Duarte R.F.,Catalan Institute of Nanoscience and Nanotechnology |
Lopez-Jimenez J.,Hospital Ramony Cajal |
Comely O.A.,University of Cologne |
Laverdiere M.,Hopital Maisonneuve Rosemont |
And 10 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2014
Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration [area under the concentration-time curve/24 h] of 500 ng/ml and 2,500 ng/ml in > 90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for 28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.) Copyright © 2014 American Society for Microbiology All Rights Reserved.
Kouroukis C.T.,Juravinski Hospital |
Fernandez L.A.V.,Health science Center |
Chua N.S.,Cross Cancer Institute |
Buckstein R.,Odette Cancer Center |
And 6 more authors.
Leukemia and Lymphoma | Year: 2011
Bortezomib and gemcitabine have each shown activity as single agents in mantle cell lymphoma (MCL), which is incurable. The purpose of this phase II study was to determine the efficacy and safety of the previously unstudied combination of bortezomib and gemcitabine in patients with relapsed or refractory MCL. Patients were eligible if they had relapsed MCL with 1-3 prior therapies. Patients were treated with gemcitabine 1000 mg/m 2 on days 1 and 8 and bortezomib 1.0 mg/m 2 IV on days 1, 4, 8, and 11, on a 21-day schedule. Twenty-six patients were evaluable for toxicity and 25 for response. The overall response rate was 60% and the median progression free survival was 11.4 months. The main adverse effects were hematological, with 40% and 48% of patients experiencing grade 3/4 thrombocytopenia and granulocytopenia, respectively. Bortezomib and gemcitabine is an active combination in relapsed and refractory MCL with clinically meaningful results. It offers a chemotherapy backbone to which other agents, less myelosuppressive, may be added. © 2011 Informa UK, Ltd.
PubMed | Memorial University of Newfoundland, Juravinski Hospital, BC Childrens and Womens Hospitals and Hamilton Health Sciences
Type: Review | Journal: Cleveland Clinic journal of medicine | Year: 2017
Anyone exposed to an infectious disease--whether a healthcare provider, patient, or contact of a patient--should be evaluated promptly and the source of the infection identified. A systematic response entails postexposure prophylactic therapy if available and indicated, infection control measures to prevent further transmission, counseling and educating those involved, and assessing those who may require work restriction or modification.
Covens A.,University of Toronto |
Vella E.T.,McMaster University |
Kennedy E.B.,McMaster University |
Kennedy E.B.,Juravinski Hospital |
And 3 more authors.
Gynecologic Oncology | Year: 2015
Objectives. Traditionally, treatment for early stage vulvar cancer has included removal of the primary tumor and inguinofemoral lymph node dissection (IFLD). Sentinel lymph node biopsy (SLNB) has been proposed as an alternative to IFLD for early stage vulvar cancer patients. The aim of this project was to systematically review and assess the potential for harms and benefits with the SLNB procedure in order tomake recommendations regarding the adoption of the procedure, selection of patients and appropriate technique and procedures. Methods. A working group with expertise in gynecologic oncology and health research methodology was formed to lead the systematic review and process of guideline development. MEDLINE, Embase and The Cochrane Database of Systematic Reviews were searched for relevant articles published up to September 2014. Outcomes of interest included detection, false negative, complication and recurrence rates and indicators related to pathology. Meta-analyses were conducted where appropriate. Results. The evidence-base of a previously published health technology assessment was adopted. An additional search to update the HTA's evidence base located three systematic reviews, and eleven individual studies that met the inclusion criteria. According to ameta-analysis, per groin detection rate for SLNB using radiocolloid tracer and blue dye was 87% [82-92]. The false negative rate with SLNB was 6.4% [4.4-8.8], and the recurrence rates with SLNB and IFLDwere 2.8% [1.5-4.4] and 1.4% [0.5-2.6], respectively. An internal and external reviewprocess elicited concerns about the necessity of performing this procedure in an appropriate organizational context. Conclusion. SLNB is recommended for women with unifocal tumors < 4 cm and clinically non-suspicious nodes in the groin, provided that specific infrastructure and human resource needs aremet. Some recommendations for appropriate techniques and procedures are also provided. © 2015 Elsevier Inc.
Pan Q.-J.,Chinese Academy of Sciences |
Hu S.-Y.,Chinese Academy of Sciences |
Zhang X.,Chinese Academy of Sciences |
Ci P.-W.,Chinese Academy of Sciences |
And 6 more authors.
