Publications by authors named "Erin Jamula"

15 Publications

  • Page 1 of 1

Cost-effectiveness of eltrombopag versus intravenous immunoglobulin for the perioperative management of immune thrombocytopenia.

Blood Adv 2021 Nov 15. Epub 2021 Nov 15.

McMaster University, Hamilton, Canada.

Eltrombopag has been shown to be non-inferior to intravenous immunoglobulin (IVIG) for improving perioperative platelet counts in patients with immune thrombocytopenia (ITP) in a randomized trial; thus, cost is an important factor for treatment and policy decisions. We used patient-level data from the trial to conduct a cost-effectiveness analysis comparing perioperative eltrombopag 50mg daily starting dose, with IVIG 1 or 2g/kg (according to local practice) from a Canadian public healthcare payer's perspective over the observation period, from preoperative day 21 to postoperative day 28. Resource utilization data were obtained from the trial data (eltrombopag, n=38; IVIG, n=36) and unit costs were collected from the Ontario Schedule of Benefits, Ontario Drug Formulary, and secondary sources. All costs were adjusted to 2020 Canadian dollars. We calculated the incremental cost per patient for all patients randomized. Uncertainty was addressed using non-parametric bootstrapping. The use of perioperative eltrombopag for patients with ITP resulted in a cost-saving of $413 Canadian dollars per patient. Compared with IVIG, the probability of eltrombopag being cost-effective was 70% even with zero willingness to pay. In a sensitivity analysis based on IVIG dose, we found that with the higher dose of IVIG (2g/kg), eltrombopag saved $2,714 per patient; whereas with the lower dose of IVIG (1g/kg), eltrombopag had a higher mean cost of $562 per patient. In summary, based on data from the randomized trial that demonstrated non-inferiority, the use of eltrombopag for the management of ITP in the perioperative setting was less costly than IVIG.
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http://dx.doi.org/10.1182/bloodadvances.2021005627DOI Listing
November 2021

Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial.

Nat Med 2021 11 9;27(11):2012-2024. Epub 2021 Sep 9.

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.

The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset ( NCT04348656 ). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm-relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94-1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02-1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57-0.95 and OR = 0.66, 95% CI 0.50-0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14-2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
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http://dx.doi.org/10.1038/s41591-021-01488-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604729PMC
November 2021

Definition of a critical bleed in patients with immune thrombocytopenia: Communication from the ISTH SSC Subcommittee on Platelet Immunology.

J Thromb Haemost 2021 08;19(8):2082-2088

Department of Medicine, McMaster Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada.

Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia.

Methods: The panel met in person and virtually to achieve consensus on the criteria for critical bleeding events among patients with ITP. Existing ITP bleeding scores and published definitions of major bleeds in patients receiving anticoagulation informed the definition of a critical ITP bleed. The Platelet Immunology Scientific Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis endorsed the definition.

Results: A critical ITP bleed was defined as: (a) a bleed in a critical anatomical site including intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (2) an ongoing bleed that results in hemodynamic instability or respiratory compromise.

Conclusion: The definition of a critical ITP bleed was developed by the ITP Emergency Management Guideline Panel and endorsed by the Platelet Immunology SSC. It incorporates both anatomic and physiologic risk and pertains to patients with confirmed or suspected ITP who typically have severe thrombocytopenia (platelet count below 20 × 10 /L).
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http://dx.doi.org/10.1111/jth.15368DOI Listing
August 2021

Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial.

Trials 2021 May 4;22(1):323. Epub 2021 May 4.

McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada.

Background: Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.

Methods: CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600).

Discussion: This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification.

Trial Registration: Clinicaltrials.gov NCT04348656 . Registered on 16 April 2020.
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http://dx.doi.org/10.1186/s13063-021-05235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094980PMC
May 2021

Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial.

Lancet Haematol 2020 Sep;7(9):e640-e648

Michael G DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada; McMaster Centre for Transfusion Research, Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Background: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin.

Methods: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 10 cells per L before major surgery or less than 50 × 10 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 10 cells per L before major surgery or 45 × 10 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204.

Findings: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; p=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; p=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred.

Interpretation: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles.

Funding: GlaxoSmithKline and Novartis.
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http://dx.doi.org/10.1016/S2352-3026(20)30227-1DOI Listing
September 2020

Sex-mismatched red blood cell transfusions and mortality: A systematic review and meta-analysis.

