Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality.

OBJECTIVES: The objective of this study was to determine our institution's compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. METHODS: We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. RESULTS: We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). CONCLUSIONS: Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.

Creation of a model to predict survival in patients with refractory coeliac disease using a multinational registry.

BACKGROUND: Refractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome. AIM: To create a prognostic model to estimate survival of patients with refractory coeliac disease. METHODS: We evaluated predictors of 5-year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5-year mortality. RESULTS: The multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11-63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5-year follow-up (cumulative 5-year all-cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5-year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38-3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22-6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61-0.85). A simple weighted three-factor risk score was created to estimate 5-year survival. CONCLUSIONS: Using data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5-year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow-up.

Factors governing long-term adherence to a gluten-free diet in adult patients with coeliac disease.

BACKGROUND: A strict gluten-free diet is the cornerstone of treatment for coeliac disease. Studies of gluten-free diet adherence have rarely used validated instruments. There is a paucity of data on long-term adherence to the gluten-free diet in the adult population. AIMS: To determine the long-term adherence to the gluten-free diet and potential associated factors in a large coeliac disease referral centre population. METHODS: We performed a mailed survey of adults with clinically, serologically and histologically confirmed coeliac disease diagnosed ≥5 years prior to survey. The previously validated Celiac Disease Adherence Test was used to determine adherence. Demographic, socio-economic and potentially associated factors were analysed with adherence as the outcome. RESULTS: The response rate was 50.1% of 709 surveyed, the mean time on a gluten-free diet 9.9 ± 6.4 years. Adequate adherence (celiac disease adherence test score <13) was found in 75.5% of respondents. A higher level of education was associated with adequate adherence (P = 0.002) even after controlling for household income (P = 0.0220). Perceptions of cost, effectiveness of the gluten-free diet, knowledge of the gluten-free diet and self-effectiveness at following the gluten-free diet correlated with adherence scores (P < 0.001). CONCLUSIONS: Long-term adherence to a gluten-free diet was adequate in >75% of respondents. Perceived cost remains a barrier to adherence. Perceptions of effectiveness of gluten-free diet as well as its knowledge, are potential areas for intervention.

The clinical predictors of aetiology and complications among 173 patients presenting to the Emergency Department with oesophageal food bolus impaction from 2004-2014.

BACKGROUND: Oesophageal food bolus impaction (OFBI) is a common gastrointestinal emergency. AIM: To describe contemporary aetiologies of OFBI, and variables that may predict eosinophilic esophagitis (EoE) related OFBI as well as complications. METHODS: Patients presenting to the Emergency Department between 2004 and 2014 with OFBI who underwent oesophagogastroduodenoscopy (EGD) were included. Clinical and endoscopic variables, as well as complications, were recorded. Aetiology of OFBI was determined by reviewing endoscopy reports. A diagnosis of EoE was confirmed via pathology (>15 eosinophils/high-powered field) at the index or follow-up EGD. Logistic regression was used to report associations of variables and complications. RESULTS: Of the 173 patients with OFBI, 139 (80%) had an aetiology recognised, the most frequent being EoE (27%, n = 47), Schatzki's ring (20%, n = 34) and oesophageal stricture (13%, n = 22). Six patients (3%) had oesophageal cancer. Patients with EoE-related OFBI tended to be younger (42 vs. 69 years, P < 0.001), male (81% vs. 52%, P = 0.001), have a prior history of OFBI (45% vs. 18%, P = 0.001), and present during spring or summer (62% vs. 44%, P = 0.04). Eighteen patients (10%) had a complication associated with OFBI, with 3 (2%) perforations. On multivariate regression, patients with EoE-related OFBI were not more likely to have a complication (OR 1.07, P = 0.92), although hypoxia at presentation (OR 59.7, P = 0.006) was associated with complications. CONCLUSIONS: Eosinophilic esophagitis accounts for over a quarter of patients with oesophageal food bolus impaction. Overall complication rate was 10%, with a 2% perforation rate. Clinical characteristics of patients with eosinophilic esophagitis differ from other patients with oesophageal food bolus impaction.

