Kassam Z.,Massachusetts Institute of Technology |
Lee C.H.,McMaster University |
Lee C.H.,Hamilton Regional Laboratory Medicine Program |
Hunt R.H.,McMaster University |
Hunt R.H.,Hamilton Health Sciences
Clinics in Laboratory Medicine | Year: 2014
Clostridium difficile infection (CDI) is one of the most common health care-associated infections in the United States. Currently, there are no standardized methods to prepare or deliver the fecal microbiota transplantation (FMT). Various methods are used to prepare the FMT, which is usually administered via nasogastric tube, colonoscopy, or by enema. Several clinical trials are underway to assess the true efficacy and safety of FMT for CDI. These trials include CDI studies assessing FMT via colonoscopy and frozen encapsulation, fresh versus frozen-and-thawed FMT by enema, FMT compared with a vancomycin taper, and FMT in the pediatric population. © 2014 Elsevier Inc.
Kassam Z.,McMaster University |
Lee C.H.,McMaster University |
Lee C.H.,Hamilton Regional Laboratory Medicine Program |
Yuan Y.,McMaster University |
And 3 more authors.
American Journal of Gastroenterology | Year: 2013
OBJECTIVES: The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.METHODS: An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I 2 =33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI-0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated. © 2013 by the American College of Gastroenterology.
Chagla Z.,McMaster University |
Quirt J.,McMaster University |
Woodward K.,McMaster University |
Neary J.,McMaster University |
Rutherford C.,Hamilton Regional Laboratory Medicine Program
Journal of Clinical Virology | Year: 2013
Norovirus infection causes a significant burden of morbidity and (in the developing world) mortality. In immunocompromised hosts, norovirus infection can become chronic, with devastating consequences. Unfortunately, therapeutic options for chronic disease are unproven, and treatment is largely supportive. We report a case of norovirus infection causing debilitating chronic gastroenteritis in a transplant patient that responded to a short course of enterally administered human immune globulin. © 2013 Elsevier B.V.
Hayward C.M.,McMaster University |
Moffat K.,Hamilton Regional Laboratory Medicine Program |
Moffat K.,McMaster University |
Liu Y.,McMaster University
Seminars in Thrombosis and Hemostasis | Year: 2012
Bleeding disorder panels often include the prothrombin time (PT)/international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen level, and thrombin time (TT). We explored the detection of abnormalities from bleeding disorders by these tests among subjects referred for bleeding disorder assessments, using data from a bleeding disorder study to determine sensitivities and specificities. Among subjects referred to hematologists for bleeding disorder assessment, coagulation defects were uncommon and the APTT and TT detected many nonsignificant abnormalities. While all test and panel specificities were acceptable (88 to 100%), coagulation screening tests were less sensitive to clinically significant abnormalities (1.0 to 2.1%) than von Willebrand disease (VWD) screens (6.7%), and light transmission platelet aggregometry (LTA) (26%). Accordingly, panels comprising PT/INR, APTT, fibrinogen, and TT had lower sensitivity to bleeding disorders (3.7%) than panels expanded to include VWD screens (8.5%), or VWD screens and LTA (30%). These findings have important implications for bleeding disorder diagnosis. Copyright © 2012 by Thieme Medical Publishers, Inc.
Maganti H.,McMaster University |
Yamamura D.,McMaster University |
Yamamura D.,Hamilton Regional Laboratory Medicine Program |
Xu J.,McMaster University
Medical Mycology | Year: 2011
In Canada, the incidence of candidemia, the bloodstream infection caused by Candida species, varied from 1.2-5.1 cases/100,000, representing the third most common type of bloodstream infections in intensive care unit patients. However, the relative contributions of nosocomial transmission in candidemia remain poorly understood. In this study, we investigated the prevalence of nosocomial clusters among the causative agents for candidemia in Hamilton, Ontario, Canada, during a period from January 2005 to February 2009. We genotyped 134 isolates from 125 unrelated patients with candidemia, among which were 87 C. albicans, 20 C. parapsilosis, 11 C. glabrata, 15 C. tropicalis, and one C. krusei. Our PCR fingerprinting analyses using three highly polymorphic primers identified a total of 99 genotypes, with 18 of them shared by 44 independent isolates. Nine pairs of isolates were obtained from the same patients at the same time and each pair had identical fingerprints. Interestingly, all 44 independent strains belonging to each of the shared genotypes were isolated from patients within 3-months stay in the Hamilton hospitals. Both inter- and intra-ward clusters were found, including one that contained strains from intensive care units in two hospitals. Our results indicated that 33% of the patients with candidemia were infected by nosocomial clusters and suggested that measures should be taken in hospitals to prevent nosocomial acquisition of Candida infections. © 2011 ISHAM.
