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Given the importance in prevention of lower extremity amputations (LEA) associated with diabetes or peripheral artery disease (PAD), we sought to document the trends of primary LEA in Quebec, Canada, from years 2006 to 2019.Using the Quebec Integrated Chronic Disease Surveillance System, we calculated crude and age-standardized annual incidence rates of primary LEA associated with diabetes and/or PAD among adults ≥40 years (99% confidence intervals [CI]), and all-cause 1-year mortality proportion trends following a primary LEA (95% CI), stratified by minor or major as the highest level of LEA during the same hospital stay and age groups. Trends were asssessed using multivariate regression models.In 2019, the crude rate of primary LEA was 116.0 per 100,000 (n=825) with 93.7 and 21.9 per 100,000 of minor (n=665) and major (n=160) LEA, respectively. A tendency of decrease by 8% (-15.0 to 0.4%) of age-standardized incidence of primary LEA was observed between 2006 and 2019, while minor LEA increased by 14.2% (3.7 to 25.9%) and major LEA decreased by 49.5% (-57.1 to -40.5%). Incidence trends remained stable among the 40-64 years, and declined by 14.6% and 20.1% for the 65-79 and ≥80 years, respectively. Major LEA decreased in all age groups, while minor LEA increased by 26.2% among the 40-64 years only. Age-standardized 1-year mortality decreased by 35.1% (95% CI: -43.4 to -25.7%) between 2006 and 2019, with a crude 1-year mortality of 11.3% in 2019.The reduction of major LEA and 1-year mortality are encouraging while increased minor LEA, especially in younger age groups, emphasizes the importance to further improve preventive care.

In heart failure, specific target doses for each drug are recommended, but some patients receive suboptimal dosing, others are undertreated or remain chronically in a titration phase, despite having no apparent contraindication or intolerance. We assessed the association of different levels of adherence to guidelines with outcomes in patients with heart failure and reduced ejection fraction (HFrEF).Medical records of patients with HFrEF followed at our heart failure (HF) clinic for at least 6 months (n = 511) were reviewed and patients categorized as: 1) optimized (25.4%); 2) in-titration (29.0%); 3) undertreated (32.7%); and 4) intolerant/contraindicated (12.9%). Risk of mortality or HF events (hospitalization, emergency visit or ambulatory administration of intravenous diuretics) within one year was assessed using Cox regression models and Kaplan-Meier curves.Compared to optimized patients, those intolerant (HR: 4.60 [95%CI: 2.23-9.48]; p 0.0001) had the highest risk of outcomes, followed by those undertreated (3.45 [1.78-6.67]; p = 0.0002) and in-titration (1.99 [0.97-4.06]; p = 0.0588). Overall predictors of outcomes included loop diuretics' use (4.54 [2.39-8.60]), undertreatment (2.38 [1.22-4.67]), intolerance/ contraindication to triple therapy (3.08 [1.47-6.42]), peripheral vascular disease (2.13 [1.29-3.50]) and NYHA class III-IV (1.89 [1.25-2.85]); all p 0.05.Level of adherence to guidelines is associated with outcomes, with intolerant/contraindicated patients having the worst prognosis and those undertreated and in-titration at intermediate risk compared to those optimized. Up-titration of therapy should be attempted whenever possible, considering patients' limitations, to potentially improve outcomes.

Introduction:The survivability of mass casualties exposed to a chemical attack is dependent on clinical knowledge, evidence-based practice, as well as protection and decontamination capabilities. The aim of this systematic review was to identify the knowledge gaps that relate to an efficient extraction and care of mass casualties caused by exposure to chemicals.Methods:This systematic review was conducted from November 2018 through September 2020 in compliance with Cochrane guidelines. Five databases were used (MEDLINE, Web of Science Core Collection, Embase, Cochrane, and CINAHL) to retrieve studies describing interventions performed to treat victims of chemical attacks (protection, decontamination, and treatment). The outcomes were patient’s health condition leading to his/her stabilization (primary) and death (secondary) due to interventions applied (medical, protection, and decontamination).Results:Of the 2,301 papers found through the search strategy, only four publications met the eligibility criteria. According to these studies, the confirmed chemical poisoning cases in acute settings resulting from the attacks in Matsumoto (1994), Tokyo (1995), and Damascus (2014) accounted for 1,333 casualties including 11 deaths. No study reported comprehensive prehospital clinical data in acute settings. No mention was made of the integration of specialized capabilities in medical interventions such as personal protective equipment (PPE) and decontamination to prevent a secondary exposure. Unfortunately, it was not possible to perform the planned meta-analysis.Conclusions:This study demonstrated gaps in clinical knowledge application regarding the medical extraction of casualties exposed during a chemical attack. Further research is required to optimize clinical practice integrating mixed capabilities (protection and decontamination) for the patient and medical staff.