The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study.

OBJECTIVES: Anticoagulants carry a significant risk of gastrointestinal bleeding (GIB). Data regarding the safety of anticoagulation continuation/cessation after GIB are limited. We sought to determine the safety and risk of continuation of anticoagulation after GIB. METHODS: We conducted a prospective observational cohort study on consecutive patients admitted to the hospital who had GIB while on systemic anticoagulation. Patients were classified into two groups at hospital discharge after GIB: those who resumed anticoagulation and those who had anticoagulation discontinued. Patients in both groups were contacted by phone 90 days after discharge to determine the following outcomes: (i) thromboembolic events, (ii) hospital readmissions related to GIB, and (iii) mortality. Univariate and multivariate Cox proportional hazards were used to determine factors associated with thrombotic events, rebleeding, and death. RESULTS: We identified 197 patients who developed GIB while on systemic anticoagulation (n=145, 74% on warfarin). Following index GIB, anticoagulation was discontinued in 76 patients (39%) at discharge. In-hospital transfusion requirements, need for intensive care unit care, and etiology of GIB were similar between the two groups. During the follow-up period, 7 (4%) patients suffered a thrombotic event and 27 (14%) patients were readmitted for GIB. Anticoagulation continuation was independently associated on multivariate regression with a lower risk of major thrombotic episodes within 90 days (hazard ratio (HR)=0.121, 95% confidence interval (CI)=0.006-0.812, P=0.03). Patients with any malignancy at time of GIB had an increased risk of thromboembolism in follow-up (HR=6.1, 95% CI=1.18-28.3, P=0.03). Anticoagulation continuation at discharge was not significantly associated with an increased risk of recurrent GIB at 90 days (HR=2.17, 95% CI=0.861-6.67, P=0.10) or death within 90 days (HR=0.632, 95% CI=0.216-1.89, P=0.40). CONCLUSIONS: Restarting anticoagulation at discharge after GIB was associated with fewer thromboembolic events without a significantly increased risk of recurrent GIB at 90 days. The benefits of continuing anticoagulation at discharge may outweigh the risks of recurrent GIB.

Systematic review: the quality of the scientific evidence and conflicts of interest in international inflammatory bowel disease practice guidelines.

BACKGROUND: Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes. AIM: We examined inflammatory bowel disease guidelines (IBD) for quality of evidence, methods of grading evidence and conflicts of interest (COI). METHODS: All 182 guidelines published by the American College of Gastroenterology, American Gastroenterological Association, British Society of Gastroenterology, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of America and European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed. Nineteen IBD guidelines were found. RESULTS: Eighty-nine per cent (n = 17/19) of the guidelines graded the levels of evidence using seven different systems. Of the 1070 recommendations reviewed, 23% (n = 249) cited level A evidence; 28% (n = 302) level B; 36% (n = 383) level C and 13% (n = 136) level D. The mean age of the guidelines was 4.2 years. In addition, 61% (n = 11/19) of the guidelines failed to comment on COI. All eight articles commenting on COI had conflicts with 81% (n = 92/113) of authors reported an average 11.7 COI. Lastly, there were variations in the recommendations between societies. CONCLUSIONS: Nearly half the IBD guideline recommendations are based on expert opinion or no evidence. Majority of the guidelines fail to disclose any COI, and when commenting, all have numerous COI. Furthermore, the guidelines are not updated frequently and there is a lack of consensus between societal guidelines. This study highlights the critical need to centralize and redesign the guidelines development process.

Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.

BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS: This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS: No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS: Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.

Body mass index and the risk of obesity in coeliac disease treated with the gluten-free diet.

