Mark Borgaonkar

Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus

BACKGROUND & AIMSnThe medical management of ulcerative colitis (UC) has improved through the development of new therapies and novel approaches that optimize existing drugs. Previous Canadian consensus guidelines addressed the management of severe UC in the hospitalized patient. We now present consensus guidelines for the treatment of ambulatory patients with mild to severe active UC.nnnMETHODSnA systematic literature search identified studies on the management of UC. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a working group of specialists.nnnRESULTSnThe participants concluded that the goal of therapy is complete remission, defined as both symptomatic and endoscopic remission without corticosteroid therapy. The consensus includes 34 statements focused on 5 main drug classes: 5-aminosalicylate (5-ASA), corticosteroids, immunosuppressants, anti-tumor necrosis factor (TNF) therapies, and other therapies. Oral and rectal 5-ASA are recommended first-line therapy for mild to moderate UC, with corticosteroid therapy for those who fail to achieve remission. Patients with moderate to severe UC should undergo a course of oral corticosteroid therapy, with transition to 5-ASA, thiopurine, anti-TNF (with or without thiopurine or methotrexate), or vedolizumab maintenance therapy in those who successfully achieve symptomatic remission. For patients with corticosteroid-resistant/dependent UC, anti-TNF or vedolizumab therapy is recommended. Timely assessments of response and remission are critical to ensuring optimal outcomes.nnnCONCLUSIONSnOptimal management of UC requires careful patient assessment, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Providing disease-related information worsens health-related quality of life in inflammatory bowel disease

BackgroundPatients with inflammatory bowel disease (IBD) have identified a need for more information about their disease. PurposeTo assess the effect of an educational intervention on health-related quality of life (HRQOL) in patients with IBD. MethodsConsecutive ambulatory IBD patients were randomized to receive four IBD-specific educational booklets or usual care. Subjects completed two disease-specific HRQOL questionnaires—the Inflammatory Bowel Disease Questionnaire (IBDQ) (range 1—poor to 7—excellent) and the Quality Index in Crohns and Colitis (QuICC) (range 1—excellent to 5—poor) at entry and after 2 weeks. The mean change in HRQOL scores at follow-up was compared between the education and control groups. Results59 subjects participated, with a mean age of 40.0 ± 11.9 years. 34 were given educational booklets and 25 received standard care. 6 patients (10%) did not complete the study. Mean IBDQ scores became significantly worse in the education group with a change of −0.17 ± 0.49 compared with controls at +0.28 ± 0.62 (p = 0.006). This could be explained by worsened disease activity in the education group. There was no significant change in the QuICC scores (p = 0.61). Education group patients who had not received prior educational material had improved mean IBDQ scores of +0.24 ± 0.47 compared with education patients who had received educational material prior to this study, with a score change of −0.25 ± 0.46 (p = 0.09). ConclusionsThe addition of educational booklets to IBD patients in a tertiary center does not improve, and may worsen, short-term HRQOL. Education of newly diagnosed or less informed patients should be studied further.

A meta-analysis of antimycobacterial therapy for Crohn's disease.

OBJECTIVE:Various therapies have been studied for the treatment of Crohns disease, including antimycobacterial therapy. Meta-analysis was used to evaluate the effect of antimycobacterial therapy in patients with Crohns disease.METHODS:Randomized, controlled trials comparing antimycobacterial therapy with placebo were identified. Key outcome data were abstracted and the results were pooled to yield odds ratios for maintenance of remission in treated versus control groups.RESULTS:A total of eight randomized trials were identified. Six trials were fully published and were included in the primary analysis. Two trials used antimycobacterial therapy in combination with corticosteroids to induce remission in patients with active Crohns disease, followed by maintenance therapy with antimycobacterial agents. In these trials, control patients received corticosteroids to induce remission but no antimycobacterial therapy. Pooling of these trials yielded an odds ratio of maintenance of remission in treatment versus control of 3.37 (95% confidence interval [CI], 1.38–8.24) in favor of antimycobacterial therapy. The remaining four trials used antimycobacterial therapy combined with standard therapy in patients with Crohns disease. In these trials, control patients received standard therapy alone. Pooling of these trials yielded an odds ratio of maintenance of remission in treatment versus control of 0.69 (95% CI, 0.39–1.21) in favor of standard therapy.CONCLUSIONS:These results suggest that antimycobacterial therapy is effective in maintaining remission in patients with Crohns disease after a course of corticosteroids combined with antimycobacterial therapy to induce remission. Treatment of Crohns disease with antimycobacterial therapy does not seem to be effective without a course of corticosteroids to induce remission. Because of the small number of studies included in this meta-analysis, the results should be interpreted with caution.

