Jack Hirsh

Human Papilloma virus (HPV) is a non-enveloped DNA virus that infects cervical epithelial cells and is a known cause of cervical cancer in women. Less known are the findings of recent epidemiological studies that associate HPV with a higher risk of atherosclerotic cardiovascular morbidity and mortality. There are at least two possible ways in which HPV infection can contribute to this process and its complications. First, HPV could directly invade atherosclerotic plaques, thereby causing plaque progression and/or instability. Although the prevailing opinion is that HPV is an infection limited to epithelial cells, some authors have reported the detection of HPV DNA and protein in atheromatous coronary arteries as well as in endothelial cells, smooth muscle cells, plasma cells and foamy macrophages located in these plaques. The transport mechanism to infect distant sites is still being elucidated but a possibility is that …

FRAIL-AF trial: more bleeding with DOACs compared with VKAs in patients with frailty? - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (43,429,590 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text FRAIL-AF trial: more bleeding with DOACs compared with VKAs in patients with frailty? Godoy A 1 , Chan NC 1 , Bhagirath V 1 , Eikelboom JW 1 , Hirsh J 2 Author information Affiliations 1. Population Health Research Institute, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, …

Background:The start of the COVID-19 pandemic caused a shift in medical education from the classroom to the virtual setting. This abrupt change led to an increase in stress among students. In response, McGill University medical students piloted an anatomy club, hosting virtual events to prepare fellow students for their examinations. Near-peer teaching is a form of education in which junior students are tutored by more experienced students.Methods:Review presentations and mock examinations were created using cadaveric images from textbooks, with a region-based approach. As anatomy examinations use in-person cadaveric models, these sessions focused on identifying pertinent anatomic landmarks for students to properly orient themselves using typical prosection views.Results:In the Fall 2021 semester, these sessions had an average attendance rate of 80%(162/202) and 81%(169/208) among the …

IntroductionCurrently approved direct oral anticoagulants (DOACs) target thrombin or coagulation factor Xa. Administered in fixed doses without routine laboratory monitoring, DOACs have simplified the approach to oral anticoagulation, when previously the choice was limited to vitamin K antagonists (VKAs).Area coveredWe discuss a) unresolved issues related to optimal use of DOACs and b) new developments including the potential for FXIa inhibitors to be effective and safer anticoagulants.Expert opinionBy simplifying oral anticoagulation, DOACs have facilitated the uptake of anticoagulation. The DOACs are approved for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism, and their indications are expanding to include the prevention of atherothrombosis. DOACs have now replaced vitamin K antagonists (VKAs) for most indications, but not all. DOACs are inferior …

Browse By Subject : Clinical Studies : Journal of Immunotherapy Articles By Subject : Journal of Immunotherapy Log in or Register Subscribe to journalSubscribe Get new issue alertsGet alerts Secondary Logo Journal Logo Advanced Search Toggle navigation Subscribe Register Login Articles & Issues For Authors Journal Info Advanced Search Skip Navigation Links Home > Browse by Subject: Clinical Studies Clinical Studies Validating a Macrophage Marker Gene Signature (MMGS) in Lung Adenocarcinoma Prognosis and Response to Immunotherapy Song, Peng; Wusiman, Dilinaer; Li, Wenbin; More Journal of Immunotherapy. July/August 2023. Abstract Favorite PDF Permissions SDC Fecal Microbiota Transplantation for Immune Checkpoint Inhibitor-Induced Colitis Is Safe and Contributes to Recovery: Two Case Reports Groenewegen, Bas; Terveer, Elisabeth M.; Joosse, Arjen; More Journal of Immunotherapy. …

Anticoagulant therapy is the cornerstone of treatment and prevention of arterial and venous thromboembolism. Taking a historical perspective, starting in the 1960s, and progressing through to 2022, we discuss key clinical trials of anticoagulants that have changed clinical practice, and examine obstacles encountered in bringing these anticoagulants to the clinic. The design of some of the early studies that shaped clinical practice was poor by current standards, but their results were influential because nothing better was available. Both heparin and vitamin K antagonists had been in clinical use for several decades before well-designed trials in the 1980s optimized their dosing and enhanced their safety and efficacy. Low-molecular-weight heparin then replaced unfractionated heparin because it had a more predictable dose–response and a longer half-life, thereby allowing it to be used conveniently in out-of-hospital …

