Immunosuppression and cancer risk in kidney transplant recipients: A retrospective cohort study.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.

Diagnostic Accuracy of Tryptase Levels for Pediatric Anaphylaxis: A Case-Control Study.

INTRODUCTION: Anaphylaxis is a severe allergic reaction which can be difficult to diagnose. Two strategies evaluating changes in tryptase levels were proposed for diagnosing anaphylaxis. Strategy 1 established a threshold of tryptase levels during reaction exceeding 2 ng/mL + 1.2* (baseline tryptase levels) as a rule for detecting anaphylaxis, while strategy 2 established the ratio of tryptase levels during reaction versus baseline tryptase exceeding a threshold of 1.685. We aimed to compare the diagnostic test accuracy of the two strategies in pediatric anaphylaxis. METHODS: We conducted a case-control study. Cases consisted of 89 patients with anaphylaxis who had reaction tryptase and subsequent baseline tryptase measured. Controls consisted of 25 patients with chronic urticaria who had two tryptase measurements. Sensitivity and specificity for each of the strategies were computed and compared using McNemar test. The area under the curve (AUC) between the two strategies was compared using the DeLong test. RESULTS: The sensitivity and specificity for strategy 1 was 53.3% and 95.0%, respectively. For strategy 2, the sensitivity and specificity was 54.4% and 85.0%, respectively. There was no significant difference between both strategies' sensitivity and specificity. The Delong test determined that the AUC was significantly (p < 0.05) higher for strategy 1 (0.69) than strategy 2 (0.64). CONCLUSION: The Delong test determined that strategy 1 was slightly better in validating anaphylaxis diagnosis than strategy 2. However, both strategies demonstrated a low sensitivity <55%.

Comparing two Peanut Desensitization Protocols in pre-school children: a Real-World Clinical Practice.

BACKGROUND: Peanut allergy is the main food allergy in childhood and poses significant health concerns. OBJECTIVE: This study aimed to critically evaluate the effectiveness and safety of Oral Immune Therapy (OIT) using crushed peanuts versus peanut puffs. METHODS: Children with an allergist diagnosed peanut allergy based on a history of an IgE-mediated reaction and a positive skin prick test for peanuts were recruited at the Montreal Children's Hospital and the Children's Clinic located in Montreal. Based on age and personal preference, initial doses of peanut were given in either puff (Bamba) or crushed peanut form. Patients continued the same dose for 2-5 weeks at home, filled out a symptom diary, and returned to the clinic for up-dosing until maintenance was reached (2 teaspoons of peanut butter). A continuation ratio regression model was used to evaluate the effect of the allergen type on the severity of anaphylactic and allergic reactions during OIT while adjusting for potential confounders. RESULTS: Between October 2020 and June 2023, 191 children (59.6% male; median age 1.95 years) were recruited. Most patients (75.1%) had eczema, and 12.7% had asthma. Oral desensitization was performed using one of two strategies according to the allergist: Crushed peanut (n=60 (31.4%)( and peanut puff (n=131 (68.6%)). Of the participants, the consumption of puff lowered reaction severity by a factor of 3.39 (95% CI, 1.4 to 8.22), in comparison to crushed peanuts. Older age markedly elevates the adjusted odds of reacting to a particular severity level as compared to a lower level by 1.19 (95% CI, 1.04 to 1.37). CONCLUSION: Modified peanut desensitization using peanut puffs has shown potential in reducing the severity of allergic reactions in younger children. Older children may experience a higher risk of severe reactions, indicating the need for age-specific approaches to desensitization protocols.

Stroke in Adults With Congenital Heart Disease: Incidence, Cumulative Risk, and Predictors.

