A Pseudo-Surfactant Chemical Permeation Enhancer to Treat Otitis Media via Sustained Transtympanic Delivery of Antibiotics.

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable noninvasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, can compromise gelation, formulation stability, and drug diffusion. To overcome this challenge, differing interactions between CPEs and the hydrogel system are explored, especially those with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and those with methyl laurate (ML), a nonionic counterpart with a similar length alkyl chain. Notably, the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM), which is not possible with the use of SDS. Ciprofloxacin and ML are shown to form a pseudo-surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70-fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest-performing formulation. Beyond improved efficacy and biocompatibility, this single-CPE formulation significantly accelerates its progression toward clinical deployment.

Computerized clinical decision support to improve stroke prevention therapy in primary care management of atrial fibrillation: a cluster randomized trial.

BACKGROUND: Despite guidelines supporting antithrombotic therapy use in atrial fibrillation (AF), under-prescribing persists. We assessed whether computerized clinical decision support (CDS) would enable guideline-based antithrombotic therapy for AF patients in primary care. METHODS: This cluster randomized trial of CDS versus usual care (UC) recruited participants from primary care practices across Nova Scotia, following them for 12 months. The CDS tool calculated bleeding and stroke risk scores and provided recommendations for using oral anticoagulants (OAC) per Canadian guidelines. RESULTS: From June 14, 2014 to December 15, 2016, 203 primary care providers (99 UC, 104 CDS) with access to high-speed Internet were recruited, enrolling 1,145 eligible patients (543 UC, 590 CDS) assigned to the same treatment arm as their provider. Patient mean age was 72.3 years; most were male (350, 64.5% UC, 351, 59.5% CDS) and from a rural area (298, 54.9% UC, 315, 53.4% CDS). At baseline, a higher than anticipated proportion of patients were receiving guideline-based OAC therapy (373, 68.7% UC, 442, 74.9% CDS; relative risk [RR] 0.97 (95% confidence interval [CI], 0.87-1.07; P = .511)). At 12 months, prescription data were available for 538 usual care and 570 CDS patients, and significantly more CDS patients were managed according to guidelines (415, 77.1% UC, 479, 84.0% CDS; RR 1.08 (95% CI, 1.01-1.15; P = .024)). CONCLUSION: Notwithstanding high baseline rates, primary care provider access to the CDS over 12 months further optimized the prescribing of OAC therapy per national guidelines to AF patients potentially eligible to receive it. This suggests that CDS can be effective in improving clinical process of care. TRIAL REGISTRATION: Clinical Trials NCT01927367. https://clinicaltrials.gov/ct2/show/NCT01927367?term=NCT01927367&draw=2&rank=1.

Resource use and cost associated with computerized decision support system and usual care in managing patients with atrial fibrillation: analysis of IMPACT-AF randomized trial data.

BACKGROUND: IMPACT-AF is a prospective, randomized, cluster design trial comparing atrial fibrillation (AF) management with a computerized decision support system (CDS) to usual care (control) in the primary care setting of Nova Scotia, Canada. The objective of this analysis was to compare the resource use and costs between CDS and usual care groups. METHODS: Case costing data, 12-month self-administered questionnaires, and monthly diaries from IMPACT-AF were used in this analysis. Descriptive statistics were used to compare costs and resource use between groups. All costs are presented in 2021 Canadian dollars and cover the 12-month period of participation in the study. RESULTS: A total of 1,145 patients enrolled in the trial. Case costing data were available for 466 participants (41.1%), 12-month self-administered questionnaire data for 635 participants (56.0%) and monthly diary data for 223 participants (19.7%). Emergency department visits and hospitalizations comprised the most expensive component of AF care. Across all three datasets, there were no statistically significant differences in costs or resource use between CDS and usual care groups. CONCLUSIONS: Although there were no significant differences in resource use or costs among CDS and usual care groups in the IMPACT-AF trial, this study provides insight into the methodology and practical challenges of collecting economic data alongside a trial. REGISTRATION: Clinicaltrials.gov (registration number: NCT01927367, date of registration: 2013-08-20).

Engineering the Structure and Rheological Properties of P407 Hydrogels via Reverse Poloxamer Addition.