Peripheral artery disease is 1 of 3 major clinical manifestations of atherosclerosis, the other 2 being coronary artery and cerebrovascular disease. Despite progress in surgery, antithrombotic therapy and therapies that modify conventional risk factors (lipid-, blood pressure-, and glucose-lowering interventions), patients with peripheral artery disease have an unacceptably high risk of vascular complications. Additional strategies to reduce this residual risk are needed. The accumulated evidence that inflammation plays an important role in the pathogenesis of atherosclerosis has spurred recent efforts to evaluate anti-inflammatory agents as an additional therapeutic approach for atherothrombosis prevention and treatment. In this review, we examine the evidence supporting the role of inflammation in atherosclerosis, review recent trials of anti-inflammatory approaches to reduce cardiovascular complications, and offer …

Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients. Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months. Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile. Results Of 100 enrolled …

About 25% of patients with atrial fibrillation treated with a direct oral anticoagulant receive their dose offlabel, with most receiving lower than recommended doses. 1 Such dose reductions are sometimes made in error, but at other times, physicians who are aware of dosing recommendations choose an off-label reduction based on clinical judgement after weighing their patient’s risk of bleeding and thromboembolism. Dose-ranging trials of all 4 direct oral anticoagulants have shown a relationship between dose and outcome, 2 so patients given a lower dose off-label in error are exposed to an unnecessary high thromboembolic risk. However, it might be appropriate to consider off-label dose reducing in high-risk patients if they were underrepresented in studies that established and validated the dosing recommendations. 2–4 Examples of such higher-risk patients include those with prior or recurrent major bleeding …

The "Forgotten Ones": The Natural and Unnatural History of Univentricular Physiology Without Fontan Palliation. - Abstract - Europe PMC Sign in | Create an account https://orcid.org Europe PMC Menu About Tools Developers Help Contact us Helpdesk Feedback Twitter Blog Tech blog Developer Forum Europe PMC plus Search life-sciences literature (42,398,056 articles, preprints and more) Search Advanced search Feedback This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy. Abstract Full text Citations & impact The "Forgotten Ones": The Natural and Unnatural History of Univentricular Physiology Without Fontan Palliation. Massarella D 1 , Oechslin E 1 Author information Affiliations 1. Toronto Adult Congenital Heart Disease Program, Division of Cardiology, Peter Munk …

Introduction Dose adjustment based on laboratory monitoring is not routinely recommended for patients treated with rivaroxaban but because an association has been reported between high drug level and bleeding, it would be of interest to know if measuring drug level once could identify patients at risk of bleeding who might benefit from a dose reduction. Objective This study was aimed to investigate the reliability of a single measurement of rivaroxaban level to identify clinic patients with persistently high levels, defined as levels that remained in the upper quintile of drug-level distribution. Methods In this prospective cohort study of 100 patients with atrial fibrillation or venous thromboembolism, peak and trough rivaroxaban levels were measured using the STA-Liquid Anti-Xa assay at baseline and after 2 months. Values of 395.8 and 60.2 ng/mL corresponded to the 80th percentile for peak and trough levels …

Methods| This was a crossover study in which participants self-measured peripheral oxygen saturation (SpO2) before, while, and after wearing a mask. The study protocol was approved by the Hamilton Integrated Research Ethics Board. We included individuals aged 65 years or older and excluded those who had comorbid cardiac or respiratory conditions that could lead to dyspnea or hypoxia at rest or who were unable to remove the mask without assistance. 4 Participants were prospectively recruited from a retirement condominium in Ontario between July 27 and August 10, 2020, following approval from the condominium’s board of directors. Residents were contacted by email, and those who were interested were approached to obtain (verbal or written) informed consent.To minimize variability, we provided participants with a 3-layer plane-shaped disposable nonmedical face mask with ear loops (Boomcare …

Background Both compression stockings and low molecular weight heparin (LMWH) are used for the prevention of post-operative venous thromboembolism (VTE) in cerebellopontine angle (CPA) tumour excisions. Objective In an attempt to optimise the prophylactic treatment in these patients, we compared LMWH (nadroparin) plus compression stockings to nadroparin as single therapy. Methods Patients undergoing CPA tumour excision in the period between January 2014 and November 2015 received nadroparin as a single therapy. Patients treated since November 2015 received, in addition to this therapy, peri-operative compression stockings as VTE prophylaxis due to a change in protocol. VTE was defined as symptomatic deep vein thrombosis or pulmonary embolism and was confirmed via radiological imaging or autopsy. Results A total of 146 consecutive patients were reviewed. Treatment groups …