BACKGROUND: Stroke is an important cause of morbidity and mortality, although there is a lack of comprehensive data on its incidence, cumulative risk, and predictors in patients with adult congenital heart disease. METHODS AND RESULTS: This retrospective study of 29 638 Quebec patients with adult congenital heart disease aged 18 to 64 years between 1998 and 2010 was based on province-wide administrative data. The cumulative risk of ischemic stroke estimated up to age 64 years was 6.1% (95% confidence interval [CI], 5.0-7.0%) in women and 7.7% (95% CI, 6.4-8.8%) in men; the risk of hemorrhagic stroke was 0.8% (95% CI, 0.4-1.2%) and 1.3% (95% CI, 0.8-1.8%), respectively. Compared with rates reported for the general Quebec population, age-sex standardized incidence rates of ischemic stroke were 9 to 12 times higher below age 55 years and 2 to 4 times higher in the age group 55 to 64 years; hemorrhagic stroke rates were 5 to 6 times (age <55 years) and 2 to 3 times higher. Using a combination of stepwise model selection and Bayesian model averaging, the strongest predictors of ischemic stroke were heart failure (odds ratio for age group 18-49 years, 5.94 [95% CI, 3.49-10.14], odds ratio for age group 50-64 years, 1.68 [95% CI, 1.06-2.66]), diabetes mellitus (odds ratio, 2.33 [95% CI, 1.66-3.28]), and recent myocardial infarction (odds ratio, 8.38 [95% CI, 1.77-39.58]). CONCLUSIONS: Among patients with adult congenital heart disease, 1 in 11 men and 1 in 15 women experienced a stroke between ages 18 and 64 years. Stroke incidence was considerably higher than in the general population, especially at a younger age. The most important predictors of ischemic stroke were heart failure, diabetes mellitus, and recent myocardial infarction. Additional research is required to see whether advances in the management of adult congenital heart disease may reduce this substantial stroke rate.

Lifetime prevalence of congenital heart disease in the general population from 2000 to 2010.

BACKGROUND: Our objective was to obtain contemporary lifetime estimates of congenital heart disease (CHD) prevalence using population-based data sources up to year 2010. METHODS AND RESULTS: The Quebec CHD database contains 28 years of longitudinal data on all individuals with CHD from 1983 to 2010. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular hearts. We used latent class bayesian models combining case definitions from physician claims, hospitalization, and surgical data to obtain point and interval prevalence estimates of CHD in the first year of life, in children (<18 years of age) and in adults. We identified 107 559 CHD patients from 1983 to 2010. Prevalence of CHD in the first year of life was 8.21 per 1000 live births (95% confidence interval, 7.47-9.02) from 1998 to 2005. In 2010, overall prevalence of CHD was 13.11 per 1000 (95% confidence interval, 12.43-13.81) in children and 6.12 per 1000 (95% confidence interval, 5.69-6.57) in adults. CHD prevalence increased by 11% in children and 57% in adults from 2000 to 2010. Prevalence in the severe CHD subgroup increased by 19% (95% confidence interval, 17%-21%) in children and 55% (51%-62%) in adults. By 2010, adults accounted for 66% of the entire CHD population. CONCLUSIONS: With an increase of >50% in CHD prevalence since 2000, by 2010 adults accounted for two thirds of patients with severe and other forms of CHD in the general population. Our findings should inform allocation of resources and the planning of workforce needs for the predominantly adult CHD population.

Epidemiology of systemic sclerosis in Quebec, Canada: a population-based study.

Background: Systemic sclerosis (SSc) is a systemic life-threatening autoimmune rheumatic disease. We aimed to assess the incidence, prevalence, mortality and spatiotemporal trends of SSc in Quebec, Canada with stratification by sex and age. Methods: SSc cases were identified from Quebec populational databases from 1989 to 2019. Negative Binomial (NB) Generalized Linear Models were used for age-standardized incidence rates (ASIR) analyses and NB random walk for prevalence and mortality. A Poisson Besag-York-Mollié regression model was used for spatial analysis. Findings: 8180 incident SSc cases were identified between 1996 and 2019 with an average age of 57.3 ± 16.3 years. The overall ASIR was 4.14/100,000 person-years (95%, Confidence Interval (CI) 4.05-4.24) with a 4:1 female predominance. ASIR increased steadily over time with an Average Annual Percent Change (AAPC) of 3.94% (95% CI 3.49-4.38). While the highest incidence rates were in those aged 60-79 years old among females and >80 years old among males, the highest AAPC (∼10%) was seen in children. Standarized incidence ratios varied geographically between 0.52 to 1.64. The average prevalence was 28.96/100,000 persons (95% CI 28.72-29.20). The Standardized Mortality Ratio (SMR) decreased from 4.18 (95% CI 3.64-4.76) in 1996 to 2.69 (95% CI 2.42-2.98) in 2019. Females had a greater SMR until 2007 and males thereafter. The highest SMR was in children and young adults [31.2 (95% CI 8.39-79.82) in the 0-19-year age group]. Interpretation: We showed an increasing trend in SSc incidence and prevalence and a decline in SMR over a 25-year period in Quebec. An uneven geographic distribution of SSc incidence was demonstrated. Funding: National Scleroderma Foundation, Canadian Dermatology Foundation/Canadian Institutes of Health Research.

Assessment of h-index and associated demographic and academic parameters for academic hematologists in Canada.

Introduction: The h-index measures researchers' productivity by assessing simultaneously the number of publications and citations. We aimed to assess the factors that could influence h-index for hematologists practicing in academic institutions in Canada. Methods: We identified universities with a hematology residency training programs/fellowships using the Canadian Resident Matching Service (CaRMS) website. We obtained the listing of faculty, sex, and academic ranks by consulting faculty directories or by contacting respective departments/universities, when directories were unavailable or incomplete. For each faculty member, we obtained years since Royal College of Physicians' and Surgeons of Canada certification or equivalent, receipt of Canadian Institute of Health Research (CIHR) grants within the last 5 years, attainment of graduate degrees (M.Sc., Ph.D., other), and the h-index. Results: The data included information collected from 372 individuals (171 females) across Canada (Atlantic Provinces: 13; Quebec: 89; Ontario: 182; Prairie Provinces: 59; British Columbia: 29). Univariate analysis showed that male sex, practicing in British Columbia, longer duration since specialty certification, completion of an M.Sc. or a Ph.D. degree, attaining a higher academic rank and receiving CIHR funding were associated with higher h-index. The results of the univariate analysis were concordant with the multivariate analysis, except that practicing in Ontario was also associated with higher h-index. Conclusion: This study provides details on the h-index curve/parameters for academic productivity of hematologists in Canada. Importantly, based on multivariate analysis, higher h-index was associated with male sex, location of practice, years since certification, attainment of M.Sc. or Ph.D. degrees, academic rank, and recent CIHR funding.

Trends of Peanut-Induced Anaphylaxis Rates Before and After the 2017 Early Peanut Introduction Guidelines in Montreal, Canada.

BACKGROUND: Food allergies, particularly peanut, represent the predominant cause of anaphylaxis. Whereas early allergen introduction has emerged as a potential preventive strategy, the precise impact of recent guidelines on peanut-induced anaphylaxis rates in Canada remains unclear. OBJECTIVE: To assess the impact of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy on peanut-induced anaphylaxis rates in Canada. METHODS: Using a comprehensive longitudinal registry capturing pediatric anaphylaxis presentations to the Montreal's Children's Hospital, we compared children with and without known peanut allergy who presented with peanut-induced anaphylaxis between 2011 and 2019 inclusive, excluding data beyond 2019 owing to the Coronavirus disease 2019 (COVID-19) pandemic. We calculated rates of peanut-induced anaphylaxis presentations per 100,000 age-adjusted all-cause emergency department visits using 4-month intervals. Interrupted time series analysis was used to compare anaphylaxis rate trends before and after 2017 for children ages 0 to 2 and 3 to 17 years. RESULTS: We examined 2,011 cases of pediatric anaphylaxis, including 429 (21%) triggered by peanuts. Compared with pre-guideline estimates, the yearly rate of change of peanut anaphylaxis rates decreased by 7.96 (95% confidence interval -14.57 to -1.36; P = .018) after 2017 among patients with new-onset anaphylaxis in children 2 years of age or younger (n = 109). No significant changes were identified for older patients ages 3 to 17, or in patients with known peanut allergy. CONCLUSIONS: Early introduction guidelines in Canada are associated with a reduced risk of new-onset peanut-induced anaphylaxis in young children within a single center in Montreal. Further research is required to assess the impact on a wider population and other food allergens.

Tree-Based Machine Learning to Identify Predictors of Psoriasis Incidence at the Neighborhood Level: A Populational Study from Quebec, Canada.