Aqueous solutions of poloxamer 407 (P407), a commercially available and nontoxic ABA triblock polymer (PEO-PPO-PEO), undergo a solution-to-gel transition with increasing temperature and are promising candidates for injectable therapeutics. The gel transition temperature, modulus, and structure are all dictated by polymer concentration, preventing independent tuning of these properties. Here, we show that addition of BAB reverse poloxamers (RPs) to P407-based solutions dramatically alters the gelation temperature, modulus, and morphology. Gelation temperature and RP localization within the hydrogel are dictated by RP solubility. Highly soluble RPs increase gelation temperature and incorporate primarily into the micelle corona regions. Alternatively, RPs with low aqueous solubility decrease gelation temperature and associate within the micelle core and core-corona interface. These differences in RP localization have significant implications for the hydrogel modulus and microstructure. The ability to tune gelation temperature, modulus, and structure through RP addition allows for the design of thermoresponsive materials with specific properties that are unobtainable with neat P407-based hydrogels.

Effects of Angled Dynamic Compression Holes in a Tibial Plateau Levelling Osteotomy Plate on Cranially Directed Fragment Displacement.

OBJECTIVE: To compare angled dynamic compression holes in a tibial plateau levelling osteotomy (TPLO) plate to a commercially available TPLO plate in an ovine cadaveric model. STUDY DESIGN: Ovine tibias (40 bones) were mounted on a custom-made securement device and radiopaque markers were placed to aid radiographic measurements. A standard TPLO procedure was performed on each tibia with either a custom-made six-hole 3.5 mm angled compression hole plate (APlate) or a six-hole 3.5 mm standard commercial plate (SPlate). Radiographs were obtained before and after tightening of the cortical screws and evaluated by an observer blinded to the plate. Measurements of cranio-caudal displacement (CDisplacement), proximo-distal displacement (PDisplacement) in relation to the long axis of the tibia, and change in tibial plateau angle (TPA) were determined. RESULTS: CDisplacement was significantly greater in APlate (median 0.85 mm, Q1-Q3: 0.575-1.325 mm) compared to SPlate (median 0.00 mm, Q1-Q3: -0.35-0.50 mm, p < 0.0001). There were no significant differences in the PDisplacement (median 0.55 mm, Q1-Q3: 0.075-1.00 mm, p = 0.5066) or TPA change (median -0.50°, Q1-Q3: -1.225-0.25°, p = 0.1846) between the two plate types. CONCLUSION: APlate increases cranially directed displacement of the osteotomy in a TPLO procedure without causing TPA change. The reduced interfragmentary distance across the whole osteotomy could improve osteotomy healing compared to standard commercial TPLO plates.

Association between divisional location and short-term outcome of liver mass resection in 124 dogs.

OBJECTIVE: To evaluate the association between divisional location of liver masses on short-term outcomes after surgical excision. STUDY DESIGN: Retrospective case series. ANIMALS: Client-owned dogs (n = 124). METHODS: Records were reviewed for demographics, surgical findings, and outcomes. The associations between mass location and mortality, intraoperative complications, and postoperative complications were tested with multivariable logistic regression models. RESULTS: Liver masses (124) were more common in the left (72) division than the central (34) and right (18) divisions. Median follow up was 286 (range: 14 to 2043) days. Intraoperative complications occurred in 14/124 dogs (11.3%) and postoperative complications in 35/122 dogs (28.7%). No association was detected between mass location and mortality in 8/124 dogs (6.5%). Postoperative complications were more likely if the incision extended to the thorax (P < .001), which was more common during resection of right divisional masses (P = .020). Postoperative complications were less likely when surgery was performed with a thoracoabdominal (TA) stapler (P = .005), by a specialist surgeon (P = .033), and in heavier dogs (P = .027). The odds of intraoperative complications were 19 times higher when surgery was performed without a TA stapler (P = .006). Intraoperative complications were less commonly associated with left (P = .007), but not central (P = .0504) divisional masses than right divisional masses. CONCLUSION: Right divisional masses were prone to intraoperative but not postoperative complications. CLINICAL SIGNIFICANCE: Clinicians should anticipate an increased risk of intraoperative complications when planning treatment of right divisional masses.

Effect of chain architecture on the structure, dynamics, and rheology of thermoresponsive poloxamer hydrogels and associated blends.