Canadian Association of Gastroenterology consensus guidelines on safety and quality indicators in endoscopy

BACKGROUNDnIncreasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality, highlight the need for clearly defined, evidence-based processes to support quality improvement in endoscopy.nnnOBJECTIVEnTo identify processes and indicators of quality and safety relevant to high-quality endoscopy service delivery.nnnMETHODSnA multidisciplinary group of 35 voting participants developed recommendation statements and performance indicators. Systematic literature searches generated 50 initial statements that were revised iteratively following a modified Delphi approach using a web-based evaluation and voting tool. Statement development and evidence evaluation followed the AGREE (Appraisal of Guidelines, REsearch and Evaluation) and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) guidelines. At the consensus conference, participants voted anonymously on all statements using a 6-point scale. Subsequent web-based voting evaluated recommendations for specific, individual quality indicators, safety indicators and mandatory endoscopy reporting fields. Consensus was defined a priori as agreement by 80% of participants.nnnRESULTSnConsensus was reached on 23 recommendation statements addressing the following: ethics (statement 1: agreement 100%), facility standards and policies (statements 2 to 9: 90% to 100%), quality assurance (statements 10 to 13: 94% to 100%), training, education, competency and privileges (statements 14 to 19: 97% to 100%), endoscopy reporting standards (statements 20 and 21: 97% to 100%) and patient perceptions (statements 22 and 23: 100%). Additionally, 18 quality indicators (agreement 83% to 100%), 20 safety indicators (agreement 77% to 100%) and 23 recommended endoscopy-reporting elements (agreement 91% to 100%) were identified.nnnDISCUSSIONnThe consensus process identified a clear need for high-quality clinical and outcomes research to support quality improvement in the delivery of endoscopy services.nnnCONCLUSIONSnThe guidelines support quality improvement in endoscopy by providing explicit recommendations on systematic monitoring, assessment and modification of endoscopy service delivery to yield benefits for all patients affected by the practice of gastrointestinal endoscopy.

The Incidence of Irritable Bowel Syndrome Among Community Subjects With Previous Acute Enteric Infection

The purpose of this study was to determine the incidence of postinfectious irritable bowel syndrome (IBS) among community subjects with positive stool studies. This was a prospective cohort study whereby all individuals with stool-positive acute enteric infection (AEI) were recruited from 3 health regions in Ontario, Canada. Each person completed questionnaires regarding preinfectious bowel habit and their bowel habit 3 months postinfection. Manning and Rome I criteria were used to diagnose irritable bowel syndrome. Two hundred thirty-one patients participated. Forty had preexisting IBS and were excluded. Of the remaining 191 patients, 7 developed irritable bowel syndrome, for an incidence of 3.7% (95% confidence interval: 1.0–6.3%). Fever during AEI was the only identifiable risk factor for developing postinfectious IBS (odds ratio, 11.96; P = .02). The incidence of postinfectious IBS in community subjects is 3.7%. Fever during the AEI may be an important risk factor for this condition.

Anti-tuberculous therapy for maintaining remission of Crohn's disease.

