Prescribing Portraits to Optimize Prescribing of Proton Pump Inhibitors in Long-Term Care: PPI-T STOP Study.

Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in Canada, particularly for older adults (at least 65 years of age). Overprescribing of long-term PPIs leads to health care system waste and is associated with adverse effects, including infections and fractures. The high prevalence of PPI prescribing in long-term care (LTC) facilities prompted an evaluation of systematic approaches to PPI deprescribing. Objective: To assess the impact of individualized prescribing portraits, a type of audit-and-feedback quality improvement intervention, on PPI deprescribing in the LTC setting. Methods: This prospective, nonblinded, uncontrolled, pre-post quality improvement study was conducted from December 2021 to April 2022 at a 126-bed LTC facility in Vancouver, British Columbia. A PPI prescribing portrait was developed for each prescriber (n = 5) at the LTC facility, containing the prescriber's personal PPI prescribing metrics as compared with those of their peers across all LTC facilities within the same health authority; an evidence summary for PPI deprescribing; and a personalized list of the prescriber's PPI-treated residents, along with their respective PPI indications and strategies for PPI deprescribing. Three months after the prescribers received their PPI prescribing portraits, the number and types of PPI deprescribing orders were recorded. Results: The implementation of prescribing portraits resulted in 17 (61%) of 28 PPI-treated residents receiving a deprescribing order by the end of the study period. Of the 28 PPI-treated residents, 20 were determined to be eligible for PPI deprescribing according to the evidence summary presented in the prescribing portrait; of these 20 residents, 16 (80%) appropriately received PPI deprescribing. Conclusions: Individualized prescribing portraits had the potential to increase evidence-based PPI deprescribing among LTC residents, beyond the extent of deprescribing previously achieved through standard of care.

Contexte: Les inhibiteurs de la pompe à protons (IPP) comptent parmi les médicaments les plus couramment prescrits au Canada, particulièrement chez les personnes âgées (au moins 65 ans). La prescription excessive d'IPP à long terme entraîne un gaspillage pour le système de santé et est associée à des effets indésirables, notamment des infections et des fractures. La prévalence élevée de la prescription d'IPP dans les établissements de soins de longue durée (SLD) a entraîné une évaluation des approches systématiques de déprescription des IPP. Objectif: Évaluer l'incidence des schémas de prescription individualisés, un type d'intervention d'amélioration de la qualité basée sur l'audit et la rétroaction, sur la déprescription des IPP dans les établissements de SLD. Méthodes: Cette étude prospective, sans insu et non contrôlée sur l'amélioration de la qualité pré-post a été menée entre décembre 2021 et avril 2022 dans un établissement de SLD de 126 lits à Vancouver, en Colombie-Britannique. Un schéma de prescription d'IPP a été élaboré pour chaque prescripteur (n = 5) de l'établissement de SLD, contenant les paramètres personnels de prescription d'IPP du prescripteur par rapport à ceux de ses pairs dans tous les établissements de SLD au sein de la même autorité sanitaire; un résumé des données probantes pour la déprescription des IPP; et une liste personnalisée des résidents du prescripteur traités par IPP, ainsi que, respectivement, leurs indications d'IPP pour la déprescription des IPP. Trois mois après la réception des schémas de prescription d'IPP des prescripteurs, le nombre et les types d'ordonnances de déprescription d'IPP ont été enregistrés. Résultats: La mise en œuvre de schémas de prescription a permis à 17 (61 %) des 28 résidents traités par IPP de recevoir une ordonnance de déprescription pendant la période d'étude. Sur les 28 résidents traités par IPP, 20 ont été jugés admissibles à la déprescription des IPP sur la base du résumé des données probantes présentées dans le schéma de prescription; sur ces 20 résidents, 16 (80 %) ont reçu de manière appropriée une déprescription d'IPP. Conclusions: Les schémas de prescription individualisés avaient le potentiel d'augmenter la déprescription d'IPP fondée sur des données probantes chez les résidents des établissements de SLD, au-delà de l'étendue de la déprescription précédemment atteinte grâce aux normes de soins.

Low- or standard-dose edoxaban versus antiplatelet therapy for leaflet thrombus and cerebral thromboembolism after TAVR: A prespecified analysis of randomized ADAPT-TAVR trial.