Poloxamers, ABA triblock polymers composed of a poly(propylene oxide) (PPO) midblock (B) and poly(ethylene oxide) (PEO) endblocks (A), are widely studied for biomedical applications. Aqueous poloxamer 407 (P407; also referred to as F127) undergoes a solution-to-gel transition with increasing temperature, driven by the formation and ordering of micelles onto periodic lattices; however, the gel temperature and resulting modulus has limited tunability. Here, reverse P407 (RP407), a BAB polymer of the same composition and molar mass but the inverted architecture, is synthesized via anionic polymerization. The micellization and gelation temperatures of RP407 are higher than that of P407 and the PPO endblocks allow for intermicelle bridging; however, both single-component solutions favor body-centered cubic (BCC) packings. Further, aqueous RP407 displays a "soft gel" region with interesting rheological behavior, including viscoelastic aging and thermal hysteresis. Combining P407 and RP407 yields solutions with intermediate transition temperatures and alters the size and micelle packing. While the single-component solutions produce BCC packings, the blends form close-packed structures and larger micelles of higher aggregation numbers. Blends of P407 with an analogous AB diblock (E111P32) display similar behavior, whereas RP407/diblock blends form intermediate-sized BCC-packed micelles. These differences in packing and aggregation alter the local environments within the gels, which could have implications for applications such as drug delivery and protein stabilization.

Prospective evaluation of the prevalence of conjunctival and intraocular bacteria in dogs undergoing phacoemulsification following a standardized aseptic preparation with 0.5% povidone iodine.

PURPOSE: To evaluate bacterial contamination of conjunctiva and aqueous humor in dogs undergoing phacoemulsification following asepsis with 0.5% povidone iodine and determine the influence of intravenous antibiotics on outcome of contamination. METHODS: Client-owned dogs were prospectively enrolled and randomly assigned to a control group, receiving 22 mg/kg intravenous cefazolin at induction prior to sampling, or experimental group receiving no antibiotic prior to sampling, masked to the surgeon. Dogs receiving antimicrobials in the pre-operative period were excluded. Asepsis was performed on all operated eyes using 0.5% iodine with minimum 3 min contact time at induction of anesthesia and repeated before surgery. A conjunctival swab and aqueous humor sample were collected prior to incision and following incision closure, respectively. Samples were submitted for aerobic and anaerobic bacterial culture and susceptibility. RESULTS: Seventy-one eyes of 42 dogs were included. Median age was 9 years. Thirty-nine and 32/71 eyes received intravenous cefazolin and no antibiotic, respectively. Median procedure time was 40 min per eye. Conjunctival cultures were positive in 6 eyes (8.5%): Serratia marcescens (5 eyes) and Cutibacterium acnes (1 eye). Aqueous humor cultures were positive in 5 eyes (7.0%): S. marcescens (2 eyes), Pseudomonas aeruginosa (2 eyes), Staphylococcus pseudointermedius (1 eye). Prevalence of positive culture did not differ between groups (p = .74), order of eyes for bilateral procedures (p = .74) and diabetic status (p = 1). CONCLUSIONS: Bacterial contamination of the conjunctiva and aqueous humor was present in 8.5% and 7.0% of dogs undergoing phacoemulsification after asepsis. Lack of IV cefazolin was not significantly associated with positive culture.

Gabapentin reduces stress and does not affect ocular parameters in clinically normal cats.

OBJECTIVE: To describe the effects of gabapentin on ocular and behavioral parameters following oral administration in healthy cats. MATERIALS AND METHODS: Masked, placebo-controlled, randomized crossover-design study. Ten young, healthy cats were scheduled for two veterinary visits 7 days apart and randomly assigned to receive a compounded capsule containing 100 mg of gabapentin or placebo (100 mg lactose powder) at the first visit and the opposite treatment at the second visit. Respiratory rate, heart rate, stress score, sedation score, compliance score, horizontal pupil diameter, intraocular pressure, and Schirmer tear test-1 were measured prior to and 1.5, 3, and 6 h following capsule administration. Stress score, sedation score, and compliance score were assigned based on established behavioral scales. Results of the two treatments were statistically compared with a p-value <0.05 considered significant. RESULTS: Respiratory rate was significantly reduced at 1.5 (p = 0.049) and 3 (p = 0.03) hours following gabapentin administration. Stress score was significantly reduced at 1.5 (p = 0.01) hours following gabapentin administration. Sedation score was significantly increased at 1.5 (p = 0.015) and 3 (p = 0.03) hours following gabapentin administration. Gabapentin had no significant effect on heart rate, compliance score, or ocular values measured in this study. CONCLUSIONS: Gabapentin reduces stress and increases sedation at 1.5 h after treatment, with no significant effect on horizontal pupil diameter, intraocular pressure or Schirmer tear test-1 results.

