Publications by authors named "Heather Murray"

159 Publications

Predictors of neurologists confirming or overturning emergency physicians' diagnosis of TIA or stroke.

CJEM 2021 Sep 1. Epub 2021 Sep 1.

Clinical Epidemiology Unit, F647, The Ottawa Hospital, Ottawa Hospital Research Institute, 1053 Carling Avenue, Ottawa, ON, K1Y 4E9, Canada.

Background: Transient ischemic attack (TIA) and non-disabling stroke are common emergency department (ED) presentations. Currently, there are no prospective multicenter studies determining predictors of neurologists confirming a diagnosis of cerebral ischemia in patients discharged with a diagnosis of TIA or stroke. The objectives were to (1) calculate the concordance between emergency physicians and neurologists for the outcome of diagnosing TIA or stroke, and (2) identify characteristics associated with neurologists diagnosing a stroke mimic.

Methods: This was a planned sub-study of a prospective cohort study at 14 Canadian EDs enrolling patients diagnosed with TIA or non-disabling stroke from 2006 to 2017. Logistic regression was used to identify factors associated with neurologists' diagnosis of cerebral ischemia. Our primary outcome was the composite outcome of cerebral ischemia (TIA or non-disabling stroke) based on the neurologists' assessment.

Results: The diagnosis of cerebral ischemia was confirmed by neurologists in 5794 patients (55.4%). The most common identified stroke mimics were migraine (18%), peripheral vertigo (7%), syncope (4%), and seizure (3%). Over a third of patients (38.4%) ultimately had an undetermined aetiology for their symptoms. The strongest predictors of cerebral ischemia confirmation were infarct on CT (OR 1.83, 95% CI 1.65-2.02), advanced age (OR comparing 75th-25th percentiles 1.67, 1.55-1.80), language disturbance (OR 1.92, 1.75-2.10), and smoking (OR 1.67, 1.46-1.91). The strongest predictors of stroke mimics were syncope (OR 0.59, 0.48-0.72), vertigo (OR 0.52, 0.45-0.59), bilateral symptoms (OR 0.60, 0.50-0.72), and confusion (OR 0.50, 0.44-0.57).

Conclusion: Physicians should have a high index of suspicion of cerebral ischemia in patients with advanced age, smoking history, language disturbance, or infarcts on CT. Physicians should discriminate in which patients to pursue stroke investigations on when deemed at minimal risk of cerebral ischemia, including those with isolated vertigo, syncope, or bilateral symptoms.
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http://dx.doi.org/10.1007/s43678-021-00181-0DOI Listing
September 2021

Time-resolved proteomic profiling of cigarette smoke-induced experimental chronic obstructive pulmonary disease.

Respirology 2021 Oct 5;26(10):960-973. Epub 2021 Jul 5.

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.

Background And Objective: Chronic obstructive pulmonary disease (COPD) is the third leading cause of illness and death worldwide. Current treatments aim to control symptoms with none able to reverse disease or stop its progression. We explored the major molecular changes in COPD pathogenesis.

Methods: We employed quantitative label-based proteomics to map the changes in the lung tissue proteome of cigarette smoke-induced experimental COPD that is induced over 8 weeks and progresses over 12 weeks.

Results: Quantification of 7324 proteins enabled the tracking of changes to the proteome. Alterations in protein expression profiles occurred in the induction phase, with 18 and 16 protein changes at 4- and 6-week time points, compared to age-matched controls, respectively. Strikingly, 269 proteins had altered expression after 8 weeks when the hallmark pathological features of human COPD emerge, but this dropped to 27 changes at 12 weeks with disease progression. Differentially expressed proteins were validated using other mouse and human COPD bronchial biopsy samples. Major changes in RNA biosynthesis (heterogeneous nuclear ribonucleoproteins C1/C2 [HNRNPC] and RNA-binding protein Musashi homologue 2 [MSI2]) and modulators of inflammatory responses (S100A1) were notable. Mitochondrial dysfunction and changes in oxidative stress proteins also occurred.