BACKGROUND: The risks of leaflet thrombosis and the associated cerebral thromboembolism are unknown according to different anticoagulation dosing after transcatheter aortic valve replacement (TAVR). The aim was to evaluate the incidence of leaflet thrombosis and cerebral thromboembolism between low-dose (30 mg) or standard-dose (60 mg) edoxaban and dual antiplatelet therapy (DAPT) after TAVR. METHODS: In this prespecified subgroup analysis of the ADAPT-TAVR trial, the primary endpoint was the incidence of leaflet thrombosis on 4-dimensional computed tomography at 6-months. Key secondary endpoints were new cerebral lesions on brain magnetic resonance imaging and neurological and neurocognitive dysfunction. RESULTS: Of 229 patients enrolled in this study, 118 patients were DAPT group and 111 were edoxaban group (43 [39.1%] 60 mg vs 68 [61.3%] 30 mg). There was a significantly lower incidence of leaflet thrombosis in the standard-dose edoxaban group than in the DAPT group (2.4% vs 18.3%; odds ratio [OR] 0.11; 95% confidence interval [CI], 0.01-0.55; P = .03). However, no significant difference was observed between low-dose edoxaban and DAPT (15.0% vs 18.3%; OR 0.79; 95% CI, 0.32-1.81; P = .58). Irrespective of different antithrombotic regiments, the percentages of patients with new cerebral lesions on brain MRI and worsening neurological or neurocognitive function were not significantly different. CONCLUSIONS: In patients without an indication for anticoagulation after TAVR, the incidence of leaflet thrombosis was significantly lower with standard-dose edoxaban but not with low-dose edoxaban, as compared with DAPT. However, this differential effect of edoxaban on leaflet thrombosis was not associated with a reduction of new cerebral thromboembolism and neurological dysfunction.

Impact of leaflet thrombosis on valve haemodynamic status after transcatheter aortic valve replacement.

OBJECTIVES: The effect of subclinical leaflet thrombosis, characterised by hypoattenuated leaflet thickening (HALT), on the valve haemodynamic function and durability of the bioprosthetic valve, is not yet determined. We determined the impact of HALT on valve haemodynamics after transcatheter aortic valve replacement (TAVR) and the predictors of haemodynamic structural valve deterioration (SVD). METHODS: The Anticoagulation vs Dual Antiplatelet Therapy for Prevention of Leaflet Thrombosis and Cerebral Embolization after Transcatheter Aortic Valve Replacement(ADAPT-TAVR) trial is a multicenter, randomised trial that compared edoxaban and dual antiplatelet therapy in patients who had undergone successful TAVR. The presence of HALT was evaluated by four-dimensional CT at 6 months and serial echocardiography performed at baseline, immediately post-TAVR and after 6 months. SVD was defined as at least one of the following: (1) mean transprosthetic gradient ≥20 mm Hg, (2) change in the mean gradient ≥10 mm Hg from baseline, or (3) new or increase in intraprosthetic aortic regurgitation of at least ≥1 grade, resulting in moderate or greater regurgitation. RESULTS: At 6 months, HALT was found in 30 of 211 (14.2%) patients. The presence of HALT did not significantly affect aortic valve mean gradients (with vs without HALT; 14.0±4.8 mm Hg vs 13.7±5.5 mm Hg; p=0.74) at 6 months. SVD was reported in 30 of 206 patients (14.6%) at 6-month follow-up echocardiography. Older age (OR: 1.138; 95% CI: 1.019 to 1.293; p=0.033), use of aortic valve size ≤23 mm (OR: 6.254; 95% CI: 2.230 to 20.569; p=0.001) and mean post-TAVR pressure gradient (OR: 1.233; 95% CI: 1.123 to 1.371; p<0.001) were independent predictors of haemodynamic SVD; however, the presence of HALT was not identified as a predictor of SVD. CONCLUSIONS: In patients who had undergone successful TAVR, aortic valve haemodynamic status was not influenced by the presence of HALT. Although HALT was not a predictor of haemodynamic SVD at 6 months, it warrants further longer-term follow-up to evaluate the effect on long-term valve durability. TRIAL REGISTRATION NUMBER: NCT03284827 (https://www. CLINICALTRIALS: gov).

Effect of Edoxaban Versus Antiplatelet Therapy on Leaflet Thrombosis and Cerebral Thromboembolism After TAVI According to Major Clinical and Anatomic Factors in Prespecified Subgroup Analysis from the ADAPT-TAVR Trial.