BACKGROUND: Psoriasis is a major global health burden affecting ~ 60 million people worldwide. Existing studies on psoriasis focused on individual-level health behaviors (e.g. diet, alcohol consumption, smoking, exercise) and characteristics as drivers of psoriasis risk. However, it is increasingly recognized that health behavior arises in the context of larger social, cultural, economic and environmental determinants of health. We aimed to identify the top risk factors that significantly impact the incidence of psoriasis at the neighborhood level using populational data from the province of Quebec (Canada) and advanced tree-based machine learning (ML) techniques. METHODS: Adult psoriasis patients were identified using International Classification of Disease (ICD)-9/10 codes from Quebec (Canada) populational databases for years 1997-2015. Data on environmental and socioeconomic factors 1 year prior to psoriasis onset were obtained from the Canadian Urban Environment Health Consortium (CANUE) and Statistics Canada (StatCan) and were input as predictors into the gradient boosting ML. Model performance was evaluated using the area under the curve (AUC). Parsimonious models and partial dependence plots were determined to assess directionality of the relationship. RESULTS: The incidence of psoriasis varied geographically from 1.6 to 325.6/100,000 person-years in Quebec. The parsimonious model (top 9 predictors) had an AUC of 0.77 to predict high psoriasis incidence. Amongst top predictors, ultraviolet (UV) radiation, maximum daily temperature, proportion of females, soil moisture, urbanization, and distance to expressways had a negative association with psoriasis incidence. Nighttime light brightness had a positive association, whereas social and material deprivation indices suggested a higher psoriasis incidence in the middle socioeconomic class neighborhoods. CONCLUSION: This is the first study to highlight highly variable psoriasis incidence rates on a jurisdictional level and suggests that living environment, notably climate, vegetation, urbanization and neighborhood socioeconomic characteristics may have an association with psoriasis incidence.

A survey of preventive measures used and their impact on central line-associated bloodstream infections (CLABSI) in intensive care units (SPIN-BACC).

BACKGROUND: The Quebec central line-associated bloodstream infections (CLABSI) in intensive care units (ICUs) Surveillance Program saw a decrease in CLABSI rates in most ICUs. Given the surveillance trends observed in recent years, we aimed to determine what preventive measures have been implemented, if compliance to measures was monitored and its impact on CLABSI incidence rates. METHODS: All hospitals participating in the Quebec healthcare-associated infections surveillance program (SPIN-BACC - n = 48) received a 77-question survey about preventive measures implemented and monitored in their ICU. The questionnaire was validated for construct, content, face validity, and reliability. We used Poisson regression to measure the association between compliance monitoring to preventive measures and CLABSI rates. RESULTS: Forty-two (88%) eligible hospitals completed the survey. Two components from the maximum barrier precautions were used less optimally: cap (88%) and full sterile body drape (71%). Preventive measures reported included daily review of catheter need (79%) and evaluation of insertion site for the presence of inflammation (90%). Two hospitals rewired lines even if an infection was suspected or documented.In adult ICUs, there was a statistically significant greater decrease in CLABSI rates in ICUs that monitored compliance to preventive insertion measures, after adjusting for teaching status and the number of hospital beds (p = 0.036). CONCLUSIONS: Hospitals participating to the SPIN-BACC program follow recommendations for CLABSI prevention, but only a minority locally monitor their application. Compliance monitoring of preventive measures for catheter insertion was associated with a decrease in CLABSI incidence rates.

Increased Serum Fibroblast Growth Factor 23 Predicts Mortality in People With HIV/HCV Coinfection.

