vulnerability to diverse stressors. We assessed the impact of frailty on outcomes after discharge in older surgical patients. METHODS: We prospectively followed patients 65 years of age or older who underwent emergency abdominal surgery at either of 2 tertiary care centres and who needed assistance with fewer than 3 activities of daily living. Preadmission frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale as "well" (score 1 or 2), "vulnerable" (score 3 or 4) or "frail" (score 5 or 6). We assessed composite end points of 30-day and 6-month all-cause readmission or death by multivariable logistic regression. RESULTS: Of 308 patients (median age 75 [range 65-94] yr, median Clinical Frailty Score 3 [range 1-6]), 168 (54.5%) were classified as vulnerable and 68 (22.1%) as frail. Ten (4.2%) of those classified as vulnerable or frail received a geriatric consultation. At 30 days after discharge, the proportions of patients who were readmitted or had died were greater among vulnerable patients (n = 27 [16.1%]; adjusted odds ratio [OR] 4.60, 95% confidence interval [CI] 1.29-16.45) and frail patients (n = 12 [17.6%]; adjusted OR 4.51, 95% CI 1.13-17.94) than among patients who were well (n = 3 [4.2%]). By 6 months, the degree of frailty independently and dose-dependently predicted readmission or death: 56 (33.3%) of the vulnerable patients (adjusted OR 2.15, 95% CI 1.01-4.55) and 37 (54.4%) of the frail patients (adjusted OR 3.27, 95% CI 1.32-8.12) were readmitted or had died, compared with 11 (15.3%) of the patients who were well. INTERPRETATION: Vulnerability and frailty were prevalent in older patients undergoing surgery and unlikely to trigger specialized geriatric assessment, yet remained independently associated with greater risk of readmission for as long as 6 months after discharge. Therefore, the degree of frailty has important prognostic value for readmission. TRIAL REGISTRATION FOR PRIMARY STUDY: ClinicalTrials.gov, no. NCT02233153.

The evaluating self-management and educational support in severely obese patients awaiting multidisciplinary bariatric care (EVOLUTION) trial: principal results.

BACKGROUND: In Canada, demand for multidisciplinary bariatric (obesity) care far outstrips capacity. Consequently, prolonged wait times exist that contribute to substantial health impairments. A supportive, educational, self-management intervention (with in-person and web-based versions) for patients wait-listed for bariatric care has already been implemented in Northern and Central Alberta, Canada, but its effectiveness is unknown. The objective of this trial is to evaluate the clinical and economic outcomes of two self-management programs of varying intensity that are currently in use. METHODS: We conducted a pragmatic, prospective, parallel-arm, randomized controlled trial of 651 wait-listed patients from two regional bariatric programs. Patients were randomized to (1) an in-person, group-based intervention (13 sessions; n = 215) or (2) a web-based intervention (13 modules; n = 225) or (3) control group (printed educational materials; n = 211). After randomization, subjects had 3 months to review the content assigned to them (the intervention period) prior to bariatric clinic entry. The primary outcome was the proportion of patients achieving 5% weight loss at 9 months. Intention-to-treat two-way comparisons were performed and adjusted for baseline age, sex, site and body mass index. RESULTS: At baseline, mean age was 40.4 ± 9.8 years, mean weight was 134.7 ± 25.2 kg, mean body mass index was 47.7 ± 7.0 kg/m2 and 83% of participants were female. A total of 463 patients (71%) completed 9 months follow-up. At least 5% weight loss was achieved by 24.2% of those in the in-person strategy, 24.9% for the web-based strategy and 21.3% for controls (adjusted p value = 0.26 for in-person vs. controls, 0.28 for web-based vs. controls, 0.96 for in-person vs. web-based). Absolute and relative (% of baseline) mean weight reductions were 3.7 ± 7.1 kg (2.7 ± 5.4%) for in-person strategy, 2.8 ± 6.7 kg (2.0 ± 4.8%) for web-based and 2.9 ± 8.8 kg (1.9 ± 5.9%) for controls (p > 0.05 for all comparisons). No between-group differences were apparent for any clinical or humanistic secondary outcomes. Total annual costs in Canadian dollars were estimated at $477,000.00 for the in-person strategy, $9456.78 for the web-based strategy and $2270.31 for provision of printed materials. DISCUSSION: Two different self-management interventions were no more effective and were more costly than providing printed education materials to severely obese patients. Our findings underscore the need to develop more potent interventions and the importance of comprehensively evaluating self-management strategies before widespread implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01860131 . Registered 17 May 2013.