Vox Sang 2019 Jul 23;114(5):505-516. Epub 2019 May 23.

McMaster Centre for Transfusion Research, McMaster University, Hamilton, ON, Canada.

Background And Objectives: Selection of a compatible red blood cell (RBC) unit does not include matching for donor sex. This systematic review and meta-analysis aims to summarize the evidence examining the impact of sex-mismatched RBC transfusion on recipient mortality.

Materials And Methods: Ovid MEDLINE, Ovid EMBASE, CINAHL, PubMed, Web of Science and the Cochrane Database of Systematic Reviews were searched from inception up to 23 November 2018. Randomized controlled trials and observational studies were included in the search. Eligible studies reported on the impact of sex-matched compared to sex-mismatched RBC transfusion on recipient mortality. Two investigators independently extracted data and assessed study quality. A three-level meta-analytic model was applied to emphasize the unknown dependence among the effect sizes.

Results: Five retrospective observational studies (n = 86 737) were included; no RCTs were found. Sex-mismatched RBC transfusions were associated with a higher risk of death compared with sex-matched transfusions (pooled hazard ratio [HR]: 1·13; 95% confidence interval [CI]: 1·02-1·24). In the subgroup of cardiovascular surgery (n = 57 712), there was no significant increase in mortality with sex-mismatched transfusions (pooled HR: 1·08; 95% CI: 0·95-1·22). The data were prone to confounding, selection bias and reporting bias. Certainty of the evidence was very low.

Conclusion: Sex-mismatched RBC transfusions were associated with an increased risk of death in this pooled analysis. However, the certainty of the evidence was very low from observational studies. The need to match donor and recipient sex for transfusions requires further investigation because of the potential widespread impact.
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http://dx.doi.org/10.1111/vox.12783DOI Listing
July 2019

Peri-Operative Eltrombopag or Immune Globulin for Patients with Immune Thrombocytopaenia (The Bridging ITP Trial): Methods and Rationale.

Thromb Haemost 2019 Mar 27;119(3):500-507. Epub 2019 Jan 27.

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background:  The Bridging ITP Trial is an open-label randomized trial designed to compare the oral thrombopoietin receptor agonist eltrombopag and intravenous immune globulin (IVIG) for patients with immune thrombocytopaenia (ITP) who require an increase in platelet count before elective surgery. Here, we report the study methods and rationale.

Methods:  We designed a multi-centre, non-inferiority randomized trial comparing daily oral eltrombopag starting 3 weeks pre-operatively, and IVIG administered 1 week pre-operatively for patients with ITP requiring a platelet count increase prior to surgery. Starting dose of eltrombopag is 50 mg daily with a weekly pre-operative dose titration schedule, and treatment is continued for 1 week after surgical haemostasis is achieved. IVIG is administered at a dose of 1 to 2 g/kg 1 week pre-operatively with the allowance for a second dose within 1 week after surgical haemostasis. The objective of the study is to demonstrate non-inferiority of eltrombopag for the primary endpoint of achieving the pre-operative platelet count threshold (50 × 10/L for minor surgery; or 100 × 10/L for major surgery) and sustaining platelet count levels above the threshold for 1 week after surgical haemostasis is achieved, without the use of rescue treatment. Secondary endpoints include thrombosis, bleeding and patient satisfaction.

Conclusion:  The Bridging ITP Trial will evaluate the efficacy and safety of eltrombopag as an alternative to IVIG in the peri-operative setting for patients with ITP. The protocol was designed to provide a management strategy that can be applied in clinical practice. CLINICALTRIALS.

Gov Identifier:  NCT01621204.
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http://dx.doi.org/10.1055/s-0038-1677531DOI Listing
March 2019

Systematic review of rituximab for autoimmune diseases: a potential alternative to intravenous immune globulin.

Transfusion 2018 11 23;58(11):2729-2735. Epub 2018 Sep 23.

Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.

Background: The anti-CD20 monoclonal antibody rituximab has immune-modulatory effects similar to intravenous immunoglobulin (IVIG). We performed a systematic review and meta-analysis to determine the efficacy and safety of rituximab in autoimmune diseases that are also treated with IVIG.