Cancer Cytopathology | Year: 2013
BACKGROUND: Liquid-based cytology (LBC) has been widely used for cervical cancer screening. Despite numerous studies and systematic reviews, to the authors' knowledge few large studies to date have focused on biopsy-confirmed cervical lesions and controversy remains concerning its diagnostic accuracy. The objective of the current study was to assess LBC for detecting biopsy-confirmed cervical intraepithelial neoplasia (CIN) and cancer. METHODS: A pooled analysis of LBC using data from 13 population-based, cross-sectional, cervical cancer screening studies performed in China from 1999 to 2008 was performed. Participants (n526,782) received LBC and human papillomavirus testing. Women found to be positive on screening were referred for colposcopy and biopsy. The accuracy of LBC for detecting biopsy-confirmed CIN of type 2 or worse (CIN21) as well as CIN type 3 or worse (CIN31) lesions was analyzed. RESULTS: Of 25,830 women included in the analysis, CIN21 was found in 107 of 2612 with atypical squamous cells (4.1%), 142 of 923 with lowgrade squamous intraepithelial neoplasia (15.4%), 512 of 784 with high-grade squamous intraepithelial neoplasia (65.3%), 29 of 30 with squamous cell carcinoma (96.7%), 4 of 27 with atypical glandular cells (14.8%), and 85 of 21,454 with normal cytology results (0.4%). No invasive cancers were found to have atypical squamous cells, atypical glandular cells, or cytologically normal slides. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of LBC for detecting CIN21 were 81.0%, 95.4%, 38.3%, 99.3 %, and 94.9%, respectively. Although Hybrid Capture 2 was more sensitive than LBC, the specificity, positive predictive value, and overall accuracy of LBC were higher than those of Hybrid Capture2 at 85.2%, 18.6%, and 85.5%, respectively. CONCLUSIONS: The results of the current study indicate that the performance of LBC can effectively predict the risk of existing CIN21 and may be a good screening tool for cervical cancer prevention in a developing country. © 2013 American Cancer Society.
Wunderink R.G.,Northwestern University |
Mandell L.,McMaster University |
Mandell L.,Juravinski Hospital
Seminars in Respiratory and Critical Care Medicine | Year: 2012
Despite potent antibiotics, community-acquired pneumonia (CAP) remains the most common cause of death from infection and the eighth overall leading cause of death in the United States. For this reason, adjunctive therapeutic measures directed at the host response rather than the pathogen are attractive. The immunomodulatory effects of macrolide antibiotics may play a significant role in management of severe CAP. The existing literature does not demonstrate a clear benefit for corticosteroids, but larger prospective randomized trials are needed. Nonsteroidal antiinflammatory drugs may benefit oxygenation but have no documented effect on mortality. Statin use before CAP diagnosis is associated with improved outcome but requires further research to determine if initiation at the time of diagnosis will affect outcome positively. Activation of the coagulation system appears to be a major pathophysiological event in severe pneumonia, but neither drotrecogin alfa activated nor tifacogin (recombinant tissue factor pathway inhibitor) have demonstrated a survival benefit. Other therapies have theoretical benefit but are not yet in the stage of clinical trials. Copyright © 2012 by Thieme Medical Publishers, Inc.
Suri R.R.,McMaster University |
Vora P.,McMaster University |
Kirby J.M.,McMaster University |
Ruo L.,McMaster University |
Ruo L.,Juravinski Hospital
Canadian Journal of Surgery | Year: 2014
Background: The management of nonstrangulating small bowel obstruction (SBO) may require surgery, but the need for and timing of surgical intervention isn't always apparent. We sought to determine whether specific features on computed tomography (CT) can predict the necessity for operative management. Methods: Two radiologists independently reviewed CT scans from all patients admitted to hospital with SBO between 2004 and 2006. We examined the association between radiographic features and operative management by univariate analysis using the χ2 or Fisher exact test. Significant factors with high concordance between radiologists were entered into a multivariable stepwise logistic regression model. Results: There were 228 patients with SBO, 63 of whom met our inclusion criteria and had CT scans available for review. Three CT features were frequently associated with operative management and had good concordance between radiologists: complete bowel obstruction, small bowel dilation greater than 4 cm and transition point. Transition point was the only significant factor predictive of operative management for SBO on multivariable logistic regression analysis (OR 19, 95% confidence interval 1.8-201, p = 0.014). Conclusion: In patients with nonstrangulating SBO, the presence of a transition point on CT scan should alert the surgeon to the increased likelihood that operative management may be required. © 2014 Association médicale canadienne.