It is unknown whether edoxaban versus dual antiplatelet therapy (DAPT) has differential treatment effects on leaflet thrombosis, cerebral thromboembolism, and neurologic or neurocognitive dysfunction according to clinical and anatomic factors after transcatheter aortic valve implantation. To investigate the relative effects of edoxaban and DAPT on leaflet and cerebral thromboembolism in patients with major risk factors. The primary end point of this study was the incidence of leaflet thrombosis on computed tomography at 6 months. The secondary end points were new cerebral lesions on brain magnetic resonance imaging and neurologic and neurocognitive dysfunction between baseline and 6-month follow-up. Cox regression models assessed the consistency of the treatment effects in the prespecified subgroups. The favorable effect of edoxaban versus DAPT on the leaflet thrombosis was consistent across multiple clinical or anatomic subgroups, without significant interaction between the drug effect and each subgroup (p for interaction for age = 0.597, gender = 0.557, body mass index = 0.866, Society of Thoracic Surgeons score = 0.307, valve type = 0.702, edoxaban reduction criteria = 0.604, and valve morphology = 0.688). However, the incidence of new cerebral lesions on brain magnetic resonance imaging and worsening of neurologic and neurocognitive function were not significantly different between the groups among the various key subgroups. The relative effects of edoxaban and DAPT on the risk of leaflet thrombosis, cerebral thromboembolism, and neurologic dysfunction were consistent across a diverse spectrum of clinical or anatomical factors. Further studies are required to define tailored antithrombotic therapy for high-risk groups with specific clinical or anatomic characteristics.

Pharmacological Treatment of Disinhibition in Acquired Brain Injury.

PURPOSE/BACKGROUND: Traumatic brain injury is a major universal public health concern and results in chronic neurobehavioral sequelae including disinhibition. Objectives of this study were to review the literature on pharmacological treatment of disinhibition post-acquired brain injury (ABI), describe a snapshot of pharmacotherapy used in ABI at a tertiary neuropsychiatric unit in British Columbia, Canada, and share expert opinion. METHODS/PROCEDURES: A retrospective chart review of 11 patients from October to December 2021 was conducted based on exclusion criteria: age greater than 18 years, primary neurodegenerative conditions, or aphasia. Patient demographics, behavioral and cognitive test results, and disinhibition treatment were recorded. A brief review of the literature was conducted to find the best available evidence of pharmacological interventions to treat disinhibition post-ABI. FINDINGS/RESULTS: In ABI, there was a high utilization of antipsychotics and benzodiazepines, at 91% and 64% respectively, in patients with severe cognitive deficit and disinhibition. Mood stabilizers and nonselective ß-blockers were less prescribed in this population at 73% and 18%. At the point of data collection, all the patients had responded well to treatment and were in the maintenance phase of their pharmacological treatment. IMPLICATIONS/CONCLUSIONS: A limited number of studies with weak methodology suggest that mood stabilizers and ß-blockers should be first line for disinhibition treatment. Our findings are complementary to the literature describing treatment of severe disinhibition. The choice of treatment for disinhibition depends on factors including nature and severity of target symptoms, level of drug evidence, patient-tailored objectives, concurrent psychiatric diagnoses, clinical experience of clinicians, adverse drug reactions, and treatment acuity.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

BACKGROUND: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear. METHODS: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation. The primary end point was an incidence of leaflet thrombosis on 4-dimensional computed tomography at 6 months. Key secondary end points were the number and volume of new cerebral lesions on brain magnetic resonance imaging and the serial changes of neurological and neurocognitive function between 6 months and immediately after transcatheter aortic valve replacement. RESULTS: A total of 229 patients were included in the final intention-to-treat population. There was a trend toward a lower incidence of leaflet thrombosis in the edoxaban group compared with the dual antiplatelet therapy group (9.8% versus 18.4%; absolute difference, -8.5% [95% CI, -17.8% to 0.8%]; P=0.076). The percentage of patients with new cerebral lesions on brain magnetic resonance imaging (edoxaban versus dual antiplatelet therapy, 25.0% versus 20.2%; difference, 4.8%; 95% CI, -6.4% to 16.0%) and median total new lesion number and volume were not different between the 2 groups. In addition, the percentages of patients with worsening of neurological and neurocognitive function were not different between the groups. The incidence of any or major bleeding events was not different between the 2 groups. We found no significant association between the presence or extent of leaflet thrombosis with new cerebral lesions and a change of neurological or neurocognitive function. CONCLUSIONS: In patients without an indication for long-term anticoagulation after successful transcatheter aortic valve replacement, the incidence of leaflet thrombosis was numerically lower with edoxaban than with dual antiplatelet therapy, but this was not statistically significant. The effects on new cerebral thromboembolism and neurological or neurocognitive function were also not different between the 2 groups. Because the study was underpowered, the results should be considered hypothesis generating, highlighting the need for further research. REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT03284827.

