Gastrointestinal Symptoms in Type 1 Diabetes: Relationship With Autoimmune and Microvascular Complications.

PURPOSE: To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. METHODS: The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. RESULTS: Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P < 0.0001). Common symptoms in children included upper and lower abdominal pain while adults more frequently reported lower GI symptoms. Participants with GI symptoms had higher hemoglobin A1c (HbA1c) levels (68 ±â€…14mmol/mol; 8.35 ±â€…1.37%) than those without symptoms (66 ±â€…15mmol/mol; 8.22 ±â€…1.40%; P = 0.041). Patients with microvascular complications (nephropathy, retinopathy, and/or neuropathy) were 1.8 times more likely to report GI symptoms (95% CI: 1.26-2.60; P < 0.01) after adjusting for age and sex. No association was observed between GI symptoms and the presence of autoimmune conditions, including thyroid and biopsy-confirmed CD (odds ratio = 1.1; 95% CI: 0.86-1.42; P = 0.45). MAIN CONCLUSIONS: These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.

Accuracy of Screening Tests for Celiac Disease in Asymptomatic Patients With Type 1 Diabetes.

INTRODUCTION: To evaluate the diagnostic performance of celiac serologic tests in asymptomatic patients with type 1 diabetes (T1D). METHODS: Patients with T1D asymptomatic for celiac disease were prospectively screened with immunoglobulin A anti-tissue transglutaminase. Test characteristics were calculated and optimal cutoffs for a positive screen determined. RESULTS: Two thousand three hundred fifty-three patients were screened and 101 proceeded to biopsy. The positive predictive value of immunoglobulin A anti-tissue transglutaminase at the assay referenced upper limit of normal (30CU) was 85.9%, and the sensitivity and specificity were 100% and 38%, respectively. DISCUSSION: Thresholds extrapolated from the general population for the diagnostic evaluation of celiac disease are not suitable for use in asymptomatic T1D patients. Population-specific screening cutoffs are required.

Impact of a Gluten-Free Diet on Quality of Life and Health Perception in Patients With Type 1 Diabetes and Asymptomatic Celiac Disease.

CONTEXT: Celiac disease (CD) is a common comorbidity seen in patients with type 1 diabetes (T1D) and is frequently asymptomatic. As chronic conditions requiring significant lifestyle changes, there are limited reports assessing changes in health-related quality of life (HRQoL) during transition to a gluten-free diet (GFD) in patients with T1D who are asymptomatic for CD. OBJECTIVE: This work aims to prospectively assess HRQoL and health perception in children and adults with T1D and asymptomatic CD after random assignment to GFD vs usual diet. METHODS: Patients with T1D aged 8 to 45 years without CD symptoms were serologically screened for CD, with positive results confirmed with intestinal biopsy. Participants were randomly assigned in an open-label fashion to a GFD or gluten-containing diet (GCD) for 12 months. Generic and diabetes-specific HRQoL and self-perceived wellness (SPW) were assessed longitudinally. RESULTS: A total of 2387 T1D patients were serologically screened. CD was biopsy-confirmed in 82 patients and 51 participants were randomly assigned to a GFD (N = 27) or GCD (N = 24). Excellent adherence to the assigned diets was observed. Overall, no changes in generic (P = .73) or diabetes-specific HRQoL (P = .30), or SPW (P = .41) were observed between groups over 12 months. Hemoglobin A1c (HbA1c) and gastrointestinal symptoms were consistent predictors of HRQoL and SPW. CONCLUSION: HRQoL and SPW were not significantly affected by the adoption of a GFD over 12 months, but worsened with symptom onset and increased HbA1c. Our findings indicate that transition to a GFD can be made successfully in this population without adversely affecting quality of life.

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Cloxacillin: A New Cause of Pill-Induced Esophagitis.