Tania Villeneuve,1 Xavier Trudel,1,2 Mahée Gilbert-Ouimet,2,3 Jacinthe Leclerc,4,5 Alain Milot,6 Hélène Sultan-Taïeb,7,8 Chantal Brisson,1,2 Jason Robert Guertin1,2 1Université Laval, Département de médecine sociale et préventive, Quebec City, Canada; 2Centre de recherche du Centre hospitalier universitaire de l’Université Laval, Quebec City, Canada; 3Université du Québec à Rimouski, Département des sciences de la santé, module des sciences infirmières, Lévis, Canada; 4Université du Québec à Trois-Rivières, Département des sciences infirmières, Trois-Rivières, Canada; 5Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, Quebec City, Canada; 6Université Laval, Département de médecine, Quebec City, Canada; 7Université du Québec à Montréal (UQAM), School of Management, Montreal, Canada; 8CINBIOSE, Montreal, CanadaCorrespondence: Jason Robert GuertinCentre de recherche du CHU de Québec – Université Laval, Axe Santé des Populations et Pratiques Optimales en Santé, Hôpital du Saint-Sacrement, 1050 Chemin Ste-Foy, local J1-09B, Québec City, Québec, G1S 4L8, CanadaTel +1 418-682-7511, poste 82516Email jason.guertin@fmed.ulaval.caBackground: Cost studies appear sporadically in the scientific literature and are rarely revised unless drastic technological advancements occur. However, health technologies and medical guidelines evolve over time. It is unclear if these changes render obsolete prior estimates. We examined this issue in a cost study in the context of patients’ first myocardial infarction (MI), a clinical area prone to such continuous evolution in care.Methods: We conducted a longitudinal cost analysis based on a Quebec cohort. Quebec health administrative databases were used to identify incident MI cases using diagnostic codes from the international classification of diseases (ICD-9 and ICD-10). Physician fees and hospitalization costs (ie, costs incurred by the hospital center) were derived from administrative databases and a university hospital’s finance department. All costs were converted to 2019 Canadian dollars. Nonparametric bootstraps were used to estimate 95% confidence intervals (CI) of the average costs of an episode of care. Generalized linear regressions were used to examine temporal trends of cost.Results: Our study sample consists of 261 patients hospitalized for a first MI. The average total cost for this first event was estimated at $5782 (95% CI: $5293 – $6373). Though total costs remained stable over time, physician fees increased by 123% ($1240 vs $2761) whereas total hospital length of stay dropped by 17% (6.6 vs 5.5 days) over the 21-year period.Conclusion: Patients’ first MI hospitalization impose an economic burden on the healthcare system. Though overall costs remained stable, our results suggest that some cost components varied over time.Keywords: cost study, methods, observational data, myocardial infarction, longitudinal study

IntroductionAntidepressant drugs are the most frequently prescribed medication for mental disorders. They are also used off-label and for non-psychiatric indications. Prescriptions of antidepressants have increased in the last decades, but no systematic review exists on the extent of their use in the community.Methods and analysisWe will conduct a systematic review to estimate the prevalence of antidepressant use in the community. We will search for studies published from 1 January 2010 in the Embase and MEDLINE databases using a combination of controlled vocabulary and keywords adjusted for each database without any language restriction. The main inclusion criterion is the presence of prevalence data of antidepressant utilization. Thus, we will include all studies with a descriptive observational design reporting the prevalence of antidepressant use in the community. Study selection (by title/abstract and full-text screening) and data extraction for included studies will be independently conducted by pairs of reviewers. We will then synthesize the data on the prevalence of antidepressant use in individuals living in the community. If possible, we will perform a meta-analysis to generate prevalence-pooled estimates. If the data allows it, we will conduct subgroup analyses by antidepressant class, age, sex, country and other sociodemographic categories. We will evaluate the risk of bias for each included study through a quality assessment using the Joanna Briggs Institute Critical Appraisal tool: Checklist for Studies Reporting Prevalence Data. DistillerSR software will be used for the management of this review.Ethics and disseminationEthical approval is not required for this review as it will not directly involve human or animal subjects. The findings of our systematic review will be disseminated through publications in peer-reviewed journals, the Qualaxia Network (https://qualaxia.org), presentations at international conferences on mental health and pharmacoepidemiology, as well as general public events.PROSPERO registration numberCRD42021247423.

Complementary and alternative medicines (CAM) are commonly used across the world by diverse populations and ethnicities but remain largely unregulated. Although many CAM agents are purported to be efficacious and safe by the public, clinical evidence supporting the use of CAM in heart failure remains limited and controversial. Furthermore, health care professionals rarely inquire or document use of CAM as part of the medical record, and patients infrequently disclose their use without further prompting. The goal of this scientific statement is to summarize published efficacy and safety data for CAM and adjunctive interventional wellness approaches in heart failure. Furthermore, other important considerations such as adverse effects and drug interactions that could influence the safety of patients with heart failure are reviewed and discussed.

Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level. The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965. Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed. Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1–5.2), and many fluctuations were observed: 1965–1974: +22.3% (95% CI 12.0–33.6); 1974–2000: − 4.1% (95% CI − 5.3 to − 2.9); 2000–2008: +30.3% (95% CI 22.6–38.4); 2008–2014: +4.1% (95% CI − 1.5 to 10.1); 2014–2017: −26.0% (95% CI − 44.7 to − 0.9); and, finally, 2017–2019: +35.4% (95% CI 3.8–76.7). Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.