Conclusion: We provide a detailed proteomic profile, identifying proteins associated with the pathogenesis and disease progression of COPD establishing a platform to develop effective new treatment strategies.
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http://dx.doi.org/10.1111/resp.14111DOI Listing
October 2021

Prospective validation of Canadian TIA Score and comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischaemic attack: multicentre prospective cohort study.

BMJ 2021 02 4;372:n49. Epub 2021 Feb 4.

Department of Emergency Medicine, Queen's University, Kingston, ON, Canada.

Objective: To validate the previously derived Canadian TIA Score to stratify subsequent stroke risk in a new cohort of emergency department patients with transient ischaemic attack.

Design: Prospective cohort study.

Setting: 13 Canadian emergency departments over five years.

Participants: 7607 consecutively enrolled adult patients attending the emergency department with transient ischaemic attack or minor stroke.

Main Outcome Measures: The primary outcome was subsequent stroke or carotid endarterectomy/carotid artery stenting within seven days. The secondary outcome was subsequent stroke within seven days (with or without carotid endarterectomy/carotid artery stenting). Telephone follow-up used the validated Questionnaire for Verifying Stroke Free Status at seven and 90 days. All outcomes were adjudicated by panels of three stroke experts, blinded to the index emergency department visit.

Results: Of the 7607 patients, 108 (1.4%) had a subsequent stroke within seven days, 83 (1.1%) had carotid endarterectomy/carotid artery stenting within seven days, and nine had both. The Canadian TIA Score stratified the risk of stroke, carotid endarterectomy/carotid artery stenting, or both within seven days as low (risk ≤0.5%; interval likelihood ratio 0.20, 95% confidence interval 0.09 to 0.44), medium (risk 2.3%; interval likelihood ratio 0.94, 0.85 to 1.04), and high (risk 5.9% interval likelihood ratio 2.56, 2.02 to 3.25) more accurately (area under the curve 0.70, 95% confidence interval 0.66 to 0.73) than did the ABCD2 (0.60, 0.55 to 0.64) or ABCD2i (0.64, 0.59 to 0.68). Results were similar for subsequent stroke regardless of carotid endarterectomy/carotid artery stenting within seven days.

Conclusion: The Canadian TIA Score stratifies patients' seven day risk for stroke, with or without carotid endarterectomy/carotid artery stenting, and is now ready for clinical use. Incorporating this validated risk estimate into management plans should improve early decision making at the index emergency visit regarding benefits of hospital admission, timing of investigations, and prioritisation of specialist referral.
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http://dx.doi.org/10.1136/bmj.n49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859838PMC
February 2021

Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data.

ESC Heart Fail 2021 02 7;8(1):652-661. Epub 2020 Dec 7.

Ionis Pharmaceuticals, Inc., 2855 Gazelle Court, Carlsbad, CA, 92010, USA.

Aims: Amyloidogenic transthyretin (ATTR) amyloidosis is a fatal disease characterized by progressive cardiomyopathy and/or polyneuropathy. AKCEA-TTR-L (ION-682884) is a ligand-conjugated antisense drug designed for receptor-mediated uptake by hepatocytes, the primary source of circulating transthyretin (TTR). Enhanced delivery of the antisense pharmacophore is expected to increase drug potency and support lower, less frequent dosing in treatment.

Methods And Results: AKCEA-TTR-L demonstrated an approximate 50-fold and 30-fold increase in potency compared with the unconjugated antisense drug, inotersen, in human hepatocyte cell culture and mice expressing a mutated human genomic TTR sequence, respectively. This increase in potency was supported by a preferential distribution of AKCEA-TTR-L to liver hepatocytes in the transgenic hTTR mouse model. A randomized, placebo-controlled, phase 1 study was conducted to evaluate AKCEA-TTR-L in healthy volunteers (ClinicalTrials.gov: NCT03728634). Eligible participants were assigned to one of three multiple-dose cohorts (45, 60, and 90 mg) or a single-dose cohort (120 mg), and then randomized 10:2 (active : placebo) to receive a total of 4 SC doses (Day 1, 29, 57, and 85) in the multiple-dose cohorts or 1 SC dose in the single-dose cohort. The primary endpoint was safety and tolerability; pharmacokinetics and pharmacodynamics were secondary endpoints. All randomized participants completed treatment. No serious adverse events were reported. In the multiple-dose cohorts, AKCEA-TTR-L reduced TTR levels from baseline to 2 weeks after the last dose of 45, 60, or 90 mg by a mean (SD) of -85.7% (8.0), -90.5% (7.4), and -93.8% (3.4), compared with -5.9% (14.0) for pooled placebo (P < 0.001). A maximum mean (SD) reduction in TTR levels of -86.3% (6.5) from baseline was achieved after a single dose of 120 mg AKCEA-TTR-L .