Comparative effectiveness and safety of gastric bypass, sleeve gastrectomy and adjustable gastric banding in a population-based bariatric program: prospective cohort study.

BACKGROUND: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program. METHODS: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data. RESULTS: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%. CONCLUSION: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.

BACKGROUND: Au Canada, la chirurgie bariatrique est effectuée principalement dans des cliniques spécialisées financées par le secteur public. Des études ont démontré que les interventions de cette nature sont supérieures à la prise en charge médicale intensive pour la perte de poids et la réduction des affections comorbides liées à l'obésité. L'objectif de notre étude était de comparer l'efficacité et l'innocuité de la dérivation gastrique Roux-en-Y par laparoscopie (DGRY), de la gastrectomie longitudinale (GL) et de la gastroplastie par anneau gastrique modulable (GAGM) dans le cadre d'un programme de traitement bariatrique basé sur la population financé par les deniers publics. METHODS: Nous avons suivi pendant 2 ans des patients ayant subi une chirurgie bariatrique. Le résultat primaire à l'étude était la variation pondérale (en kilogrammes). Nous avons analysé la variation intergroupe au moyen d'une régression multivariable et utilisé la méthode d'imputation des données manquantes par report de la dernière observation. RESULTS: Nous avons retenu 150 patients consécutifs (51 DGRY; 51 GL; 48 GAGM). Au début de l'étude, l'âge moyen était de 43,5 ± 9,5 ans, 87,3 % des patients étaient des femmes, et leur indice de masse corporelle (IMC) avant l'opération était de 46,2 ± 7,4. Après 2 ans, la perte de poids moyenne (pourcentage du poids de départ) était de 36,6 ± 19,5 kg (26,1 ± 12,2 %) pour la DGRY, de 21,4 ± 16,0 kg (16,4 ± 11,6 %) pour la GL, et de 7,0 ± 9,7 kg (5,8 ± 7,9 %) pour la GAGM (p < 0,001). La variation de l'IMC était plus grande pour le groupe DGRY (13,0 ± 6,6) que pour les 2 autres groupes (7,6 ± 5,7 pour la GL et 2,6 ± 3,5 pour la GAGM; p < 0,001). L'incidence sur le diabète, l'hypertension et la dyslipidémie était également plus grande après la DGRY qu'après la GAGM (p < 0,05 pour tous). Il n'y a eu aucun décès. Le taux de fuites anastomotiques et liées aux sutures était de 1,3 %. CONCLUSION: Dans le cadre d'un programme de chirurgie bariatrique basé sur une population et financé par le secteur public, la DGRY et la GL ont entraîné une plus grande perte de poids que la GAGM. La dérivation a donné lieu à la plus forte réduction des affections comorbides liées à l'obésité. Toutes les interventions se sont avérées sécuritaires.

Association between frailty and 30-day outcomes after discharge from hospital.

BACKGROUND: Readmissions after hospital discharge are common and costly, but prediction models are poor at identifying patients at high risk of readmission. We evaluated the impact of frailty on readmission or death within 30 days after discharge from general internal medicine wards. METHODS: We prospectively enrolled patients discharged from 7 medical wards at 2 teaching hospitals in Edmonton. Frailty was defined by means of the previously validated Clinical Frailty Scale. The primary outcome was the composite of readmission or death within 30 days after discharge. RESULTS: Of the 495 patients included in the study, 162 (33%) met the definition of frailty: 91 (18%) had mild, 60 (12%) had moderate, and 11 (2%) had severe frailty. Frail patients were older, had more comorbidities, lower quality of life, and higher LACE scores at discharge than those who were not frail. The composite of 30-day readmission or death was higher among frail than among nonfrail patients (39 [24.1%] v. 46 [13.8%]). Although frailty added additional prognostic information to predictive models that included age, sex and LACE score, only moderate to severe frailty (31.0% event rate) was an independent risk factor for readmission or death (adjusted odds ratio 2.19, 95% confidence interval 1.12-4.24). INTERPRETATION: Frailty was common and associated with a substantially increased risk of early readmission or death after discharge from medical wards. The Clinical Frailty Scale could be useful in identifying high-risk patients being discharged from general internal medicine wards.

Optimizing senior's surgical care - Elder-friendly Approaches to the Surgical Environment (EASE) study: rationale and objectives.