IntroductionThe use of weapons of mass destruction against civilian populations is of serious concern to public health authorities. Chemical weapons are of particular concern. A few studies have investigated medical responses in prehospital settings in the immediate aftermath of a chemical attack, and they were limited by the paucity of clinical data. This study aims to describe the acute management of patients exposed to a chemical attack from the incident site until their transfer to a medical facility.Methods and analysisThis international multicentric observational study addresses the period from 1970 to 2036. An online electronic case report form was created to collect data; it will be hosted on the Biomedical Telematics Laboratory Platform of the Quebec Respiratory Health Research Network. Participating medical centres and their clinicians are being asked to provide contextual and clinical information, including the use of protective equipment and decontamination capabilities for the medical evacuation of the patient from the incident site of the chemical attack to the moment of admission at the medical facility. In brief, variables are categorised as follows: (1) chemical exposure (threat); (2) prehospital and hospital/medical facility capabilities (staffing, first aid, protection, decontamination, disaster plans and medical guidelines); (3) clinical interventions before hospital admission, including the use of protection and decontamination and (4) outcomes (survivability vs mortality rates). Judgement criteria focus on decontamination drills applied to any of the patient’s conditions.Ethics and disseminationThe Sainte-Justine Research Centre Ethics Committee approved this multicentric study and is acting as the main evaluating centre. Study results will be disseminated through various means, including conferences, indexed publications in medical databases and social media.Trial registration numberNCT05026645.

Background It is unclear whether generics are as safe as brand-name drugs in cardiology. For public health surveillance purposes, we evaluated if switching from the brand-name losartan, valsartan, or candesartan impacted the occurrence of the following outcomes: emergency room (ER) consultations, hospitalizations, or death. Study Design This was a retrospective cohort study. Methods This study was conducted in the Quebec Integrated Chronic Disease Surveillance System, including healthcare administrative data of the population of Quebec, Canada. We included brand-name users of losartan, valsartan, or candesartan aged ≥ 66 years who had undergone ≥ 30 days of stable treatment on the brand-name drug prior to cohort entry (substitution time-distribution matching was used to prevent immortal time bias). Outcomes up to 1 year were compared between groups using multivariable Cox proportional hazards regression models (validity assumptions were verified). Results In our cohorts (losartan, n =15,783; valsartan, n =16,907; candesartan, n =26,178), mean age was 76–78 years, 59–66% were female, 90–92% had hypertension, and 13–15% had heart failure. Validity assumptions were violated for losartan only. For patients switched to generic valsartan, the hazard ratio (95% confidence interval) was 1.07 (0.99–1.14) for ER consultation, 1.26 (1.14–1.39) for hospitalization, and 1.01 (0.61–1.67) for death. The corresponding rates for candesartan were 1.00 (0.95–1.05), 0.96 (0.89–1.03), and 0.57 (0.37–0.88), respectively. Conclusions We observed an increased risk of hospitalizations for patients switched to generic valsartan, and a decreased risk of death for patients switched to generic candesartan, compared with those who continued taking the brand-name drug. The differences between generic and brand-name drugs may lead to some differences in public health outcomes, but this safety signal must be further studied using other cohorts and settings. Electronic supplementary material The online version of this article (10.1007/s40268-020-00307-2) contains supplementary material, which is available to authorized users.