Conclusions: These findings suggest an improved safety and tolerability profile with the increase in potency achieved by productive receptor-mediated uptake of AKCEA-TTR-L by hepatocytes and supports further development of AKCEA-TTR-L for the treatment of ATTR polyneuropathy and cardiomyopathy.
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http://dx.doi.org/10.1002/ehf2.13154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835591PMC
February 2021

Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia.

Leukemia 2021 06 16;35(6):1782-1787. Epub 2020 Oct 16.

Cancer Research Program, Hunter Medical Research Institute, School of Biomedical Sciences and Pharmacy Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia.

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http://dx.doi.org/10.1038/s41375-020-01050-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179851PMC
June 2021

Healing Rates of Venous Leg Ulcers Managed With Compression Therapy: A Secondary Analysis of Data.

J Wound Ostomy Continence Nurs 2020 Sep/Oct;47(5):477-483

Erin M. Rajhathy, RN, BScN, MClSc, NSWOC, WOCC(C), South East Local Health Integration Network, Kingston, Ontario, Canada. Heather D. Murray, RN, BScN, MClSc, NSWOC, London Health Science Center, London, Ontario, Canada. Veronica A. Roberge, RN, BScN, MClSc, NSWOC, Castlegar, British Columbia, Canada. Kevin Y. Woo, PhD, RN, NSWOC, WOCC(C), FAPWCA, Faculty of Nursing, Queens University, Kingston, Ontario, Canada.

Purpose: The purpose of this study was to explore average time to heal for patients with venous leg ulcers (VLUs) receiving standard of care that included compression and advanced wound dressings.

Design: Secondary analysis of an existing electronic database.

Subject And Settings: A convenience sample consisting of 1323 patients with VLUs from various community care sectors (homecare and clinics) across Canada.

Methods: The Wound Studies database used in the analysis consisted of data from 6 studies conducted prospectively between 1999 and 2009 in which the treatment and delivery of care for all lower leg ulcers (venous, arterial, and mixed) in Canada was examined. From these studies, only patients with VLUs, with an ankle-brachial pressure index of greater than 0.8, and surface area measurements of the ulcers at baseline, 3 months, and 6 months were included. Descriptive statistics were used to determine the proportion of patients who achieved closure at 3 and 6 months and explore the weekly and monthly healing rates for those who did and did not achieve closure. Logistic regression analysis was performed to identify predictive factors for healing.

Results: A total of 777 patients (mean age 69 years) met inclusion criteria. The proportion of patients who achieved closure at 3 and 6 months was 42.2% and 48.6%, respectively. Of the participants who achieved wound closure, monthly mean healing rate, measured by percentage of reduction in surface area, was 33.4% (0.56 cm, SD 1.4 [median 0.15 cm]) through month 3, and 31.0% (0.70 cm, SD 1.6 [median 0.08 cm]) through month 6. The overall monthly surface area reduction was 30%.

Conclusion: Study findings suggest a monthly surface area reduction of 30% provides a baseline healing rate for VLUs managed with compression therapy and advanced dressings. Findings also suggest standard of care is not sufficient for healing in over 50% of the population, as the proportion of those who achieved closure at 3 and 6 months was 42.2% and 48.6%, respectively.
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http://dx.doi.org/10.1097/WON.0000000000000693DOI Listing
June 2021

Accelerated diagnostic algorithms with hs-cTn have ≥ 92% sensitivity but lower specificity for diagnosing AMI.

Ann Intern Med 2020 06;172(12):JC71

Queen's University, Kingston, Ontario, Canada (H.M., E.S.).