BACKGROUND: It is estimated that seniors (≥65 years old) account for >50% of acute inpatient hospital days and are presenting for surgical evaluation of acute illness in increasing numbers. Unfortunately, conventional acute care models rarely take into account needs of the elderly population. The failure to consider these special needs have resulted in poor outcomes, longer lengths of hospital stay and have likely increased the need for institutional care. Acute Care for the Elderly models on medical wards have demonstrated decreased cost, length of hospital stay, readmissions and improved cognition, function and patient/staff satisfaction. We hypothesize that specific Elder-friendly Approaches to the Surgical Environment (EASE) interventions will similarly improve health outcomes in a cost-effective manner. METHODS/DESIGN: Prospective, before-after study with a concurrent control group. Four cohorts of 140 consecutively-screened older patients (≥65 years old) will be enrolled (560 patients in total). The EASE interventions involves co-locating all older surgical patients on a single unit, involving an interdisciplinary care team (including a geriatric specialist) in the development of individual care plans, implementing evidence-informed elder-friendly practices, use of a reconditioning program, and optimizing discharge planning. Subjects will be followed via chart review for their hospital stay, and will then complete in-person or telephone interviews at 6 weeks and 6 months after discharge. Measured outcomes include clinical (postoperative major in-hospital complication or death [primary composite outcome]; death or readmission within 30-days of initial discharge; length of hospital stay), humanistic (quality of life; functional, cognitive, and nutritional status) and economic (health care resource utilization and costs) endpoints. Within-site mean change scores will be computed for the composite primary outcome and the overall covariate-adjusted between-site pre-post difference will be the dependent variable analyzed using generalized linear mixed model procedures including adjustment for clustering. DISCUSSION: Our findings will generate new knowledge on outcomes from acute surgical care in older patients and validate a novel elder-friendly surgical model including assessment of both clinical and economic benefits. If effective, we expect the EASE initiatives to be generalizable to other surgical centres. TRIAL REGISTRATION: Clinicaltrials.govidentifier: NCT02233153.

Weight loss required by the severely obese to achieve clinically important differences in health-related quality of life: two-year prospective cohort study.

BACKGROUND: Guidelines and experts describe 5% to 10% reductions in body weight as 'clinically important'; however, it is not clear if 5% to 10% weight reductions correspond to clinically important improvements in health-related quality of life (HRQL). Our objective was to calculate the amount of weight loss required to attain established minimal clinically important differences (MCIDs) in HRQL, measured using three validated instruments. METHODS: Data from the Alberta Population-based Prospective Evaluation of Quality of Life Outcomes and Economic Impact of Bariatric Surgery (APPLES) study, a population-based, prospective Canadian cohort including 150 wait-listed, 200 medically managed and 150 surgically treated patients were examined. Two-year changes in weight and HRQL measures (Short-Form (SF)-12 physical (PCS; MCID = 5) and mental (MCS; MCID = 5) component summary score, EQ-5D Index (MCID = 0.03) and Visual Analog Scale (VAS; MCID = 10), Impact of Weight on Quality of Life (IWQOL)-Lite total score (MCID = 12)) were calculated. Separate multivariable linear regression models were constructed within medically and surgically treated patients to determine if weight changes achieved HRQL MCIDs. Pooled analysis in all 500 patients was performed to estimate the weight reductions required to achieve the pre-defined MCID for each HRQL instrument. RESULTS: Mean age was 43.7 (SD 9.6) years, 88% were women, 92% were white, and mean initial body mass index was 47.9 (SD 8.1) kg/m2. In surgically treated patients (two-year weight loss = 16%), HRQL MCIDs were reached for all instruments except the SF-12 MCS. In medically managed patients (two-year weight loss = 3%), MCIDs were attained in the EQ-index but not the other instruments. In all patients, percent weight reductions to achieve MCIDs were: 23% (95% confidence interval (CI): 17.5, 32.5) for PCS, 25% (17.5, 40.2) for MCS, 9% (6.2, 15.0) for EQ-Index, 23% (17.3, 36.1) for EQ-VAS, and 17% (14.1, 20.4) for IWQOL-Lite total score. CONCLUSIONS: Weight reductions to achieve MCIDs for most HRQL instruments are markedly higher than the conventional threshold of 5% to 10%. Surgical, but not medical treatment, consistently led to clinically important improvements in HRQL over two years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00850356.

Case management reduces global vascular risk after stroke: secondary results from the The preventing recurrent vascular events and neurological worsening through intensive organized case-management randomized controlled trial.