Resumo Objetivo Avaliar o impacto de um programa de melhoria da qualidade relacionado aos indicadores de frequência de sondas nasoenterais obstruídas, do tempo despendido pela equipe de enfermagem no preparo e na administração de medicamentos orais por essa via, e dos custos associados ao incidente. Método Estudo de intervenção voltado para a comparação pré (Fase I) e pós (Fase II) implementação de um Programa Melhoria da Qualidade, proposto pelo Institute for Healthcare Improvement . Foram observadas 92 doses de medicamentos na Fase I e 66 doses na Fase II. Foram necessários quatro ciclos Plan-Do-Study-Act (PDSA) para atingir a meta proposta para o programa de melhoria. Resultados Houve redução no tempo médio gasto pelo profissional no preparo e na administração de medicamentos sólidos via sonda nasoenteral em ambas as fases. As frequências de sondas obstruídas reduziram de 33,3% (Fase I) para 7,4% (Fase II) e nenhuma sonda apresentou-se obstruída durante os ciclos 1, 2 e 4. O custo médio da obstrução por paciente foi de R$ 1.251,05 ao mês na Fase I e de R$ 23,31 na Fase II. Após as mudanças testadas, foi verificada economia de tempo para a equipe de enfermagem e de custo para a instituição. Conclusão Os ciclos PDSA foram eficazes na redução de não conformidades no preparo e na administração de medicamentos via sonda nasoenteral. Tal melhoria impactou a frequência de obstrução, os custos relacionados e o tempo médio gasto pelo profissional de enfermagem durante o preparo e a administração das doses. Resumen Objetivo Evaluar el impacto de un programa de mejora de la calidad relacionado con los indicadores de frecuencia de sondas nasoenterales obstruidas, del tempo invertido por el equipo de enfermería en la preparación y en la administración de medicamentos orales por esa vía y de los costos asociados con el incidente. Métodos Estudio de intervención direccionado para la comparación previa (Fase I) y posterior (Fase II) a la implementación de un Programa Mejora de la Calidad, propuesto por el Institute for Healthcare Improvement . Se observaron 92 dosis de medicamentos en la Fase I y 66 dosis en la Fase II. Se necesitaron cuatro ciclos Plan-Do-Study-Act (PDSA) para alcanzar la meta propuesta para el programa de mejora. Resultados Hubo reducción del tiempo promedio consumido por el profesional en la preparación y en la administración de medicamentos sólidos por sonda nasoenteral en ambas fases. La frecuencia de la obstrucción de las sondas se redujo del 33,3 % (Fase I) para el 7,4 % (Fase II) y ninguna sonda presentó obstrucción durante los ciclos 1, 2 y 4. El costo promedio de la obstrucción por paciente fue de R$ 1.251,05 al mes en la Fase I y de R$ 23,31 en la Fase II. Después de someter a pruebas los cambios, se verificó un ahorro de tiempo para el equipo de enfermería y de costo para la institución. Conclusión Los ciclos PDSA fueron eficaces en la reducción de no conformidades en la preparación y en la administración de medicamentos por sonda nasoenteral. Esa mejora impactó la frecuencia de obstrucción, los costos relacionados y el tiempo promedio consumido por el profesional de enfermería durante la preparación y la administración de las dosis. Abstract Objective Evaluate the impact of a quality improvement program related to the frequency indicators of obstructed nasogastric tubes, the time the nursing team spent on oral medication preparation and administration through this route, and the costs associated with the incident. Method Intervention study aimed at comparing pre (Phase I) and post (Phase II) implementation of a Quality Improvement Program, proposed by Institute for Healthcare Improvement . Ninety-two medication doses were observed in Phase I and 66 doses in Phase II. Four Plan-Do-Study-Act (PDSA) cycles were needed to achieve the proposed target for the improvement program. Results The average time the professional spent on solid medication preparation and administration through nasogastric tube decreased in both phases. Frequencies of obstructed tubes dropped from 33.3% (Phase I) to 7.4% (Phase II) and no probe was obstructed during cycles 1, 2, and 4. The average cost of the obstruction per patient was R$ 1,251.05 per month in Phase I and R$ 23.31 in Phase II. After testing the changes, time savings for the nursing team and cost savings for the institution were verified. Conclusion The PDSA cycles were effective in reducing non-conformities in medication preparation and administration via nasogastric tube. This improvement influenced the obstruction frequency, related costs, and the average time the nursing professional spent on the preparation and administration of the medication doses.

Introduction: Non-traumatic lower limb amputations (LLA) represent an important complication of diabetes (DM) and peripheral arterial disease (PAD). In Quebec, Canada, the latest data between 1996 to 2004 suggested a reduction in the incidence of LLA while other Canadian provinces observed a recent increase between 2010 and 2016. Our objective was to update the incidence trends of LLA in Quebec from fiscal years 2006 to 2019. Methods: Age-standardized incidence of LLA among individuals ≥40 years was assessed using the Quebec Integrated Chronic Disease Surveillance System (n=4,527,533 in 2019). The mean age of incident cases and the presence / duration of DM and/or PAD was collected. Estimations were presented for all, by sexes and by types of LLA (minor: below the knee; major: knee and above), with 99% confidence intervals (CI). Results: Between 2006 and 2019, incident cases of LLA increased from 818 to 1,099 but age-standardized incidence remained stable (Figure 1) for both sexes. Men had a higher age-standardized incidence of LLA then women (32.7 per 100,000 [99% CI: 29.7-35.9] vs 12.9 per 100,000 [11.2-14.9] in 2019). From 2006 to 2019, the age-standardized incidence of major LLA showed a relative decrease of 48% while minor LLA remained stable (Figure 1). Reduction in age-standardized incidence of major LLA was attributable to men (3.8 per 100,000 [2.7-5.3] to 1.7 per 100,000 [1.1-2.6]). The mean age of incident cases went from 68.2 to 69.5 years from 2006 to 2019 (72.4 for women and 68.3 for men in 2019). Ninety-eight percent of LLA had DM, while 95% had PAD and 95% had both in 2019. Between 2006 and 2019, the average time between the first LLA and DM diagnosis increased from 7.0 to 14.7 years and from 2.0 to 2.6 years for PAD. Conclusions: Although the age-standardized incidence of LLA is stable, men remain at higher risk then women. The portrait of incident cases is changing towards an older average age, longer DM duration and a reduction of major LLA. These results emphasize the importance to improve further preventive care of LLA in Quebec.

Introduction: The progression of type 2 diabetes (T2D) is unique to each patient and can be depicted through individual temporal trajectories. Latent group trajectory methods (latent growth mixture models [LGMM] or latent class growth analysis [LCGA]) can be used to classify similar individual trajectories in a priori non-observed groups (latent groups), sharing common characteristics. Although increasingly used in the field of T2D epidemiology, many questions remain regarding the utilization of these methods. Objective: To review the literature of longitudinal studies using latent group trajectory methods among individuals with T2D. Methods: MEDLINE (Ovid), EMBASE, CINAHL and Web of Science were searched through August 25 th , 2021. Data were collected on the type of method used (LGMM or LGCA), characteristics of studies and quality of reporting using the GRoLTS-Checklist. Results: From the 4,694 citations screened, a total of 38 studies were included. The studies were published between 2010 and 2021. Total follow-ups ranged from 8 weeks to 11 years, with 95% (36 out of 38) studies with a follow-up of 1 year of more. The characteristics of studies are presented in Table 1. Regarding the quality of reporting, trajectory groups were adequately presented, however many studies failed to report important decisions made for the trajectory group identification. Many studies considered trajectory groups as exposures to a subsequent outcome. Yet, issues in relation with selection bias, immortal bias and residual confounding were suspected and poorly addressed. Conclusions: Although LCGA were preferred, the context of utilization, data sources and research questions were diverse and unrelated to the type of method used. We recommend authors to clearly report the decisions made in trajectory groups identification.