Study Design And Methods: The most common indications for immune modulation with IVIG, as identified from a 2012 regional audit in Canada, were chronic inflammatory demyelinating polyneuropathy (CIDP), immune thrombocytopenia (ITP), myasthenia gravis, multifocal motor neuropathy, Guillain-Barré syndrome, systemic lupus erythematosus (SLE), Sjogren's syndrome, and pemphigus vulgaris. We searched MEDLINE, EMBASE, and the Cochrane Library until July 2016 for studies evaluating rituximab in each of these conditions. The primary outcome in our meta-analysis was clinical response at 6 months as defined by disease-specific criteria in randomized trials. We also calculated pooled proportions of responders within disease types from observational studies.

Results: Ninety-five rituximab studies were identified: 86 were observational studies in patients with ITP (n = 1746), SLE (n = 1047), pemphigus vulgaris (n = 564), Sjogren's syndrome (n = 138), myasthenia gravis (n = 66), and CIDP (n = 31) and nine were randomized controlled trials (n = 992) in patients with ITP, SLE, and Sjogren's syndrome that compared rituximab with placebo plus standard of care. Among randomized trials, response rates were higher with rituximab (relative risk, 1.38; 95% confidence interval [CI], 1.05-1.83). The pooled proportion of rituximab responses ranged from 94% (95% CI, 88%-98%) for pemphigus vulgaris to 48% (95% CI, 30%-66%) for CIDP. Rituximab was generally well tolerated in observational studies although in the randomized trials, adverse events were more common in the rituximab group.

Conclusion: Rituximab is an immune-modulating agent with biologic activity across many autoimmune conditions. Our data support the use of comparative trials with broad eligibility criteria to evaluate rituximab as an alternative to IVIG in autoimmune diseases.
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http://dx.doi.org/10.1111/trf.14841DOI Listing
November 2018

Impact of organizational interventions on reducing inappropriate intravenous immunoglobulin (IVIG) usage: A systematic review and meta-analysis.

Transfus Apher Sci 2018 Apr 31;57(2):215-221. Epub 2018 Jan 31.

McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada; Department of Oncology, McMaster University, Hamilton, Ontario, Canada.

Background: With increasing global use of intravenous immunoglobulin (IVIG), there is interest in its appropriate usage. Efforts to regulate IVIG usage have primarily taken the form of organizational interventions implemented in hospitals to monitor and improve physician prescribing. Similar interventions have proven effective in reducing the inappropriate and total hospital usage of other blood products, but their efficacy on IVIG use is less understood. Thus, we performed a systematic review of studies reporting the change in inappropriate IVIG use following such interventions in hospitals or regions.

Methods: A systematic search was carried out using MEDLINE and EMBASE (1966-June 2016) for English language studies if they 1) were primary research, 2) described an organizational intervention to target plasma, IVIG, or albumin, and 3) reported appropriateness of usage and total usage preand post-intervention. Review Manager v5.0 was utilized to perform a random-effects meta-analysis on eligible IVIG studies, where the risk ratio (RR) of inappropriate IVIG transfusion comparing pre- and postintervention periods was calculated with 95% confidence intervals (CI).

Results: Our search retrieved three retrospective cohort studies, where metaanalysis encompassing 2100 episodes of IVIG transfusion demonstrated no decrease in inappropriate IVIG use (RR 1.55, 95% CI 0.78-3.07). Heterogeneity between studies was considerable (I2 = 89%).

Conclusion: Organizational interventions were ineffective at changing inappropriate IVIG use, but more high-quality studies describing the effects of these interventions are required before any conclusions can be drawn. Futureresearch efforts should also be directed at evolving evidence-based IVIGguidelines to improve patient safety and burdens on healthcare systems.
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http://dx.doi.org/10.1016/j.transci.2018.01.008DOI Listing
April 2018

Assessment of the Measurement Error in Cyclosporine Levels Drawn Between Peripheral and Central Sources.

Am J Clin Pathol 2017 Dec;149(1):76-81

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.

Objectives: Cyclosporine is often monitored by drug levels drawn through central venous catheters (CVCs), which may be falsely elevated due to reversible drug adsorption onto the catheter. Therefore, we assessed the correlation between cyclosporine levels drawn peripherally and through CVCs.