Source Citation: Lee CC, Huang SS, Yeo YH, et al. Am J Emerg Med. 2019. [Epub ahead of print]. 31932131.
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http://dx.doi.org/10.7326/ACPJ202006160-071DOI Listing
June 2020

Just the Facts: Methicillin-resistant and soft tissue abscess in the emergency department.

CJEM 2020 03;22(2):149-151

Kingston Health Sciences Centre, Kingston, ON.

Soft tissue abscess used to be an easy emergency department (ED) presentation: perform an incision and drainage (I + D) and discharge your patient. Times have changed. Methicillin-resistant Staphylococcus aureus (MRSA) is now a major cause of soft tissue abscess in ED patients. MRSA is, by definition, resistant to cloxacillin and cephalosporins. Almost all Canadian strains are susceptible to vancomycin and linezolid. MRSA strains are variably susceptible to trimethoprim-sulfamethoxazole (TMP-SMX), tetra/doxycycline, and clindamycin, with pooled Canadian clindamycin resistance just over 40%.
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http://dx.doi.org/10.1017/cem.2019.452DOI Listing
March 2020

Teaching Evidence-Based Medicine to Medical Students Using Wikipedia as a Platform.

Acad Med 2020 03;95(3):382-386

H. Murray is associate professor, Department of Emergency Medicine and Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada; ORCID: https://orcid.org/0000-0002-8448-2566. M. Walker is research scientist, Department of Emergency Medicine, Queen's University, Kingston, Ontario, Canada; ORCID: https://orcid.org/0000-0002-9312-0874. J. Dawson is research associate at the CHEO Research Institute, Ottawa, Ontario and the Wikipedian in Residence for Cochrane; ORCID: http://orcid.org/0000-0003-1141-9619. N. Simper is researcher, Centre for Teaching and Learning, Queen's University, Kingston, Ontario, Canada; ORCID: http://orcid.org/0000-0002-1309-1074. L.A. Maggio is associate professor, Department of Medicine, and associate director, Scholarly Communication, Graduate Programs in Health Professions Education, Uniformed Services University of the Health Sciences, Bethesda, Maryland; ORCID: http://orcid.org/0000-0002-2997-6133.

Problem: While ideal curricular structures for effective teaching of evidence-based medicine (EBM) have not been definitively determined, optimal strategies ensure that EBM teaching is interactive and clinically based, aligns with major trends in education and health care, and uses longitudinally integrated, whole-task activities.

Approach: The authors developed a longitudinal, semester-long project, embedded in a first-year medicine course, through which they taught EBM using Wikipedia as a platform. Students worked individually and in small groups to choose a medicine-related Wikipedia article, identify information gaps, search for high-quality resources, appraise the sources, and incorporate the new information into the article (i.e., by editing Wikipedia). Students also applied their new appraisal skills to critique a second article. The authors used an online tool to track and record student editing, and they obtained qualitative data on student perceptions of the project via survey. Duplicate marking of a sample of assignments was performed using the Valid Assessment of Learning in Undergraduate Education critical thinking rubric developed by Finley and Rhodes.

Outcomes: In fall 2017, 101 students made over 1,000 unique edits to 16 online Wikipedia articles, adding over 10,000 words. Through thematic analysis of qualitative data, the authors highlighted several aspects of the project that students appreciated, as well as barriers related to completing their projects. Correlation of the 17 consenting students' final assignments with the critical thinking rubric supports the assignment structure as a tool for assessing critical thinking.

Next Steps: This authentic task adheres to the principles of high-quality EBM instruction and could be implemented by a variety of health care educational programs. Modifications to the delivery model are underway to address challenges identified.
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http://dx.doi.org/10.1097/ACM.0000000000003085DOI Listing
March 2020

The Effective Use of Videos in Medical Education.

Acad Med 2020 06;95(6):970

instructor of pediatrics, Harvard Medical School associate professor of biomedical ethics, psychiatry, and public health sciences, University of Virginia professor of medicine, humanities, and public health sciences, Penn State College of Medicine Associate professor of emergency medicine and public health, Queen's University assistant professor of medicine, Johns Hopkins Bayview Medical Center professor of psychiatry and behavioral sciences, Johns Hopkins Medicine.

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http://dx.doi.org/10.1097/ACM.0000000000003056DOI Listing
June 2020

Can we safely use a wait and see approach for patients with recent onset atrial fibrillation?

