R N Fedorak

University of Alberta, Edmonton, Alberta, Canada

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Publications (139)934.58 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The efficacy of adalimumab in maintaining remission in Crohn's disease patients may wane over time, leading to secondary loss of response that is often managed with dose escalation. However, the response to adalimumab dose escalation and long-term outcomes after escalation have not been well evaluated.AimsTo characterise the short- and long-term clinical responses to adalimumab dose escalation for secondary loss of response.MethodsA retrospective cohort study evaluating Crohn's disease out-patients requiring adalimumab dose escalation for secondary loss of response from 2003 to 2013 was conducted. The primary outcome was the proportion of patients achieving symptomatic clinical response to dose escalation and subsequent development of tertiary loss of response. Duration of regained response was assessed by Kaplan–Meier analysis.ResultsNinety-two CD patients met inclusion criteria with mean duration of follow-up of 170.2 weeks (±129.6 weeks). Disease distribution was predominantly ileal (37/92, 40.2%) or ileocolonic (43/92, 46.7%), with equal distribution of inflammatory (34.8%), stricturing (27.2%), and penetrating (38.0%) disease phenotypes. At 24 weeks post-dose escalation, 74/92 (80.4%) patients had symptomatic clinical response. Among responders, median duration of sustained response was 69.2 weeks (IQR 29.4–107.1) but 42/74 (56.8%) responders experienced subsequent tertiary loss of response at a median time of 47.9 weeks (IQR 24.7–80.3). C-reactive protein >10.0 mg/L at the time of dose escalation predicted tertiary loss of response in univariate analysis (OR 3.32, 95% CI: 1.18–9.37).Conclusions In patients with Crohn's disease, adalimumab dose escalation is effective for recapturing symptomatic response after secondary loss of response, but more than half will eventually experience a tertiary loss of response.
    Alimentary Pharmacology & Therapeutics 09/2014; · 4.55 Impact Factor
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    ABSTRACT: Background Medical therapy is standard treatment for ulcerative colitis with colectomy reserved for medically refractory disease or malignancy. The introductions of ciclosporin in 1994 and anti-TNF therapy in 2005 have extended medical management options.AimThe aim of this study was to determine whether the colectomy incidence rate for medically refractory ulcerative colitis has changed since the introduction of anti-TNF therapy.Methods Adult patients with a diagnosis of ulcerative colitis and who subsequently underwent an urgent or elective colectomy for medically refractory disease in Edmonton, Canada between 1 January 1998 and 31 December 2011 were identified. Log-linear regression was used to estimate the annual percent change in the total colectomy incidence rate (urgent and elective combined) and the urgent and elective incidence rates individually, before and after 2005, the year infliximab was approved for use in ulcerative colitis. Temporal trends of drug utilisation in this study population were also described.ResultsDuring 1998–2011, 481 patients with ulcerative colitis underwent a colectomy for medically refractory disease. There was negligible change in the total colectomy incidence rate from 1998 to 2005, with an annual percent change of 4.4% (95% confidence interval (CI): −1.12% to 10.16%). From 2005-2011, following the approval and increasing use of anti-TNF therapy, the total colectomy incidence rate decreased by 16.1% (95% CI: −21.32% to −10.54%) every year to 0.9 per 100 ulcerative colitis patients in 2011.Conclusion The total incidence rate of colectomy for medically refractory ulcerative colitis has declined substantially since 2005, paralleling the increased use of anti-TNF therapy in this patient population.