Protocol, rationale and design of DAbigatran for Stroke PreVention In Atrial Fibrillation in MoDerate or Severe Mitral Stenosis (DAVID-MS): a randomised, open-label study.

INTRODUCTION: Current international guidelines recommend non-vitamin K oral anticoagulants (NOACs) for stroke prevention among patients with non-valvular atrial fibrillation (AF) at significant ischaemic stroke risk given the superior safety and comparable efficacy of NOACs over warfarin. Nonetheless, the safety and effectiveness of NOACs have not been evaluated in patients with AF with underlying moderate or severe mitral stenosis (MS), hence the recommended stroke prevention strategy remains warfarin therapy. METHOD AND ANALYSIS: MS remains disproportionately prevalent in Asian countries compared with the developed countries. This prospective, randomised, open-label trial with blinded endpoint adjudication aims to evaluate the safety and efficacy of dabigatran for stroke prevention in AF patients with moderate or severe MS. Patients with AF aged ≥18 years with moderate or severe MS not planned for valvular intervention in the coming 12 months will be randomised in a 1:1 ratio to receive dabigatran 110 mg or 150 mg two times per day or warfarin with international normalised ratio 2-3 in an open-label design. Patients with estimated creatinine clearance <30 mL/min, or with a concomitant indication for antiplatelet therapy will be excluded. The primary outcome is a composite of stroke and systemic embolism. Secondary outcomes are ischaemic stroke, systemic embolism, haemorrhagic stroke, intracranial haemorrhage, major bleeding and death. The estimated required sample size is approximately 686 participants. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of the University of Hong Kong and Hong Kong West Cluster, Hospital Authority, Hong Kong for Fung Yiu King Hospital, Grantham Hospital, Queen Mary Hospital and Tung Wah Hospital in Hong Kong. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04045093); pre-results.

ScatterNet: A Deep Subjective Similarity Model for Visual Analysis of Scatterplots.

Similarity measuring methods are widely adopted in a broad range of visualization applications. In this work, we address the challenge of representing human perception in the visual analysis of scatterplots by introducing a novel deep-learning-based approach, ScatterNet, captures perception-driven similarities of such plots. The approach exploits deep neural networks to extract semantic features of scatterplot images for similarity calculation. We create a large labeled dataset consisting of similar and dissimilar images of scatterplots to train the deep neural network. We conduct a set of evaluations including performance experiments and a user study to demonstrate the effectiveness and efficiency of our approach. The evaluations confirm that the learned features capture the human perception of scatterplot similarity effectively. We describe two scenarios to show how ScatterNet can be applied in visual analysis applications.

Detecting adverse drug reactions in discharge summaries of electronic medical records using Readpeer.

BACKGROUND: Hospital discharge summaries offer a potentially rich resource to enhance pharmacovigilance efforts to evaluate drug safety in real-world clinical practice. However, it is infeasible for experts to read through all discharge summaries to find cases of drug-adverse event (AE) relations. PURPOSE: The objective of this paper is to develop a natural language processing (NLP) framework to detect drug-AE relations from unstructured hospital discharge summaries. BASIC PROCEDURES: An NLP algorithm was designed using customized dictionaries of drugs, adverse event (AE) terms, and rules based on trigger phrases, negations, fuzzy logic and word distances to recognize drug, AE terms and to detect drug-AE relations. Furthermore, a customized annotation tool was developed to facilitate expert review of discharge summaries from a tertiary hospital in Singapore in 2011. MAIN FINDINGS: A total of 33 trial sets with 50 to 100 records per set were evaluated (1620 discharge summaries) by our algorithm and reviewed by pharmacovigilance experts. After every 6 trial sets, drug and AE dictionaries were updated, and rules were modified to improve the system. Excellent performance was achieved for drug and AE entity recognition with over 92% precision and recall. On the final 6 sets of discharge summaries (600 records), our algorithm achieved 75% precision and 59% recall for identification of valid drug-AE relations. PRINCIPAL CONCLUSIONS: Adverse drug reactions are a significant contributor to health care costs and utilization. Our algorithm is not restricted to particular drugs, drug classes or specific medical specialties, which is an important attribute for a national regulatory authority to carry out comprehensive safety monitoring of drug products. Drug and AE dictionaries may be updated periodically to ensure that the tool remains relevant for performing surveillance activities. The development of the algorithm, and the ease of reviewing and correcting the results of the algorithm as part of an iterative machine learning process, is an important step towards use of hospital discharge summaries for an active pharmacovigilance program.

Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention of Recurrent Cardiovascular Events in a Real-World Cohort of Post-Acute Myocardial Infarction Patients.

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

Is There a Reason for the Proton Pump Inhibitor? An Assessment of Prescribing for Residential Care Patients in British Columbia.

BACKGROUND: The use of proton pump inhibitors (PPIs) may cause significant harm to patients in the residential care setting, as these patients are often frail with multiple morbidities. The extent of non-evidence-based use of PPIs in residential care sites of the Fraser Health Authority in British Columbia is unknown. OBJECTIVE: To determine the proportion of non-evidence-based use of PPI therapy for residential care patients of the Fraser Health Authority. METHODS: This retrospective cross-sectional study was conducted in 6 Fraser Health residential care facilities in British Columbia between April 1, 2015, and March 31, 2016. Two definitions of "evidence-based indications" were used. The first definition encompassed broad evidence-based indications for PPI use, specifically gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), gastritis, esophagitis, Barrett esophagus, and gastrointestinal protection from concurrent oral steroids, oral nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. The second definition involved common evidence-based indications for PPI use, specifically GERD or PUD. Descriptive statistics were used to evaluate the primary outcome: the proportion of PPI orders without a documented broad or common evidence-based indication for PPI treatment. RESULTS: A total of 331 residential care patients and 407 PPI orders were assessed. The proportion of PPI orders without a documented broad evidence-based indication was 16.2% (66/407). The proportion of PPI orders without a documented common evidence-based indication was 43.7% (178/407). The most frequently documented reason for a PPI order was GERD (214/407 or 52.6%). PPI orders for patients with GERD and gastrointestinal bleeding had the longest duration of therapy during residential care admission, averaging 205.1 and 218.1 days, respectively. CONCLUSION: About 1 in 6 PPI orders for Fraser Health residential care patients did not have a documented broad evidence-based indication, and about 2 in 5 PPI orders did not have a documented common evidence-based indication. These results indicate a need to assess the appropriateness of therapy for every patient with an active PPI order in residential care facilities.