Methods: Bone marrow transplantation patients had a weekly collection of both peripheral and CVC draws from dual-lumen catheters simultaneously to assess cyclosporine levels after research ethics approval. Our primary outcome was the proportion of paired samples that were incongruent-defined as the mean of the CVC level being greater than 2 standard deviations from the peripheral level mean.

Results: After approaching 27 eligible patients, 20 patients (77.8%) provided samples. Of 53 paired samples, seven were incongruent (13.2%). Peripheral and CVC levels correlated (r = 0.91) and agreed well.

Conclusion: Despite potential for preanalytical error due to adsorption, cyclosporine infusion and monitoring via CVCs produce results similar to monitoring via peripheral blood draws.
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http://dx.doi.org/10.1093/ajcp/aqx145DOI Listing
December 2017

Safety of uninterrupted anticoagulation in patients requiring elective coronary angiography with or without percutaneous coronary intervention: a systematic review and metaanalysis.

Chest 2010 Oct 30;138(4):840-7. Epub 2010 Apr 30.

Department of Medicine, McMaster University and St Joseph's Healthcare, Hamilton, ON, Canada.

Background: Patients who are receiving vitamin K antagonist (VKA) therapy pose challenges when they require surgery or invasive procedures because the risk for bleeding during the procedure must be balanced against the risk of an atherothrombotic event if the VKA is interrupted. However, it may be possible to safely perform some procedures, such as coronary angiography with or without percutaneous coronary intervention (PCI), without VKA interruption.

Methods: We undertook a systematic review and metaanalysis to assess the safety of a periprocedural management strategy of uninterrupted VKA (U-VKA) vs interrupted VKA (I-VKA) with or without bridging with low-molecular-weight heparin in patients undergoing elective coronary angiography with or without PCI.

Results: Eight studies were included in the review. Most were of moderate to very low quality. A strategy of U-VKA appears to confer approximately one-half the risk (odds ratio, 0.43; 95% CI, 0.26-0.73) of experiencing an access site bleeding complication within 1 week of the procedure compared with a strategy of I-VKA. The U-VKA strategy was associated with a pooled access site bleeding complication rate of 4.0% (95% CI, 3.0-7.0), and although high heterogeneity precluded pooling of such a rate in the I-VKA group, these rates ranged from 2% to 14%.

Conclusion: Although it appears that coronary angiography with or without PCI can be safely performed without interrupting VKA, the low methodologic quality of existing studies precludes any definitive conclusions. Randomized trials assessing different anticoagulation strategies are needed to establish evidence-based practice guidelines in this setting.
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http://dx.doi.org/10.1378/chest.09-2603DOI Listing
October 2010

Periprocedural anticoagulation practices in warfarin-treated patients who require elective angiography with or without percutaneous coronary intervention: a retrospective chart review.

Thromb Res 2010 Apr 17;125(4):351-2. Epub 2009 Nov 17.

Department of Medicine, McMaster University and St Joseph's Healthcare, Hamilton ON, Canada.

Introduction: It may be possible to safely perform some procedures without interrupting warfarin therapy. Coronary angiography with or without percutaneous coronary intervention (PCI) is one such procedure. However, before further high quality research can be performed in this area, information such as current practice and associated event rates is required.

Materials And Methods: We performed a retrospective chart review of 100 charts from a tertiary interventional cardiology referral centre. The primary outcome was access site bleeding. The perioperative anticoagulation strategy for each patient was also recorded.

Results And Conclusions: All patients were managed with a strategy of warfarin interruption with or without bridging with a heparin. This was associated with an access site event rate of 2%. These results can be used to inform the design of high quality prospective studies, aimed at determining optimal anticoagulation management strategy in warfarin-treated patients who require coronary angiography or PCI.
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http://dx.doi.org/10.1016/j.thromres.2009.10.015DOI Listing
April 2010

Acute, but not resolved, influenza A infection enhances susceptibility to house dust mite-induced allergic disease.