    Alimentary Pharmacology & Therapeutics 07/2014; · 4.55 Impact Factor
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    ABSTRACT: The Epstein-Barr Virus (EBV) is truly prolific, with a prevalence of more than 90% in the adult human population. There are, however, little data available on the prevalence of EBV among patients with Inflammatory Bowel Disease (IBD), a population that is frequently immunosuppressed and thus at risk for severe, often fatal, primary infection. To identify the prevalence of EBV in a population of patients with IBD and to compare it with that of the general population. A database of 2500 IBD patients previously followed at the University of Alberta IBD Centre was queried; 60 of these patients were randomly chosen to participate. A total of 220 patients attending the IBD Centre for clinical appointment were also prospectively asked to participate. Participants completed serological testing for VCA-IgM, VCA-IgG and EBNA-IgG, to determine prior EBV exposure. A total of 263 patients underwent testing. Results for EBV seroprevalence of specific age groups were as follows: 18-20 years (n = 17), 29% seronegative; 21-25 years (n = 31), 29% seronegative; 26-30 years (n = 35), 31-35 years (n = 18) and 36-40 years (n = 25), 100% seropositive. Finally, 3% of those older than 40 (n = 117) were seronegative. EBV seroprevalence was similar for Crohn's disease and ulcerative colitis. Azathioprine was associated with seropositivity (P = 0.048). The prevalence of EBV seronegativity in the IBD population aged 18-25 years was similar to that described in the general population, and above age 25 years, seropositivity approached 100%.
    Alimentary Pharmacology & Therapeutics 09/2013; · 4.55 Impact Factor
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    ABSTRACT: Tumour necrosis factor (TNF)-antagonists have an established role in the treatment of inflammatory bowel diseases (IBDs), however, subtherapeutic drug levels and the formation of anti-drug antibodies (ADAs) may decrease their efficacy. The evidence supporting the use of therapeutic drug monitoring (TDM) based clinical algorithms for infliximab (IFX) and their role in clinical practice will be discussed. The literature was reviewed to identify relevant articles on the measurement of IFX levels and antibodies-to-infliximab. Treatment algorithms for IBD have evolved from episodic monotherapy used in patients refractory to all other treatments, to long-term combination therapy initiated early in the disease course. Improved remission rates have been observed with this paradigm shift, nevertheless many patients ultimately lose response to therapy. Although empiric dose optimization or switching agents constitute the current standard of care for secondary failure, these interventions have not been applied in an evidence-based manner and are probably not cost-effective. Multiple TDM-based algorithms have been developed to identify patients that may benefit from measurement of IFX and ADA levels to guide adjustments to therapy. Therapeutic drug monitoring offers a rational approach to the management of secondary failure to IFX. This concept has gained momentum based on evidence from case series, cohort studies and post-hoc analyses of randomised controlled trials.
    Alimentary Pharmacology & Therapeutics 07/2013; · 4.55 Impact Factor
  • T W Lee, R Singh, R N Fedorak
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    ABSTRACT: Infliximab is a chimeric monoclonal antibody to tumour necrosis factor alpha (TNFα) with efficacy in inducing and maintaining remission of inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis and psoriasis. Infliximab is generally administered over 2h with a further 1-h postinfusion observation. This time interval has substantial impact on healthcare resources and is costly in terms of patient's time away from work. To examine the safety and tolerability of a 1-h, relative to a 2-h maintenance of infusion of infliximab, and to determine the effect of corticosteroid premedication and concurrent immunosuppressor use on infusion reaction rates. A prospective cohort study with variable follow-up duration of 2165 consecutive infliximab infusions in 415 patients during 2009 was conducted. Diagnosis, infusion episode number, infusion rate, premedication, concurrent immunosuppressor therapy, the nature and the outcome of infusion reactions were examined. The majority of infusions (74%) were for management of inflammatory bowel disease. Infusion reactions clustered within the first eight infusions with subsequent sporadic reactions. The infusion reaction incidence rate per 1000 person days in 274 1-h infusions from 54 patients and 1356 2-h infusions from 256 patients were 0.08 and 0.28 respectively (P=0.07). Poisson regression model confirmed that the concurrent use of immunosuppressor therapy was associated with a lower infusion reaction rate, whereas corticosteroid premedication was not. During maintenance therapy, infliximab infusion can be safely administered over 1h in patients with no past history of significant infliximab infusion reaction. Corticosteroid premedication had no impact on the infusion reaction rates.
