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Li C.,Nanjing Medical University | Hirsh J.,MacMaster University | Xie C.,MacMaster University | Johnston M.A.,Henderson Hospital | Eikelboom J.W.,Hamilton General Hospital
Journal of Thrombosis and Haemostasis | Year: 2012

Background: Guidelines recommend stopping aspirin and clopidogrel 7 to 10days before surgery to allow time for replacement of permanently inhibited platelets by newly released uninhibited platelets.Objectives: The purpose of the present study was to determine the rate of offset of the anti-platelet effects of aspirin and clopidogrel after stopping treatment and the proportion of untreated donor platelets that are required to reverse their anti-platelet effects. Methods: Cohort 1 consisted of 15 healthy subjects who received aspirin 81mgday -1 or clopidogrel 75mgday -1 for 7days and underwent serial blood sampling until platelet function testing results normalized. Cohort 2 consisted of 36 healthy subjects who received aspirin 325mgday -1, clopidogrel 75mgday -1, aspirin 81mgday -1 plus clopidogrel 75mgday -1 or no treatment for 7days and underwent a single blood sampling. Results: In cohort 1, arachidonic acid (AA)-induced light transmission aggregation (LTA) returned to baseline levels in all subjects within 4days of stopping aspirin, coinciding with the partial recovery of plasma thromboxane B 2 concentrations. ADP-induced LTA did not return to baseline levels until 10days after stopping clopidogrel. In cohort 2, AA-induced LTA in patient treated with aspirin reached control levels after mixing with 30% untreated donor platelets whereas ADP-induced LTA in patients treated with clopidogrel reached control levels only after the addition of 90% or more donor platelets. Conclusions: Platelet aggregation recovers within 4days of stopping aspirin but clopidogrel must be stopped for 10days to achieve a normal aggregatory response. © 2012 International Society on Thrombosis and Haemostasis.


Gersh B.J.,Mayo Medical School | Sliwa K.,Hatter Institute of Cardiovascular Research | Mayosi B.M.,University of Cape Town | Yusuf S.,Hamilton General Hospital
European Heart Journal | Year: 2010

The epidemic of cardiovascular disease (CVD) is a global phenomenon, and the magnitude of its increase in incidence and prevalence in low-and middle-income countries (LIMIC) has potentially major implications for those high-income countries that characterize much of the developed world. Cardiovascular disease remains the leading cause of death in the world and approximately 80 of all cardiovascular-related deaths occur in LIMIC and at a younger age in comparison to high-income countries. The economic impact in regard to loss of productive years of life and the need to divert scarce resources to tertiary care is substantial. The 'epidemiologic transition' provides a useful framework for understanding changes in the patterns of disease as a result of societal and socioeconomic developments in different countries and regions of the world. A burning but as yet unanswered question is whether gains made over the last four decades in reducing cardiovascular mortality in high-income countries will be offset by changes in risk factor profiles, and in particular obesity and diabetes. Much of the population attributable risk of myocardial infarction is accountable on the basis of nine modifiable traditional risk factors, irrespective of geography. Developing societies are faced with a hostile cardiovascular environment, characterized by changes in diet, exercise, the effects of tobacco, socioeconomic stressors, and economic constraints at both the national and personal level in addition to exposure to potential novel risk factors and perhaps a genetic or programmed foetal vulnerability to CVD in later life. There are major challenges for primary and secondary prevention including lack of data, limited national resources, and the lack of prediction models in certain populations. There are two major approaches to prevention: public health/community-based strategies and clinic-based with a targeted approach to high-risk patients and combinations of these. There are concerns that in comparison with communicable diseases, cardiovascular and chronic diseases have a relatively low priority in the global health agenda and that this requires additional emphasis.The human race has had long experience and a fine tradition in surviving adversity, but we now face a task for which we have little experience, the task of surviving prosperity Alan Gregg 1890-1957, Rockefeller Foundation. © The Author 2010.


Sherbino J.,Hamilton General Hospital | Frank J.R.,University of Ottawa | Snell L.,McGill University
Academic Medicine | Year: 2014

Purpose: To determine a consensus definition of a clinician-educator and the related domains of competence. Method: During September 2010 to March 2011, the authors conducted a two-phase mixed-methods national study in Canada using (1) focus groups of deans of medicine and directors of medical education centers to define the attributes, domains of competence, and core competencies of clinician-educators using a grounded theory analysis, and (2) a survey of 1,130 deans, academic chairs, and residency program directors to validate the focus group results. Results The 22 focus group participants described being active in clinical practice, applying theory to practice, and engaging in education scholarship-but not holding a particular administrative position-as essential attributes of clinician-educators. Program directors accounted for 68% of the 350 survey respondents, academic chairs for 19%, and deans for 13% (response rate: 31%). Among respondents, 85% endorsed the need for physicians with advanced training in medical education to serve as educational consultants. Domains of clinician-educator competence endorsed by >85% of respondents as important or very important were assessment, communication, curriculum development, education theory, leadership, scholarship, and teaching. With regard to training requirements, 55% endorsed a master's degree in education as effective preparation, whereas 39% considered faculty development programs effective. Conclusions: On the basis of this study's findings, the authors defined a clinician-educator as a clinician active in health professional practice who applies theory to education practice, engages in education scholarship, and serves as a consultant to other health professionals on education issues.


