Quinze années de recherche au RISQ : bilan des connaissances sur l’impact des traitements

Cet article fait le bilan de six recherches évaluatives menées par une équipe de chercheurs du RISQ (Recherche et intervention sur les substances psychoactives – Québec) sur les traitements offerts au Québec, principalement dans les centres de réadaptation publics, entre 1991 et 2005. Objectifs. Ces études avaient pour but d’évaluer : 1) si les participants provenant de centres de traitement en toxicomanie du Québec améliorent leur situation pendant et après leur traitement ; 2) quelles sont les sphères de vie où se produisent ces améliorations ; et 3) y a-t-il un lien entre les changements observés et l’exposition des participants au traitement. Méthode. Il s’agit d’une méthode dite « naturaliste » : les participants ont été exposés au traitement régulier offert dans les centres où ils étaient suivis. À l’aide de l’IGT-ASI, leur situation en matière de consommation de substances psychoactives et leur situation biopsychosociale ont été évaluées lors de trois temps de mesure, soit à leur arrivée en traitement, puis à des intervalles d’environ six et 12 mois. On a également mesuré la quantité (heures d’exposition au traitement) et la durée de l’intervention qu’ils ont reçue. Résultats. On observe de façon constante, dans les six groupes à l’étude, une amélioration des participants aux échelles « alcool » et « drogues » de l’IGT-ASI de même qu’à la plupart des dimensions évaluées par cet instrument entre le temps 1 et le temps 2, de même que le maintien de cette amélioration au temps 3. Par ailleurs, il n’y a pas de différence significative entre les participants qui ont eu peu ou pas de traitement et ceux qui en ont eu beaucoup. Interprétation. Le sens et la portée de ces résultats sont discutés par les auteurs, notamment en lien avec les limites de ces études. Sont présentées également les stratégies de recherches développées ultérieurement pour répondre aux questions soulevées par ces études.This article reports on six evaluative research projects led by a research team at the RISQ (Recherche et intervention sur les substances psychoactives – Québec) on treatments offered in Quebec, mainly in public rehabilitation centres, between 1991 and 2005. Objectives: The goal of these studies was to evaluate: 1) whether the participants from drug addiction treatment centres in Quebec improved their situation during and after their treatment; 2) the spheres of life in which these improvements occurred; and 3) whether there was a relationship between the changes observed and the participants’ exposure to the treatment. Method: The method is referred to as a “naturalist” approach: participants were exposed to the regular treatment offered in the centres where they were followed. By means of the ASI-IGT, their situation concerning consumption of psychoactive substances and their bio-psychosocial condition were evaluated at three measurement times, on their arrival in treatment, then at intervals of approximately 6 and 12 months. Measurements also included the quantity (hours of exposure to treatment) and the duration of the intervention they received. Results: In the six groups under study, a constant improvement of the participants on the ASI-IGT “alcohol” and “drug” scales was observed as well as most of the dimensions evaluated by this tool in time 1 and time 2, and maintenance of this improvement in time 3. There was no significant difference between the participants who had little or no treatment and those who had a great deal. Interpretation: The meaning and the extent of these results are discussed by the authors, particularly in relation to the limitations of these studies. Research strategies developed thereafter to respond to the questions raised by these studies are also presented.Este artículo hace un resumen de quince años de investigaciones evaluativas llevadas a cabo por un equipo de investigadores del RISQ (Recherche et intervention sur les substances psychoactives – Québec) sobre los tratamientos que se ofrecieron en Quebec, principalmente en los centros de readaptación públicos, entre 1991 y 2005. Objetivos. Estos estudios tuvieron como objetivo evaluar: 1) si los participantes provenientes de centros de toxicomanía de Quebec mejoraron su situación durante y después del tratamiento ; 2) cuáles son las esferas de vida en las que se producen estas mejoras ; y 3) verificar si hay un vínculo entre los cambios observados y la exposición de los participantes al tratamiento. Método. Se trata de un método llamado «naturalista»: los participantes fueron expuestos al tratamiento regular que se ofrecía en los centros en los que se les hacía el seguimiento. Por medio del IGT-ASI se evaluó su situación en materia de consumo de sustancias psicoactivas y su situación biopsicosocial en tres momentos de medida, es decir, a su llegada al tratamiento y luego a intervalos de alrededor de 6 y 12 meses. Se midió asimismo la cantidad (horas de exposición al tratamiento) y la duración de la intervención recibida. Resultados. Se observa de manera constante, en los seis grupos estudiados, un mejoramiento de los participantes en las escalas de «alcohol» y «drogas» del IGT-ASI así como en la mayoría de las dimensiones evaluadas por este instrumento entre el tiempo 1 y el tiempo 2, y el mantenimiento de esta mejoría en el tiempo 3. Por otra parte, no hay una diferencia significativa entre los participantes que han tenido poco o ningún tratamiento y los que han recibido mucho. Interpretación. Los autores discuten el significado y el alcance de estos resultados, principalmente en conexión con los límites de estos estudios. Se presentan asimismo estrategias de investigación desarrolladas posteriormente para responder a las preguntas que surgen de estos estudios