BackgroundAntidepressant drugs are the most frequently prescribed medication for mental disorders. They are also used off-label and for non-psychiatric indications. Prescriptions of antidepressants have increased in the last decades, but no systematic review exists on the extent of their use in the community.Methods and analysisWe will conduct a systematic review to estimate the prevalence of antidepressant use in the community. We will search for studies published from 2010 in the Embase and MEDLINE databases. Study selection (by title/abstract and full-text screening) and data extraction for included studies will be independently conducted by pairs of reviewers. We will then synthesize the data on the prevalence of antidepressant use in individuals living in the community. If possible, we will perform a meta-analysis to generate prevalence-pooled estimates. If the data allows it, we will conduct subgroup analyses by antidepressant class, age, sex, country or other sociodemographics. We will evaluate the risk of bias for each included study through a quality assessment using the Joanna Briggs Institute Critical Appraisal tool: Checklist for Studies Reporting Prevalence Data. DistillerSR software will be used for the management of this review.Ethics and disseminationEthical approval is not required for this review as it will not involve human or animal subjects. The findings of our systematic review will be disseminated through publications in peer-reviewed journals, the Qualaxia Network (https://qualaxia.org), presentations to international conferences on mental health and pharmacoepidemiology, as well as general public events.PROSPERO registration detailsCRD42021247423

Introduction: In the last decade, an increase in the prevalence and a reduction in the incidence of diabetes have been observed in many countries including Canada. Yet, some Canadian provinces depicted an elevation in incidence rates among younger age groups. Our objective was to document these trends in the province of Quebec from fiscal years 2001 to 2017. Hypothesis: Prevalence is increasing because of raising incidence in individuals aged Methods: Prevalence, incidence and all-cause mortality among cases of diabetes ≥20 years were assessed using the Quebec Integrated Chronic Disease Surveillance System (n=6,551,045 in 2017). Estimations were age-standardized or stratified by 10-year age groups. Results: In 2017, the crude prevalence and incidence of diabetes were 9.9% [99% confidence interval: 9.9-10.0] (n=651,370) and 6.0 per 1,000 inhabitants [5.9-6.0] (n=35,355), respectively. Between 2001 and 2017, the age-standardized prevalence increased by 43% (6.3% [6.3-6.3] to 9.0% [9.0-9.1]), while age-standardized incidence decreased by 29% (8.3 per 1,000 [8.2-8.4] to 5.9 per 1,000 [5.9-6.0]). In every age group, the prevalence increased steadily with progressive stabilization from 2011 and onward, except for the 60-69 years old group who depicted a reduction from 2012 to 2017. Incidence remained stable among Conclusions: The rise and stabilization of diabetes prevalence could be due to a reduction in incidence in patients aged ≥50 years and mortality among all age groups. Prevention of diabetes should be a priority among individuals aged

Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient’s arrythmia could be drug-induced is important.

Post-marketing studies involve the detection and interpretation of potential problems associated with the use of a given drug. Post-marketing spontaneous pharmacovigilance systems, such as the Canada Vigilance program, may constitute a gold mine of free data for drug safety research. However, the quantity and the quality of data remain to be demonstrated. To assess the feasibility to use the Canada Vigilance database for academic drug safety research, and to document the characteristics of data that are extractable. This is a descriptive retrospective analysis study design. The beta-blocker and anticoagulant adverse reactions (AR) in Canada were analyzed. Tests for data extraction from the Canada Vigilance database were performed in October 2019; data were then available from January 1, 1966 to June 30, 2019. There were 41 variables with extractable data. For anticoagulants, data were extracted in Excel and.pdf file format, while it was only plain text.pdf files for beta-blockers. Overall, there were 4707 reported ARs with the use of anticoagulants and 6332 cases reported for beta-blockers. The trend of ARs related to anticoagulants steadily increased in the study period, with a notable increase in 2009 while direct oral anticoagulants were marketed. The proportion of missing data varied from 0 to 98%, but most important variables were all available. It was not possible to distinguish brand names and generic drugs in the database. It seems feasible to use data from the Canadian Post-marketing Spontaneous Pharmacovigilance System for academic drug safety research. Upcoming studies should validate the quality of reports compared to actual medical charts.