Costandi J.,Hamilton General Hospital | Costandi J.,McMaster University | Melone M.,Hamilton General Hospital | Zhao A.,McMaster University | And 2 more authors.
Circulation Research | Year: 2011

Rationale: Obese individuals are at high risk for developing atherosclerosis primarily attributable to elevated plasma concentrations of apolipoprotein (apo)B-containing particles, including very-low-density lipoprotein (VLDL). Plasma levels of the adipose tissue adipokine resistin are increased in human obesity, and resistin expression is positively correlated with coronary atherosclerosis and VLDL levels. Objective: We sought to determine for the first time whether resistin directly stimulates human hepatocyte production of apoB-containing particles and to elucidate the mechanisms responsible. Methods and Results: Treatment of human hepatocytes with resistin at levels observed in human obesity stimulated apoB secretion up to 10-fold, because of increased microsomal triglyceride transfer protein (MTP) activity and decreased expression/phosphorylation of proteins in the insulin signaling pathways (insulin receptor substrate-2, Akt, and extracellular signal-regulated kinase). Resistin also increased hepatocyte lipid content by stimulating de novo lipogenesis via the SREBP1 and SREBP2 pathways. Furthermore, obese serum with elevated resistin levels induced greater hepatocyte stimulation of apoB secretion than lean human serum, an effect that was ameliorated by antibody immunoprecipitation removal of serum resistin. Conclusions: Resistin has a direct deleterious impact on human hepatic lipid and lipoprotein regulation. Resistin greatly increased hepatocyte VLDL apoB and lipid secretion because of MTP activation and induction of hepatocyte insulin resistance. Conversely, antibody removal of serum resistin ameliorated human serum stimulation of apoB secretion. Increased hepatic cellular lipids mediated by resistin reflects the fatty liver/steatosis observed with elevated resistin in humans. Thus, human resistin is a novel therapeutic target for mitigating common hepatic pathophysiological processes associated with human obesity, dyslipidemia and atherosclerosis. © 2011 American Heart Association. All rights reserved.


Raju N.C.,Prince Charles Hospital | Eikelboom J.W.,Hamilton General Hospital | Eikelboom J.W.,McMaster University
Current Opinion in Cardiology | Year: 2012

PURPOSE OF REVIEW: Apparently conflicting meta-analysis results have led to renewed debate about the role of aspirin for the primary prevention of cardiovascular disease. We review the results of meta-analyses comparing aspirin with placebo or no aspirin for the primary prevention of cardiovascular disease and critically evaluate whether aspirin provides a net benefit. RECENT FINDINGS: The results of four independently conducted meta-analyses between 2009 and 2012 involving between 95 000 and 102 621 individuals at low risk of cardiovascular disease are consistent with the results of the 2002 Antithrombotic Trialists' Collaboration meta-analysis, which found that aspirin reduces cardiovascular events primarily by reducing nonfatal myocardial infarction (MI). There is no convincing evidence that aspirin reduces cardiovascular mortality, but estimates from all of the meta-analyses suggest a modest reduction in all-cause mortality. Aspirin reduces ischaemic stroke but increases haemorrhagic stroke and major bleeding. SUMMARY: The meta-analysis results consistently indicate that, in individuals at low risk for cardiovascular disease, aspirin reduces the risk of MI at the cost of an increase in major bleeding and produces a modest nominally significant reduction in total mortality. These results suggest that recommendations for primary prevention with aspirin should be individualized, taking into account the balance between benefits and risks and individual values and preferences. © 2012 Wolters Kluwer Health.


Worster A.,Hamilton General Hospital
CJAM Canadian Journal of Addiction Medicine | Year: 2014

Background: Methadone can prolong the QT interval, a precursor to ventricular dysrhythmias. Measurement of the QT interval can vary with intrinsic and extrinsic factors. Our objective was to assess the agreement and repeatability between different QT interval measurements. Methods: We recorded ECGs daily for five consecutive days from adults receiving a stable, single daily dose of methadone for opioid dependence. We compared manually measured QT intervals and the calculated QTc intervals to automated measurements. Results: We obtained 123 ECGs from 26 patients receiving a mean methadone dose of 71 mg/day (range 5 to 240 mg). The manually measured QT intervals from leads II and V5 were similar and consistent (95% limits of agreement -46 to 59 ms), as were the corresponding manual QTc. However, the automated QT reported by the ECG was less consistent (95% limits of agreement -85 to 65 ms), especially at higher QT intervals and at methadone doses over 100 mg/day. Only one of the two subjects at greatest risk for torsades de pointes was identified based on the automated QT reading, while six other patients had at least one automated QTc over 480 ms that could not be confirmed on manual measurement. Conclusions: Accurate identification of QT prolongation in methadone patients is difficult because of intrinsic patient variability in QT length and accuracy of automated measurements. When contemplating ECG screening for this population, these challenges are best overcome with manual and serial QT measurements, especially at doses exceeding 100 mg/day, and interpretation using a QT nomogram to determine risk of ventricular dysrhythmia.