OBJECTIVESnTo evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohns disease.nnnSEARCH STRATEGYnWe searched the Inflammatory Bowel Disease Trials Register, the Cochrane Controlled Trials Register and MEDLINE from 1966 to 1998 (supplemented by a manual search of Index Medicus from 1966 to 1994). We also searched for abstracts in Gut, Gastroenterology, and The American Journal of Gastroenterology from 1990 to 1996. Date of most recent search: August 1998.nnnSELECTION CRITERIAnRandomized trials of anti-tuberculous therapy in patients with Crohns disease.nnnDATA COLLECTION AND ANALYSISnData on the number of patients maintaining remission for each treatment group were abstracted. These data were pooled to yield Mantel-Haenszel odds ratios and numbers needed to treat for maintenance of remission in treated versus control groups.nnnMAIN RESULTSnA total of seven randomized trials which included 355 patients were identified. Two trials used anti-tuberculous therapy (clofazimine or clofazimine, rafmpin, ethambutol, and dapsone) in combination with corticosteroids to induce remission. Maintenance therapy consisted of the anti-tuberculous agents without corticosteroids. Control patients received corticosteroids to induce remission but no anti-tuberculous therapy. The analysis of all seven trials yielded an odds ratio for maintenance of remission of 1.36 (95% CI 0.87-2. 13). Removing the two studies that were published as abstracts did not significantly affect this result: the pooled odds ratio was 1.14 (95% CI 0.71-1.83). The two trials reported as abstracts were excluded from subgroup analyses because they did not include any information on adjunct therapy. Subgroup analysis of the two trials which used steroids to induce remission yielded an odds ratio for maintenance of remission of 3.37 (95% CI 1.38-8.24). The number needed to treat was three. However, these two trials included only 89 patients, and the results should be interpreted with caution. The remaining three trials compared the combination of anti-tuberculous therapy and standard therapy with standard therapy alone. The pooled odds ratio was 0.70 (95% CI 0.39-1.25).nnnREVIEWERS CONCLUSIONSnAnti-tuberculous therapy may be effective in maintaining remission in patients with Crohns disease when remission has been induced with corticosteroids combined with anti-tuberculous therapy. However, the results which support this conclusion come from a subgroup of only two trials with small numbers of patients and should be interpreted with caution. Use of this therapy cannot be recommended on the basis of this evidence.

Individuals Homozygous for the H63D Mutation Have Significantly Elevated Iron Indexes

Our objective was to assess the iron indexes of patients with one or more mutations of the HFE gene with a specific interest in studying the effect of the H63D/H63D genotype. Eight hundred twenty subjects who underwent HFE mutational testing for C282Y and H63D mutations were retrospectively identified. Data collected included age, gender, HFE genotype, and values for serum ferritin, iron saturation, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Compared to the Wild/Wild genotype (0.34 ± 0.17), genotypes H63D/C282Y (0.44 ± 0.14 P < 0.01), H63D/H63D (0.51 ± 0.21 P < 0.01), and C282Y/C282Y (0.64 ± 0.20 P < 0.01) had significantly higher transferrin saturation levels and were independent predictors of higher iron saturation in multivariate regression analysis. Compared to the Wild/Wild genotype, no abnormal HFE genotypes had significantly higher ferritin levels, although the genotype H63D/H63D was an independent predictor of higher serum ferritin (P = 0.02) in regression analysis. There was no significant difference in the proportion of patients with abnormally elevated AST (P = 0.64) or ALT (P = 0.80) between groups. H63D homozygotes have elevated transferrin saturation compared to the Wild genotype, comparable to that of C282Y homozygotes and compound heterozygotes. The clinical significance of this finding is unclear but warrants further study.

The 2012 Sage Wait Times Program: Survey of Access to Gastroenterology in Canada

BACKGROUNDnPeriodically surveying wait times for specialist health services in Canada captures current data and enables comparisons with previous surveys to identify changes over time.nnnMETHODSnDuring one week in April 2012, Canadian gastroenterologists were asked to complete a questionnaire (online or by fax) recording demographics, reason for referral, and dates of referral and specialist visits for at least 10 consecutive new patients (five consultations and five procedures) who had not been seen previously for the same indication. Wait times were determined for 18 indications and compared with those from similar surveys conducted in 2008 and 2005.nnnRESULTSnData regarding adult patients were provided by 173 gastroenterologists for 1374 consultations, 540 procedures and 293 same-day consultations and procedures. Nationally, the median wait times were 92 days (95% CI 85 days to 100 days) from referral to consultation, 55 days (95% CI 50 days to 61 days) from consultation to procedure and 155 days (95% CI 142 days to 175 days) (total) from referral to procedure. Overall, wait times were longer in 2012 than in 2005 (P<0.05); the wait time to same-day consultation and procedure was shorter in 2012 than in 2008 (78 days versus 101 days; P<0.05), but continued to be longer than in 2005 (P<0.05). The total wait time remained longest for screening colonoscopy, increasing from 201 days in 2008 to 279 days in 2012 (P<0.05).nnnDISCUSSIONnWait times for gastroenterology services continue to exceed recommended targets, remain unchanged since 2008 and exceed wait times reported in 2005.

