Publications by authors named "Mark Hewitt"

Objective: The purpose of this case study was to report the management of a patient with posterior tibialis tendon injury concurrent with gender-affirming hormone therapy (GAHT).

Clinical Features: A 31-year-old transgender male presented to a chiropractic clinic with spontaneous, right medial foot pain following running that day. Medical history revealed bilateral congenital pes planus and intramuscular administration of testosterone for 8 years.

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Objectives: To compare the safety and efficacy of ketamine and etomidate as induction agents to facilitate emergent endotracheal intubation.

Data Sources: We searched MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov from inception to April 3, 2024.

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Responding to global standards and legislative updates in Canada, including Bill S-5 (2023), toxicity testing is shifting towards more ethical, methods. Traditional two-dimensional (2D) monolayer cell cultures, limited in replicating the complex environment, have prompted the development of more relevant three-dimensional (3D) spheroidal hepatocyte cultures. This study introduces the first 3D spheroid model for McA-RH7777 cells, assessing xenobiotic receptor activation, cellular signaling, and toxicity against dexamethasone and naphthenic acid (NA)-fraction components; NAFCs.

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Critical care medicine is a specialty that brings together a truly wide spectrum of patient populations, disease states, and treatment methods. This article highlights 10 important pieces of research from 2023 (and 1 from 2022) in critical care. The literature was screened for new evidence relevant to internal medicine physicians and hospitalists whose focus of practice is not critical care but who may be taking care of seriously ill patients.

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Article Synopsis
  • A systematic review and network meta-analysis was conducted to compare the effectiveness and safety of different intravenous medications used for procedural sedation and analgesia in emergency departments and ICUs.
  • The analysis included 82 randomized controlled trials involving over 8,000 patients and focused on sedation recovery time, patient satisfaction, and adverse events related to the medications.
  • Results showed that propofol had a shorter recovery time than midazolam-opioids, while ketamine-propofol combinations improved patient satisfaction; however, certain adverse events varied by medication combinations.
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Background: Extracorporeal membrane oxygenation (ECMO) is routinely used in patients with severe respiratory failure and has been increasingly needed during the COVID-19 pandemic. In patients treated with ECMO, significant intracranial hemorrhage (ICH) risk exists due to circuit characteristics, anticoagulation, and disease characteristics. ICH risk may be substantially higher in COVID-19 patients than patients treated with ECMO for other indications.

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Environmental pollutants can disrupt chemical communication between aquatic organisms by interfering with the production, transmission, and/or detection of, as well as responses to, chemical cues. Here, we test the hypothesis that early-life exposure to naphthenic acid fraction compounds (NAFCs) from oil sands tailings disrupts antipredator-associated chemical communication in larval amphibians. Wild adult wood frogs (Rana sylvatica) captured during their natural breeding period were combined (1 female:2 males) in six replicate mesocosms filled with either uncontaminated lakewater or with NAFCs isolated from an active tailings pond in Alberta, Canada, at nominal 5 mg/L concentrations.

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The extraction of surface mined bitumen from oil sands deposits in northern Alberta, Canada produces large quantities of liquid tailings waste, termed oil sands process-affected water (OSPW), which are stored in large tailings ponds. OSPW-derived chemicals from several tailings ponds migrating past containment structures and through groundwater systems pose a concern for surface water contamination. The present study investigated the toxicity of groundwater from near-field sites adjacent to a tailings pond with OPSW influence and far-field sites with only natural oil sands bitumen influence.

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The extraction of bitumen from surface mining in the Athabasca Oil Sands Region (AOSR) produces large quantities of oil sands process-affected water (OSPW) that needs to be stored in settling basins near extraction sites. Chemical constituents of OSPW are known to impair bone health in some organisms, which can lead to increased fracture risk and lower reproductive fitness. Naphthenic acid fraction components (NAFCs) are thought to be among the most toxic class of compounds in OSPW; however, the effect of NAFCs on osteoblast development is largely unknown.

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Exposure to compounds present in petroleum and wastewaters from oil and gas extraction sites in the Alberta Oil Sands Region can impair reproductive health. It has been established that acid extractable organics found in oil sands process-affected water (OSPW) such as naphthenic acids (NA-fraction components; NAFC) can adversely affect reproductive outcomes. We have shown that NAFC exposure results in a significant upregulation of GDF15 in placental trophoblasts, a cellular stress marker known to be involved in human embryonic development and necessary for the maintenance of pregnancy.

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In this chapter, we review the state of the art of predicting human hepatotoxicity using in silico techniques. There has been significant progress in this area over the past 20 years but there are still some challenges ahead. Principally, these challenges are our partial understanding of a very complex biochemical system and our ability to emulate that in a predictive capacity.