Rhythm Control Vs Rate Control in a Contemporary Ambulatory Atrial Fibrillation Cohort: Post Hoc Analysis of the IMPACT-AF Trial.

Background: We examined the characteristics and outcomes in a contemporary ambulatory population of patients with atrial fibrillation (AF), comparing rate control with rhythm control. Methods: This is a post hoc analysis of a cluster-randomized trial (Integrated Management Program Advancing Community Treatment of Atrial Fibrillation [IMPACT-AF]) in ambulatory AF patients from 2016 to 2018, which compared use of a clinical decision support tool for general practitioners to usual care. This analysis compared patients managed with rate vs rhythm control, at entry into the study. Outcomes included AF-related emergency department (ED) visits, unplanned cardiovascular hospitalizations, and bleeding events at 12 months. Results: A total of 870 patients were included in this analysis, 99 (11.4%) in the rhythm-control group, and 40% women. In the rhythm-control group, the mean age was younger (70 ± 11.4 vs 72.7 ± 9.5 years, P = 0.03), a higher number were paroxysmal (80% vs 43%, P < 0.001), and CHADS2 scores were lower. The rate of AF-related ED visits was higher in the rhythm-control group (17.2 vs 7.3%, P = 0.003), and repeat visits (rate ratio 3.03, 95% confidence interval [1.99-4.52], P < 0.001). The number of repeat ED visits was independently associated with female sex and being in the rhythm-control group. Conclusions: Both rate- and rhythm-control patients have recurrent ED visits, with a higher rate in patients treated with rhythm control. These findings are observational, but taken in the context of current guidelines could help develop further therapies aimed at improving symptom burden in both rhythm- and rate-control patients to broadly improve healthcare utilization in the AF population.

Contexte: Nous avons examiné les caractéristiques et le devenir de patients ambulatoires contemporains atteints de fibrillation auriculaire (FA) dans le cadre d'une comparaison entre la maîtrise de la fréquence cardiaque et la maîtrise du rythme cardiaque. Méthodologie: Nous avons effectué une analyse a posteriori d'un essai à répartition aléatoire par grappes ( I ntegrated M anagement P rogram A dvancing C ommunity T reatment of A trial F ibrillation [IMPACT-AF]) mené de 2016 à 2018 chez des patients ambulatoires atteints de FA en vue de comparer un outil d'aide à la décision clinique destiné aux omnipraticiens avec les soins habituels. Notre analyse a permis d'établir une comparaison entre les patients pris en charge par une maîtrise de la fréquence cardiaque et ceux pris en charge par une maîtrise du rythme cardiaque lors de leur inscription à l'essai. Les paramètres d'évaluation comprenaient les consultations aux urgences liées à la FA, les hospitalisations imprévues ayant des causes cardiovasculaires et les épisodes hémorragiques à 12 mois. Résultats: Au total, 870 patients ont été inclus dans cette analyse; 99 (11,4 %) faisaient partie du groupe pris en charge par une maîtrise du rythme cardiaque, et 40 % étaient de femmes. Dans le groupe pris en charge par une maîtrise du rythme cardiaque, l'âge moyen était moindre (70 ± 11,4 ans vs 72,7 ± 9,5 ans, P = 0,03), un plus grand nombre de patients présentaient une FA paroxystique (80 % vs 43 %, P < 0,001) et les scores CHADS2 étaient moins élevés. Le taux de consultations aux urgences liées à la FA était plus élevé dans le groupe pris en charge par une maîtrise du rythme cardiaque (17,2 vs 7,3 %, P = 0,003) tout comme le taux de consultations répétées aux urgences (rapport des taux de 3,03, intervalle de confiance à 95 % de 1,99 à 4,52, P < 0,001). Le nombre de consultations répétées aux urgences était indépendamment associé au sexe féminin et à l'inclusion dans le groupe pris en charge par une maîtrise du rythme cardiaque. Conclusions: Des consultations répétées aux urgences ont été notées tant chez les patients pris en charge par une maîtrise de la fréquence cardiaque que chez ceux pris en charge par une maîtrise du rythme cardiaque quoique plus fréquemment chez ces derniers. Nos constats sont de type observationnel. Néanmoins, dans le contexte des lignes directrices actuelles, ils pourraient contribuer à la mise au point d'autres traitements visant à atténuer le fardeau des symptômes tant chez les patients pris en charge par une maîtrise du rythme cardiaque que chez ceux pris en charge par une maîtrise de la fréquence cardiaque et ainsi permettre globalement une meilleure utilisation des soins de santé chez les patients atteints de FA.

Impact of small molecule and reverse poloxamer addition on the micellization and gelation mechanisms of poloxamer hydrogels.

Poloxamer 407 (P407) is widely used for targeted drug-delivery because it exhibits thermoresponsive gelation behavior near body temperature, stemming from a disorder-to-order transition. Hydrophobic small molecules can be encapsulated within P407; however, these additives often negatively impact the rheological properties and lower the gelation temperatures of the hydrogels, limiting their clinical utility. Here we investigate the impact of adding two BAB reverse poloxamers (RPs), 25R4 and 31R1, on the thermal transitions, rheological properties, and assembled structures of P407 both with and without incorporated small molecules. By employing a combination of differential scanning calorimetry (DSC), rheology, and small-angle x-ray scattering (SAXS), we determine distinct mechanisms for RP incorporation. While 25R4 addition promotes inter-micelle bridge formation, the highly hydrophobic 31R1 co-micellizes with P407. Small molecule addition lowers thermal transition temperatures and increases the micelle size, while RP addition mitigates the decreases in modulus traditionally associated with small molecule incorporation. This fundamental understanding yields new strategies for tuning the mechanical and structural properties of the hydrogels, enabling design of drug-loaded formulations with ideal thermal transitions for a range of clinical applications.

Feline ureteral obstruction: a case-control study of risk factors (2016-2019).

OBJECTIVES: Ureteral obstruction (UO) in cats causes acute kidney injury and typically requires surgical intervention. Information is required about potentially modifiable risk factors to inform prevention strategies. METHODS: A case-control study was performed to assess risk factors associated with feline UO. Cases were defined as cats with either of the following: (1) ureteral obstruction (ureteroliths: 13/18; unknown: 5/18) confirmed with pyelography; or (2) a creatinine concentration >140 µmol/l with both UO (ureteroliths: 6/10; blood clots: 3/10; pyonephrosis: 1/10) and pyelectasia ⩾5 mm on abdominal ultra sonography. Controls were defined as cats without evidence of UO on history, physical examination and abdominal ultrasound. Age, sex, breed (domestic shorthair/longhair), diet (predominantly dry, mixed or predominantly moist food), housing (indoors or mixed) and plasma total calcium were evaluated for their association with UO using multivariable logistic regression. A receiver operator characteristic (ROC) curve was created to evaluate the predictive ability of the final model. RESULTS: In total, 168 cats (28 cases, 140 controls) were included. Age, sex, breed, housing and total calcium were not significantly associated with UO; however, diet was. Compared with cats eating a predominantly moist food diet, cats fed a predominantly dry food diet were 15.9 times more likely to develop a UO (95% confidence interval 2.9-295; P = 0.009). There was no difference in the association between diet and UO in cats fed a mixed diet vs cats fed a predominantly moist food diet (P = 0.25). The area under the ROC curve was 72%. CONCLUSIONS AND RELEVANCE: Changes in diet formulation could provide a simple and economical method to reduce the risk of UO.

Radioactive iodine dose and survival in cats with hyperthyroidism (2015-2020).