Ali S.A.,Juravinski Hospital |
Jaspan T.,University of Nottingham |
Marenah C.,City Hospital Campus |
Vyas H.,University of Nottingham
American Journal of Forensic Medicine and Pathology | Year: 2012
Hypernatremia has been causally linked with subdural hematoma (SDH), but more recently this has been called into question. Conversely, there is a well-established link between SDH and injury. We wish to examine the evidence base that hypernatremia in infants and young children causes SDH.We present 2 cases of children with severe hypernatremia whose intracranial contents were assessed by imaging in the first case and postmortem examination in the second. Neither demonstrated SDH. The first case was important as the hypernatremia was iatrogenic occurring in a controlled hospital environment.We also searched the literature from 1950 to 2007, collecting data on all reported cases of hypernatremia in children younger than 7 years whose intracranial contents were examined by imaging, surgery, and/or postmortem examination. Of 124 cases reported in 31 articles, 112 cases developed hypernatremia in the community, and 12 in the hospital. Subdural hematoma was demonstrated in 7 cases, all of which had developed hypernatremia in the community under circumstances that would make it difficult to exclude nonaccidental injury. None of the 12 cases that developed hypernatremia in a controlled hospital environment had SDH.The evidence base supporting the hypothesis that hypernatremia causes SDH is poor, depending on isolated reports with uncertain histories. Copyright © 2012 by Lippincott Williams & Wilkins.
PubMed | McMaster University, Juravinski Hospital and Dundas Valley Secondary School
Type: Journal Article | Journal: Systematic reviews | Year: 2016
Mesothelin is a membrane-bound glycoprotein. Although the biologic function of mesothelin is not very clear, researchers have found that it plays a role in the survival, proliferation, and migration of tumor cells. Identified as a tumor-associated biomarker, mesothelin is more often overexpressed in triple-negative breast cancer (TNBC) than in common luminal breast tumor subtype or normal tissues. The objective of this review is to determine the association between the expression of mesothelin and overall survival in patients with TNBC.We will search the following electronic databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science with no time or language restriction. Prospective or retrospective longitudinal studies that investigate mesothelin expression in TNBC or the prognosis of TNBC with mesothelin baseline measurement will be selected. Two reviewers will independently assess every abstract or full text for inclusion. Data on clinical outcomes, as well as on study design, research setting, study population, demographic characteristics of the participants, and methodological quality, will be extracted using a structured codebook developed by the authors. A pooled measure of associations will be assessed through meta-analyses if appropriate. Heterogeneity across the included studies will be evaluated using the I (2) statistics. Findings will be reported according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The quality of evidence and risk of bias of the studies will be evaluated.The aim of this systematic review is to synthesize the evidence regarding the association between the expression of mesothelin and the survival outcomes of patients with TNBC. A better understanding of the expression frequency and prognostic value of mesothelin in TNBC will be essential to identifying a novel therapeutic target.PROSPERO CRD42016036212.
PubMed | University of British Columbia, McMaster University and Juravinski Hospital
Type: Journal Article | Journal: Journal of thrombosis and haemostasis : JTH | Year: 2016
ESSENTIALS: It is not known if D-dimer testing alone can safely exclude pulmonary embolism (PE). We studied the safety of using a quantitative latex agglutination D-dimer to exclude PE in 808 patients. 52% of patients with suspected PE had a negative D-dimer test and were followed for 3 months. The negative predictive value of D-dimer testing alone was 99.8%, suggesting it may safely exclude PE.Strategies are needed to exclude pulmonary embolism (PE) efficiently without the need for imaging tests. Although validated rules for clinical probability assessment can be combined with D-dimer testing to safely exclude PE, the rules can be complicated or partially subjective, which limits their use.To determine if PE can be safely excluded in patients with a negative D-dimer without incorporating clinical probability assessment.We enrolled consecutive outpatients and inpatients with suspected PE from four tertiary care hospitals. All patients underwent D-dimer testing using the MDA D-dimer test, a quantitative latex agglutination assay. PE was excluded in patients with a D-dimer less than 750 g FEU L(-1) without further testing.with D-dimer levels of 750 g FEU L(-1) or higher underwent standardized imaging tests for PE. All patients in whom PE was excluded had anticoagulant therapy withheld and were followed for 3 months for venous thromboembolism (VTE). Suspected events during follow-up were adjudicated centrally.Eight hundred and eight patients were enrolled, of whom 99 (12%) were diagnosed with VTE at presentation. Four hundred and twenty (52%) patients had a negative D-dimer level at presentation and were not treated with anticoagulants; of these, one had VTE during follow-up. The negative predictive value of D-dimer testing for PE was 99.8% (95% confidence interval, 98.7-99.9%).A negative latex agglutination D-dimer assay is seen in about one-half of patients with suspected PE and reliably excludes PE as a stand-alone test.