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Our study evaluated whether exposure to naphthenic acid fraction compounds (NAFCs) extracted from oil sands process-affected waters (OSPW) has adverse effects on fish embryos that persist into later life. We exposed fathead minnow (Pimephales promelas) embryos to concentrations of NAFCs found in OSPW (2.5-54 mg/L) for 7 days (1 day postfertilization to hatch), then raised surviving larvae in outdoor mesocosms of uncontaminated lake water for 1 month.

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Guidelines published in 2021 have supported natriuretic peptide (NP) testing for the prognostication in patients with acute coronary syndrome (ACS) and for the diagnosis of chronic and acute heart failure (HF). Our objective was to determine if the addition of N-terminal pro B-type NP (NT-proBNP) and glucose to high-sensitivity cardiac troponin (hs-cTn) could better identify emergency department (ED) patients with potential ACS at low- and high-risk for a serious cardiovascular outcome over the next 72 h. The presentation sample in two different ED cohorts which enrolled patients with symptoms suggestive of ACS within six hours of pain onset (Cohort-1, = 126 and Cohort-2, = 143) that had Abbott hs-cTnI, Roche hs-cTnT, NT-proBNP and glucose were evaluated for NT-proBNP alone and combined with hs-cTn and glucose for the primary outcome (composite which included death, myocardial infarction, HF, serious arrhythmia and refractory angina) via receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC) and diagnostic estimates derived.

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Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements.

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Polycyclic aromatic compounds (PACs) are ubiquitous across environmental media in Canada, including surface water, soil, sediment and snowpack. Information is presented according to pan-Canadian sources, and key geographical areas including the Great Lakes, the Alberta Oil Sands Region (AOSR) and the Canadian Arctic. Significant PAC releases result from exploitation of fossil fuels containing naturally-derived PACs, with anthropogenic sources related to production, upgrading and transport which also release alkylated PACs.

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The aim of the present study was to evaluate the effects of exposure to Chilean pulp mill effluent extracts on developing postfertilized medaka embryos before and after sex definition relative to sex steroids (testosterone and 17beta-estradiol) and a wood phytoestrogen (beta-sitosterol). Our study included 2 waterborne semichronic exposure experiments, using a 24-h post fertilization (hpf) unknown-sex FLFII (female leucophore free) group and a second 72-hpf FLFII phenotypic sex-identified group (male autofluorescence leucophore) strain of medaka embryos. Chronic exposure of both FLFII strain embryo groups showed similar delay in time to hatch and decreased hatchability.

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Industrial wastewaters and urban discharges contain complex mixtures of chemicals capable of impacting reproductive performance in freshwater fish, called endocrine-disrupting compounds (EDCs). In Chile, the issue was highlighted by our group beginning over 15 years ago, by analyzing the impacts of pulp and paper mill effluents (PPME) in the Biobio, Itata, and Cruces River basins. All of the rivers studied are important freshwater ecosystems located in the Mediterranean region of Central Chile, each with a unique fish biodiversity.

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Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics' (OCD) hs-cTnI assay to OCD's contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, = 1147 samples), from five different EDs.

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Objective: To synthesize the available evidence examining the efficacy and safety of levetiracetam compared with phenytoin or fosphenytoin in benzodiazepine-refractory pediatric status epilepticus.

Data Sources: We searched (from inception until April 27, 2020) Ovid MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials.

Study Selection: Two reviewers, independently and in duplicate, screened citations and manuscripts for eligible randomized controlled trials.

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The prediction of human toxicities from animal toxicity tests is often poor, and is now discouraged and in some cases banned, especially those involving the LD test. However, there is a vast number of historical LD data in both public and in-house repositories that are being put to little use. This study examined the correlations between human lethality (doses and concentrations) of 36 MEIC chemicals and the median values of a large number of mouse and rat LD values obtained for four different routes of administration.

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Rationale: The objective of this study was to identify unique chemical tracers of oil sands process-affected water (OSPW) to enable definitive discrimination of tailings pond seepage from natural bitumen-influenced waters from the Canadian Alberta McMurray formation.

Methods: The approach involved comparing unknowns from an unprecedented sample set of OSPW (n = 4) and OSPW-affected groundwaters (n = 15) with natural bitumen-influenced groundwaters (n = 20), using high-performance liquid chromatography/electrospray ionisation high-resolution mass spectrometry (HPLC/ESI-HRMS) operated in both polarities.

Results: Four unknown chemical entities were identified as potential tracers of OSPW seepage and subsequently subjected to structural elucidation.

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Effects-directed analysis (EDA) is used to identify the principal toxic components within a complex mixture using iterative steps of chemical fractionation guided by bioassay results. Bioassay selection can be limited in EDA because of the volume requirements for many standardized test methods, and therefore, a reduced-volume acute toxicity test that also provides whole-organism responses is beneficial. To address this need, a static, 7-d, water-only, reduced-volume method (50 mL, 10 organisms) was developed for Hyalella azteca that substantially decreases the volume requirements of standard-volume acute test exposures (200-500 mL of test solution, 15-20 organisms) while maintaining water quality and meeting control survival criteria.

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