Drugs, alcohol, and criminal behaviour : a profile of inmates in canadian federal institutions

The scientific literature often mentions that there is a statistical connection between alcohol and drug consumption and criminal behaviour. However, there is little information available which would make it possible to quantify this connection, and specify the impact that drugs and alcohol have on criminal behaviour. Consumption of psychoactive substances has two major effects: intoxication and addiction. These effects are related, respectively, to the psycho-pharmacological and economic-compulsive models of the connection between drugs and crime. The first model associates drug use and intoxication with a decrease in cognitive functions and a lack of self-control, leading to aggressive impulses, violence and lack of inhibitions. The second model refers to the huge costs that are associated with being addicted to certain drugs. A person addicted to these drugs would need to engage in lucrative criminal activities in order to pay for them. This article explores and attempts to further define the links between alcohol, illicit drugs and criminal behaviour, taking into account the types of drugs consumed and the types of criminal behaviour displayed

Increased Susceptibility to Dextran Sulfate Sodium Induced Colitis in the T Cell Protein Tyrosine Phosphatase Heterozygous Mouse

T cell protein tyrosine phosphatase (TC-PTP / PTPN2) is an enzyme that is essential for the proper functioning of the immune system and that participates in the control of cell proliferation, and inflammation. We previously observed that TC-PTP−/− mice display various immunodeficiencies, hypersensitivity to LPS and die within three weeks of birth due to anemia and widespread inflammation. A recent analysis of the Wellcome Trust Case Control Consortium (WTCC) genome wide scan data, reported in 2007, indicated a potential role for TC-PTP in inflammatory bowel disease (IBD). To further investigate the potential role of TC-PTP in IBD, we studied heterozygous TC-PTP mutant mice challenged with dextran sulfate sodium (DSS) in their drinking water. In comparison to control animals, we observed significant changes in the colon mucosa of DSS-treated TC-PTP+/− mice, in the ratio of colon to body weight, as well as an up-regulation of mRNA transcripts for IL-6, IL-23, 1L-12β, IFN-γ, TNF-α. Moreover, up-regulation of serum IL-6 levels in DSS-treated TC-PTP+/− mice confirms that mice with a single copy of the TC-PTP gene display increased susceptibility to systemic inflammation due to bowel epithelial erosion resulting from DSS challenge. Our findings support the lack of modulation of Janus kinases 1 and 3 (Jak1, Jak3), and the downstream signal transducer and activator of transcription 1,3 and 5 (Stat1, Stat3, Stat 5) by PTPN2 in the development of IBD like condition. Pathological and molecular analysis reveal that the deficiency of TC-PTP results in pro-inflammatory condition in the bowel of heterozygous TC-PTP+/− mice. These novel findings in TC-PTP hemi-deficiency support the hypothesis that TC-PTP is an important regulator of inflammatory cytokine signaling and that it may be implicated in the pathophysiology of IBD

Les drogues, l’alcool et la criminalité : profil des détenus fédéraux canadiens

Il est souvent fait mention dans la documentation scientifique d’une association statistique entre la consommation d’alcool, de drogues illicites et la criminalité. Cependant, on trouve peu d’information permettant d’estimer l’importance de cette relation et de la préciser. La consommation de substances psychoactives se caractérise par deux propriétés importantes, soit une éventuelle intoxication et la dépendance. Ces deux propriétés renvoient respectivement aux modèles psycho-pharmacologique et économico-compulsif tentant d’expliquer la relation drogue-crime. Le premier modèle associe l’usage et l’intoxication à une diminution de la performance des fonctions cognitives et de contrôle donnant libre cours, entre autres, aux pulsions agressives et à la violence. On réfère ainsi souvent aux théories de la désinhibition. Le deuxième modèle fait référence à l’énorme pression économique qui repose sur les épaules d’un consommateur dépendant de certaines drogues, et à la nécessité d’exercer des activités criminelles lucratives dans le but de se procurer l’argent nécessaire à la consommation. Cet article explore les liens entre la consommation d’alcool, de drogues illicites et la criminalité, en cherchant à les préciser en tenant compte d’une part du type de substances et d’autre part du type de criminalité en question

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

7 Montreal Sculptors = 7 sculpteurs de Montréal

Seven Montréal sculptors briefly discuss concepts of sculpture in relation to their work. Biographical notes