OBJECTIVES: Radioactive iodine (131I) is the preferred treatment for feline hyperthyroidism but neither the optimal 131I dose nor consistent predictors of post-treatment azotaemia have been determined. The aims of the study were to evaluate the relationships between: (1) 131I dose and survival; and (2) pretreatment and post-treatment serum creatinine concentration. METHODS: Medical records of hyperthyroid cats treated with 131I at a single referral hospital were reviewed. Information regarding signalment, body weight, pretreatment and post-treatment serum total thyroxine concentration (TT4), serum creatinine concentration, 131I dose and survival were determined. Multivariable Cox proportional hazards analysis was used to identify variables associated with survival. Multivariable linear regression analysis was used to identify variables associated with post-treatment serum creatinine concentration. RESULTS: One hundred and ninety-eight (79 male, 119 female) cats were treated for hyperthyroidism with 131I (median dose 138 MBq; interquartile range 92-168). Median survival time was 1153 days (range 16-1871). Post-treatment serum creatinine (P <0.001) and age (P = 0.049) were significantly associated with survival. Every 10 µmol/l increase in post-treatment serum creatinine concentration and every year increase in age was associated with a 1.07-fold (confidence interval [CI] 1.04-1.11) and 1.17-fold (CI 1.00-1.37) increase in the daily hazard of death, respectively. Pretreatment serum creatinine concentration was directly, and post-treatment serum TT4 concentration was inversely, associated with post-treatment serum creatinine concentration. Every 1 µmol/l increase in pretreatment serum creatinine concentration was associated with an increase in post-treatment serum creatinine concentration of 0.7 µmol/l (SE 0.17; P <0.001). Conversely, every 1 nmol/l decrease in post-treatment serum TT4 concentration was associated with a 1.2 µmol/l (SE 0.61; P <0.001) increase in post-treatment serum creatinine concentration. CONCLUSIONS AND RELEVANCE: Post-treatment serum TT4 concentration was associated with post-treatment azotaemia, which was associated with survival. Although 131I dose was not directly associated with survival, dosing strategies that minimise post-treatment hypothyroidism and azotaemia could improve patient survival.

Combination vinblastine and palladia for high-grade and metastatic mast cell tumors in dogs.

High-grade and metastatic canine mast cell tumors carry a guarded prognosis because of their unpredictable biologic behavior. An ideal chemotherapy regime is yet to be established. The aim of this study was to review the efficacy and toxicity of combination vinblastine and toceranib for high-grade and metastatic mast cell tumors. Twenty-eight dogs were categorized with either high-grade, lymph node metastasis or Stage IV disease. Demographics, disease, and treatment variables were compared between categories (Kruskal-Wallis test for continuous data and Fisher's Exact test for categorical data). Survival times and progression-free intervals (PFI) were calculated and compared between groups (log rank test). The PFI was 310 d [95% confidence interval (CI): 155 to 1425] and overall survival was 373 d (95% CI: 226 to 1219). There was no difference between disease categories for PFI (P = 0.9) or survival (P = 0.5). The protocol was well-tolerated with increased liver enzyme activity and gastrointestinal toxicity most frequently observed. Progression-free intervals and survival times were similar in dogs with high-grade, metastatic and Stage IV disease.

Combinaison vinblastine et Palladia pour les mastocytomes métastatiques et de haut grade chez le chien. Les mastocytomes canins métastatiques et de haut grade ont un pronostic réservé en raison de leur comportement biologique imprévisible. Un traitement idéal de chimiothérapie n'a pas encore été établi. Le but de cette étude était d'examiner l'efficacité et la toxicité de l'association vinblastine et tocéranib pour les mastocytomes de haut grade et métastatiques.Vingt-huit chiens ont été classés soit avec une maladie de haut grade, des métastases ganglionnaires ou avec une maladie de stade IV. Les variables démographiques, de maladie et de traitement ont été comparées entre les catégories (test de Kruskal-Wallis pour les données continues et test exact de Fisher pour les données catégorielles). Les temps de survie et les intervalles sans progression (PFI) ont été calculés et comparés entre les groupes (test de log-rank). Le PFI était de 310 jours [intervalle de confiance à 95 % (IC): 155 à 1425] et la survie globale était de 373 jours (IC 95 %: 226 à 1219). Il n'y avait pas de différence entre les catégories de maladie pour le PFI (P = 0,9) ou la survie (P = 0,5). Le protocole a été bien toléré avec une augmentation de l'activité des enzymes hépatiques et une toxicité gastro-intestinale les plus fréquemment observées. Les PFI et les temps de survie étaient similaires chez les chiens atteints d'une maladie de haut grade, ceux avec des métastases et ceux de stade IV.(Traduit par Dr Serge Messier).

Renal Crest Proliferative Lesions in Cats with Chronic Kidney Disease.