BACKGROUND: Survivors of ischemic stroke/transient ischemic attack (TIA) are at high risk for other vascular events. We evaluated the impact of 2 types of case management (hard touch with pharmacist or soft touch with nurse) added to usual care on global vascular risk. METHODS: This is a prespecified secondary analysis of a 6-month trial conducted in outpatients with recent stroke/TIA who received usual care and were randomized to additional monthly visits with either nurse case managers (who counseled patients, monitored risk factors, and communicated results to primary care physicians) or pharmacist case managers (who were also able to independently prescribe according to treatment algorithms). The Framingham Risk Score [FRS]) and the Cardiovascular Disease Life Expectancy Model (CDLEM) were used to estimate 10-year risk of any vascular event at baseline, 6 months (trial conclusion), and 12 months (6 months after last trial visit). RESULTS: Mean age of the 275 evaluable patients was 67.6 years. Both study arms were well balanced at baseline and exhibited reductions in absolute global vascular risk estimates at 6 months: median 4.8% (Interquartile range (IQR) 0.3%-11.3%) for the pharmacist arm versus 5.1% (IQR 1.9%-12.5%) for the nurse arm on the FRS (P = .44 between arms) and median 10.0% (0.1%-31.6%) versus 12.5% (2.1%-30.5%) on the CDLEM (P = .37). These reductions persisted at 12 months: median 6.4% (1.2%-11.6%) versus 5.5% (2.0%-12.0%) for the FRS (P = .83) and median 8.4% (0.1%-28.3%) versus 13.1% (1.6%-31.6%) on the CDLEM (P = .20). CONCLUSIONS: Case management by nonphysician providers is associated with improved global vascular risk in patients with recent stroke/TIA. Reductions achieved during the active phase of the trial persisted after trial conclusion.

Weight loss and outcomes in wait-listed, medically managed, and surgically treated patients enrolled in a population-based Bariatric program: prospective cohort study.

BACKGROUND: Multidisciplinary bariatric care is increasingly being delivered in Canada within publicly funded regional programs. Demand is high, wait lists are long, and clinical effectiveness is unknown. OBJECTIVE: To examine the "real-world" outcomes associated with a publicly funded, population-based regional bariatric (medical and surgical) program. RESEARCH DESIGN: Prospective observational cohort. SUBJECTS: Five hundred consecutive patients (150 wait-listed, 200 medically treated, 150 surgically treated) from the Edmonton Weight Wise program were enrolled. MEASURES: The primary outcome was weight change (kg). Between-group changes were analyzed using multivariable regression adjusted for age, sex, and baseline weight and "last-observation-carried-forward" was used for missing data. Subjects transitioning between groups (wait-list to medical or medical to surgery) were censored when crossing over. RESULTS: At baseline, mean age was 43.7 ± 9.6 years, mean body mass index was 47.9 ± 8.1 kg/m, and 88% were female. A total of 412 subjects (82%) completed 2-year follow-up and 143 (29%) subjects crossed over to the next treatment phase. Absolute and relative (% of baseline) mean weight reductions were 1.5 ± 8.5 kg (0.9 ± 6.1%) for wait-listed, 4.1 ± 11.6 kg (2.8 ± 8.1%) for medically treated, and 22.0 ± 19.7 kg (16.3 ± 13.5%) for surgically treated (P<0.001) subjects. For surgery, weight reductions were 7.0 ± 9.7 kg (5.8 ± 7.9%) with banding, 21.4 ± 16.0 kg (16.4 ± 11.6%) with sleeve gastrectomy, and 36.6 ± 19.5 kg (26.1 ± 12.2%) with gastric bypass (P<0.001). Rates of hypertension, diabetes, and dyslipidemia decreased to a significantly greater degree with surgery than medical management (P<0.001) and stayed the same or increased in wait-listed subjects. CONCLUSIONS: Population-based bariatric care, particularly bariatric surgery, was clinically effective. Weight and cardiometabolic risk was relatively stable wait-listed patients receiving "usual care."

Case management for blood pressure and lipid level control after minor stroke: PREVENTION randomized controlled trial.