Indicators of safety compromise in gastrointestinal endoscopy

INTRODUCTIONnThe importance of quality indicators has become increasingly recognized in gastrointestinal endoscopy. Patient safety requires the identification and monitoring of occurrences associated with harm or the potential for harm. The identification of relevant indicators of safety compromise is, therefore, a critical element that is key to the effective implementation of endoscopy quality improvement programs.nnnOBJECTIVEnTo identify key indicators of safety compromise in gastrointestinal endoscopy.nnnMETHODSnThe Canadian Association of Gastroenterology Safety and Quality Indicators in Endoscopy Consensus Group was formed to address issues of quality in endoscopy. A subcommittee was formed to identify key safety indicators. A systematic literature review was undertaken, and articles pertinent to safety in endoscopy were identified and reviewed. All complications and measures used to document safety were recorded. From this, a preliminary list of 16 indicators was compiled and presented to the 35-person consensus group during a three-day meeting. A revised list of 20 items was subsequently put to the consensus group for vote for inclusion on the final list of safety indicators. Items were retained only if the consensus group highly agreed on their importance.nnnRESULTSnA total of 19 indicators of safety compromise were retained and grouped into the three following categories: medication-related - the need for CPR, use of reversal agents, hypoxia, hypotension, hypertension, sedation doses in patients older than 70 years of age, allergic reactions and laryngospasm⁄bronchospasm; procedure-related early - perforation, immediate postpolypectomy bleeding, need for hospital admission or transfer to emergency department from the gastroenterology unit, instrument impaction, severe persistent abdominal pain requiring evaluation proven to not be perforation; and procedure-related delayed - death within 30 days of procedure, 14-day unplanned hospitalization, 14-day unplanned contact with a health provider, gastrointestinal bleeding within 14 days of procedure, infection or symptomatic metabolic complications.nnnCONCLUSIONSnThe 19 indicators of safety compromise in endoscopy, identified by a rigorous, evidence-based consensus process, provide clear outcomes to be recorded by all facilities as part of their continuing quality improvement programs.

Iron overload is rare in patients homozygous for the H63D mutation.

BACKGROUNDnPrevious research has suggested that the H63D HFE mutation is associated with elevated iron indexes. However, the true penetrance of this mutation remains unclear.nnnOBJECTIVEnTo assess the proportion of H63D homozygotes with laboratory abnormalities consistent with iron overload.nnnMETHODSnThe present study was a retrospective analysis of all individuals referred for HFE genotyping in Newfoundland and Labrador between 1999 and 2009, who were found to be homozygous for the H63D mutation. Using electronic health records, results of ferritin, transferrin saturation, aspartate aminotransferase and alanine aminotransferase testing performed closest to the time of genetic testing were recorded for each patient. Iron overload was classified using previously published definitions from the HealthIron study. SPSS version 17.0 (IBM Corporation, USA) was used for descriptive statistics and to compare means using one-way ANOVA.nnnRESULTSnBetween 1999 and 2009, 170 individuals tested positive for H63D⁄H63D. At the time of genotyping, 28.8% had an elevated mean (± SD) ferritin level of 501±829 μg⁄L and 15.9% had an elevated transferrin saturation of 0.45±0.18. At genotyping, 94 individuals had sufficient data available to classify iron overload status. Only three (3.2%) had documented iron overload while the majority (85.1%) had no evidence of iron overload. Sixty individuals had follow-up data available and, of these, only four (6.7%) had documented iron overload, while 45 (75.0%) had no evidence of iron overload. Only one individual had evidence of iron overload-related disease at genotyping and at follow-up.nnnCONCLUSIONSnH63D homozygosity was associated with an elevated mean ferritin level, but only 6.7% had documented iron overload at follow-up. The penetrance of the H63D mutation appeared to be low.