Portable gluten sensors: qualitative assessments by adults and adolescents with coeliac disease.

BACKGROUND: Portable gluten sensors are now commercially available to the public, although there is genuine uncertainty within the medical community over whether they should be used for coeliac disease management. The present study described qualitatively the experience of using a portable gluten sensor for 15 adults and 15 adolescents with coeliac disease participating in a 3-month pilot clinical trial. METHODS: Participants were 30 individuals, aged 13-70 years, with biopsy-confirmed coeliac disease on a gluten-free diet. All received a portable gluten sensor and were randomised to low, medium, and high numbers of single-use capsules. Open-ended questions addressed likes and dislikes using the portable gluten sensor after 3 months. Major themes were identified and described. RESULTS: Participants liked that the portable gluten sensor provided extra assurance to check foods presented as gluten-free, the convenient size and portability, the added sense of control, and overall peace-of-mind. Participants disliked having attention drawn to them when using the sensor and feeling as if they were deterring others from eating. Participants also disliked the physical difficulty associated with using the capsules, questionable accuracy and the inability to test fermented foods. Adults were more enthusiastic about the sensor than adolescents. CONCLUSIONS: Positive and negative experiences may be expected when using commercially available portable gluten sensors to help manage coeliac disease. As future versions of this and other gluten sensors become available, it will be important to investigate the relationship between users' experience with the sensors and long-term outcomes such as mucosal healing and quality of life.

Diminished quality of life among adolescents with coeliac disease using maladaptive eating behaviours to manage a gluten-free diet: a cross-sectional, mixed-methods study.

BACKGROUND: Certain approaches to managing a strict gluten-free diet (GFD) for coeliac disease (CD) may lead to impaired psychosocial well-being, a diminished quality of life (QOL) and disordered eating. The present study aimed to understand adolescents' approaches to managing a GFD and the association with QOL. METHODS: Thirty adolescents with CD (13-17 years old) following the GFD for at least 1 year completed the Celiac Dietary Adherence Test (CDAT) and QOL survey. Their approaches to GFD management were explored using a semi-structured interview, where key themes were developed using an iterative process, and further analysed using a psychosocial rubric to classify management strategies and QOL. CDAT ratings were compared across groups. RESULTS: Gluten-free diet management strategies were classified on a four-point scale. Adaptive eating behaviours were characterised by greater flexibility (versus rigidity), trust (versus avoidance), confidence (versus controlling behaviour) and awareness (versus preoccupation) with respect to maintaining a GFD. Approximately half the sample (53.3%) expressed more maladaptive approaches to maintaining a GFD and those who did so were older with lower CD-Specific Pediatric Quality of Life (CDPQOL) scores, mean subscale differences ranging from 15.0 points for Isolation (t = 2.4, P = 0.03, d.f. = 28) to 23.4 points for Limitations (t = 3.0, P = 0.01, d.f. = 28). CONCLUSIONS: Adolescents with CD who manage a GFD with maladaptive eating behaviours similar to known risk factors for feeding and eating disorders experience diminished QOL. In accordance with CD management recommendations, we recommend ongoing follow-up with gastroenterologists and dietitians and psychosocial support referrals, as needed.

Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis.

BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis. AIMS: To investigate the prevalence of CD among individuals with osteoporosis. METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression. RESULTS: We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI = 1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I2  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%). CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

Factors associated with villus atrophy in symptomatic coeliac disease patients on a gluten-free diet.