BACKGROUND: Optimization of systolic blood pressure and lipid levels are essential for secondary prevention after ischemic stroke, but there are substantial gaps in care, which could be addressed by nurse- or pharmacist-led care. We compared 2 types of case management (active prescribing by pharmacists or nurse-led screening and feedback to primary care physicians) in addition to usual care. METHODS: We performed a prospective randomized controlled trial involving adults with recent minor ischemic stroke or transient ischemic attack whose systolic blood pressure or lipid levels were above guideline targets. Participants in both groups had a monthly visit for 6 months with either a nurse or pharmacist. Nurses measured cardiovascular risk factors, counselled patients and faxed results to primary care physicians (active control). Pharmacists did all of the above as well as prescribed according to treatment algorithms (intervention). RESULTS: Most of the 279 study participants (mean age 67.6 yr, mean systolic blood pressure 134 mm Hg, mean low-density lipoprotein [LDL] cholesterol 3.23 mmol/L) were already receiving treatment at baseline (antihypertensives: 78.1%; statins: 84.6%), but none met guideline targets (systolic blood pressure ≤ 140 mm Hg, fasting LDL cholesterol ≤ 2.0 mmol/L). Substantial improvements were observed in both groups after 6 months: 43.4% of participants in the pharmacist case manager group met both systolic blood pressure and LDL guideline targets compared with 30.9% in the nurse-led group (12.5% absolute difference; number needed to treat = 8, p = 0.03). INTERPRETATION: Compared with nurse-led case management (risk factor evaluation, counselling and feedback to primary care providers), active case management by pharmacists substantially improved risk factor control at 6 months among patients who had experienced a stroke. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00931788.

Prioritization and willingness to pay for bariatric surgery: the patient perspective.

BACKGROUND: Access to publicly funded bariatric surgery is limited, potential candidates face lengthy waits, and no universally accepted prioritization criteria exist. We examined patients' perspectives regarding prioritization for surgery. METHODS: We surveyed consecutively recruited patients awaiting bariatric surgery about 9 hypothetical scenarios describing patients waiting for surgery. Respondents were asked to rank the priority of these hypothetical patients on the wait list relative to their own. Scenarios examined variations in age, clinical severity, functional impairment, social dependence and socioeconomic status. Willingness to pay for faster access was assessed using a 5-point ordinal scale and analyzed using multivariable logistic regression. RESULTS: The 99 respondents had mean age of 44.7 ± 9.9 years, 76% were women, and the mean body mass index was 47.3 ± SD 7.6. The mean wait for surgery was 34.4 ± 9.4 months. Respondents assigned similar priority to hypothetical patients with characteristics identical to theirs (p = 0.22) and higher priority (greater urgency) to those exhibiting greater clinical severity (p < 0.001) and functional impairment (p = 0.003). Lower priority was assigned to patients at the extremes of age (p = 0.006), on social assistance (p < 0.001) and of high socioeconomic status (p < 0.001). Most (85%) respondents disagreed with payment to expedite access, although participants earning more than $80 000/year were less likely to disagree. CONCLUSION: Most patients waiting for bariatric surgery consider greater clinical severity and functional impairments related to obesity to be important prioritization indicators and disagreed with paying for faster access. These findings may help inform future efforts to develop acceptable prioritization strategies for publicly funded bariatric surgery.

CONTEXTE: Les régimes publics donnent un accès limité à la chirurgie bariatrique; les candidats potentiels font face à des attentes prolongées et il n'existe pas de critères de priorisation universellement acceptés. Nous avons analysé le point de vue des patients relativement à la priorisation des candidats à la chirurgie. MÉTHODES: Nous avons recruté consécutivement des patients en attente de chirurgie bariatrique et nous les avons interrogés au sujet de 9 scénarios hypothétiques décrivant des patients en attente de chirurgie. Nous avons demandé aux répondants de classer ces patients hypothétiques par ordre de priorité sur la liste d'attente par rapport à la priorité de leur propre cas. Les scénarios présentaient des variations d'âge, de gravité de l'état clinique, d'atteintes fonctionnelles, de dépendance sociale et de statut socioéconomique. Nous avons déterminé au moyen d'une échelle ordinale en 5 points si les patients étaient disposés à payer pour accéder plus rapidement au traitement et nous avons analysé les réponses par régression logistique multivariée. RÉSULTATS: Les 99 répondants avaient en moyenne 44,7 ± 9,9 ans, 76 % étaient des femmes dont l'indice de masse corporelle moyen était de 47,3 ± 7,6. Le temps d'attente moyen pour la chirurgie était de 34,4 ± 9,4 mois. Les répondants ont assigné une priorité similaire aux patients hypothétiques dont les caractéristiques étaient identiques aux leurs (p = 0,22) et une priorité plus élevée (urgence supérieure) à ceux qui présentaient un état clinique plus grave (p < 0,001) et une détérioration fonctionnelle plus prononcée (p = 0,003). Une priorité moins grande a été assignée aux patients qui se trouvaient aux 2 extrémités de l'éventail des âges (p = 0,006), aux bénéficiaires de l'aide sociale (p < 0,001) et aux personnes de statut socioéconomique élevé (p < 0,001). La plupart des répondants (85 %) se sont exprimés contre le paiement pour accélérer l'accès, même si les participants qui gagnaient plus de 80 000 $ par année étaient moins enclins à s'y opposer. CONCLUSION: La plupart des patients en attente d'une chirurgie bariatrique considèrent que la gravité de l'état clinique et les atteintes fonctionnelles associées à l'obésité sont d'importants indicateurs de priorisation et s'opposent à payer pour un accès plus rapide à l'intervention. Ces observations pourraient guider une éventuelle mise au point de stratégies de priorisation pour la chirurgie bariatrique financée par les régimes publics.