CONTEXTE: L'emploi d'inhibiteurs de la pompe à protons (IPP) peut causer des torts importants aux patients qui résident en centre d'hébergement et de soins de longue durée, car souvent ces personnes sont fragiles et souffrent de multiples maladies. On ignore quelle est la proportion d'utilisation d'IPP ne reposant pas sur des données probantes dans les centres d'hébergement et de soins de longue durée de la Fraser Health Authority en Colombie-Britannique. OBJECTIF: Déterminer la proportion d'utilisation de traitement par IPP ne reposant pas sur des données probantes chez les patients en centre d'hébergement et de soins de longue durée de la Fraser Health Authority. MÉTHODES: Cette étude rétrospective transversale a été menée dans six centres d'hébergement et de soins de longue durée de la Fraser Health en Colombie-Britannique, entre le 1er avril 2015 et le 31 mars 2016. Deux définitions du terme « indications fondées sur des données probantes ¼ ont été utilisées. La première définition englobait des indications larges fondées sur des données probantes appuyant l'utilisation d'IPP, plus particulièrement : pour traiter le reflux gastro-œsophagien, l'ulcère gastroduodénal, la gastrite, l'œsophagite et l'œsophage de Barrett ainsi que pour fournir une protection gastrique contre les effets indésirables de la prise de médicaments anti-inflammatoires oraux stéroïdiens ou non stéroïdiens, d'antiplaquettaires et d'anticoagulants. La seconde définition comprenait les indications usuelles fondées sur des données probantes pour appuyer l'utilisation d'IPP, plus précisément : le reflux gastro-œsophagien ou l'ulcère gastroduodénal. Des statistiques descriptives ont été employées pour analyser le principal paramètre d'évaluation : la proportion d'ordonnances d'IPP pour lesquelles aucune indication, large ou usuelle, fondée sur des données probantes n'a été consignée. RÉSULTATS: Au total, les dossiers de 331 résidents de centres d'hébergement et de soins de longue durée et 407 ordonnances d'IPP ont été évalués. La proportion d'ordonnances d'IPP pour lesquelles aucune indication large fondée sur des données probantes n'a été consignée était de 16,2 % (66/407). La proportion d'ordonnances d'IPP pour lesquelles aucune indication usuelle fondée sur des données probantes n'a été consignée était de 43,7 % (178/407). La raison la plus souvent consignée pour l'émission d'une ordonnance d'IPP était le reflux gastro-œsophagien (214/407 ou 52,6 %). Les ordonnances d'IPP destinées aux patients souffrant de reflux gastro-œsophagien ou d'hémorragie gastro-intestinale étaient celles pour lesquelles la durée du traitement était la plus longue au cours du séjour en centre d'hébergement et de soins de longue durée, soit respectivement de 205,1 et 218,1 jours en moyenne. CONCLUSION: Environ 1 ordonnance d'IPP sur 6 pour les patients de centres d'hébergement et de soins de longue durée de la Fraser Health ne reposait pas sur une indication large consignée et fondée sur des données probantes et environ 2 ordonnances d'IPP sur 5 ne s'appuyaient pas sur une indication usuelle consignée et fondée sur des données probantes. Les résultats révèlent la nécessité d'évaluer la pertinence des traitements par IPP pour chaque patient ayant une ordonnance active d'IPP dans les centres d'hébergement et de soins de longue durée.

Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial.

BACKGROUND: This study sought to evaluate the optimal treatment for in-stent restenosis (ISR) of drug-eluting stents (DESs). METHODS: This is a prospective, multicenter, open-label, randomized study comparing the use of drug-eluting balloon (DEB) versus second-generation everolimus-eluting stent for the treatment of DES ISR. The primary end point was in-segment late loss at 9-month routine angiographic follow-up. RESULTS: A total of 172 patients were enrolled, and 74 (43.0%) patients underwent the angiographic follow-up. The primary end point was not different between the 2 treatment groups (DEB group 0.15±0.49 mm vs DES group 0.19±0.41 mm, P=.54). The secondary end points of in-segment minimal luminal diameter (MLD) (1.80±0.69 mm vs 2.09±0.46 mm, P=.03), in-stent MLD (1.90±0.71 mm vs 2.29±0.48 mm, P=.005), in-segment percent diameter stenosis (34%±21% vs 26%±15%, P=.05), and in-stent percent diameter stenosis (33%±21% vs 21%±15%, P=.002) were more favorable in the DES group. The composite of death, myocardial infarction, or target lesion revascularization at 1 year was comparable between the 2 groups (DEB group 7.0% vs DES group 4.7%, P=.51). CONCLUSIONS: Treatment of DES ISR using DEB or second-generation DES did not differ in terms of late loss at 9-month angiographic follow-up, whereas DES showed better angiographic results regarding minimal MLD and percent diameter stenosis. Both treatment strategies were safe and effective up to 1year after the procedure.

LDSScanner: Exploratory Analysis of Low-Dimensional Structures in High-Dimensional Datasets.

Many approaches for analyzing a high-dimensional dataset assume that the dataset contains specific structures, e.g., clusters in linear subspaces or non-linear manifolds. This yields a trial-and-error process to verify the appropriate model and parameters. This paper contributes an exploratory interface that supports visual identification of low-dimensional structures in a high-dimensional dataset, and facilitates the optimized selection of data models and configurations. Our key idea is to abstract a set of global and local feature descriptors from the neighborhood graph-based representation of the latent low-dimensional structure, such as pairwise geodesic distance (GD) among points and pairwise local tangent space divergence (LTSD) among pointwise local tangent spaces (LTS). We propose a new LTSD-GD view, which is constructed by mapping LTSD and GD to the axis and axis using 1D multidimensional scaling, respectively. Unlike traditional dimensionality reduction methods that preserve various kinds of distances among points, the LTSD-GD view presents the distribution of pointwise LTS ( axis) and the variation of LTS in structures (the combination of axis and axis). We design and implement a suite of visual tools for navigating and reasoning about intrinsic structures of a high-dimensional dataset. Three case studies verify the effectiveness of our approach.

