Assessment of corrected JT-peak (JTpc) and Tpeak-to-Tend (TpTec) as proarrhythmia biomarkers in non-human primates: Outcome from a HESI consortium.

Introduction: Corrected QT interval (QTc)is an established biomarker for drug-induced Torsade de Pointe (TdP), but with concerns for a false positive signal. Clinically, JTpc and TpTec have emerged as ECG sub-intervals to differentiate predominant hERG vs. mixed ion channel blocking drugs that prolong QTc.

Human Cardiomyocyte Action Potential Modeling: Exploring Ion Channel Input Combinations.

modeling offers an opportunity to supplement and accelerate cardiac safety testing. With in silico modeling, computational simulation methods are used to predict electrophysiological interactions and pharmacological effects of novel drugs on critical physiological processes. The O'Hara-Rudy's model was developed to predict the response to different ion channel inhibition levels on cardiac action potential duration (APD) which is known to directly correlate with the QT interval.

An Adaptive Unscented Kalman Filter for the Estimation of the Vehicle Velocity Components, Slip Angles, and Slip Ratios in Extreme Driving Manoeuvres.

This paper presents a novel unscented Kalman filter (UKF) implementation with adaptive covariance matrices (ACMs), to accurately estimate the longitudinal and lateral components of vehicle velocity, and thus the sideslip angle, tire slip angles, and tire slip ratios, also in extreme driving conditions, including tyre-road friction variations. The adaptation strategies are implemented on both the process noise and measurement noise covariances. The resulting UKF ACM is compared against a well-tuned baseline UKF with fixed covariances.

The incidence of spontaneous arrhythmias in telemetered beagle dogs, Göttingen Minipigs and Cynomolgus non-human primates: A HESI consortium retrospective analysis.

Introduction: Characterization of the incidence of spontaneous arrhythmias to identify possible drug-related effects is often an important part of the analysis in safety pharmacology studies using telemetry.

Methods: A retrospective analysis in non-clinical species with and without telemetry transmitters was conducted. Electrocardiograms (24 h) from male and female beagle dogs (n = 131), Göttingen minipigs (n = 108) and cynomolgus non-human primates (NHP; n = 78) were analyzed.

Polysorbate 80-Induced Anaphylactoid Reaction and the Effects on Cardiovascular Function: Dose Threshold and Species Comparison.

Polysorbate 80 (PS80) is commonly used in pre-clinical formulations. The dose threshold for cardiovascular (CV) changes and hypersensitivity reaction in the dog was assessed and compared to other species. PS80 was administered by intravenous (IV) bolus (.

Impact of the Connected Medicine collaborative in improving access to specialist care: a cross-sectional analysis.

Background: In 2017, the Canadian Foundation for Healthcare Improvement launched the Connected Medicine collaborative to support the implementation, spread and adaptation of 2 innovative remote consult solutions - the Champlain Building Access to Specialists through eConsultation (BASE) eConsult service and the Rapid Access to Consultative Expertise (RACE) service - across Canada. We evaluated the impact of the programs implemented through the collaborative.

Methods: We conducted a cross-sectional analysis of data from provincial teams that participated in the Connected Medicine collaborative, which took place between June 2017 and December 2018 in 7 provinces across Canada (British Columbia, Alberta, Saskatchewan, Manitoba, Quebec, New Brunswick, Newfoundland and Labrador).

Combined Cardiopulmonary Assessments Using Impedance and Digital Implants in Conscious Freely Moving Cynomolgus Monkeys, Beagle Dogs, and Göttingen Minipigs: Pharmacological Characterization and Social Housing Effects.

Respiratory monitoring, using impedance with implanted telemetry in socially housed animals, was not possible until the recent development of digital signal transmission. The objective of this study was to evaluate digital telemetry monitoring of cardiopulmonary parameters (respiratory rate, tidal volume, minute volume, electrocardiography (DII), systemic arterial blood pressure, physical activity, and body temperature) in conscious, single-housed, non-rodent species commonly used in toxicology studies following administration of positive/negative controls (saline, dexmedetomidine, morphine, amphetamine, and doxapram), and also, the effects of various social housing arrangements in untreated female and/or male cynomolgus monkeys, Beagle dogs, and Göttingen minipigs (n = 4 per species). Aggressions were observed in socially housed male minipigs, however, which prevented pair-housed assessments in this species.

How long are Canadians waiting to access specialty care? Retrospective study from a primary care perspective.

Objective: To calculate patient wait times for specialist care using data from primary care clinics across Canada.

Design: Retrospective chart audit.

Setting: Primary care clinics.

Reprint of "EEG: Characteristics of drug-induced seizures in rats, dogs and non-human primates".