The evaluating self-management and educational support in severely obese patients awaiting multidisciplinary bariatric care (EVOLUTION) trial: rationale and design.

BACKGROUND: In Canada, demand for multidisciplinary bariatric (obesity) care far outstrips capacity. Consequently, prolonged wait times exist and contribute to substantial health impairments.A supportive, educational intervention (with in-person and web-based versions) designed to enhance the self-management skills of patients wait-listed for multidisciplinary bariatric medical and surgical care has been variably implemented across Alberta, Canada. However, its effectiveness has not been evaluated. Our objectives were: 1. To determine if this program improves clinical and humanistic outcomes and is cost-effective compared to a control intervention; and 2. To compare the effectiveness and cost-effectiveness of in-person group-based versus web-based care. We hypothesize that both the web-based and in-person programs will reduce body weight and improve outcomes compared to the control group. Furthermore, we hypothesize that the in-person version will be more effective but more costly than the web-based version. METHODS/DESIGN: This pragmatic, prospective controlled trial will enrol 660 wait-listed subjects (220 per study arm) from regional bariatric programs in Alberta and randomly assign them to: 1. an in-person, group-based intervention (9 modules delivered over 10 sessions); 2. a web-based intervention (13 modules); and 3. controls who will receive mailed literature. Subjects will have three months to review the content assigned to them (the intervention period) after which they will immediately enter the weight management clinic. Data will be collected at baseline and every 3 months for 9 months (study end), including: 1. Clinical [5% weight loss responders (primary outcome), absolute and % weight losses, changes in obesity-related comorbidities]; 2. Humanistic (health related quality of life, patient satisfaction, depression, and self-efficacy); and 3. Economic (incremental costs and utilities and cost per change in BMI assessed from the third party health care payor perspective) outcomes. Covariate-adjusted baseline-to-nine-month change-scores will be compared between groups for each outcome using linear regression for continuous outcomes and logistic regression for dichotomous ones. DISCUSSION: Our findings will determine whether this intervention is effective and cost-effective compared to controls and if online or in-person care delivery is preferred. This information will be useful for clinicians, health-service providers and policy makers and should be generalizable to similar publically-funded bariatric care programs. TRIAL REGISTRATION: Trial Identifier: NCT01860131.

A liquid chromatography-mass spectrometric method for the quantification of azithromycin in human plasma.

A liquid chromatographic mass spectrometric assay for the quantification of azithromycin in human plasma was developed. Azithromycin and imipramine (as internal standard, IS) were extracted from 0.5 mL human plasma using extraction with diethyl ether under alkaline conditions. Chromatographic separation of drug and IS was performed using a C18 column at room temperature. A mobile phase consisting of methanol, water, ammonium hydroxide and ammonium acetate was pumped at 0.2 mL/min. The mass spectrometer was operated in positive ion mode and selected ion recording acquisition mode. The ions utilized for quantification of azithromycin and IS were m/z 749.6 (M + H)(+) and m/z 591.4 (fragment) for azithromycin, and 281.1 m/z for internal standard; retention times were 6.9 and 3.4 min, respectively. The calibration curves were linear (r(2) > 0.999) in the concentration ranges of 10-1000 ng/mL. The mean absolute recoveries for 50 and 500 ng/mL azithromycin and 1 µg/ mL IS were >75%. The percentage coefficient of variation and mean error were <11%. Based on validation data, the lower limit of quantification was 10 ng/mL. The present method was successfully applied to determine azithromycin pharmacokinetic parameters in two obese volunteers. The assay had applicability for use in pharmacokinetic studies.

Self-Measured Blood Pressure Telemonitoring Programs: A Pragmatic How-to Guide.