5α-Reductase Inhibitors for Treatment of Benign Prostatic Hyperplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: Finasteride and dutasteride are competitive inhibitors of 5α-reductase enzymes and are commonly used to treat symptomatic benign prostatic hyperplasia (BPH). OBJECTIVE: To compare the efficacy and safety of finasteride and dutasteride in terms of clinically important outcomes. DATA SOURCES: A literature search was performed using the search terms "prostatic hyperplasia", "prostatic hypertrophy", "dutasteride", "finasteride", "quality of life", "adverse drug reaction", and "mortality". The Embase, PubMed, Cochrane Central Register of Controlled Trials, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Latin American and Caribbean Health Sciences Literature databases were searched from inception to December 2015. STUDY SELECTION AND DATA EXTRACTION: Randomized controlled trials, quasi-randomized trials, and systematic reviews comparing finasteride with dutasteride, either as monotherapy or in combination with α-blockers, for treatment of men with BPH were included. The outcomes of interest included need for prostate-related surgery, episodes of acute urinary retention, withdrawals due to adverse events, number of patients experiencing serious adverse events, mortality, and sexual dysfunction. DATA SYNTHESIS: Four studies involving a total of 1879 patients were included in the analysis. There were no significant differences in any of the clinically important outcomes examined: for prostate-related surgery, odds ratio (OR) 2.01 (95% confidence interval [CI] 0.18-22.24); for episodes of acute urinary retention, OR 1.47 (95% CI 0.68-3.19); for number of withdrawals due to adverse events, OR 1.10 (95% CI 0.68-1.75); for total number of patients experiencing adverse events, OR 0.94 (95% CI 0.78-1.14); for number of patients experiencing serious adverse events, OR 1.31 (95% CI 0.87-1.97); and for sexual dysfunction, OR 0.83 (95% CI 0.64-1.08). CONCLUSION: There is insufficient evidence to suggest that either finasteride or dutasteride offers an advantage in efficacy or safety over the other, in terms of clinically important outcomes.

CONTEXTE: Le finastéride et le dutastéride sont des inhibiteurs compétitifs de l'enzyme 5 alpha-réductase. Ils sont fréquemment employés comme traitement symptomatique de l'hyperplasie bénigne de la prostate (HBP). OBJECTIF: Comparer l'efficacité et l'innocuité du finastéride et du dutastéride en ce qui concerne les résultats thérapeutiques cliniquement importants. SOURCES DES DONNÉES: Une recherche documentaire a été effectuée à l'aide des termes « hyperplasie de la prostate ¼, « hypertrophie de la prostate ¼, « dutastéride ¼, « finastéride ¼, « qualité de vie ¼, « réaction indésirable aux médicaments ¼ et « mortalité ¼. Les bases de données Embase, PubMed, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature et Latin American and Caribbean Health Sciences Literature ainsi que le Registre central Cochrane des essais comparatifs ont été interrogées pour la période allant de leur création à décembre 2015. SÉLECTION DES ÉTUDES ET EXTRACTION DES DONNÉES: Les essais comparatifs à répartition aléatoire, les essais quasi-aléatoires et les analyses systématiques qui comparent le finastéride et le dutastéride, en monothérapie ou en association avec des α-bloquants, pour le traitement de la HBP chez l'homme, ont été retenus. Parmi les résultats d'intérêt, on comptait : la nécessité de recourir à une chirurgie de la prostate, les épisodes de rétention urinaire aiguë, les retraits de l'étude pour cause d'événements indésirables, le nombre total de patients ayant subi des événements indésirables graves, la mortalité et le dysfonctionnement sexuel. SYNTHÈSE DES DONNÉES: Quatre études comptant au total 1879 patients ont été retenues pour l'analyse. Aucune différence significative n'a été relevée en ce qui touche les résultats thérapeutiques cliniquement importants : la nécessité de recourir à une chirurgie de la prostate (risque relatif approché [RRA] de 2,01, intervalle de confiance [IC] à 95 % de 0,18 à 22,24), les épisodes de rétention urinaire aiguë (RRA de 1,47, IC à 95 % de 0,68 à 3,19), le nombre de retraits de l'étude pour cause d'événements indésirables (RRA de 1,10, IC à 95 % de 0,68 à 1,75), le nombre total de patients ayant subi des événements indésirables (RRA de 0,94, IC à 95 % de 0,78 à 1,14); le nombre de patients ayant subi des événements indésirables graves (RRA de 1,31, IC à 95 % de 0,87 à 1,97) et le dysfonctionnement sexuel (RRA de 0,83, IC à 95 % de 0,64 à 1,08). CONCLUSION: Il n'y a pas suffisamment de données probantes pour croire que le finastéride ou le dutastéride offrent, l'un par rapport à l'autre, un avantage quant à l'efficacité ou à l'innocuité, en ce qui concerne les résultats thérapeutiques cliniquement importants.

