Variant discovery using next-generation sequencing and its future role in pharmacogenetics.

Next-generation sequencing (NGS) has enabled the discovery of a multitude of novel and mostly rare variants in pharmacogenes that may alter a patient's therapeutic response to drugs. In addition to single nucleotide variants, structural variation affecting the number of copies of whole genes or parts of genes can be detected. While current guidelines concerning clinical implementation mostly act upon well-documented, common single nucleotide variants to guide dosing or drug selection, and large-scale functional assessment of rare variant effects on protein function are at the forefront of pharmacogenetic research to facilitate their clinical integration.

A Large-Scale Fifteen-Year Minimum Survivorship of a Cementless Triple Tapered Femoral Stem.

Background: This study reports the long-term outcomes of a metaphyseal fit-and-fill cementless femoral component in total hip arthroplasty (THA) with a follow-up of 15-19 years.

Methods: We conducted a retrospective review of 376 consecutive THAs (345 patients), using a triple tapered stem performed between 2000 and 2003 with a view to assessing survivorship and radiological and functional outcomes. Images were assessed for initial alignment, terminal osteolysis, or subsidence, while clinical outcomes were assessed using the St Michael's Hip Score.

Response to commentary on "the middle fossa approach with self-drilling screws: a novel technique for BONEBRIDGE implantation".

The aim of this letter is to respond to a commentary on a published article on the middle fossa approach to BONEBRIDGE implantation with self-drilling screws published by the senior authors.

Strong independent associations between gait biomechanics and pain in patients with knee osteoarthritis.

We investigated the simple and multivariate associations between knee pain and gait biomechanics. 279 patients with medial knee osteoarthritis (OA) and discordant changes in pain between limbs after walking completed bilateral three-dimensional gait analysis. For each limb, patients rated their pain before and after a 6-min walk and the change in pain was recorded as an increase (≥1 points) or not (≤0 points).

The middle fossa approach with self-drilling screws: a novel technique for BONEBRIDGE implantation.

Background: Bone conduction implants can be used in the treatment of conductive or mixed hearing loss. The BONEBRIDGE bone conduction implant (BB-BCI) is an active, transcutaneous device. BB-BCI implantation can be performed through either the transmastoid or retrosigmoid approach with their respective limitations.

Condylar-Stabilized TKR May Not Fully Compensate for PCL-Deficiency: An In Vitro Cadaver Study.

Increased-congruency bearing options are widely available in numerous total knee replacement (TKR) systems, with the intended purpose of compensating for posterior-cruciate ligament (PCL) deficiency. However, their ability to provide adequate stability in this setting has been debated. This in vitro joint simulator study measured changes in knee joint kinematics and stability during passive flexion-extension motions and simulated activities of daily living resulting from TKR with condylar-stabilized (CS) TKR without a PCL versus cruciate-retaining (CR) TKR.

Improving patient flow in a regional anaesthesia block room.

University Hospital is a tertiary academic centre in London, Ontario, Canada. A designated space known as the block room (BR) supports a model of care to perform regional anaesthesia prior to entering the resource intense operating room (OR). Stress due to time pressure was reported by BR staff.

Assessing Preoperative Mobility in Total Hip Arthroplasty: A SAFE T database study.

Unlabelled: This study examined whether individuals undergoing total hip arthroplasty who are self-rated as "highly active", demonstrated higher pre-operative activity levels than others.

Methods: 483 patients were retrospectively identified; 241 were "highly active" and 242 were not. They were compared using WOMAC, self-reported activity and 6-Minute Walk Test (6MWT).

Targeted next generation sequencing as a tool for precision medicine.

Background: Targeted next-generation sequencing (NGS) enables rapid identification of common and rare genetic variation. The detection of variants contributing to therapeutic drug response or adverse effects is essential for implementation of individualized pharmacotherapy. Successful application of short-read based NGS to pharmacogenes with high sequence homology, nearby pseudogenes and complex structure has been previously shown despite anticipated technical challenges.

Use of the Novel C-MAC Video Stylet in a Case of Predicted Difficult Intubation: A Case Report.

Video laryngoscopes are commonly used to manage difficult airways, among other devices. However, they present a challenge when inserting the blade in patients with a limited mouth opening, and an adequate visualization of the glottis does not always translate into successful intubation. The C-MAC Video-Stylet-with its small diameter and flexible tip-offers an effective alternative.

Patients with immunological diseases or on peritoneal dialysis are prone to false positive flow cytometry crossmatch.

Despite implementation of virtual crossmatches, flow cytometry crossmatches (FCXM) are still used by many transplant centers to determine immunological risk before kidney transplantation. To determine if common profiles of patients prone to false positive FCXM exist, we examined the demographics and native diseases of kidney patients tested with autologous FCXM (n = 480). Improvements to FCXM and cell isolation methods significantly reduced the positive rate from 15.

The Effects of Resection Technique on Implant Migration in Single Radius Posterior-Stabilized Total Knee Replacement.