Self-measured blood pressure (SMBP) telemonitoring is the process of securely storing and tele-transmitting reliably measured, patient self-performed blood pressure (BP) measurements to healthcare teams, while ensuring that these data are viewable and clinically actionable for the purposes of improving hypertension diagnosis and management. SMBP telemonitoring is a vital component of an overall hypertension control strategy. Herein, we present a pragmatic guide for implementing SMBP in clinical practice and provide a comprehensive list of resources to assist with implementation. Initial steps include defining program goals and scope, selecting the target population, staffing, choosing appropriate (clinically validated) BP devices with proper cuff sizes, and selecting a telemonitoring platform. Adherence to recommended data transmission, security, and data privacy requirements is essential. Clinical workflow implementation involves patient enrollment and training, review of telemonitored data, and initiating or titrating medications in a protocolized fashion based upon this information. Utilizing a team-based care structure is preferred and calculation of average BP for hypertension diagnosis and management is important to align with clinical best practice recommendations. Many stakeholders in the United States are engaged in overcoming challenges to SMBP program adoption. Major barriers include affordability, clinician and program reimbursement, availability of technological elements, challenges with interoperability, and time/workload constraints. Nevertheless, it is anticipated that uptake of SMBP telemonitoring, still at a nascent stage in many parts of the world, will continue to grow, propagated by increased clinician familiarity, broader platform availability, improvements in interoperability, and reductions in costs that occur with scale, competition, and technological innovation.

Tolerability of bedtime diuretics: a prospective cohort analysis.

OBJECTIVES: We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia. DESIGN: Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration. SETTING: 352 community family practices across 4 Canadian provinces between March 2017 and September 2020. PARTICIPANTS: 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics. INTERVENTION: Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks. RESULTS: At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes. CONCLUSIONS: Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated. TRIAL REGISTRATION NUMBER: NCT02990663.

Effect of gastric bypass surgery on azithromycin oral bioavailability.

OBJECTIVES: Azithromycin is used widely for community-acquired infections. The timely administration of azithromycin in adequate doses minimizes treatment failure. Gastric bypass, a procedure that circumvents the upper gut, may compromise azithromycin plasma levels. We hypothesized that azithromycin concentrations would be reduced following gastric bypass. METHODS: A single-dose pharmacokinetic study in 14 female post-gastric bypass patients and 14 sex- and body mass index (BMI)-matched controls (mean age 44 years and BMI 36.4 kg/m(2)) was performed. Subjects were administered two 250 mg azithromycin tablets at time 0 and plasma azithromycin levels were sampled at 0.5, 1, 1.5, 2, 3, 5, 7 and 24 h. The AUC of the plasma azithromycin concentrations from time 0 to 24 h (AUC(0-24)) was the primary outcome. RESULTS: Azithromycin concentrations were lower in gastric bypass patients compared with controls throughout the entire duration of sampling. Compared with controls, the AUC(0-24) was reduced in gastric bypass subjects by 32% [1.41 (SD 0.51) versus 2.07 (0.75) mg ·â€Šh/L; P = 0.008], and dose-normalized AUC(0-24) was reduced by 33% [0.27 (0.12) versus 0.40 (0.13) kg ·â€Šh/L; P = 0.009]. Peak azithromycin concentrations were 0.260 (0.115) in bypass subjects versus 0.363 (0.200) mg/L in controls (P = 0.08), and were reached at 2.14 (0.99) h in gastric bypass subjects and 2.36 (1.17) h in controls (P = 0.75). CONCLUSIONS: Azithromycin AUC was reduced by one-third in gastric bypass subjects compared with controls. The potential for early treatment failure exists, and dose modification and/or closer clinical monitoring of gastric bypass patients receiving azithromycin should be considered.

Characteristics of the population eligible for and receiving publicly funded bariatric surgery in Canada.

BACKGROUND: Bariatric surgery is the most effective current treatment for severe obesity. Capacity to perform surgery within Canada's public health system is limited and potential candidates face protracted wait times. A better understanding of the gaps between demand for surgery and the capacity to provide it is required. The purpose of this study was to quantify and characterize the bariatric surgery-eligible population in Canada in comparison to surgery-ineligible subjects and surgical recipients. METHODS: Data from adult (age > 20) respondents of the 2007-09 nationally representative Canadian Health Measures Survey (CHMS) were analyzed to estimate the prevalence and characteristics of the surgery-eligible and ineligible populations. Federally mandated administrative healthcare data (2007-08) were used to characterize surgical recipients. RESULTS: In 2007-09, an estimated 1.5 million obese Canadian adults met eligibility criteria for bariatric surgery. 19.2 million were surgery-ineligible (3.4 million obese and 15.8 million non-obese). Surgery-eligible Canadians had a mean BMI of 40.1 kg/m2 (95% CI 39.3 to 40.9 kg/m2) and, compared to the surgery-ineligible obese population, were more likely to be female (62 vs. 44%), 40-59 years old (55 vs. 48%), less educated (43 vs. 35%), in the lowest socioeconomic tertile (41 vs. 34%), and inactive (73 vs. 59%). Self-rated mental health and quality of life were lower and comorbidity was higher in surgery-eligible respondents compared with the ineligible populations. The annual proportion of Canadians eligible for surgery that actually underwent a publicly funded bariatric surgery between 2007-09 was 0.1%. Surgical recipients (n = 847) had a mean age of 43.6 years (SD 11.1) and 82% were female. With the exception of type 2 diabetes, obesity-related comorbidity prevalence was much lower in surgical recipients compared to those eligible for surgery. CONCLUSIONS: The proportion of bariatric surgery-eligible Canadians that undergo publicly funded bariatric surgery is very low. There are notable differences in sociodemographic profiles and prevalence of comorbidities between surgery-eligible subjects and surgical recipients.