Eplerenone for hypertension.

BACKGROUND: Eplerenone is an aldosterone receptor blocker that is chemically derived from spironolactone. In Canada, it is indicated for use as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction. It is also used as adjunctive therapy for patients with heart failure following myocardial infarction. Additionally, it is indicated for the treatment of mild and moderate essential hypertension for patients who cannot be treated adequately with other agents. It is important to determine the clinical impact of all antihypertensive medications, including aldosterone antagonists, to support their continued use in essential hypertension. No previous systematic reviews have evaluated the effect of eplerenone on cardiovascular morbidity, mortality, and magnitude of blood pressure lowering in patients with hypertension. OBJECTIVES: To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults. Outcomes of interest were all-cause mortality, cardiovascular events (fatal or non-fatal myocardial infarction), cerebrovascular events (fatal or non fatal strokes), adverse events or withdrawals due to adverse events, and systolic and diastolic blood pressure. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers up to 3 March 2016. We handsearched references from retrieved studies to identify any studies missed in the initial search. We also searched for unpublished data by contacting the corresponding authors of the included studies and pharmaceutical companies involved in conducting studies on eplerenone monotherapy in primary hypertension. The search had no language restrictions. SELECTION CRITERIA: We selected randomized placebo-controlled trials studying adult patients with primary hypertension. We excluded studies in people with secondary or gestational hypertension and studies where participants were receiving multiple antihypertensives. DATA COLLECTION AND ANALYSIS: Three review authors independently reviewed the search results for studies meeting our criteria. Three review authors independently extracted data and assessed trial quality using a standardized data extraction form. A fourth independent review author resolved discrepancies or disagreements. We performed data extraction and synthesis using a standardized format on Covidence. We conducted data analysis using Review Manager 5. MAIN RESULTS: A total of 1437 adult patients participated in the five randomized parallel group studies, with treatment durations ranging from 8 to 16 weeks. The daily doses of eplerenone ranged from 25 mg to 400 mg daily. Meta-analysis of these studies showed a reduction in systolic blood pressure of 9.21 mmHg (95% CI -11.08 to -7.34; I2 = 58%) and a reduction of diastolic pressure of 4.18 mmHg (95% CI -5.03 to -3.33; I2 = 0%) (moderate quality evidence).There may be a dose response effect for eplerenone in the reduction in systolic blood pressure at doses of 400 mg/day. However, this finding is uncertain, as it is based on a single included study with low quality evidence. Overall there does not appear to be a clinically important dose response in lowering systolic or diastolic blood pressure at eplerenone doses of 50 mg to 400 mg daily. There did not appear to be any differences in the number of patients who withdrew due to adverse events or the number of patients with at least one adverse event in the eplerenone group compared to placebo. However, only three of the five included studies reported adverse events. Most of the included studies were of moderate quality, as we judged multiple domains as being at unclear risk in the 'Risk of bias' assessment. AUTHORS' CONCLUSIONS: Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo, with no difference of effect between doses of 50 mg/day to 200 mg/day. A dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure and there is insufficient evidence for doses above 200 mg/day. There is currently no available evidence to determine the effect of eplerenone on clinically meaningful outcomes such as mortality or morbidity in hypertensive patients. The evidence available on side effects is insufficient and of low quality, which makes it impossible to draw conclusions about potential harm associated with eplerenone treatment in hypertensive patients.