BACKGROUND: People with HIV and hepatitis C virus (HCV) coinfection experience excess mortality because of multiple causes. Identification of biomarkers associated with mortality beyond that attributable to liver fibrosis may be relevant for prognostication. Fibroblast growth factor 23 (FGF23), a phosphotropic hormone, predicts adverse outcomes in several chronic conditions. We aimed to investigate whether elevated FGF23 predicts all-cause mortality in patients with HIV/HCV coinfection. METHODS: We included patients with HIV/HCV coinfection from the Canadian Coinfection Cohort with available serum FGF23, fibrosis biomarker fibrosis-4 (FIB-4), and at least 1-year follow-up. Elevated FGF23 and advanced liver fibrosis were defined as FGF23 > 241 reference unit/mL and FIB-4 > 3.25, respectively. All-cause mortality was analyzed using survival analysis. The effect of advanced liver fibrosis as a mediator on mortality was estimated by mediation analysis. RESULTS: Three hundred twenty-one patients were included (24% with elevated FGF23, 19% with advanced liver fibrosis). During a mean follow-up period of 8.4 years, 34% of the cohort died. The incidence rate of all-cause mortality was higher in patients with elevated FGF23 (66.1 per 1000 person-years, 95% confidence interval 45.8 to 92.3) relative to patients without elevated FGF23 (37.5 per 1000 person-years, 95% confidence interval 29.6 to 46.9). After adjusting for potential confounders, elevated FGF23 was associated with significant direct and indirect effects (mediated through advanced liver fibrosis) on all-cause mortality, with 57% of deaths not mediated through advanced fibrosis. CONCLUSIONS: In patients with HIV/HCV coinfection, FGF23 may be used as prognostic biomarker for risk stratification accounting also for death causes other than those attributable to liver fibrosis.

Gambling With Cardiovascular Disease Risk Models: How to Choose and How to Use.

Cardiovascular risk assessment has been shown to improve physicians' and patients' understanding of an individual's future risk of cardiovascular disease (CVD). It has also been shown to improve the management of cardiovascular risk factors including hypertension and dyslipidemia. Given the challenges of engaging patients to adhere to healthy lifestyle habits or take medications for hypertension and dyslipidemia, the primary role of CVD risk assessment should be to open a discussion about the patient's risk for CVD and associated conditions like adult-onset diabetes. Calculating a patient's long-term risk and estimating the benefits of lifestyle changes or risk factor management may then be used to support long-term patient adherence. However, risk assessment is only a first step and must be followed by evidence-based health-promotion strategies and risk factor medications that have been proven to work.

Discussing coronary risk with patients to improve blood pressure treatment: secondary results from the CHECK-UP study.

OBJECTIVES: Hypertension is common among patients with dyslipidemia but is often poorly treated. The objective of this analysis was to evaluate how a decision aid, used by primary care physicians to improve lipid therapy, impacted on the treatment of hypertension. STUDY DESIGN: Data were analyzed from patients enrolled in a randomized trial focusing primarily on the treatment of dyslipidemia. Patients received usual care or a coronary risk profile every three months to monitor the risk reduction following lifestyle changes and/or pharmacotherapy to treat dyslipidemia. Hypertension management was assessed based on a post hoc analysis of individuals whose blood pressure exceeded current national hypertension guidelines. RESULTS: There were 2,631 subjects who completed the study. Among 1,352 patients without diagnosed hypertension, 30% were above target on at least three consecutive visits. Among 1,279 individuals with known hypertension, 69% were above target on at least two consecutive visits. Overall, patients receiving risk profiles were more likely to receive appropriate antihypertensive therapy (OR = 1.40, 95% CI 1.11-1.78) compared to those receiving usual care. After adjustment for inter-physician variability and potential confounders, the use of the risk profile was associated with an increased likelihood of starting therapy (OR = 1.78, 95% CI 1.06-3.00) or modifying therapy (OR = 1.40, 95% CI 1.03-1.91). CONCLUSIONS: In this clinical trial of dyslipidemia management, inadequately controlled hypertension was common, occurring in nearly 50% of individuals. Ongoing coronary risk assessment was associated with more appropriate blood pressure management. Cardiovascular risk assessment decision aids should be further evaluated in a randomized trial of hypertension therapy.

Patient knowledge of coronary risk profile improves the effectiveness of dyslipidemia therapy: the CHECK-UP study: a randomized controlled trial.