CJEM 2019 11;21(6):715-716

Department of Emergency Medicine, Queen's University, Kingston, ON.

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http://dx.doi.org/10.1017/cem.2019.403DOI Listing
November 2019

Psychiatric Advance Directives: Origins, Benefits, Challenges, and Future Directions.

J Psychiatr Pract 2019 Jul;25(4):303-307

Psychiatric advance directives (PADs) are legal documents that allow individuals with psychiatric illness to designate decisions, while competent, about their future psychiatric care were they to lose competency due to psychiatric illness in the future. Among other items, these documents often include preferences regarding a surrogate decision-maker, types of medications, doses and routes of medications, seclusion and restraints, electroconvulsive therapy, and instructions for care of their property while incapacitated. While the concept and legal recognition of PADs has existed in the United States for several decades, use of PADs by patients and familiarity with PADs among mental health providers remain limited. This column reviews the origin of PADs, discusses several commonly considered arguments for and against the use of these documents, and concludes with a discussion of how PADs are currently used in the United States and their potential future role in mental health treatment.
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http://dx.doi.org/10.1097/PRA.0000000000000401DOI Listing
July 2019

Cangrelor versus Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A Randomized Controlled Trial.

Thromb Haemost 2019 Jul 26;119(7):1171-1181. Epub 2019 May 26.

Heart and Lung Centre, New Cross Hospital, Wolverhampton, United Kingdom.

Background:  Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery.

Objectives:  This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI).

Materials And Methods:  In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341).

Results:  P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups.

Conclusion:  Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.
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http://dx.doi.org/10.1055/s-0039-1688789DOI Listing
July 2019

Measuring the effects of listening for leisure on outcome after stroke (MELLO): A pilot randomized controlled trial of mindful music listening.

Int J Stroke 2020 02 2;15(2):149-158. Epub 2019 Apr 2.

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

Background: Cognitive deficits and low mood are common post-stroke. Music listening is suggested to have beneficial effects on cognition, while mindfulness may improve mood. Combining these approaches may enhance cognitive recovery and improve mood early post-stroke.

Aims: To assess the feasibility and acceptability of a novel mindful music listening intervention.

Methods: A parallel group randomized controlled feasibility trial with ischemic stroke patients, comparing three groups; mindful music listening, music listening and audiobook listening (control group), eight weeks intervention. Feasibility was measured using adherence to protocol and questionnaires. Cognition (including measures of verbal memory and attention) and mood (Hospital Anxiety and Depression Scale) were assessed at baseline, end of intervention and at six-months post-stroke.

Results: Seventy-two participants were randomized to mindful music listening ( = 23), music listening ( = 24), or audiobook listening ( = 25). Feasibility and acceptability measures were encouraging: 94% fully consistent with protocol; 68.1% completing ≥6/8 treatment visits; 80-107% listening adherence; 83% retention to six-month endpoint. Treatment effect sizes for cognition at six month follow-up ranged from d = 0.00 ([-0.64,0.64], music alone), d = 0.31, ([0.36,0.97], mindful music) for list learning; to d = 0.58 ([0.06,1.11], music alone), d = 0.51 ([-0.07,1.09], mindful music) for immediate story recall; and d = 0.67 ([0.12,1.22], music alone), d = 0.77 ([0.16,1.38]mindful music) for attentional switching compared to audiobooks. No signal of change was seen for mood. A definitive study would require 306 participants to detect a clinically substantial difference in improvement (z-score difference = 0.66,  = 0.017, 80% power) in verbal memory (delayed story recall).

Conclusions: Mindful music listening is feasible and acceptable post-stroke. Music listening interventions appear to be a promising approach to improving recovery from stroke.
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http://dx.doi.org/10.1177/1747493019841250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045280PMC
February 2020

Web-based physiotherapy for people affected by multiple sclerosis: a single blind, randomized controlled feasibility study.

Clin Rehabil 2019 Mar 4;33(3):473-484. Epub 2018 Dec 4.

1 School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.

Objective:: To examine the feasibility of a trial to evaluate web-based physiotherapy compared to a standard home exercise programme in people with multiple sclerosis.