Seizures are amongst the most frequent neurological issues encountered in pre-clinical safety testing. The objective was to characterize EEG morphologies and premonitory signs in drug-induced seizures in preclinical species. A comparative (inter-species) retrospective analysis for drug-induced seizures recorded by video-telemetry was conducted in rats (n = 53), dogs (n = 195), and non-human primates (n = 234).

Incidence of spontaneous arrhythmias in freely moving healthy untreated Sprague-Dawley rats.

Spontaneous arrhythmia characterization in healthy rats can support interpretation when studying novel therapies. Male (n = 55) and female (n = 40) Sprague-Dawley rats with telemetry transmitters for a derivation II ECG. Arrhythmias were assessed from continuous ECG monitoring over a period of 24-48 h, and data analyzed using an automated detection algorithm with 100% manual over-read.

EEG: Characteristics of drug-induced seizures in rats, dogs and non-human primates.

Seizures are amongst the most frequent neurological issues encountered in pre-clinical safety testing. The objective was to characterize EEG morphologies and premonitory signs in drug-induced seizures in preclinical species. A comparative (inter-species) retrospective analysis for drug-induced seizures recorded by video-telemetry was conducted in rats (n = 53), dogs (n = 195), and non-human primates (n = 234).

A Proof-of-Concept Evaluation of JTPc and Tp-Tec as Proarrhythmia Biomarkers in Preclinical Species: A Retrospective Analysis by an HESI-Sponsored Consortium.

Introduction: Based on the ICH S7B and E14 guidance documents, QT interval (QTc) is used as the primary in vivo biomarker to assess the risk of drug-induced torsades de pointes (TdP). Clinical and nonclinical data suggest that drugs that prolong the corrected QTc with balanced multiple ion channel inhibition (most importantly the l-type calcium, Cav1.2, and persistent or late inward sodium current, Nav1.

Can we perform a prenatal diagnosis of vasa previa to improve its obstetrical and neonatal outcomes?

Introduction: Vasa previa (VP) is defined as a condition in which the fetal blood vessels, unsupported by the placenta or the umbilical cord, run through the membranes of the lower uterine segment. It is associated with a high risk of stillbirth by exsanguination. This study aimed to assess the clinical context of diagnosis of VP in order to elaborate a strategy for its prenatal diagnosis and to improve its obstetrical and neonatal outcomes.

Cardiac contractility: Correction strategies applied to telemetry data from a HESI-sponsored consortium.

Introduction: QT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dt interpretation.

Nissen Sleeve (N-Sleeve) operation: preliminary results of a pilot study.

Background: Sleeve gastrectomy (SG) is one of the most frequently performed bariatric procedures worldwide. Despite its impressive results, there is a growing concern about the relationship between SG and gastroesophageal reflux disease (GERD).

Objectives: We present our pilot study of patients operated with a Nissen anti-reflux valve added to a standard SG.

Robotic Versus Laparoscopic Total Mesorectal Excision (TME) for Sphincter-Saving Surgery: Is There Any Difference in the Transanal TME Rectal Approach? : A Single-Center Series of 120 Consecutive Patients.

Background: Robotic total mesorectal excision (R-TME), a novel way for minimally invasive treatment of rectal cancer, was shown in previous studies to be safe and effective. However, comparison with laparoscopic total mesorectal excision (L-TME) has drawn contradictory disputes, especially concerning operative high-risk patients. The aim of this study was to compare R-TME and L-TME on the rectal technical approach.

[Spontaneous renal forniceal rupture with suspicious ovarian mass].

Extravasation of urine following rupture of the renal fornix is a rare complication mostly caused by obstruction secondary to distal ureteric stones. This 35-year-old woman was referred with back pain. Her CT scan revealed rupture of the renal fornix secondary to a pelvic mass.

A review of available prosthetic material for abdominal wall repair.

Abdominal wall incisional and inguinal hernia repair can call for utilization of implants or prostheses as an alternative to simple suture techniques. The various implants can be synthetic, biologic or mixed: their physicochemical properties condition the mechanical results and the long-term outcome of the repair. The increasing number of available materials allows the surgeon to choose between a wide variety depending on the indication, the site of implantation, the surgical approach and whether the operative field is contaminated or not.

Factors associated with asthma control among adults in five New England states, 2006-2007.

Background: Despite the National Asthma Education and Prevention Program (NAEPP) guidelines that specify the goals of asthma control and management strategies, the number of patients with uncontrolled asthma remains high, and factors associated with uncontrolled asthma are unknown.

Objective: The aim was to examine the relationship between asthma control and socio-demographic characteristics, health-care access and use, asthma education, and medication use among adults with active asthma residing in New England.

Methods: Data from the 2006-2007 Behavior Risk Factor Surveillance System Adult Asthma Call-Back Survey were analyzed using multinomial logistic regression.