BACKGROUND: Despite increasing evidence that treating dyslipidemia reduces cardiovascular events, many patients do not achieve recommended lipid targets. METHODS: To determine whether showing physicians and patients the patient's calculated coronary risk can improve the effectiveness of treating dyslipidemia in a primary care setting, patients were randomized to receive usual care or ongoing feedback regarding their calculated coronary risk and the change in this risk after lifestyle changes, pharmacotherapy, or both to treat dyslipidemia. Outcomes, based on intention-to-treat analysis, included changes in blood lipid levels, coronary risk, and the frequency of reaching lipid targets. RESULTS: Two hundred thirty primary care physicians enrolled 3,053 patients. After 12 months of follow-up, 2,687 patients (88.0%) remained in the study. After adjustment for baseline lipid values, significantly greater mean reductions in low-density lipoprotein cholesterol levels and the total cholesterol to high-density lipoprotein cholesterol ratio were observed in patients receiving risk profiles (51.2 mg/dL [to convert to millimoles per liter, multiply by 0.0259] and 1.5, respectively) vs usual care (48.0 mg/dL and 1.3, respectively), but the differences were small (-3.3 mg/dL; 95% confidence interval [CI], -5.4 to -1.1 mg/dL; and -0.1; 95% CI, -0.2 to -0.1, respectively). Patients in the risk profile group were also more likely to reach lipid targets (odds ratio, 1.26; 95% CI, 1.07 to 1.48). A significant dose-response effect was also noted when the impact of the risk profile was stronger in those with worse profiles. CONCLUSIONS: Discussing coronary risk with the patient is associated with a small but measurable improvement in the efficacy of lipid therapy. The value of incorporating risk assessment in preventive care should be further evaluated.

Evaluation of the cost-effectiveness of evolocumab in the FOURIER study: a Canadian analysis.

BACKGROUND: Evolocumab, a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, has been shown to reduce low-density lipoprotein levels by up to 60%. Despite the absence of a reduction in overall or cardiovascular mortality in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, some believe that, with longer treatment, such a benefit might eventually be realized. Our aim was to estimate the potential mortality benefit over a patient's lifetime and the cost per year of life saved (YOLS) for an average Canadian with established coronary artery disease. We also sought to estimate the price threshold at which evolocumab might be considered cost-effective for secondary prevention in Canada. METHODS: We calibrated the Cardio-metabolic Model, a well-validated tool for predicting cardiovascular events and life expectancy, to the reduction in nonfatal events seen in the FOURIER trial. Assuming that long-term treatment will eventually result in mortality benefits, we estimated YOLSs and cost per YOLS with evolocumab treatment plus a statin compared to a statin alone. We then estimated the annual drug costs that would provide a 50% chance of being cost-effective at willingness-to-pay values of $50 000 and $100 000. RESULTS: In secondary prevention in patients similar to those in the FOURIER study, evolocumab treatment would save an average of 0.34 (95% confidence interval [CI] 0.27-0.41) life-years at a cost of $101 899 (95% CI $97 325-$106 473), yielding a cost per YOLS of $299 482. We estimate that to have a 50% probability of achieving a cost per YOLS below $50 000 and $100 000 would require annual drug costs below $1200 and $2300, respectively. INTERPRETATION: At current pricing, the use of evolocumab for secondary prevention is unlikely to be cost-effective in Canada.

Preventing cardiovascular disease among Canadians: what are the potential benefits of treating hypertension or dyslipidemia?

BACKGROUND: Treatments for hypertension and dyslipidemia to prevent the development of cardiovascular disease compete for the same finite number of health care dollars. Therefore, the potential benefits of treating Canadians without cardiovascular disease or diabetes who would currently be targeted by the national treatment guidelines were estimated and compared. STUDY DESIGN: Canadian Heart Health Surveys data were used to estimate the number of Canadians requiring intervention. The Cardiovascular Life Expectancy Model, a previously validated Markov model, was used to calculate the increased life expectancy and decreased morbidity associated with treating risk factors to target. RESULTS: Among 8.44 million adults 40 to 74 years of age without cardiovascular disease or diabetes, it was estimated that approximately 2.33 million would require treatment for dyslipidemia and 2.34 million for hypertension. The estimated Framingham 10-year coronary risk averaged 12.4% versus 9.6%, respectively. Treating dyslipidemia was associated with an average increased life expectancy of 1.67 years and 1.81 years of life free of cardiovascular disease. Treating hypertension was expected to increase life expectancy by 0.94 years and years of life free of cardiovascular disease by 1.29 years. The population benefits associated with treating dyslipidemia or hypertension would be 2.5 million and 1.4 million person years of life saved, respectively. Overall, the person years of treatment required to save one year of life was estimated to average 20 years for dyslipidemia therapy and 38 years for hypertension. CONCLUSIONS: The potential benefits associated with treating hypertension or dyslipidemia to prevent cardiovascular disease are substantial. However, compared with hypertension guidelines, dyslipidemia guidelines target higher-risk patients. Accordingly, given the relative efficacy of each treatment, the forecasted benefits associated with treating dyslipidemia are substantially greater than those associated with hypertension therapy.