Design:: Multi-centre, randomized controlled, feasibility study.

Setting:: Three multiple sclerosis out-patient centres.

Participants:: A total of 90 people with multiple sclerosis (Expanded Disability Status Scale 4-6.5).

Interventions:: Participants were randomized to a six-month individualized, home exercise programme delivered via web-based physiotherapy ( n = 45; intervention) or a sheet of exercises ( n = 45; active comparator).

Outcome Measures:: Outcome measures (0, three, six and nine months) included adherence, two-minute walk test, 25 foot walk, Berg Balance Scale, physical activity and healthcare resource use. Interviews were undertaken with 24 participants and 3 physiotherapists.

Results:: Almost 25% of people approached agreed to take part. No intervention-related adverse events were recorded. Adherence was 40%-63% and 53%-71% in the intervention and comparator groups. There was no difference in the two-minute walk test between groups at baseline (Intervention-80.4(33.91)m, Comparator-70.6(31.20)m) and no change over time (at six-month Intervention-81.6(32.75)m, Comparator-74.8(36.16)m. There were no significant changes over time in other outcome measures except the EuroQol-5 Dimension at six months which decreased in the active comparator group. For a difference of 8(17.4)m in two-minute walk test between groups, 76 participants/group would be required (80% power, P > 0.05) for a future randomized controlled trial.

Conclusion:: No changes were found in the majority of outcome measures over time. This study was acceptable and feasible by participants and physiotherapists. An adequately powered study needs 160 participants.
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http://dx.doi.org/10.1177/0269215518817080DOI Listing
March 2019

CJEM Debate Series#PhysicianProductivity - Measuring and understanding causes of variability in emergency physician performance are essential to improve emergency department efficiency.

CJEM 2018 11;20(6):821-825

§Department of Emergency Medicine,Dalhousie University (Halifax, NS),Saint John Regional Hospital,Saint John,NB.

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http://dx.doi.org/10.1017/cem.2018.459DOI Listing
November 2018

Intravenous Iron in Patients Undergoing Maintenance Hemodialysis.

N Engl J Med 2019 01 26;380(5):447-458. Epub 2018 Oct 26.

From the Department of Renal Medicine, King's College Hospital (I.C.M., C.W.), and University College London (D.C.W.), London, Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, Hull (S.B.), Lister Hospital, Stevenage (K.F.), and University of Hertfordshire, Hertfordshire (K.F.), the Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford (P.A.K.), the British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and the Robertson Centre for Biostatistics (H.M., I.F.), University of Glasgow, Glasgow, Freeman Hospital, Newcastle upon Tyne (C.R.V.T.), and the Oxford Kidney Unit, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford (C.G.W.) - all in the United Kingdom; and the Division of Cardiology and Metabolism, Department of Cardiology, Berlin-Brandenburg Center for Regenerative Therapies, German Center for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin Berlin, Berlin (S.D.A.).

Background: Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited.

Methods: In a multicenter, open-label trial with blinded end-point evaluation, we randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 μg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 μg per liter or a transferrin saturation of <20% being a trigger for iron administration). The primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis. These end points were also analyzed as recurrent events. Other secondary end points included death, infection rate, and dose of an erythropoiesis-stimulating agent. Noninferiority of the high-dose group to the low-dose group would be established if the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25.

Results: A total of 2141 patients underwent randomization (1093 patients to the high-dose group and 1048 to the low-dose group). The median follow-up was 2.1 years. Patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336), as compared with 145 mg (interquartile range, 100 to 190) in the low-dose group. The median monthly dose of an erythropoiesis-stimulating agent was 29,757 IU in the high-dose group and 38,805 IU in the low-dose group (median difference, -7539 IU; 95% confidence interval [CI], -9485 to -5582). A total of 320 patients (29.3%) in the high-dose group had a primary end-point event, as compared with 338 (32.3%) in the low-dose group (hazard ratio, 0.85; 95% CI, 0.73 to 1.00; P<0.001 for noninferiority; P=0.04 for superiority). In an analysis that used a recurrent-events approach, there were 429 events in the high-dose group and 507 in the low-dose group (rate ratio, 0.77; 95% CI, 0.66 to 0.92). The infection rate was the same in the two groups.