A large variety of medications can cause pill-induced esophagitis. Herein we present a case of cloxacillin-induced esophagitis. A 66-year-old male presented with an acute onset of epigastric and retrosternal pain on the 5th day of a course of oral cloxacillin prescribed for erysipelas. Initial clinical and imaging assessment was negative and he was sent home. A few days later, he returned with persistent severe retrosternal pain; endoscopy at the same day revealed a normal upper esophagus, several small stellate erosions in the midesophagus, and a normal squamocolumnar junction with a small hiatus hernia. Treatment with esomeprazole 40 mg bid and Mucaine(R) suspension resulted in complete resolution of his symptoms. Pill-induced esophagitis may be underreported by patients, when symptoms are mild and unrecognized and/or underdiagnosed by the clinicians as a cause of retrosternal pain, odynophagia, or dysphagia. Failure of early recognition may result in unnecessary diagnostic investigations and prolongation of the patient's discomfort. This case signifies the importance of enhancing clinician awareness for drug-associated esophageal injury when assessing patients with retrosternal pain, as well as the value of prophylaxis against this unpleasant condition by universally recommending drinking enough water in an upright position during ingestion of any oral medication.

Non-operative Management of Necrotic Pancreatic Collection and Bleeding Pseudoaneurysm Communicating with Bowel Lumen at Multiple Sites: a Case Report and Review of the Literature.

Pancreatic pseudocysts and foci of walled-off necrosis (WON) are well-known complications of acute pancreatitis. We present a case of severe gallstone pancreatitis complicated by WON, fistulization to the bowel and gastrointestinal bleeding. Bleeding was localized to a pseudoaneurysm of the gastroduodenal artery within the WON using imaging and endoscopy. Angiography and image-guided therapy were then used to control bleeding with coil-embolization. To our knowledge, this is the first report of non-operative management of a patient with severe pancreatitis complicated by WON and a bleeding pseudoaneurysm with multiple communications to the hollow viscera. Therapeutic options are discussed and a thorough literature review is included.

The Impact of Magnetic Resonance Enterography and Capsule Endoscopy on the Re-classification of Disease in Patients with Known Crohn's Disease: A Prospective Israeli IBD Research Nucleus (IIRN) Study.

BACKGROUND AND AIMS: The classification of Crohn's disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification. METHODS: Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared. RESULTS: Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%). CONCLUSION: VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients.

Inflammatory pouch disease: The spectrum of pouchitis.

Restorative proctocolectomy with ileal-pouch anal anastomosis (IPAA) is the operation of choice for medically refractory ulcerative colitis (UC), for UC with dysplasia, and for familial adenomatous polyposis (FAP). IPAA can be a treatment option for selected patients with Crohn's colitis without perianal and/or small bowel disease. The term "pouchitis" refers to nonspecific inflammation of the pouch and is a common complication in patients with IPAA; it occurs more often in UC patients than in FAP patients. This suggests that the pathogenetic background of UC may contribute significantly to the development of pouchitis. The symptoms of pouchitis are many, and can include increased bowel frequency, urgency, tenesmus, incontinence, nocturnal seepage, rectal bleeding, abdominal cramps, and pelvic discomfort. The diagnosis of pouchitis is based on the presence of symptoms together with endoscopic and histological evidence of inflammation of the pouch. However, "pouchitis" is a general term representing a wide spectrum of diseases and conditions, which can emerge in the pouch. Based on the etiology we can sub-divide pouchitis into 2 groups: idiopathic and secondary. In idiopathic pouchitis the etiology and pathogenesis are still unclear, while in secondary pouchitis there is an association with a specific causative or pathogenetic factor. Secondary pouchitis can occur in up to 30% of cases and can be classified as infectious, ischemic, non-steroidal anti-inflammatory drugs-induced, collagenous, autoimmune-associated, or Crohn's disease. Sometimes, cuffitis or irritable pouch syndrome can be misdiagnosed as pouchitis. Furthermore, idiopathic pouchitis itself can be sub-classified into types based on the clinical pattern, presentation, and responsiveness to antibiotic treatment. Treatment differs among the various forms of pouchitis. Therefore, it is important to establish the correct diagnosis in order to select the appropriate treatment and further management. In this editorial, we present the spectrum of pouchitis and the specific features related to the diagnosis and treatment of the various forms.

Celiac Disease and Type 1 Diabetes in Adults: Is This a High-Risk Group for Screening?

The association between celiac disease (CD), an autoimmune condition involving intestinal inflammation related to gluten ingestion, and type 1 diabetes has long been recognized. CD prevalence rates 4 to 6 times greater in adults with type 1 diabetes than in the general population. Much of the existing literature focuses on important implications related to the impact of a gluten-free diet on short-term outcomes in metabolic control and quality of life. Canadian Diabetes Association guidelines recommend targeted CD screening in patients with type 1 diabetes who have classic symptoms, such as abdominal pain, bloating, diarrhea, unexplained weight loss or labile metabolic control; however, a significant proportion (40% to 60%) of patients may have mild or absent symptoms. Recent evidence suggests that adult patients with both conditions are at higher risk for diabetes microvascular comorbidities, increased mortality and impaired bone health if the CD is untreated. The purpose of this review is to describe the association between CD and type 1 diabetes and to summarize recent literature that evaluates risks in patients with both conditions.

Bougie dilators: simple, safe and cost-effective treatment for Crohn's-related fibrotic anal strictures.

Anal strictures with fibrotic induration have been shown to develop in up to 50% of all patients with Crohn's disease (CD) with anal ulceration. We evaluate the technical feasibility, safety and long-term efficacy of bougie dilation for a subgroup of patients with symptomatic Crohn's-related fibrotic anal strictures. Bougie dilation is simple to perform, relatively inexpensive and has a low risk of complications.

The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) protocol: a randomised controlled study to evaluate treatment of asymptomatic coeliac disease in type 1 diabetes.

INTRODUCTION: Coeliac disease (CD) is an autoimmune condition characterised by gluten-induced intestinal inflammation, and observed at a 5-10 fold greater prevalence in type 1 diabetes. While universal screening for CD in patients with diabetes is frequently advocated, objective data is limited as to benefits on diabetes control, bone health or quality of life related to the adoption of a gluten-free diet (GFD) in the large proportion of patients with diabetes with asymptomatic CD. The Celiac Disease and Diabetes-Dietary Intervention and Evaluation Trial (CD-DIET) study is a multicenter, randomised controlled trial to evaluate the efficacy and safety of a GFD in patients with type 1 diabetes with asymptomatic CD. METHODS AND ANALYSIS: Children and adults (8-45 years) with type 1 diabetes will be screened for asymptomatic CD. Eligible patients with biopsy-proven CD will be randomly assigned in a 1:1 ratio to treatment with a GFD for 1 year, or continue with a gluten-containing diet. The primary outcome will evaluate the impact of the GFD on change in glycated haemoglobin. Secondary outcomes will evaluate changes in bone mineral density, blood glucose variability and health-related quality of life between GFD-treated and the regular diet group over a 1-year period. The study was initiated in 2012 and has subsequently expanded to multiple paediatric and adult centres in Ontario, Canada. ETHICS AND DISSEMINATION: The findings from this study will provide high-quality evidence as to the impact of GFD treatment on glycaemic control and complications in asymptomatic children and adults with CD and type 1 diabetes. TRIAL REGISTRATION NUMBER: NCT01566110.

The association of age and race and the risk of large bowel polyps.

BACKGROUND: Blacks have a higher incidence of colorectal cancer and a younger age at diagnosis compared with whites. Few studies have investigated racial differences in risk of metachronous adenomas and serrated polyps and whether this risk differs by polyp characteristics or age of patient. METHODS: We analyzed data pooled from three placebo-controlled adenoma chemoprevention trials to explore racial differences in the risk of large bowel polyps in patients ≤50 and >50 years of age. Using generalized linear regression, we estimated risk ratios (RR) and 95% confidence intervals (CI) as measures of the association between race and risk of one or more adenomas or serrated polyps after randomization. RESULTS: Among the 2,605 subjects who completed at least one follow-up exam, blacks ≤50 years of age had a higher risk of any conventional adenoma (RR, 1.70; 95% CI, 0.99-2.92) and advanced neoplasms (RR, 4.05; 95% CI, 1.43-11.46) and a nonsignificantly lower risk of serrated polyps (RR, 0.75; 95% CI, 0.34-1.62) compared with whites. Among patients >50 years, there was no racial difference in risk of adenomas (RR, 1.08; 95% CI, 0.92-1.27) or advanced neoplasms (RR, 1.05; 95% CI, 0.71- 1.56). However, blacks had a significantly lower risk of serrated polyps (RR, 0.65; 95% CI, 0.49-0.87) than whites. CONCLUSIONS: Our results demonstrate a higher risk of metachronous adenomas in blacks compared with whites at younger ages. IMPACT: Our results suggest that the racial disparity in colorectal cancer incidence may be due to an excess of neoplasia in younger blacks.

Inflammatory bowel disease and thromboembolism.

Patients with inflammatory bowel disease (IBD) have an increased risk of vascular complications. Thromboembolic complications, both venous and arterial, are serious extraintestinal manifestations complicating the course of IBD and can lead to significant morbidity and mortality. Patients with IBD are more prone to thromboembolic complications and IBD per se is a risk factor for thromboembolic disease. Data suggest that thrombosis is a specific feature of IBD that can be involved in both the occurrence of thromboembolic events and the pathogenesis of the disease. The exact etiology for this special association between IBD and thromboembolism is as yet unknown, but it is thought that multiple acquired and inherited factors are interacting and producing the increased tendency for thrombosis in the local intestinal microvasculature, as well as in the systemic circulation. Clinicians' awareness of the risks, and their ability to promptly diagnose and manage tromboembolic complications are of vital importance. In this review we discuss how thromboembolic disease is related to IBD, specifically focusing on: (1) the epidemiology and clinical features of thromboembolic complications in IBD; (2) the pathophysiology of thrombosis in IBD; and (3) strategies for the prevention and management of thromboembolic complications in IBD patients.

E-mail communication in the management of gastroenterology patients: a review.

E-mail correspondence between physicians and patients can be a useful tool to improve communication efficiency, provide economic and ecological benefits, improve therapeutic interventions and adherence, and enhance self-management. The model of self-management in chronic disease has become an integral component of North American and British medicine. From a practical standpoint, the use of e-mail between physicians and patients can complement the self-management model. E-mail communication has many benefits from both patient and physician perspectives. E-mail contact reduces the inefficiencies associated with telecommunications. Physicians are able to better document out-of-office patient encounters and provide access to specialist care for patients in remote locations. This use of e-mail has the potential to increase patient safety through physician approval of self-manager actions, including earlier initiation of needed treatments. Fewer clinic visits afford additional time for new consultations and sicker patients, reducing the overall burden on referral and wait times. The present article reviews some of the literature regarding physician-patient e-mail communication in the general ambulatory setting, in the context of chronic disease and with a specific focus on inflammatory bowel disease (IBD). The authors provide a framework for the use of e-mail communication in the IBD population, with emphasis on the concept of e-mail use. Also illustrated are the benefits and disadvantages, and examples of the e-mail contract as proposed by the Canadian Medical Protective Association. Examples of specific e-mail communication topics are provided for several IBD scenarios. Potential negative consequences of this mode of communication are also discussed.

Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn's disease.

BACKGROUND & AIMS: Methotrexate and infliximab are effective therapies for Crohn's disease (CD). In the combination of maintenance methotrexate-infliximab trial, we evaluated the potential superiority of combination therapy over infliximab alone. METHODS: In a 50-week, double-blind, placebo-controlled trial, we compared methotrexate and infliximab with infliximab alone in 126 patients with CD who had initiated prednisone induction therapy (15-40 mg/day) within the preceding 6 weeks. Patients were assigned randomly to groups given methotrexate at an initial weekly dose of 10 mg, escalating to 25 mg/week (n = 63), or placebo (n = 63). Both groups received infliximab (5 mg/kg of body weight) at weeks 1, 3, 7, and 14, and every 8 weeks thereafter. Prednisone was tapered, beginning at week 1, and discontinued no later than week 14. The primary outcome was time to treatment failure, defined as a lack of prednisone-free remission (CD Activity Index, <150) at week 14 or failure to maintain remission through week 50. RESULTS: Patients' baseline characteristics were similar between groups. By week 50, the actuarial rate of treatment failure was 30.6% in the combination therapy group compared with 29.8% in the infliximab monotherapy group (P = .63; hazard ratio, 1.16; 95% confidence interval, 0.62-2.17). Prespecified subgroup analyses failed to show a benefit in patients with short disease duration or an increased level of C-reactive protein. No clinically meaningful differences were observed in secondary outcomes. Combination therapy was well tolerated. CONCLUSIONS: The combination of infliximab and methotrexate, although safe, was no more effective than infliximab alone in patients with CD receiving treatment with prednisone. ClincialTrials.gov number, NCT00132899.

Postoperative health-care utilization in Crohn's disease: the impact of specialist care.

OBJECTIVES: Crohn's disease (CD) patients frequently require surgery. We sought to characterize postoperative health-care utilization and its impact on outcomes. METHODS: We assembled a population-based cohort of CD patients who underwent first surgery in Ontario, Canada, between 1996 and 2009. We compared intra-individual preoperative and postoperative health-care utilization and characterized utilization of early postoperative gastrointestinal care (EPGIC) and its impact on health outcomes. RESULTS: For the 2,943 CD patients who underwent surgery, the 5-year risk of recurrent surgery was 26%. In the 5th postoperative year, the average annual number of inflammatory bowel disease (IBD)-related clinic visits, emergency department visits, endoscopy procedures, radiological procedures, and hospitalizations decreased by 62, 62, 82, 78, and 89% compared with prior to surgery. Regional utilization of EPGIC varied between 18 and 62% and correlated with the number of gastroenterologists within a regional local health integration network (ρ=0.71; P=0.006). EPGIC was associated with reduced risk of late postoperative CD-related hospitalizations (at least 1 year after surgery; adjusted incidence ratio (IRR), 0.82; 95% confidence interval (CI): 0.72-0.94). Other predictors of late hospitalizations included having an emergency department visit within 6 months (adjusted IRR, 2.60; 95% CI: 2.21-3.05), lower income, and higher comorbidity. Individuals residing in regions with high aggregate EPGIC utilization experienced lower rates of hospitalization compared with those in regions with low utilization (adjusted IRR, 0.83; 95% CI: 0.70-0.95). CONCLUSIONS: IBD-related health-care utilization decreased significantly up to 5 years following surgery. EPGIC may reduce late CD-related hospitalizations following surgery.

How well is Helicobacter pylori treated in usual practice?

BACKGROUND: Helicobacter pylori is a WHO class I carcinogen also associated with nonmalignant gastrointestinal diseases. Effective treatment exists, and all persons infected with H pylori should receive treatment. However, data regarding the rates of treatment prescription in clinical practice are lacking. OBJECTIVE: To determine the rates of H pylori treatment in usual practice. METHODS: Patients with histological evidence of H pylori infection between January 1, 2007, and December 31, 2007, at Sunnybrook Health Sciences Centre (Toronto, Ontario) were identified. Charts were reviewed to determine the rates of H pylori treatment and confirmation of eradication, when indicated. Questionnaires were subsequently sent to endoscopists of patients identified as not having received treatment to determine the reasons for lack of treatment. RESULTS: A total of 102 patients were H pylori positive and were appropriate candidates for treatment, of whom 58 (57%) were male and 78 (76%) were outpatients, with 92 (90%) receiving eradication therapy. When indicated, 15 of 22 (68%) patients received confirmation of eradication, 13 of 18 (72%) patients underwent repeat endoscopy and 86% received complete therapy. Outpatients were more likely to receive eradication therapy (OR 10.3 [95% CI 2.6 to 40.4]; P=0.001) and complete therapy (OR 13.2 [95% CI 3.8 to 45.7]; P=0.0001) compared with inpatients. Having a follow-up appointment resulted in higher treatment rates (OR 12.0 [95% CI 3.0 to 47.5]; P=0.001). CONCLUSION: During the time period studied, adequate rates of H pylori treatment were achieved in outpatients and patients who had formal follow-up at Sunnybrook Health Sciences Centre. However, some aspects of care remain suboptimal including treatment of inpatients and care following treatment. Additional studies are required to identify strategies to improve the care of patients infected with H pylori.