Background: Generic drugs constitute lower cost alternatives when the original drug patent expires. Two large systematic reviews and meta-analyses (2008; 2016) concluded to similarity in outcomes between brand-name and generic drugs in cardiology. These meta-analyses were possibly biased by the inclusion of ≥ 50% comparative bioavailability studies, not designed nor powered to detect a difference in efficacy or safety between drug types. We aimed to summarize best evidences regarding the effectiveness and safety of generic versus brand-name drugs used in cardiology. Methods: To conduct this systematic review of the literature, scientific databases (MEDLINE and EMBASE) were searched from the latest date among their inception or January 1984, to March 2018. Original research reports comparing the clinical impact of brand-name vs. generic cardiovascular drugs on humans treated in real-life setting were included. Meta-Analyses and subgroup analyses were performed. Heterogeneity (I 2 ) and risk of bias were tested. Results: Among the 3,148 screened abstracts, 72 met inclusion criteria. The studies included a total of 1,048,499 patients who used generic or brand-name cardiovascular drugs. Mean age was 65 +/- 10 years old and 42% were women. The most commonly studied therapeutic classes were antiplatelets, statins and anticoagulants. Platelet function, international normalized ratio and systolic blood pressure were similar in generic and brand-name groups. The risk of bias was modest to serious in the majority of studies. The overall relative risk of all-cause hospitalizations was 1.14 (95% Confidence interval: 1.06 to 1.23; I 2 : 98%), while it was 1.05 (0.98 to 1.14; I 2 : 68%) for cardiovascular hospitalizations (both pooled: 1.10 [1.04 to 1.15]; I 2 : 93%). Conclusion: The risk of hospitalization seemed higher for patients exposed to generics. However, evidences are insufficient and too heterogeneous to conclude that generics are as effective and safe as brand-name drugs in cardiology.

Previous systematic reviews (2008; 2016) concluded similarity in outcomes between brand-name and generic drugs in cardiology, but they included ≥ 50% comparative bioavailability studies, not designed or powered to detect a difference in efficacy or safety between drug types. We aimed to summarise best-evidence regarding the effectiveness and safety of generic versus brand-name drugs used in cardiology. For this systematic review of the literature, scientific databases (MEDLINE and EMBASE) were searched from January 1984 to October 2018. Original research reports comparing the clinical impact of brand-name versus generic cardiovascular drugs on humans treated in a real-life setting, were selected. Meta-analyses and subgroup analyses were performed. Heterogeneity (I2) and risk of bias were tested. Among the 3148 screened abstracts, 72 met the inclusion criteria (n ≥ 1,000,000 patients, mean age 65 ± 10 years; 42% women). A total of 60% of studies showed no difference between drug types, while 26% concluded that the brand-name drug was more effective or safe, 13% were inconclusive and only 1% concluded that generics did better. The overall crude risk ratio of all-cause hospital visits for generic versus brand-name drug was 1.14 (95% confidence interval: 1.06–1.23; I2: 98%), while it was 1.05 (0.98–1.14; I2: 68%) for cardiovascular hospital visits. The crude risk ratio was not statistically significant for randomised controlled trials only (n = 4; 0.92 [0.63–1.34], I2: 35%). The crude risk of hospital visits was higher for patients exposed to generic compared to brand-name cardiovascular drugs. However, the evidence is insufficient and too heterogeneous to draw any firm conclusion regarding the effectiveness and safety of generic drugs in cardiology.

Background Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery–induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery. Methods Fifty-eight severely obese patients (46.1 ± 6.1 kg/m2, 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery. Results Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (VO2peak) increased significantly (P Conclusions A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery.

Background The prevalence of mood disorders was estimated at 5.4% according to the latest Canadian survey. It has been suggested to use administrative data and self-reported data to optimize the estimation for mental health care in the population. Using administrative data, algorithms (combination of codes from the International Classification of Diseases) had been previously developed to identify the population with mood and anxiety disorders. However, the specific prevalence of each component of mood disorders (depressive, bipolar and adjustment disorders) are still unknown in Quebec, Canada. Objective To 1) identify the population diagnosed respectively with depressive, bipolar and adjustment disorders in administrative data, and 2) provide annual prevalence estimates of each component. Method Data were extracted from the Quebec Integrated Chronic Disease Surveillance System and the entire population of Quebec (2000–2017) was included in this study (8.3 million; 2017). The prevalence of depressive, bipolar and adjustment disorders were estimated using specific algorithms. Results The annual prevalence of depressive disorders was 3.7% in 2000–2001; it decreased to 2.8% in 2016–2017. In comparison, the prevalence of bipolar disorders was 0.8% in 2000–2001, decreasing to 0.6% in 2016–2017, and the prevalence of adjustment disorders was 1.3% in 2000–2001 and increased to 1.6% in 2016–2017. Conclusion Using specific algorithms, we observed that the trend of adjustment disorders is increasing while trends of depressive and bipolar disorders are decreasing. Further studies should assess if the related burden of care respectively follows the same trends as policy makers’ allocations of resources may need to be adapted.