Conclusions: Among patients undergoing hemodialysis, a high-dose intravenous iron regimen administered proactively was superior to a low-dose regimen administered reactively and resulted in lower doses of erythropoiesis-stimulating agent being administered. (Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25 .).
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http://dx.doi.org/10.1056/NEJMoa1810742DOI Listing
January 2019

Targeting Oncogenic Signaling in Mutant FLT3 Acute Myeloid Leukemia: The Path to Least Resistance.

Int J Mol Sci 2018 Oct 16;19(10). Epub 2018 Oct 16.

School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia.

The identification of recurrent driver mutations in genes encoding tyrosine kinases has resulted in the development of molecularly-targeted treatment strategies designed to improve outcomes for patients diagnosed with acute myeloid leukemia (AML). The receptor tyrosine kinase FLT3 is the most commonly mutated gene in AML, with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) or missense mutations in the tyrosine kinase domain (FLT3-TKD) present in 30⁻35% of AML patients at diagnosis. An established driver mutation and marker of poor prognosis, the FLT3 tyrosine kinase has emerged as an attractive therapeutic target, and thus, encouraged the development of FLT3 tyrosine kinase inhibitors (TKIs). However, the therapeutic benefit of FLT3 inhibition, particularly as a monotherapy, frequently results in the development of treatment resistance and disease relapse. Commonly, FLT3 inhibitor resistance occurs by the emergence of secondary lesions in the gene, particularly in the second tyrosine kinase domain (TKD) at residue Asp835 (D835) to form a 'dual mutation' (ITD-D835). Individual FLT3-ITD and FLT3-TKD mutations influence independent signaling cascades; however, little is known about which divergent signaling pathways are controlled by each of the FLT3 specific mutations, particularly in the context of patients harboring dual ITD-D835 mutations. This review provides a comprehensive analysis of the known discrete and cooperative signaling pathways deregulated by each of the FLT3 specific mutations, as well as the therapeutic approaches that hold the most promise of more durable and personalized therapeutic approaches to improve treatments of FLT3 mutant AML.
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http://dx.doi.org/10.3390/ijms19103198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214138PMC
October 2018

Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data.

Am J Nephrol 2018 10;48(4):260-268. Epub 2018 Oct 10.

Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom.

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown.

Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible. Enrolled patients were randomized to a proactive, high-dose IV iron arm (iron sucrose 400 mg/month unless ferritin > 700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 µg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years.

Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry.

Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice.

Trial Registration: EudraCT number: 2013-002267-25.
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http://dx.doi.org/10.1159/000493551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262676PMC
January 2020

The effect of an infographic promotion on research dissemination and readership: A randomized controlled trial.

CJEM 2018 11 5;20(6):826-833. Epub 2018 Oct 5.

*Department of Emergency Medicine,University of Saskatchewan,Saskatoon,SK.

Objective: Journals use social media to increase the awareness of their publications. Infographics show research findings in a concise and visually appealing manner, well suited for dissemination on social media platforms. We hypothesized that infographic abstracts promoted on social media would increase the dissemination and online readership of the parent research articles.

Methods: Twenty-four articles were chosen from the six issues of CJEM published between July 2016 and June 2017 and randomized to infographic or control groups. All articles were disseminated through the journal’s social media accounts (Twitter and Facebook). Control articles were promoted using a screen capture image of each article’s abstract on the journal’s social media accounts. Infographic articles were promoted similarly using a visual infographic. Infographics were also published and promoted on the CanadiEM.org’s website and social media channels. Abstract views, full-text views, and the change in Altmetric score were compared between groups using unpaired two-tailed t-tests.

Results: There were no significant differences in the groups at baseline. Abstract views (mean, 95% CI) were higher in the infographics (379, 287-471) than the control group (176, 136-215, p<0.001). Mean change in Altmetric scores was higher in the infographics (26, 18-34) than in the control group (3, 2-4, p<0.0001). There was no difference in full-text views between the infographics (50, 0-101) and control groups (25, 18-32).

