Adaptation of the Systematic Review Framework to the Assessment of Toxicological Test Methods: Challenges and Lessons Learned With the Zebrafish Embryotoxicity Test.

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods.

Albuminuria, Reduced Kidney Function, and the Risk of ST - and non-ST-segment-elevation myocardial infarction.

Background Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST-segment-elevation myocardial infarction ( STEMI ) and non-ST-segment-elevation myocardial infarction ( NSTEMI ) differ in the chronic kidney disease population is unknown. Methods and Results Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR ) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used.

Serial imaging after pulmonary embolism and correlation with functional limitation at 12 months: Results of the ELOPE Study.

Introduction: Risk factors for exercise limitation after acute pulmonary embolism (PE) are unknown. As a planned sub-study of the prospective, multicenter ELOPE (Evaluation of Long-term Outcomes after PE) Study, we aimed to describe the results of serial imaging by computed tomography pulmonary angiography (CTPA) and perfusion scan during 1 year after a first episode of acute pulmonary embolism, and to assess the association between imaging parameters and exercise limitation at 1 year.

Methods: In a prospective cohort study, 100 patients were recruited between June 2010 and February 2013 at five Canadian university-affiliated hospitals.

Predictors of response to opicinumab in acute optic neuritis.

Objective: The objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab.

Methods: RENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint.

Pilot trials in thrombosis: Purpose and pitfalls.

Randomized controlled trials provide important evidence to guide clinical practice. These full-scale trials are expensive, time consuming and many are never successfully completed. Well conducted pilot studies help with full-scale trial design, assessment and optimization of feasibility, and can avoid the waste of resources associated with starting a full-scale trial that will not succeed.

Pharmacological reversal of the direct oral anticoagulants-A comprehensive review of the literature.

The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC-associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians' ability to evaluate and manage DOAC-associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures.

Occult cancer detection in venous thromboembolism: the past, the present, and the future.

Unprovoked venous thromboembolism (VTE) can be the first manifestation of an undiagnosed cancer. Recently published studies have suggested that approximately 4-5% of patients with new unprovoked VTE will be diagnosed with cancer within 12 months of follow-up. Therefore, it is important for clinicians to keep a low threshold of suspicion for occult cancer in this patient population.

The apolipoprotein C-III (Gln38Lys) variant associated with human hypertriglyceridemia is a gain-of-function mutation.

Recent cell culture and animal studies have suggested that expression of human apo C-III in the liver has a profound impact on the triacylglycerol (TAG)-rich VLDL production under lipid-rich conditions. The apoC-III Gln38Lys variant was identified in subjects of Mexican origin with moderate hypertriglyceridemia. We postulated that Gln38Lys (C3), being a gain-of-function mutation, promotes hepatic VLDL assembly/secretion.

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation.

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by motor neuron degeneration, although defects in multiple cell types and tissues have also been implicated. Three independent laboratories recently identified immune organ defects in SMA. We therefore propose a novel pathogenic mechanism contributory to SMA, resulting in higher susceptibility to infection and exacerbated disease progression caused by neuroinflammation.

The association between platelet transfusions and bleeding in critically ill patients with thrombocytopenia.

Background: Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown.

Patients/methods: Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU).

Periprosthetic Infection following Primary Hip and Knee Arthroplasty: The Impact of Limiting the Postoperative Surveillance Period.

BACKGROUND Hip and knee arthroplasty infections are associated with considerable healthcare costs. The merits of reducing the postoperative surveillance period from 1 year to 90 days have been debated. OBJECTIVES To report the first pan-Canadian hip and knee periprosthetic joint infection (PJI) rates and to describe the implications of a shorter (90-day) postoperative surveillance period.

Incident reporting systems: a comparative study of two hospital divisions.

Background: Previous studies of incident reporting in health care organizations have largely focused on single cases, and have usually attended to earlier stages of reporting. This is a comparative case study of two hospital divisions' use of an incident reporting system, and considers the different stages in the process and the factors that help shape the process.

Method: The data was comprised of 85 semi-structured interviews of health care practitioners in general internal medicine, obstetrics and neonatology; thematic analysis of the transcribed interviews was undertaken.

Clinical utilization of genomics data produced by the international Pseudomonas aeruginosa consortium.

The International Pseudomonas aeruginosa Consortium is sequencing over 1000 genomes and building an analysis pipeline for the study of Pseudomonas genome evolution, antibiotic resistance and virulence genes. Metadata, including genomic and phenotypic data for each isolate of the collection, are available through the International Pseudomonas Consortium Database (http://ipcd.ibis.

Cancer-Related Pain Management and the Optimal Use of Opioids.

Pain relief is vital to the treatment of cancer. Despite the widespread use and recognition of clinical recommendations for the management of cancer-related pain, avoidable suffering is still prevalent in patients with malignant disease. A gap exists between what is known about pain medical management and actual practices of patients, caregivers, healthcare professionals and institutions.

The trajectory of life. Decreasing physiological network complexity through changing fractal patterns.

In this position paper, we submit a synthesis of theoretical models based on physiology, non-equilibrium thermodynamics, and non-linear time-series analysis. Based on an understanding of the human organism as a system of interconnected complex adaptive systems, we seek to examine the relationship between health, complexity, variability, and entropy production, as it might be useful to help understand aging, and improve care for patients. We observe the trajectory of life is characterized by the growth, plateauing and subsequent loss of adaptive function of organ systems, associated with loss of functioning and coordination of systems.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease.

Background: Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings.