Donald G. MacIntosh

Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial

Background: Adalimumab induced clinical remission after four weeks in patients with active Crohn’s disease in the CLASSIC I trial. Objective: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn’s disease in a follow-on randomised controlled trial (CLASSIC II). Methods: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56. Results: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open-label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well-tolerated in all patients. Conclusions: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment.

Early combined immunosuppression for the management of Crohn's disease (REACT): a cluster randomised controlled trial

BACKGROUND Conventional management of Crohns disease features incremental use of therapies. However, early combined immunosuppression (ECI), with a TNF antagonist and antimetabolite might be a more effective strategy. We compared the efficacy of ECI with that of conventional management for treatment of Crohns disease. METHODS In this open-label cluster randomised controlled trial (Randomised Evaluation of an Algorithm for Crohns Treatment, REACT), we included community gastroenterology practices from Belgium and Canada that were willing to be assigned to either of the study groups, participate in all aspects of the study, and provide data on up to 60 patients with Crohns disease. These practices were randomly assigned (1:1) to either ECI or conventional management. The computer-generated randomisation was minimised by country and practice size. Up to 60 consecutive adult patients were assessed within practices. Patients who were aged 18 years or older; documented to have Crohns disease; able to speak or understand English, French, or Dutch; able to access a telephone; and able to provide written informed consent were followed up for 2 years. The primary outcome was the proportion of patients in corticosteroid-free remission (Harvey-Bradshaw Index score ≤ 4) at 12 months at the practice level. This trial is registered with ClinicalTrials.gov, number NCT01030809. FINDINGS This study took place between March 15, 2010, and Oct 1, 2013. Of the 60 practices screened, 41 were randomly assigned to either ECI (n=22) or conventional management (n=19). Two practices (one in each group) discontinued because of insufficient resources. 921 (85%) of the 1084 patients at ECI practices and 806 (90%) of 898 patients at conventional management practices completed 12 months follow-up and were included in an intention-to-treat analysis. The 12 month practice-level remission rates were similar at ECI and conventional management practices (66·0% [SD 14·0] and 61·9% [16·9]; adjusted difference 2·5%, 95% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. INTERPRETATION Although ECI was not more effective than conventional management for controlling Crohns disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. FUNDING AbbVie Pharmaceuticals.

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

BACKGROUND Increasing 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. OBJECTIVE To identify processes and indicators of quality and safety relevant to high-quality endoscopy service delivery. METHODS A 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. RESULTS Consensus 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. DISCUSSION The consensus process identified a clear need for high-quality clinical and outcomes research to support quality improvement in the delivery of endoscopy services. CONCLUSIONS The 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 endoscopy Global Rating Scale - Canada: Development and implementation of a quality improvement tool

BACKGROUND Increasing use of gastrointestinal endoscopy, particularly for colorectal cancer screening, and increasing emphasis on health care quality highlight the need for endoscopy facilities to review the quality of the service they offer. OBJECTIVE To adapt the United Kingdom Global Rating Scale (UK-GRS) to develop a web-based and patient-centred tool to assess and improve the quality of endoscopy services provided. METHODS Based on feedback from 22 sites across Canada that completed the UK endoscopy GRS, and integrating results of the Canadian consensus on safety and quality indicators in endoscopy and other Canadian consensus reports, a working group of endoscopists experienced with the GRS developed the GRS-Canada (GRS-C). RESULTS The GRS-C mirrors the two dimensions (clinical quality and quality of the patient experience) and 12 patient-centred items of the UK-GRS, but was modified to apply to Canadian health care infrastructure, language and current practice. Each item is assessed by a yes⁄no response to eight to 12 statements that are divided into levels graded D (basic) through A (advanced). A core team consisting of a booking clerk, charge nurse and the physician responsible for the unit is recommended to complete the GRS-C twice yearly. CONCLUSION The GRS-C is intended to improve endoscopic services in Canada by providing endoscopy units with a straightforward process to review the quality of the service they provide.

Indicators of safety compromise in gastrointestinal endoscopy

INTRODUCTION The 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. OBJECTIVE To identify key indicators of safety compromise in gastrointestinal endoscopy. METHODS The 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. RESULTS A 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. CONCLUSIONS The 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.

An international survey of polypectomy training and assessment

Background and study aims Colonic polypectomy is acknowledged to be a technically challenging part of colonoscopy. Training in polypectomy is recognized to be often inconsistent. This study aimed to ascertain worldwide practice in polypectomy training. Patients and methods An electronic survey was distributed to endoscopic trainees and trainers in 19 countries asking about their experiences of receiving and delivering training. Participants were also asked about whether formal polypectomy training guidance existed in their country. Results Data were obtained from 610 colonoscopists. Of these responses, 348 (57.0 %) were from trainers and 262 (43.0 %) from trainees; 6.6 % of trainers assessed competency once per year or less often. Just over half (53.1 %) of trainees had ever had their polypectomy technique formally assessed by any trainer. Approximately half the trainees surveyed (51.1 %) stated that the principles of polypectomy had only ever been taught to them intermittently. Of those trainees with the most colonoscopy experience, who had performed over 500 procedures, 48.2 % had had training on removing large polyps of over 10 mm; 46.2 % (121 respondents) of trainees surveyed held no record of the polypectomies they had performed. Only four of the 19 countries surveyed had specific guidelines on polypectomy training. Conclusions A significant number of competent colonoscopists have never been taught how to perform polypectomy. Training guidelines worldwide generally give little direction as to how trainees should acquire polypectomy skills. The learning curve for polypectomy needs to be defined to provide reliable guidance on how to train colonoscopists in this skill.

Duodenal Villous Atrophy in a TTG-Negative Patient Taking Olmesartan: A Case Report and Review of the Literature

Olmesartan, an angiotensin II receptor antagonist used to treat hypertension, is associated with few adverse effects. Here, a case of severe sprue-like enteropathy and acute kidney injury is described in a 68-year-old male taking olmesartan for 3-4 years. He presented to hospital with a five-week history of diarrhea, vomiting, and a 20 lb weight loss. Anti-TTG was negative with a normal IgA. Biopsies of the distal duodenum and duodenal cap revealed marked blunting of the villi with near complete villous atrophy of the biopsies from the bulb. There was an increase in intraepithelial lymphocytes as well as neutrophils in the surface epithelium. The patients diarrhea improved upon discontinuation of olmesartan and he returned to his previous weight. Repeat endoscopy four months later demonstrated complete resolution of inflammatory change with normal villous architecture. Long-term olmesartan use is associated with severe sprue-like enteropathy. The mechanism of intestinal injury is unknown. Duodenal biopsy results may mimic other enteropathies such as celiac disease. Physicians should consider medications as potential etiologies of enteropathy.

Quality indicators for gastrointestinal endoscopy units

Lukejohn W. Day, MD, Jonathan Cohen, MD, FASGE, David Greenwald, MD, FASGE, Bret T. Petersen, MD, FASGE, Nancy S. Schlossberg, BSN, RN, Joseph J. Vicari, MD, MBA, FASGE, Audrey H. Calderwood, MD, FASGE, Frank J. Chapman, MBA, Lawrence B. Cohen, MD, Glenn Eisen, MD, MPH, FASGE, Patrick D. Gerstenberger, MD, FASGE, Ralph David Hambrick, III, RN, John M. Inadomi, MD, Donald MacIntosh, MD, Justin L. Sewell, MD, MPH, Roland Valori, MD

M1018 Quality Indicators for Colonoscopy in Canada: the Canadian Association of Gastroenterology (cag) Endoscopy Quality Initiative (EQI) Practice Audit Project

Gastroenterology (CAG) Endoscopy Quality Initiative (EQI) Practice Audit Project David Armstrong,1 Roger Hollingworth,2 Donald MacIntosh,3 Joanne Cabrera,4 Ying Chen,1 Sandra Daniels,5 Stuart Gittens,6 Ron Bridges,4 Paul Sinclair,5 Catherine Dubé4 1McMaster University, Hamilton, 2Credit Valley Hospital, Mississauga, 3Dalhousie University, Halifax, 4University of Calgary, 5Canadian Association of Gastroenterology, Oakville, 6ECD Solutions, Atlanta

Should the Children of Patients with Hemochromatosis be Screened for the Disease

Idiopathic hemochromatosis is an underdiagnosed treatable condition inherited in an autosomal recessive pattern. Since early treatment is of demonstrated value, screening of high risk groups of individuals in a valuable exercise in preventive medicine. Although examination of siblings is always recommended, the frequency of the hemochromatosis gene makes the screening of children of patients with hemochromatosis an important undertaking, as illustrated by the families described in this report.