    Alimentary Pharmacology & Therapeutics 07/2011; 34(2):181-7. · 4.55 Impact Factor
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    ABSTRACT: Three-dimensional digitization of highly reflective and transparent objects using multi-wavelength range sensing." Machine Vision and Applications, 12 Pages, December 2010.Mind the gaps: Confocal endomicroscopy revealed increased density of small bowel epithelial gaps in inflammatory bowel disease.
    Computers & Graphics 03/2011; 55(35):978-1. · 0.79 Impact Factor
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    ABSTRACT: Tumour necrosis factor-blockade with infliximab has advanced the treatment of Crohn's disease. While infliximab is efficacious, it remains to be determined whether patients who enter clinical remission with an anti-tumour necrosis factor therapy can have their treatment stopped and retain the state of remission. To assess in patients with Crohn's disease who obtained infliximab-induced remission, the proportion who relapsed after infliximab discontinuation. This longitudinal cohort study examined patients from a University-based IBD referral centre. Forty eight patients with Crohn's disease in full clinical remission and who then discontinued infliximab were followed up for up to 7 years. Crohn's disease relapse was defined as an intervention with Crohn's disease medication or surgery. Kaplan-Meier analysis of the proportion of patients with sustained clinical benefit demonstrated that 50% relapsed within 477 days after infliximab discontinuance. In contrast, 35% of patients remained well, and without clinical relapse, up to the end of the nearly 7-year follow-up. In patients with Crohn's disease with an infliximab-induced remission, stopping infliximab results in a predictable relapse in a majority of patients. Nevertheless, a small percentage of patients sustain a long-term remission.
    Alimentary Pharmacology & Therapeutics 11/2010; 32(9):1129-34. · 4.55 Impact Factor
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    N Gies, K I Kroeker, K Wong, R N Fedorak
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    ABSTRACT: Aliment Pharmacol Ther 2010; 32: 522-528 Summary Background Randomized, controlled trials have demonstrated that anti-TNF agents are efficacious in inducing remission in cases of Crohn's disease and ulcerative colitis. However, response rates for anti-TNF agents in 'real life' clinical practice are less well-defined. Aims To examine the response rates and long-term outcomes of infliximab and adalimumab treatment for out-patients with ulcerative colitis and to study the variables associated with response rates. Methods In a prospective study, a single-centre out-patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician's global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results Fifty-three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions This long-term follow-up of a single-centre cohort of ulcerative colitis patients demonstrates that 'real-life' out-patient treatment with infliximab and adalimumab is effective in induction and maintenance of response.
    Alimentary Pharmacology & Therapeutics 08/2010; 32(4):522-8. · 4.55 Impact Factor
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    ABSTRACT: Intestinal microflora play a critical role in the initiation and perpetuation of chronic inflammatory bowel diseases. In genetically susceptible hosts, bacterial colonization results in rapid-onset chronic intestinal inflammation. Nevertheless, the intestinal and systemic immune response to faecal bacteria and antigen exposure into a sterile intestinal lumen of a post-weaned animal with a mature immune system are not understood clearly. This study examined the effects of faecal bacteria and antigen exposure on the intestinal mucosal and systemic immune system in healthy axenic mice. Axenic wild-type mice were inoculated orally with a crude faecal slurry solution derived from conventionally raised mice and were analysed prior to and then at days 3, 7, 14 and 28 post-treatment. Ingestion of faecal slurry resulted in a transient, early onset of proinflammatory interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and interleukin (IL)-17 response that was maximal at day 3. In contrast, the transient release of the anti-inflammatory cytokines IL-10 and IL-4 occurred later and was maximal at day 7. Both responses subsided by day 14. This early cytokine imbalance was associated with a brief rise in colonic and caecal histopathological injury score at day 7. The bacterial antigen-specific systemic response was found to follow the intestinal immune response with a maximal release of both pro- and anti-inflammatory cytokines at day 7. Thus, first exposure of healthy axenic wild-type mice to normal faecal flora and antigens results in an early proinflammatory cytokine response and transient colonic inflammation that then resolves in conjunction with a subsequent anti-inflammatory cytokine profile.