In a histopathological study of the renal crest (RC) of kidneys of cats with chronic kidney disease (CKD), 58/90 (64%) had epithelial proliferation. Of these, 33 cats had hyperplasia of the collecting duct (CD) epithelium (CDH) alone, eight had hyperplasia of the urothelium covering the RC (RCUH), of which one had concurrent abaxial renal pelvic urothelial hyperplasia (UH), and eight had both CDH and RCUH. CDH or RCUH were present in five cats with marked dysplasia of the CD epithelium (CDD) and four cats with invasive carcinomas, which also had epithelial dysplasia. All nine cats with marked dysplasia or neoplasia of the RC also had substantially altered RC contours due to focal haemorrhage, papillary necrosis or fibrosis. Three of the carcinomas had a strong desmoplastic response. In control cats, both urothelial (RC and renal pelvis) and tubular (CD and distal tubular) cells were immunopositive for cytokeratin (CK; AE1/AE3), tubular epithelial cells were positive for vimentin (Vim) and aquaporin 2 (Aq2), while urothelial cells were positive for p63. PAX8 immunolabelling was difficult to validate. CD and UH labelling was similar to control tissue. While urothelial dysplasia had the same immunolabelling pattern as UH and control tissue, CDD was generally immunonegative for Aq2. As immunolabelling of the four carcinomas did not distinguish between tubular and urothelial origin, with three positive for both Vim and p63, all were broadly designated as RC carcinomas. Overall, proliferative epithelial lesions are common in cats with CKD and form a continuum from simple hyperplasia to neoplasia of the urothelium or CD of the RC.

Lessons learned from Integrated Management Program Advancing Community Treatment of Atrial Fibrillation (IMPACT-AF): a pragmatic clinical trial of computerized decision support in primary care.

BACKGROUND: Integrated Management Program Advancing Community Treatment of Atrial Fibrillation (IMPACT-AF) was a pragmatic, cluster randomized trial assessing the effectiveness of a clinical decision support (CDS) tool in primary care, Nova Scotia, Canada. We evaluated if CDS software versus Usual Care could help primary care providers (PCPs) deliver individualized guideline-based AF patient care. METHODS: Key study challenges including CDS development and implementation, recruitment, and data integration documented over the trial duration are presented as lessons learned. RESULTS: Adequate resources must be allocated for software development, updates and feasibility testing. Development took longer than projected. End-user feedback suggested network access and broadband speeds impeded uptake; they felt further that the CDS was not sufficiently user-friendly or efficient in supporting AF care (i.e., repetitive alerts). Integration across e-platforms is crucial. Intellectual property and other issues prohibited CDS integration within electronic medical records and provincial e-health platforms. Double login and data entry were impediments to participation or reasons for provider withdrawal. Data integration challenges prevented easy and timely data access, analysis, and reporting. Primary care study recruitment is resource intensive. Altogether, 203 PCPs and 1145 of their patients participated, representing 25% of eligible providers and 12% of AF patients in Nova Scotia, respectively. The most effective provider recruitment strategy was in-office, small group lunch-and-learns. PCPs with past research experience or who led patient consent were top recruiters. The study office played a pivotal role in achieving patient recruitment targets. CONCLUSIONS: A rapid growth in healthcare data is leading to widespread development of CDS. Our experience found practical issues to address for such applications to succeed. Feasibility testing to assess the utility of any healthcare CDS prior to implementation is recommended. Adequate resources are necessary to support successful recruitment for future pragmatic trials. CDS tools that integrate multiple co-morbid guidelines across eHealth platforms should be pursued. TRIAL REGISTRATION: ClinicalTrials.gov NCT01927367. Registered on August 22, 2013.

Patient-Reported Outcomes and Patient-Reported Experience of Patients With Atrial Fibrillation in the IMPACT-AF Clinical Trial.