Abdominal obesity and presence of the metabolic syndrome (MetS) are associated with cardiac abnormalities. Among those, left ventricular diastolic dysfunction (LVDD) is the most frequently encountered in clinical practice. Few studies evaluated the reversibility of LVDD by an approach promoting lifestyle modifications in abdominally obese subjects with MetS.We assessed the impact of a 1-year lifestyle modification program combining nutritional and physical activity counseling on LVDD and metabolic profile of abdominally obese men with MetS. Echocardiograms, oral glucose tolerance test, lipids profile, dual energy X-ray absorptiometry, computed tomography scans (visceral obesity assessment), heart rate variability (HRV), as well as maximal and submaximal exercise tests were performed in participants before and after a 1-year program combining healthy eating and a physical activity/exercise program.Fifty-one abdominally obese men participated in this study. At baseline, 86% of the participants had LVDD (n = 44). After the 1-year program, LVDD improved in 57% of participants (n = 29, P 0.0001). All metabolic, adiposity, and exercise tolerance measures improved from baseline (P 0.0001), but were not associated with improvement in LVDD. Participants who improved LVDD had better exercise performance at baseline. Exercise tolerance during the submaximal exercise test, parasympathetic cardiac autonomic activity, and fasting insulin predicted 50% of LVDD improvements.There was a significant improvement in LVDD after a 1-year lifestyle intervention program in abdominally obese men with MetS, such an improvement being associated with increased exercise tolerance, enhanced HRV, and reduced insulin levels.

BACKGROUND Blood pressure measurement in severe obesity may be technically challenging as the cuff of the device may not fit adequately around the upper arm. The aim of the study was to assess the agreement between intra-arterial blood pressure values (gold standard) compared with forearm blood pressure measurements in severely obese patients in different arm positions. METHODS Thirty-three severely obese patients and 21 controls participated in the study. Pairs of intra-arterial blood pressures were compared with simultaneous forearm blood pressure measurement using an oscillometric device in 4 positions: (i) supine, (ii) semi-fowler with the forearm resting at heart level, (iii) semi-fowler with the arm downward, and (iv) semi-fowler with the arm raised overhead. Degree of agreement between measurements was assessed. RESULTS Overall, correlations of systolic and diastolic blood pressure measurements between the gold standard and forearm blood pressure were 0.95 (n = 722; P < 0.001) and 0.89 (n = 482; P < 0.001), respectively. Systolic blood pressure measured using the forearm approach in the supine and the semi-fowler positions with arm downward showed the best agreement when compared with the gold standard (-4 ± 11 (P < 0.001) and 2 ± 14 mm Hg (P = 0.19), respectively). In the control group, better agreement was found between the supine and semi-fowler positions with the arm resting at heart level (1 ± 9 mm Hg (P = 0.29) and -3 ± 10 mm Hg (P = 0.01), respectively). CONCLUSIONS Forearm systolic blood pressure consistently agreed with the gold standard in the supine position. This method can be of use in clinical settings when upper-arm measurement is challenging in severe obesity.

Background: Even with many direct oral anticoagulant options, brand-name or generic warfarin is still widely used to prevent atherothrombotic events in cardiology. Federal standards regulate bioequivalence of generic vs. brand-name drugs through comparative bioavailability studies but does not regulate clinical equivalence nor tolerability in a “real-life” settings. Through public health surveillance, we have evaluated the impact of the generic warfarin commercialization on health care utilization: emergency room (ER) consultations or hospitalizations. Methods: We used an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System, a surveillance system from the second populous province in Canada (~8.3 million in 2017). Rates of health care utilization for warfarin users (n=280,158) aged ≥ 66 years were calculated for 6-month periods, 5 years before up to 15 years after warfarin commercialization (from January 1996 to January 2016). Periods before and after generic warfarin commercialization were compared by negative binomial segmented regression models for all users with a specific variable for generic or brand-name users. Sensitivity analyses were also conducted. Results: Generic warfarin analogs (n=5) were commercialized from January 2001. There was an approximated mean rate of 1134 ER or hospitalizations for 1000 brand-name and generic users per 6-month period, similar before and after generics commercialization. After generics commercialization, there was an immediate increase in rates of health care utilization for generic (9.9%) vs. brand-name users (0%), a statistically significant difference (9.9% [95% confidence interval: 4.4% to 15.5%], p = 0.0001). Rates of health care utilization remained stable and higher for generic vs. brand-name users throughout the period after generics commercialization. Conclusion: Among generic warfarin users, we observed an increased rates of health care utilization soon after generics commercialization. Risk and survival analysis studies controlling for potential confounders are required to deepen this pharmacovigilance signal as stricter licensing process may be required.

Background— Once the patent of a brand-name drug expires, generic drugs are commercialized, and substitution from brand-name to generics may occur. Generic drug equivalence is evaluated through comparative bioavailability studies. Few studies have assessed outcomes after generic drug commercialization at a population level. We evaluated the impact of 3 generic angiotensin II receptor blockers commercialization on adverse events: hospitalizations or emergency room consultations. Methods and Results— This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. Rates of adverse events for losartan, valsartan, and candesartan users (N=136 177) aged ≥66 years were calculated monthly, 24 months before and 12 months after generics commercialization. Periods before and after generics commercialization were compared by negative binomial segmented regression models. Sensitivity analyses were also conducted. For all users, there was a monthly mean rate of 100 adverse events for 1000 angiotensin II receptor blocker users before and after generic commercialization. Among generic users of losartan, valsartan, and candesartan, there was an increase in rates of adverse events of 8.0% (difference of proportions versus brand-name, 7.5% [95% confidence interval, −0.9% to 15.9%]; P =0.0643), 11.7% (difference of proportions, 17.1% [95% confidence interval, 9.9%–24.3%]; P P P =0.0033) ≤1 year after generics commercialization. Similar results were found in sensitivity analyses. Conclusions— Among generic users, immediate or delayed differences in adverse events rates were observed right after generic commercialization for 3 antihypertensive drugs. Rates of adverse events remained higher for generic users. Increases were more pronounced for generic candesartan, which is the studied product with the largest difference in comparative bioavailability. Risk and survival analysis studies controlling for several potential confounding factors are required to better characterize generic substitution.