    Clinical & Experimental Immunology 03/2010; 161(1):187-96. · 3.41 Impact Factor
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    ABSTRACT: Interleukin-12 (IL-12) and interleukin-23 (IL-23) are inflammatory cytokines linked to the Th-1 and Th-17 phenotypes associated with Crohn's disease (CD). We investigated the activity and safety of apilimod mesylate (formerly STA-5326), an oral IL-12 and IL-23 inhibitor, in patients with active CD. We performed a multicenter, Phase 2, randomized, double-blinded, placebo-controlled study to evaluate the efficacy of apilimod mesylate in treating 220 adult patients with moderate-to-severe CD (Crohn's Disease Activity Index [CDAI] score 220-450). Patients were stratified according to C-reactive protein (CRP) levels and corticosteroid use and were randomly assigned to receive placebo or apilimod mesylate 50 mg daily or 100 mg daily. The study was divided into an induction phase (43 days) and a maintenance phase (125 days). The primary analysis involved a comparison of the proportion of patients experiencing clinical response, defined as at least a 100-point decrease in CDAI score from baseline at day 29. Data on adverse events were also collected. In all, 220 of the planned 282 patients were enrolled when the Data Monitoring Committee determined that the drug was not efficacious as a treatment and closed enrollment. A clinical response was experienced by 18 patients (24.7%) in the 50-mg daily (QD) group (n = 73) and 19 patients (25.7%) in the 100 mg QD group (n = 74), as compared with 21 patients (28.8%) in the placebo group (n = 73) on day 29 (P = 0.71 for each comparison). No significant adverse safety signal was observed. Apilimod was well-tolerated but did not demonstrate efficacy over placebo in patients with active CD.
    Inflammatory Bowel Diseases 11/2009; 16(7):1209-18. · 5.12 Impact Factor
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    ABSTRACT: The management of Crohn's disease is rapidly changing. The advent of potent immunomodulatory and biologic therapies has led to more demanding endpoints for clinical trials than only clinical response and remission. Complete withdrawal of corticosteroids, healing of endoscopically visible lesions, and prevention of structural damage are only a few new endpoints that are finding their way into the clinical trials of today and those that are being developed for the future. Given the importance of selecting the most appropriate and relevant endpoints, the International Organization for Inflammatory Bowel Diseases (IOIBD) decided to develop guidelines that could be used by individual researchers, the pharmaceutical industry, and the regulatory bodies. The current document is to be read as a "position paper," which is the result of several years of discussion and consensus finding that was finally approved by the entire membership of the group. The proposed instruments will need further validation and standardization to demonstrate that they are reliable in stable disease and responsive to change, and to determine the cutoff points for response and remission.