Health status, quality of life, and satisfaction of patients awaiting multidisciplinary bariatric care.

BACKGROUND: Protracted, multi-year wait times exist for bariatric care in Canada. Our objective was to examine wait-listed patients' health status and perceptions regarding the consequences of prolonged wait times using a cross-sectional study design nested within a prospective cohort. METHODS: 150 consecutive consenting subjects wait-listed for multi-disciplinary bariatric assessment in a population-based medical/surgical bariatric program were surveyed. Health status was measured using a visual analogue scale (VAS). A Waiting List Impact Questionnaire (WLIQ) examined employment, physical stress, social support, frustration, quality of life, and satisfaction with care. Multivariable linear regression analysis adjusted for age, sex and BMI identified independent predictors of lower VAS scores. RESULTS: 136 (91%) subjects were women, mean age was 43 years (SD 9), mean BMI was 49.4 (SD 8.3) kg/m2 and average time wait-listed was 64 days (SD 76). The mean VAS score was 53/100 (SD 22). According to the WLIQ, 47% of subjects agreed/strongly agreed that waiting affected their quality of life, 65% described wait times as 'concerning' and 81% as 'frustrating'. 86% reported worsening of physical symptoms over time. Nevertheless, only 31% were dissatisfied/very dissatisfied with their overall medical care. Independent predictors of lower VAS scores were higher BMI (beta coefficient 0.42; p = 0.03), unemployment (13.7; p = 0.01) and depression (10.3; p = 0.003). CONCLUSIONS: Patients wait-listed for bariatric care self-reported very impaired health status and other adverse consequences, attributing these to protracted waits. These data may help benchmark the level of health impairment in this population, understand the physical and mental toll of waiting, and assist with wait list management. TRIAL REGISTRATION: Clinicaltrials.gov NCT00850356.

Epidemiology of Resistant Hypertension in Canada.

BACKGROUND: Resistant hypertension is associated with cardiovascular morbidity and mortality. The objective of this study was to estimate the prevalence of apparent treatment-resistant hypertension in Canadian adults and examine the characteristics of those affected. METHODS: A nationally representative cross-sectional study was conducted with the use of Canadian Health Measures Survey (2007-2017) data. The frequency of respondents with uncontrolled blood pressure despite 3 or more antihypertensive medications of different drug classes (and at least 1 agent being a diuretic), or treatment with 4 or more agents regardless of blood pressure, was determined. RESULTS: A total of 245,700 people were identified to have apparent treatment-resistant hypertension, representing 5.3% (95% confidence interval [CI] 4.5%-6.2%) of adults treated for hypertension in Canada. Respondents who had uncontrolled blood pressure with 3 or more antihypertensive drugs were more likely women (55.8%, 95% CI 41.1%-70.4%), 70 years of age or older (45.3% 95% CI 32.8%-57.9%), and overweight or obese (84.2%, 95% CI 72.3%-96.1%). Respondents with apparent treatment-resistant hypertension also had a high likelihood of chronic kidney disease (36.0%, 95% CI 21.4%-50.6%), diabetes (35.2%, 95% CI 21.7%-48.7%), dyslipidemia (68.0%, 95% CI 55.2%-80.8%), and history of heart attack (9.9%, 95% CI 4.8%-15.1%) or stroke (7.1%, 95% CI 0-14.4%). CONCLUSIONS: Despite being prescribed at least 3 antihypertensive drugs, a considerable proportion of Canadians, especially women, have difficulty achieving blood pressure control, predisposing them to a higher risk of cardiovascular complications and death.