BACKGROUND: Coeliac disease is increasingly diagnosed and weight changes are common after adoption of a gluten-free diet (GFD), however data on body mass index (BMI) changes are limited. AIM: To assess changes in BMI after diagnosis in a large coeliac population. METHODS: A total of 1018 patients with biopsy confirmed coeliac disease seen at our centre were studied retrospectively. Initial and follow-up BMIs were recorded, as was GFD adherence as assessed by an expert dietitian. RESULTS: A total of 679 patients with at least two recorded BMIs and GFD adherence data were included in the study. Mean follow-up was 39.5 months. Compared to regional population data, the coeliac cohort was significantly less likely to be overweight or obese (32% vs. 59%, P < 0.0001). Mean BMI increased significantly after GFD initiation (24.0 to 24.6; P < 0.001). 21.8% of patients with normal or high BMI at study entry increased their BMI by more than two points. CONCLUSIONS: Individuals with coeliac disease have lower BMI than the regional population at diagnosis. BMI increases on the GFD, especially in those that adhere closely to the GFD. On the GFD, 15.8% of patients move from a normal or low BMI class into an overweight BMI class, and 22% of patients overweight at diagnosis gain weight. These results indicate that weight maintenance counselling should be an integral part of coeliac dietary education.

Noncoeliac enteropathy: the differential diagnosis of villous atrophy in contemporary clinical practice.

BACKGROUND: Duodenal villous atrophy (DVA) is a key diagnostic finding in coeliac disease (CD). However, the differential diagnosis for this finding is broad. AIM: To identify conditions causing noncoeliac enteropathy (NCE) with villous atrophy and methods to differentiate between CD and NCE in clinical practice. METHODS: Through record review we identified patients with DVA due to conditions other than CD. Patient demographics, clinical features and relevant investigations were compared with CD patients. Rates of CD misdiagnosis, and response to treatments were recorded. RESULTS: Thirty cases of NCE were identified with ten different aetiologies. Unspecified immune-mediated enteropathy was the most common aetiology; affecting 10 patients. Gastrointestinal symptoms were more common in NCE than those in CD patients (P < 0.01). Twenty of the 24 NCE patients tested were HLA-DQ2/DQ8 negative. Twenty-six NCE patients were negative for IgA tissue transglutaminase (tTG) (P = 0.0001). Intraepithelial lymphocytosis was absent in 10 (33.3%) patients. Twenty-one NCE patients initially misdiagnosed with CD and one with gluten intolerance were prescribed a gluten free diet (GFD). Fifteen of 22 had repeat biopsy and none showed histological improvement. CONCLUSIONS: Although coeliac disease is the most common cause of DVA, noncoeliac enteropathy is not rare and may easily be mistaken for coeliac disease. Noncoeliac enteropathy is suggested by a normal initial tTG (87%), lack of intraepithelial lymphocytosis on biopsy, and lack of histological response to a gluten free diet. Subjective response to gluten free diet has poor predictive value for coeliac disease. Noncoeliac enteropathy can often be confirmed by negative HLA-DQ2/DQ8 testing and targeted investigations can ascertain a definitive aetiology in most cases.

A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease.

BACKGROUND: Increasing numbers of individuals are now being diagnosed with coeliac disease. The only accepted treatment for coeliac disease is lifelong adherence to a strict gluten-free diet (GFD). Individuals' ability to adhere to the GFD varies, but systematic studies guiding the assessment of adherence are currently lacking. AIM: We sought to compare the predictive value of self-report and four serologic tests compared to expert nutritionist evaluation. METHODS: In all, 154 individual adults with biopsy-proven coeliac disease rated their adherence to the GFD on a Likert scale. Serum antibody titres of IgA anti-tissue transglutaminase, and IgA and IgG anti-deamidated gliadin peptides were determined. Using anova and ROC analyses, results were compared to a standardized evaluation by an expert nutritionist blinded to the participants' self-rated adherence and serology results. RESULTS: All serologic measures as well as participant reported adherence were significantly associated with GFD adherence as assessed by expert nutritionist evaluation. However, on ROC analysis no measure performed satisfactorily. The performance of serologic testing, but not self-report, improved with increased time on the GFD. CONCLUSION: Although current serologic tests have very high sensitivities and specificities for the diagnosis of coeliac disease, they cannot replace trained nutritionist evaluation in the assessment of GFD adherence.