The prevalence of erectile dysfunction in the primary care setting: importance of risk factors for diabetes and vascular disease.

BACKGROUND: The prevalence of erectile dysfunction (ED) and associated risk factors has been described in many clinical settings, but there is little information regarding men seen by primary care physicians. We sought to identify independent factors associated with ED in a primary care setting. METHODS: We surveyed a cross-sectional sample of 3921 Canadian men, aged 40 to 88 years, seen by primary care physicians. Participants completed a full medical history, physical examination, and measurement of fasting blood glucose and lipid levels. We used the International Index of Erectile Function to define ED as a score of less than 26 on the erectile function domain. RESULTS: The overall prevalence of ED was 49.4%. The presence of cardiovascular disease (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.16-1.81; P<.01) or diabetes (OR, 3.13; 95% CI, 2.35-4.16; P<.001) increased the probability of ED after adjustment for other confounders. Among those individuals without cardiovascular disease or diabetes, the calculated 10-year Framingham coronary risk (OR, 1.03 per 1% increase; 95% CI, 1.02-1.05; P<.001) and fasting blood glucose levels (OR, 1.14 per 18-mg/dL [1-mmol/L] increase; 95% CI, 1.04-1.24; P<.01) were independently associated with ED. Erectile dysfunction was also independently associated with undiagnosed hyperglycemia (OR, 1.46; 95% CI, 1.02-2.10; P = .04), impaired fasting glucose (OR, 1.26; 95% CI, 1.08-1.46; P = .004), and the metabolic syndrome (OR, 1.45; 95% CI, 1.24-1.69; P<.001). CONCLUSIONS: Cardiovascular disease, diabetes, future coronary risk, and increasing fasting glucose levels are independently associated with ED. It remains to be determined if ED precedes the development of these conditions.

Cardiac output as a predictor in congenital heart disease: Are we stating the obvious?

BACKGROUND: Significant pulmonary regurgitation, declining right-sided ejection fraction, increased right ventricular (RV) volumes as well as left ventricular (LV) dysfunction have all been identified as predictors of poor outcomes in patients with congenital heart disease (CHD). The prognostic value of the cardiac output (CO) in these patients however has never been studied. METHODS: All consecutive ambulatory adult patients with CHD referred for magnetic resonance imaging (MRI) at the Montreal Children's Hospital between June 2007 and May 2009 were included. Right ventricular (RV) and left ventricular (LV) variables including end diastolic and end systolic volumes (EDV, ESV respectively), ejection fractions (EF) and regurgitant volumes were obtained. Cardiac index (CI) was calculated. Patients were followed for cardiac-related hospitalizations and cardiac interventions. RESULTS: Ninety-six patients were included. Median follow up was 3.9 ± 1.4 years. Nineteen percent of patients had a systemic CI<2.4 l/min/m(2). LVEDV, LVEF and RVEF were significantly diminished in the low CI group with a significant increase in RVESV and total regurgitant volume. Best predictors of low CI were LVEF (AUC=0.74), RVEF (AUC=0.71), total RV regurgitant volume (AUC=0.64) and RVESV (AUC=0.563). Low systemic CI was the best predictor of cardiac-related hospitalizations (hazard ratio 3.5, 95% confidence interval 1.5-8.5) and cardiac interventions (hazard ratio 2.2, 95% confidence interval 1.3-4.0), superior to LVEF, RVEF, total regurgitant volume and RVESV parameters. CONCLUSIONS: In patients with congenital heart disease, cardiac index is the best predictor of cardiac hospitalizations and cardiac interventions.