Warkentin T.E.,McMaster University |
Warkentin T.E.,Hamilton Regional Laboratory Medicine Program |
Warkentin T.E.,Hamilton Health Sciences
Hematology/Oncology Clinics of North America | Year: 2010
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect characterized by platelet activation, hypercoagulability, and increased risk of thrombosis, both venous and arterial. A diagnosis of HIT usually signifies that heparin products, including unfractionated and low-molecular-weight heparin, are contraindicated. Although it is uncertain whether heparin continuation really worsens clinical outcomes, it is clear that vitamin K antagonists such as warfarin do worsen outcomes, as they promote microvascular thrombosis, with the potential for limb amputation (venous limb gangrene). Thus, alternative nonheparin anticoagulants are at the forefront of HIT therapy. This review proposes that alternative anticoagulants (danaparoid, fondaparinux) that share certain properties of heparin-namely its irreversible antithrombin-mediated inhibition of factor Xa-and that have relatively long half-lives, have several advantages in the therapy for HIT over short-acting agents that inhibit thrombin directly (recombinant hirudin, argatroban, and bivalirudin). © 2010 Elsevier Inc.
Ditomasso J.,Hamilton Regional Laboratory Medicine Program |
Liu Y.,McMaster University |
Heddle N.M.,McMaster University
Transfusion and Apheresis Science | Year: 2012
Hemovigilance systems are important programs for: monitoring trends of known risks; evaluating effectiveness of steps taken to reduce risks; providing data to support recommendations for change and guideline development; and contributing overall to the safety of transfusion. The Transfusion Transmitted Injury Surveillance System is the hemovigilance system implemented in Canada. It evolved in 1999 as a pilot program and expanded across Canada in 2005. Each province reports their adverse reactions to the transfusion of blood products and plasma proteins to the Public Health Agency of Canada (PHAC) at predetermined intervals. PHAC reconciles, summarizes the data and publishes a report approximately 2. years after the data are collected. This is considered a passive reporting system but in spite of the delays, the program provides useful information to address a variety of questions. Examples include: assessing the impact of a provincial patient transfusion history registry in Québec on reporting of hemolytic transfusion reactions; identifying trends of bacterial contamination of blood products and assessing the impact of interventions on these events; and the impact of male-only plasma on the incidence of Transfusion Related Acute Lung Injury. Although hemovigilance data has been successfully used to improve blood safety, we must continue to explore ways to utilize such data to improve and implement safe transfusion practices. © 2012 Elsevier Ltd.
Linkins L.-A.,McMaster University |
Moffat K.,McMaster University |
Moffat K.,Hamilton Regional Laboratory Medicine Program
Journal of Thrombosis and Haemostasis | Year: 2014
Rivaroxaban is a direct factor Xa inhibitor approved for prevention of stroke, prevention and treatment of venous thromboembolism and secondary prevention of acute coronary syndrome in many countries. As the use of this agent increases, so does the potential for overdose, both intentional and unintentional. Clinical data on overdoses of rivaroxaban in humans are limited. We report the case of a 42-year-old man who took an overdose of 1400 mg of rivaroxaban and describe how resolution of the anticoagulant effect was monitored using readily available coagulation assays. © 2014 International Society on Thrombosis and Haemostasis.
Pai M.,McMaster University |
Pai M.,Hamilton Regional Laboratory Medicine Program |
Chan A.,McMaster University |
Barr R.,McMaster University
British Journal of Haematology | Year: 2013
Heavy menstrual bleeding (HMB) is a common clinical problem; population-based studies estimate that approximately 10-35% of women report this symptom during their lifetime, while about 5% of women consult a physician for evaluation of HMB. Patients with HMB account for 15% of all referrals to gynaecologists and are frequently seen by haematologists in bleeding disorder clinics as well. Heavy menstrual bleeding can be caused by a wide variety of local and systemic factors, so a careful clinical and laboratory evaluation is often necessary to determine the aetiology and guide appropriate management. This review discusses the definition, causes and clinical outcomes of HMB. It outlines a diagnostic approach and focuses on medical (as opposed to surgical) treatments. Throughout, areas of controversy and opportunities for further research are highlighted. © 2013 John Wiley & Sons Ltd.
Bunimov N.,McMaster University |
Fuller N.,McMaster University |
Hayward C.M.P.,McMaster University |
Hayward C.M.P.,Hamilton Regional Laboratory Medicine Program
Seminars in Thrombosis and Hemostasis | Year: 2013
Genetic investigations have led to important advances in our knowledge of genes, proteins, and microRNA that influence circulating platelet counts, platelet size, and function. The application of genome-wide association studies (GWAS) to platelet traits has identified multiple loci with a significant association to platelet number, size, and function in aggregation and granule secretion assays. Moreover, the genes altered by disease-causing mutations have now been identified for several platelet disorders, including X-linked recessive, autosomal dominant, and autosomal recessive platelet disorders. Some mutations that cause inherited platelet disorders involve genes that GWAS have associated to platelet traits. Although disease-causing mutations in many rare and syndromic causes of platelet disorders have now been characterized, the genetic mutations that cause common inherited platelet disorders, and impair platelet aggregation and granule secretion, are largely unknown. This review summarizes current knowledge on the genetic loci that influence platelet traits, including the genes with well-characterized mutations in certain inherited platelet disorders. Copyright © 2013 by Thieme Medical Publishers, Inc.