J Immunol 2009 Mar;182(5):3095-104

Division of Respiratory Diseases and Allergy, Center for Gene Therapeutics and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

The impact of respiratory viral infections on the emergence of the asthmatic phenotype is a subject of intense investigation. Most experimental studies addressing this issue have used the inert Ag OVA with controversial results. We examined the consequences of exposure to a low dose of the common aeroallergen house dust mite (HDM) during the course of an influenza A infection. First, we delineated the kinetics of the immune-inflammatory response in the lung of mice following intranasal infection with influenza A/PR8/34. Our data demonstrate a peak response during the first 10 days, with considerable albeit not complete resolution at day 39 postinfection (p.i.). At day 7 p.i., mice were exposed, intranasally, to HDM for 10 consecutive days. We observed significantly enhanced eosinophilic inflammation, an expansion in Th2 cells, enhanced HDM-specific IgE and IgG1 responses and increased mucous production. Furthermore, lung mononuclear cells produced enhanced IFN-gamma and IL-5, unchanged IL-13, and reduced IL-4. These immunologic and structural changes lead to marked lung dysfunction. This allergic phenotype occurs at a time when there is a preferential increase in plasmacytoid dendritic cells over myeloid dendritic cells, activated CD8(+) T cells, and increased IFN-gamma production, all of which have been proposed to inhibit allergic responses. In contrast, the inflammatory response elicited by HDM was reduced when exposure occurred during the resolution phase (day 40 p.i.). Interestingly, this was not associated with a reduction in sensitization. Thus, the proinflammatory environment established during an acute influenza A infection enhances Th2-polarized immunity to a low dose of HDM and precipitates marked lung dysfunction.
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http://dx.doi.org/10.4049/jimmunol.0802837DOI Listing
March 2009

Safety of continuing warfarin therapy during cataract surgery: a systematic review and meta-analysis.

Thromb Res 2009 Jul 23;124(3):292-9. Epub 2009 Feb 23.

Department of Medicine, McMaster University and St Joseph's Healthcare, Hamilton, ON, Canada.

Background: In patients who are receiving warfarin therapy and require cataract surgery, it may be possible to continue warfarin in the perioperative period but the safety of this management strategy has not been systematically evaluated.

Methods: We performed a systematic review of the literature to assess the safety (bleeding events) of continuing warfarin before and after cataract surgery. We included studies that enrolled patients undergoing cataract surgery who were anticoagulated with warfarin alone and that reported bleeding events as an outcome. Study quality was assessed using a validated form. Odds ratios and bleeding rates were pooled to give summary estimates of bleeding risk.

Results: We identified 11 studies (5 cohort and 6 case series) assessing bleeding risk associated with warfarin continuation during cataract surgery. Patients who continued warfarin had an increased risk for bleeding (odds ratio; 3.26; 95% confidence interval [CI]: 1.73-6.16). The overall incidence of bleeding (95% CI) was 10% (5-19). Almost all bleeding events were self-limiting and not significant, consisting of dot hyphemae or subconjunctival hemorrhages. No patient had compromised visual acuity related to a bleeding event.

Conclusion: Patients who are receiving warfarin therapy and undergo cataract surgery without warfarin interruption have an increased risk for bleeding but such bleeds are not clinically significant. The low quality of studies assessed, however, precludes definitive conclusions as to the risk for bleeding in patients who continue warfarin around the time of cataract surgery.
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http://dx.doi.org/10.1016/j.thromres.2009.01.007DOI Listing
July 2009

Comparison of pain and ecchymosis with low-molecular-weight heparin vs. unfractionated heparin in patients requiring bridging anticoagulation after warfarin interruption: a randomized trial.

J Thromb Thrombolysis 2009 Oct 14;28(3):266-8. Epub 2009 Feb 14.

Department of Medicine, McMaster University, Hamilton, Canada.

Background: Subcutaneous (SC) low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) are safe and efficacious for bridging anticoagulation after warfarin interruption. Although LMWH and UFH are self-administered by >90% of patients, factors that may be important to patients such as differences in pain and ecchymosis have not been explored.

Methods: We randomized 24 patients to receive SC LMWH or SC UFH twice-daily during the perioperative period. Injection associated pain was recorded using a visual analogue scale and area of ecchymosis was measured by digital photography of the injection site on the day of the procedure.

Results: The area of ecchymosis was 2-fold higher with UFH than LMWH (19.4 cm(2) vs. 8.98 cm(2); P = 0.33) and pain was similar with both treatments (115 mm vs. 171 mm; P = 0.25), though neither finding attained statistical significance.

Conclusions: This exploratory study was underpowered to detect differences between the groups. Further studies are needed to reliably compare pain and ecchymosis in LMWH vs. UFH.
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http://dx.doi.org/10.1007/s11239-009-0312-8DOI Listing
October 2009
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