Background: Clopidogrel is widely used to prevent atherothrombotic events. Federal standards regulate bioequivalence of generic and brand-name drugs through comparative bioavailability studies but does not regulate clinical equivalence nor tolerability in “real-life” settings. We evaluated the impact of the generic clopidogrel commercialization on some adverse events: emergency room consultations (ER) or hospitalizations. Methods: This is an interrupted time series analysis using the Quebec Integrated Chronic Disease Surveillance System. Rates of adverse events for clopidogrel users (n=75,130) aged ≥ 66 years were calculated monthly, 12 months before and 12 months after generics commercialization. Periods before and after generics commercialization were compared by negative binomial segmented regression models for all users with a specific variable for generic and brand-name users after generics commercialization. Results: Generic clopidogrel analogs (n=6) were commercialized in 2012. There was an approximated monthly mean rate of 157 adverse events per 1000 brand-name and generic users-month. After generics commercialization, there was an immediate increase in rates of adverse events for generic vs. brand-name users (22 vs. 2%, p < 0.0001, Figure 1). This was explained by increased rates of ER (+22%) and hospitalizations (+20%) the month of generic clopidogrel commercialization. Hospitalization trend up to 1 year after generics commercialization was stable for generic users but reduced for brand-name users (-0.9 vs. -2.9%, p = 0.01), while ER trends were comparable (-1.1 vs. -1.8%, p = 0.2443). Conclusion: Among generic clopidogrel users, increased rates of ER and hospitalizations were observed soon after generics commercialization. The trend of hospitalizations was also affected following generic clopidogrel commercialization. Risk and survival analysis studies controlling for potential confounding are required to better characterize generic substitution.

Background: Substitution from brand-name to generic drugs is one way to reduce costs of pharmacological treatments. Generic drugs licensing is obtained through comparative bioavailability studies for which a variation of up to 20% is generally accepted. However, “real-life” efficacy and tolerance of generic drugs are not studied prior to commercialization. We aimed to evaluate the impact of brand-name to generic losartan, valsartan or candesartan substitution on serious adverse events (hospitalizations, emergency room consultations [ER] or mortality). Method: Three cohorts of persistent angiotensin II receptor blockers (ARB) users (losartan [brand-name and 8 generics], valsartan [brand-name and 5 generics] and candesartan [brand-name and 3 generics])aged ≥ 66 years were constituted using data from the Quebec Integrated Chronic Disease Surveillance System. Generic exposition was determined by substitution time-distribution matching. Time free of adverse events up to 365 days after the onset of generic exposition was compared between groups by survival analysis using Cox regression models adjusted for age, sex, comorbidities, concomitant treatments, socioeconomic status, previous brand-name drug, healthcare resources utilization and prescriber’s speciality, to provide hazard ratio (HR). Sensitivity analysis including non-persistent users was also conducted. Results: Within cohorts (losartan, n = 15,469; valsartan, n = 17,205; and candesartan, n = 25,008), proportions of exposed to generic substitution vs. unexposed who had at least one adverse event were respectively: 35% vs. 25%, 34% vs. 28% and 31% vs. 27% (all, p p < 0.0001]; 1.22 [ p < 0.0001] and 1.08 [ p = 0.0317]) and ER (HR: 1.55; 1.20 and 1.16, all = p < 0.0001). Regarding mortality, HR were respectively: 0.63 [ p = 0.1456]; 0.95 [ p = 0.8487] and 0.43 [ p < 0.0001]). Survival was not significantly different for exposed to generic losartan and valsartan substitution. However, even if the time free of hospitalizations and ER was 8% and 16% shorter for patients exposed to generic candesartan substitution, their survival was 2.3 times better when compared to patients who remained on brand-name candesartan (unexposed). Sensitivity analysis yield similar results. Conclusion: Substitution to generic antihypertensive drugs is associated with a significantly reduced delay before hospitalizations and ER for the three ARBs but a better survival for patients exposed to generic candesartan substitution only. Better bioavailability of generics versions of candesartan or differences in health cares between users could explain these differences.

Numerous models have been developed over the last decades to simulate the fate of pesticides at the watershed scale. Based on a literature review, we inventoried thirty-six models categorized as management, research, screening or multimedia models, each of them having specific strengths and weaknesses. Given this large number of models, it may be difficult for potential users (stakeholders or scientists) to find the most suited one with respect to their needs. To help in this process, this paper proposes a pragmatic approach based on a multi-criteria analysis. Selection criteria are defined following the user's needs and classified in five classes: modelling characteristics, output variables, model applicability, possibilities to simulate best management practices (BMPs) and ease of use. The relative importance of each criterion is quantified by a weight and the total score of a model is calculated by adding the resulting weights of satisfied criteria. This selection framework is illustrated with a case study that consists in selecting a model to develop water quality standards at the watershed scale with respect to the implementation of BMPs. This resulted in the selection of three models: BASINS, SWAT and GIBSI.