    Inflammatory Bowel Diseases 09/2009; 15(10):1599-604. · 5.12 Impact Factor
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    ABSTRACT: Guidelines regarding the use of infliximab in Crohn's disease were previously published by the Canadian Association of Gastroenterology in 2004. However, recent clinical findings and drug developments warrant a review and update of these guidelines. To review and update Canadian guidelines regarding the use of tumour necrosis factor-alpha antibody therapy in both luminal and fistulizing Crohn's disease. A consensus group of 25 voting participants developed a series of recommendation statements that addressed pertinent clinical questions and gaps in existing knowledge. An iterative voting and feedback process was used in advance of the consensus meeting in conjunction with a systematic literature review to refine the voting statements. These statements were brought to a formal consensus meeting held in Montreal, Quebec (March 2008), wherein each statement underwent discussion, reformulation, voting and subsequent revision until group consensus was obtained (at least 80% agreement). The 47 voting statements addressed three themes: induction therapy, maintenance therapy and safety issues. As a result of the iterative process, 23 statements achieved consensus and were submitted for publication. In the past five years, tumour necrosis factor-alpha antagonist therapy has become a cornerstone in the management of moderate-to-severe Crohn's disease refractory to conventional treatment algorithms. The evidentiary base supporting the use of these drugs in Crohn's disease is substantial and strengthened by results from longterm clinical and molecular studies. However, significant gaps in knowledge exist, particularly with regard to treatment failure. Confidence in the safety of these drugs is increasing, provided that therapy is administered in a clinical setting in which potential complications can be readily recognized and treated.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 04/2009; 23(3):185-202. · 1.53 Impact Factor
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    ABSTRACT: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom-free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Eighteen eligible patients between the ages of 3-17 with mild to moderate acute UC received open-label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI <or=3) was achieved in 56% of children (n = 10); response (decrease in SCCAI >or=2, but final score <or=5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post-VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%.
    Inflammatory Bowel Diseases 01/2009; 15(5):760-8. · 5.12 Impact Factor
  • Journal of Crohns & Colitis - J CROHNS COLITIS. 01/2009; 3(1).
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    ABSTRACT: Infliximab is a chimeric, monoclonal anti-tumour necrosis factor-alpha antibody. It has been previously demonstrated to be an effective treatment for patients with Crohn's disease who do not achieve the desired response with conventional treatments. Although the etiology of ulcerative colitis (UC) differs from that of Crohn's disease, randomized controlled trials have demonstrated that infliximab is also beneficial for the treatment of moderate to severe UC in patients who are either intolerant of or refractory to immunosuppressant agents or steroids, or those who are steroid-dependent. A review of the literature is followed by practical recommendations regarding infliximab that address the needs of clinicians and UC patients. Where there is a lack of evidence-based information, the expert panel provides its combined opinion derived from the members' clinical experiences.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 04/2008; 22(3):261-72. · 1.53 Impact Factor
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    ABSTRACT: Alkaline sphingomyelinase, an enzyme found exclusively in bile and the intestinal brush border, hydrolyzes sphingomyelin into ceramide, sphingosine and sphingosine-1-phosphate, thereby inducing epithelial apoptosis. Reduced levels of alkaline sphingomyelinase have been found in premalignant and malignant intestinal epithelia and in ulcerative colitis tissue. Probiotic bacteria can be a source of sphingomyelinase. To determine the effect of VSL#3 probiotic therapy on mucosal levels of alkaline sphingomyelinase, both in a mouse model of colitis and in patients with ulcerative colitis. Interleukin-10 gene-deficient (IL10KO) and wild type control mice were treated with VSL#3 (10(9) colony-forming units per day) for three weeks, after which alkaline sphingomyelinase activity was measured in ileal and colonic tissue. As well, 15 patients with ulcerative colitis were treated with VSL#3 (900 billion bacteria two times per day for five weeks). Alkaline sphingomyelinase activity was measured through biopsies and comparison of ulcerative colitis disease activity index scores obtained before and after treatment. Lowered alkaline sphingomyelinase levels were seen in the colon (P=0.02) and ileum (P=0.04) of IL10KO mice, as compared with controls. Treatment of these mice with VSL#3 resulted in upregulation of mucosal alkaline sphingomyelinase activity in both the colon (P=0.04) and the ileum (P=0.01). VSL#3 treatment of human patients who had ulcerative colitis decreased mean (+/- SEM) ulcerative colitis disease activity index scores from 5.3+/-1.8946 to 0.70+/-0.34 (P=0.02) and increased mucosal alkaline sphingomyelinase activity. Mucosal alkaline sphingomyelinase activity is reduced in the intestine of IL10KO mice with colitis and in humans with ulcerative colitis. VSL#3 probiotic therapy upregulates mucosal alkaline sphingomyelinase activity.