Background Recent reports suggest an important contribution from frequent off-label use of apixaban 2.5 mg twice daily to the higher rates of thromboembolic events observed in observational studies (OSs) relative to in randomized controlled trials (RCTs), and consequently, advocate against such use in all patients. Objectives To examine factors contributing to the higher thromboembolic event rates, we estimated the prevalence of off-label use in contemporary practice, and compared patient characteristics and rates of stroke/systemic embolism, major bleeding, and mortality by apixaban dose and by study design in a systematic review and meta-analysis. Results and Discussion We identified 18 OSs and 2 RCTs that included 155,228 and 11,928 patients, respectively. Patients in OSs more often received apixaban 2.5 mg twice daily (31.3% vs. 5.1%), were older (mean age 73.8 vs. 69.8 years), and had …

Trauma patients present to the emergency department with a spectrum of fibrinolytic activity. This wide variance in fibrinolysis activity is a complex multifactorial process impacted by the degree of hemorrhagic shock and the amount of tissue injury the individual sustains. The fibrinolytic activity of the trauma patient at presentation to the hospital has prognostic and therapeutic implications. Those patients with high fibrinolytic activity (hyperfibrinolysis) are at risk of mortality from hemorrhage, whereas those patients with low fibrinolytic activity (shutdown or hypofibrinolysis) are at an increased risk of delayed mortality from traumatic brain injury or organ failure. These phenotypes of fibrinolysis acutely following injury change with resuscitation, and the majority of trauma patients will transition to a fibrinolytic resistant state several hours after injury. The mechanism for this near-global transition to this acquired fibrinolysis …

Background Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and clinical data from 144 French patients with HIT were analyzed in comparison with the literature. Methods The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay. In the literature, only cohorts of at least 20 HIT patients published from 1992 were selected for a comparative analysis. Results Two-thirds of patients were hospitalized in surgery and most were treated with unfractionated heparin (83.2% vs. 16.8% with low molecular weight heparin only). Thrombotic events in 54 patients (39.7%) were mainly venous (41/54). However, arterial thrombosis was more frequent after cardiac surgery (13.2% vs. 2.4% in other surgeries, p = 0.042) with a shorter recovery time (median …

With current clinical practice, postoperative venous thromboembolism (VTE) risk is not only well controlled, but it is steadily decreasing, especially in orthopaedic surgery, thanks to fast-track and day case procedures, new surgical techniques, and potent antithrombotic agents. Thromboprophylaxis is becoming increasingly adapted to these patients. Aspirin is also extensively prescribed in total hip replacement and total knee replacement procedures in the United States and Australia. Mechanical prophylaxis is sometimes applied alone but most often combined with anticoagulant agents. However, large evidence-based studies are still needed to confirm these optimistic tendencies. In the meantime, physicians have to keep strong control over the VTE risk to prevent the reappearance of pulmonary embolism after admission to the surgical wards.

Until recently, attempts to improve the benefit of aspirin by adding another antithrombotic agent have not resulted in a mortality reduction in patients with chronic symptomatic atherosclerosis. In this population, COMPASS is the only one among six trials to show a significant mortality reduction, thereby providing evidence of a clear net clinical benefit with the combination of low-dose rivaroxaban plus aspirin. In this systematic review, we sought to determine whether the mortality benefit of the combination arm in COMPASS is best explained by greater statistical power or by a more favorable efficacy–safety profile than the other regimens evaluated in patients with chronic symptomatic atherosclerosis.

Objective This study aimed to determine whether switching from low-molecular-weight heparin (LMWH) to unfractionated heparin (UFH) or its continuation in the peripartum affected anesthesia choice or bleeding complications. Study Design A retrospective cohort study of 189 anticoagulated pregnant women who delivered at the University of Illinois at Chicago Hospital and Health Science System from 2005 to 2016. Demography, anesthesia choice, and bleeding complications were compared between the two groups. Results There were 138 (73%) women on LMWH versus 51 (27%) who switched from LMWH to UFH during the peripartum. The demographics were similar, 123 women were on prophylactic: 81 (66%) were on LMWH and 42 (34%) switched to UFH. Of the 66 women on therapeutic anticoagulation, 57 (86%) continued on LMWH, while 9 (14%) switched to UFH. No difference in neuraxial …

This chapter presents examples of clinical problems related to diagnosis, prevention and treatment of thrombosis and then to consider the impact that the results of these studies have had on clinical practice. The methodological requirements for evaluation of a diagnostic test have been reviewed in many excellent texts. Twenty years ago patients with clinically suspected venous thrombosis were diagnosed on clinical features alone even though there was evidence in the literature that clinical diagnosis is nonspecific and that it was well known that the treatment of venous thrombosis is expensive, requires hospitalisation and is potentially dangerous. The methodological requirements for performing intervention studies of either prophylaxis or treatment are also well defined. The interpretation of prophylactic studies of venous thrombosis has not been straightforward because substitute outcome measures are usually …