Background: Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) reduce cardiovascular disease (CVD) events, but a recent meta-analysis of selected studies suggested that ARBs may increase cancer risks. Objective: Candesartan, irbesartan, telmisartan, valsartan, and losartan were assessed for incident cancers in 15 large parallel long-term multicenter double-blind clinical trials of these agents involving 138 769 participants. Patients and methods: Individuals at high CVD risk were randomized to telmisartan (three trials, n = 51 878), irbesartan (three trials, n = 14 859), valsartan (four trials, n = 44 264), candesartan (four trials, n = 18 566), and losartan (one trial, n = 9193) and followed for 23-60 months. Incident cancer cases were compared in patients randomized to ARBs versus controls. In five trials (n = 42 403), the ARBs were compared to ACEi and in 11 trials (n = 63 313) to controls without ACEi. In addition, in seven trials (n = 47 020), the effect of ARBs with ACEi was compared to ACEi alone and in two trials ARBs with ACEi versus ARB alone (n = 25 712). Results: Overall, there was no excess of cancer incidence with ARB therapy compared to controls in the 15 trials [4549 (6.16%) cases of 73 808 allocated to ARB versus 3856 (6.31%) of 61 106 assigned to non-ARB controls; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.95-1.04] overall or when individual ARBs were examined. ORs comparing combination therapy with ARB along with ACEi versus ACEi was 1.01 (95% CI 0.94-1.10), combination versus ARB alone 1.02 (95% CI 0.91-1.13), ARB alone versus ACEi alone 1.06 (95% CI 0.97-1.16) and ARB versus placebo/control without ACEi 0.97 (95% CI 0.91-1.04). There was no excess of lung, prostate or breast cancer, or overall cancer deaths associated with ARB treatment. Conclusion: There was no significant increase in the overall or site-specific cancer risk from ARBs compared to controls. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Oczkowski S.,Hamilton General Hospital
Critical Care | Year: 2015

There is increasing recognition of the stress and burnout suffered by critical care workers. Physicians have a responsibility to teach learners the skills required not only to treat patients, but to cope with the demands of a stressful profession. Humor has been neglected as a strategy to help learners develop into virtuous and resilient physicians. Humor can be used to reduce stress, address fears, and to create effective health care teams. However, there are forms of humor which can be hurtful or discriminatory. In order to maximize the benefits of humor and to reduce its harms, we need to teach and model the effective and virtuous use of humor in the intensive care unit. © 2015 Oczkowski; licensee BioMed Central.


Wu V.,Hamilton General Hospital | Huff H.,Hamilton General Hospital | Bhandari M.,Hamilton General Hospital
Trauma, Violence, and Abuse | Year: 2010

Objective: To examine patterns of physical injury associated with intimate partner violence (IPV) among women presenting to emergency room departments. Data sources: Systematic searches of Medline, EMBASE, and CINAHL electronic databases from their earliest entries up to February, 2008. Reference lists from the studies included from the electronic database search were reviewed for published and unpublished studies. The authors contacted study authors regarding published and unpublished information. Review methods: After titles and abstracts were initially screened by a single reviewer, two reviewers screened the remaining full-text articles for inclusion into the review. Studies were included if they pertained in whole or in part to women who presented to an emergency department because of IPV and reported the location or type of injuries. Studies without comparison groups of non-IPV women and case series/case reports were excluded. The authors performed a meta-analysis of the available data using the random effects model. Results: The authors identified 262 potentially relevant titles and abstracts, of which 7 articles were included in the review. The association between head, neck, or facial injuries and IPV was higher among studies that excluded women with verifiable injuries such as witnessed falls or motor vehicle collisions (pooled odds ratio (OR) 24 (95% CI [15, 38]). Thoracic, abdominal, or pelvic injuries were nonspecific for IPV (pooled OR 1.07 (95% CI [0.89, 1.29]). Injuries in the upper extremities were suggestive of non-IPV etiology (pooled OR 0.51 (95% CI [0.41, 0.54]), as were lower extremity injuries (pooled OR 0.15 (95% CI [0.04, 0.56]). Conclusions: Among women presenting to emergency room departments, unwitnessed head, neck, or facial injuries are significant markers for IPV. Conversely, extremity injuries are less likely to have been the consequence of IPV. © The Author(s) 2010.


Weitz J.I.,Hamilton General Hospital
European journal of haematology. Supplementum | Year: 2010

Although parenteral anticoagulants are suitable for short-term indications, oral anticoagulants are preferable for long-term use. Vitamin K antagonists (VKAs) such as warfarin are the only oral anticoagulants currently licensed for long-term use. Although effective, VKAs have multiple limitations that explain, at least in part, their under-use for stroke prevention in patients with atrial fibrillation (AF) and in other indications. Even when they are prescribed, the level of anticoagulation with VKAs is frequently outside the therapeutic range, potentially compromising safety and efficacy. These limitations have prompted development of new oral anticoagulants that target thrombin or Factor Xa. Designed to be given in fixed doses without routine anticoagulation monitoring, these new agents have the potential to revolutionize long-term anticoagulation therapy.

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