Background The IMPACT-AF (Integrated Management Program Advancing Community Treatment of Atrial Fibrillation) trial is a prospective, randomized, cluster design trial comparing atrial fibrillation management with a computerized clinical decision support system with usual care (control) in the primary care setting of Nova Scotia, Canada. The objective of this analysis was to assess and compare patient-reported health-related quality of life and patient-reported experience with atrial fibrillation care between clinical decision support and control groups. Methods and Results Health-related quality of life was measured using the EuroQol 5-dimensional 5-level scale, whereas patient-reported experience was assessed using a self-administered satisfaction questionnaire, both assessed at baseline and 12 months. Health utilities were calculated using the Canadian EuroQol 5-dimensional 5-level value set. Descriptive statistics and generalized estimating equations were used to compare between groups. Among 1145 patients enrolled in the trial, 717 had complete EuroQol 5-dimensional 5-level data at baseline. The mean age of patients was 73.53 years, and 61.87% were men. Mean utilities at baseline were 0.809 (SD, 0.157) and 0.814 (SD, 0.157) for clinical decision support and control groups, respectively. At baseline, most patients in both groups reported being "very satisfied" with the care received for their atrial fibrillation. There were no statistically significant differences in utility scores or patient satisfaction between groups at 12 months. Conclusions Health-related quality of life of patients remained stable over 12 months, and there was no significant difference in patient satisfaction or utility scores between clinical decision support and control groups. Registration information clinicaltrials.gov. Identifier: NCT01927367.

Outcomes of baervedlt implant surgery in 17 dogs (20 eyes) with primary closed-angle glaucoma (2013-2019).

OBJECTIVE: To report outcomes and follow-up of Baerveldt implant surgery in dogs with primary closed-angle glaucoma (PCAG). MATERIALS AND METHODS: Record review of client-owned dogs with PCAG that underwent Baerveldt implant surgery during a 6-year period. Postoperative intraocular pressure (IOP), vision and daily number of anti-glaucoma drops at fixed time points (3, 12, and 24 months) were compared with preoperative values; complications were recorded. Success was defined as IOP <20 mm Hg and a positive menace response and navigation/tracking ability. RESULTS: Twenty eyes (17 dogs) were included. Mean follow-up was 575 days (range 30-1767 days) from implant surgery to last examination. Three months postoperatively 15/20 (75%) eyes had IOP <20 mm Hg and 14/20 (70%) eyes had vision. Twelve months postoperatively 11/17 (65%) eyes had IOP <20 mm Hg and 12/19 (63%) eyes had vision. Twenty-four months postoperatively 8/14 (57%) eyes had IOP <20 mm Hg and 7/15 (47%) eyes had vision. Denominators differ between time points as eyes were included when duration after surgery reached the relevant postoperative time point or failure was documented earlier. Within 3 months postoperatively 16/20 (80%) eyes had ≥1 complication, including transient IOP >20 mm Hg (14/20; 70% eyes), fibrin (12/20; 60% eyes), and hypotony (4/20; 20% eyes). After 3 months, postoperatively 13/16 (81%) eyes had ≥1 complication, including cataracts (13/16; 81% eyes), bleb fibrosis (3/16; 19% eyes), and conjunctival wound breakdown (1/16; 6% eyes). One patient (1 eye) was euthanized for blindness and 5/20 (25%) eyes were enucleated. CONCLUSIONS: The technique was effective in controlling IOP and maintaining vision in most dogs in this study.

Canada's Evolving Medicare: End-of-Life Care.

A challenging issue in contemporary Canadian Medicare is the evolution of end-of-life care. Utilizing data from the 2016 and 2018 Health Care in Canada (HCIC) surveys, this paper compares the support and priorities of the adult public (n = 1500), health professionals (n = 400), and administrators (n = 100) regarding key components for end-of-life care just prior to and post legalization of medical assistance in dying (MAiD) in Canada. In 2016 and 2018, the public, health professionals and administrators strongly supported enhanced availability of all proposed end-of-life care options: pain management, hospice and palliative care, home care supports, and medically assisted death. In 2018, when asked which option should be top priority, the public rated enhanced medically assisted death first (32%), followed by enhanced hospice and palliative care (22%) and home care (21%). Enhanced hospice and palliative care was the top priority for health professionals (33%), while administrators rated enhanced medically assisted death first (26%). Despite legalization and increasing support for MAiD over time, health professionals have increasing fear of legal or regulatory reprisal for personal involvement in medically assisted death, ranging from 38% to 84% in 2018, versus 23% to 42% in 2016. While administrators fear doubled since 2016 (40%-84%), they felt the necessary system supports were in place to easily implement medically assisted death. Optimal management of end-of-life care is strongly supported by all stakeholders, although priorities for specific approaches vary. Over time, professionals increasingly supported MAiD but with a rising fear of legal/regulatory reprisal despite legalization. To enhance future end-of-life care patterns, continued measurement and reporting of implemented treatment options and their system supports, particularly around medically assisted death, are needed.