Conclusion: The promotion of CJEM articles using infographics on social media and the CanadiEM.org website increased Altmetric scores and abstract views. Infographics may have a role in increasing awareness of medical literature.
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http://dx.doi.org/10.1017/cem.2018.436DOI Listing
November 2018

More than 2 billion pairs of eyeballs: Why aren't you sharing medical knowledge on Wikipedia?

Authors:
Heather Murray

BMJ Evid Based Med 2019 Jun 14;24(3):90-91. Epub 2018 Aug 14.

Departments of Emergency Medicine and Public Health Sciences, Queen's University, Kingston, Ontario, Canada.

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http://dx.doi.org/10.1136/bmjebm-2018-111040DOI Listing
June 2019

The lifestyle behaviours of young adults with intellectual disabilities as they transition from school to adulthood: A pilot and feasibility study.

J Appl Res Intellect Disabil 2018 Nov 28;31(6):1154-1163. Epub 2018 Jun 28.

Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

Background: In the general population, the transition from adolescence to adulthood has been identified as a "high-risk" period for weight gain. There has been no research examining health behaviours over this transition in adults with intellectual disabilities.

Methods/design: The feasibility of recruitment, retention and relevant health behaviours were measured in 31 adolescents with mild-moderate intellectual disabilities. Anthropometric, objective physical activity, dietary and self-determination measures were collected over a 12-month transitional period from school to adulthood.

Results: Key results suggest weight and BMI increased significantly from month 6 to month 12 (p = 0.044 and p = 0.043). Waist circumference increased significantly from baseline to month 12 (p = 0.049), and from month 6 to month 12 (p = 0.03).

Discussion: Recruiting and retaining young adults with intellectual disabilities over a 12-month health behaviour study is feasible. The data indicate the transition from school to adulthood may be the start of a high-risk period for weight gain.
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http://dx.doi.org/10.1111/jar.12489DOI Listing
November 2018

Health Outcomes of Medically and Economically Vulnerable Adults: A Comparison of Former Foster Youth and Nonfoster Youth.

Fam Community Health 2018 Jul/Sep;41(3):159-167

University of Tennessee at Chattanooga.

Medically and economically vulnerable adults experience various challenges that can impact their health. Within this vulnerable population, there may be individuals who are even more vulnerable, those who have a history of involvement with the foster care system. The purpose of this study was to evaluate the difference of reported health-related problems between adults with previous foster care experience and other vulnerable adults. Physical, mental, and relational health was evaluated in this study. Practice and policy implications for mental health and medical professionals are discussed.
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http://dx.doi.org/10.1097/FCH.0000000000000190DOI Listing
December 2018

Participants' experiences of music, mindful music, and audiobook listening interventions for people recovering from stroke.

Ann N Y Acad Sci 2018 May 4. Epub 2018 May 4.

Mental Health and Wellbeing, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom.

Existing research evidence suggests that both music listening and mindfulness interventions may have beneficial effects on mood and cognition poststroke. This mixed-methods study, nested within a pilot randomized controlled trial investigating the feasibility and acceptability of combining music listening and brief mindfulness training poststroke, explored study participants' experiences of engaging in the interventions. Fifty-six stroke survivors who were randomized to receive an 8-week intervention of mindful music listening (n = 15), music listening (n = 21), or audiobook listening (n = 20, control) using self-selected material participated in a postintervention individual semistructured interview with a researcher not involved in their intervention delivery. Interview questions focused on affective, cognitive, and physical experiences. Data were coded and analyzed using thematic analysis. Across groups, listening was associated with positive distraction from thoughts and worries. Mindful music listening was most strongly associated with relaxation and concentration, improved attentional control, and emotion regulation, as well as enjoyment. Music listening was most strongly associated with increased activity, memory reminiscence, and improved mood. In addition, participants provided valuable feedback on intervention feasibility and acceptability. The findings suggest that the interventions were feasible and enjoyable for people recovering from stroke.
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http://dx.doi.org/10.1111/nyas.13618DOI Listing
May 2018

Finding FOAM and not Froth.

Authors:
Heather Murray

CJEM 2018 03;20(2):162-163

*Department of Emergency Medicine,Queen's University,Kingston,ON.

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http://dx.doi.org/10.1017/cem.2018.21DOI Listing
March 2018
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