The purpose of the present study was to measure the effects of gap balancing and resection techniques on migration of a single total knee replacement implant design. A total of 23 patients (24 knees) were recruited on referral to either a surgeon performing gap balancing or a surgeon performing measured resection and followed prospectively. All patients received a fixed bearing, posterior stabilized total knee replacement implant of a single radius femoral component design with cement fixation, and all aspects of care outside of resection technique were identical.

Can women in labor give informed consent to epidural analgesia?

There are reasons to believe that decision-making capacity (mental competence) of women in labor may be compromised in relation to giving informed consent to epidural analgesia. Not only severe labor pain, but also stress, anxiety, and premedication of analgesics such as opioids, may influence women's decisional capacity. Decision-making capacity is a complex construct involving cognitive and emotional components which cannot be reduced to 'understanding' alone.

Loss of receptor interacting protein kinases 3 and caspase-8 augments intrinsic apoptosis in tubular epithelial cell and promote kidney ischaemia-reperfusion injury.

Background: Ischaemia-reperfusion injury (IRI) is associated with programmed cell death that promotes inflammation and organ dysfunction. Necroptosis is mediated by members of receptor interacting protein kinases (RIPK1/3). Inhibition of RIPK1/3 provides a pro-survival benefit in kidney IRI.

Unpacking the Literature on Stress and Resiliency: A Narrative Review Focused on Learners in the Operating Room.

Purpose: The operating room is a high pressure environment for surgical trainees as they attempt to reach a high level of performance in the midst of a multitude of stressors. The purpose of this work was to examine the relationships between stress, coping, and psychological resilience and their effects on performance and learning in surgical training.

Methods: A narrative review was carried out of the existing literature on stress, coping, and resilience in surgeons and surgical trainees.

Development, administration, and validity evidence of a subspecialty preparatory test toward licensure: a pilot study.

Background: Trainees in medical subspecialties lack validated assessment scores that can be used to prepare for their licensing examination. This paper presents the development, administration, and validity evidence of a constructed-response preparatory test (CRPT) administered to meet the needs of nephrology trainees.

Methods: Learning objectives from the licensing examination were used to develop a test blueprint for the preparatory test.

Identification and Characterization of Trimethylamine-N-oxide Uptake and Efflux Transporters.

Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo.

New oral agents for treating dyslipidemia.

Purpose Of Review: We provide an overview of orally administered lipid-lowering therapies under development.

Recent Findings: Recent data support statins for intermediate risk primary prevention, and ezetimibe for high-risk secondary prevention. Novel agents in development include bempedoic acid and gemcabene, and work continues on one remaining cholesteryl ester transfer protein inhibitor, anacetrapib, to determine whether this class can reduce cardiovascular risk.

Myotonic Dystrophy and Huntington's Disease Care: "We Like to Think We're Making a Difference".

Background: Patient-centered care for individuals with myotonic dystrophy (DM1) and Huntington's disease (HD)-chronic, progressive, and life-limiting neurological conditions-may be challenged by patients' cognitive and behavioral impairments. However, no research has explored health care providers' (HCPs') perspectives about patient-centered care provision for these patients along their disease trajectory.

Methods: Constructivist grounded theory informed the iterative data collection and analysis process.

Knee Arthroscopy in the Setting of Knee Arthroplasty.

Knee arthroplasty is an effective and reproducible way of treating advanced knee arthritis; however, results are not always favorable. Knee arthroscopy has been described in symptomatic knee arthroplasty, but opinion is divided over its utility. The purpose of this systematic review is to examine existing evidence supporting knee arthroscopy in the setting of knee arthroplasty.

Extramural Pilot Project: Designated On-Call Intensivist in Tertiary Care Centre Improves Access to Critical Care Consultation/Referral and Resources.

Timely consultation with an intensivist will promote early and appropriate management of critically ill patients. We determined whether implementing a call roster of intensivists who did not have on-call responsibilities in an intensive care unit (ICU) and who received referrals from community physicians would improve access to critical care services. This program created efficiencies to critical care services by: timely access to consultation with an intensivist (<10 minutes) and/or subspecialist, timely referral to an appropriate institution (<30 minutes) and optimal resource utilization by determining the availability of ICU beds at non-tertiary care hospitals capable of providing the care needs of the patient, thus relieving pressure on the neighbouring tertiary/quaternary care centre.

Picturing the Experience of Living With Myotonic Dystrophy (DM1): A Qualitative Exploration Using Photovoice.

Background: Myotonic dystrophy presents with multisystemic complications, and there is a well-recognized myotonic dystrophy personality profile that is characterized by executive dysfunction, an avoidant personality, and impaired cognition. Understanding symptom impact on patients' lives is crucial for providing appropriate patient-centered care; however, much of the myotonic dystrophy literature reflects the biomedical model, and there is a paucity of articles exploring patient experience.

Objective: The aim of this study was to use a novel research approach to explore the experiences of patients with myotonic dystrophy.