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 04/2008; 22(3):237-42. · 1.53 Impact Factor
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    ABSTRACT: Bowel commensals appear to be an important source of antigens that drive the chronic immune inflammation characteristic of Crohn's disease and ulcerative colitis [inflammatory bowel diseases (IBD)]. Biopsy-associated bacteria are assumed to be particularly relevant in bacteriological investigations of IBD because they are assumed to be located on the mucosal surface and hence close to immunological cells. This investigation analysed the bacterial collections associated with bowel biopsies, aspirates of residual fluid after bowel cleansing and faeces from IBD patients and non-IBD subjects in Edmonton, Canada, and Mexico City, Mexico. Temporal temperature gradient gel electrophoresis of 16S rRNA gene sequences produced profiles of the bacterial collections and their similarities were compared. Similarity analysis showed that the profiles did not cluster according to disease status, but that Canadian and Mexican profiles could be differentiated by this method. Comparison of biopsy, aspirate and faecal samples obtained from the same subject showed that, on average, the profiles were highly similar. Therefore, biopsy-associated bacteria are likely to represent, at least in part, contaminants from the fluid, which resembles a faecal solution, that pools in the bowel after cleansing prior to endoscopy.
    Journal of Medical Microbiology 02/2008; 57(Pt 1):111-7. · 2.30 Impact Factor
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    ABSTRACT: To evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic autoantibodies (pANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCAs), as single agents and in combination, for the diagnosis of Crohn's disease (CD) and ulcerative colitis (UC), including in cases of indeterminate colitis (IC). The sera from a total of 98 patients were studied: 77 with CD, 16 with UC and five with IC. The medical records of these patients were reviewed for disease diagnosis, demographic data, and patient symptoms and medications. ELISAs were utilized to detect the presence of ASCAs and deoxyribonuclease-sensitive pANCAs, and these results were then compared with the patients' clinical data. For UC, a positive pANCA test alone provided a sensitivity of 50% and a specificity of 82%. For CD, a positive ASCA test alone provided a sensitivity of 40% and a specificity of 100%. A combination of pANCA-positive and ASCA-negative results showed a sensitivity of 50% and specificity of 90% for the diagnosis of UC. Similarly, the combination of ASCA-positive and pANCA-negative results provided a sensitivity and specificity of 32% and 100% for the diagnosis of CD, respectively. Interestingly, 80% of IC patients showed serology results consistent with UC. Although this combination of serological markers provides a diagnostic tool with generally high specificities, the low sensitivities of these serological markers, most notably in terms of CD, preclude the possibility that they can replace the tools currently used for inflammatory bowel disease diagnosis and management. It is possible, however, that these serological markers may prove beneficial in the management of IC.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 02/2008; 22(1):33-6. · 1.53 Impact Factor
  • Gastroenterology 01/2008; 134(4). · 12.82 Impact Factor
  • Gastroenterology 01/2008; 134(4). · 12.82 Impact Factor

Publication Stats

4k Citations
934.58 Total Impact Points

Institutions

  • 1989–2013
    • University of Alberta
      • • Division of Gastroenterology
      • • Department of Medicine
      • • Department of Pediatrics
      • • Division of General Internal Medicine
      • • Department of Medical Microbiology and Immunology
      • • Department of Surgery
      Edmonton, Alberta, Canada
  • 2007
    • Royal Alexandra Hospital
      Edmonton, Alberta, Canada
  • 2000
    • McGill University
      • Division of Gastroenterology
      Montréal, Quebec, Canada
  • 1999
    • Canadian Association of Gastroenterology
      Edmonton, Alberta, Canada
  • 1997
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Academic Medical Center
      Amsterdam, North Holland, Netherlands
  • 1988
    • Columbia University
      • Department of Medicine
      New York City, NY, United States