BACKGROUND: Duodenal injury persists in some coeliac disease patients despite gluten-free diet, and is associated with adverse outcomes. AIM: To determine the prevalence and clinical risk factors for persistent villus atrophy among symptomatic coeliac disease patients. METHODS: A nested cross-sectional analysis was performed on coeliac disease patients with self-reported moderate or severe symptoms while following a gluten-free diet, who underwent protocol-mandated duodenal biopsy upon enrolment in the CeliAction clinical trial. Demographic factors, symptom type, medication use, and serology were examined to determine predictors of persistent villus atrophy. RESULTS: Of 1345 symptomatic patients, 511 (38%, 95% CI, 35-41%) were found to have active coeliac disease with persistent villus atrophy, defined as average villus height to crypt depth ratio ≤2.0. On multivariable analysis, older age (OR, 5.1 for ≥70 vs. 18-29 years, 95% CI, 2.5-10.4) was a risk factor while longer duration on gluten-free diet was protective (OR, 0.37, 95% CI, 0.24-0.55 for 4-5.9 vs. 1-1.9 years). Villus atrophy was associated with use of proton-pump inhibitors (PPIs; OR, 1.6, 95% CI, 1.1-2.3), non-steroidal anti-inflammatory drugs (NSAIDs; OR, 1.64, 95% CI, 1.2-2.2), and selective serotonin reuptake inhibitors (SSRIs; OR, 1.74, 95% CI, 1.2-2.5). Symptoms were not associated with villus atrophy after adjusting for covariates. Conclusions A majority of symptomatic coeliac disease patients did not have active disease on follow-up histology. Symptoms were poorly predictive of persistent mucosal injury. The impact of NSAIDs, PPIs, and SSRIs on mucosal healing in coeliac disease warrants further study.

Coeliac disease: the association between quality of life and social support network participation.

BACKGROUND: There is little information available on the use of social support systems for patients with coeliac disease (CD). We performed a cross-sectional study aiming to examine the association between participation in different types of social support networks and quality of life (QOL) in adults with CD. METHODS: A survey including a validated CD specific QOL instrument was administered online and in-person to adults with CD who were following a gluten-free diet. Participation in social support networks (type, frequency and duration) were assessed. RESULTS: Among the 2138 participants, overall QOL scores were high, averaging 68.9 out of 100. Significant differences in QOL scores were found for age, length of time since diagnosis and level of education. Most (58%) reported using no social support networks. Of the 42% reporting use of social support networks (online 17.9%, face-to-face 10.8% or both 12.8%), QOL scores were higher for those individuals who used only face-to-face social support compared to only online support (72.6 versus 66.7; P < 0.0001). A longer duration of face-to-face social support use was associated with higher QOL scores (P < 0.0005). By contrast, a longer duration and increased frequency of online social support use was associated with lower QOL scores (P < 0.03). CONCLUSIONS: Participation in face-to-face social support networks is associated with greater QOL scores compared to online social support networks. These findings have potential implications for the management of individuals with CD. Emphasis on face-to-face support may improve long-term QOL and patient outcomes.

The coeliac stomach: gastritis in patients with coeliac disease.

BACKGROUND: Lymphocytic gastritis (LG) is an uncommon entity with varying symptoms and endoscopic appearances. This condition, as well as two forms of H. pylori-negative gastritis [chronic active gastritis (CAG) and chronic inactive gastritis (CIG)], appears to be more common in patients with coeliac disease (CD) based on single-centred studies. AIM: To compare the prevalence of LG, CAG and CIG among those with normal duodenal histology (or nonspecific duodenitis) and those with CD, as defined by villous atrophy (Marsh 3). METHODS: We analysed all concurrent gastric and duodenal biopsy specimens submitted to a national pathology laboratory during a 6-year period. We performed multiple logistic regression to identify independent predictors of each gastritis subtype. RESULTS: Among patients who underwent concurrent gastric and duodenal biopsy (n = 287,503), the mean age was 52 and the majority (67%) were female. Compared to patients with normal duodenal histology, LG was more common in partial villous atrophy (OR: 37.66; 95% CI: 30.16-47.03), and subtotal/total villous atrophy (OR: 78.57; 95% CI: 65.37-94.44). CD was also more common in CAG (OR for partial villous atrophy 1.93; 95% CI: 1.49-2.51, OR for subtotal/total villous atrophy 2.42; 95% CI: 1.90-3.09) and was similarly associated with CIG (OR for partial villous atrophy 2.04; 95% CI: 1.76-2.35, OR for subtotal/total villous atrophy 2.96; 95% CI: 2.60-3.38). CONCLUSIONS: Lymphocytic gastritis is strongly associated with coeliac disease, with increasing prevalence correlating with more advanced villous atrophy. Chronic active gastritis and chronic inactive gastritis are also significantly associated with coeliac disease. Future research should measure the natural history of these conditions after treatment with a gluten-free diet.

Development and validation of a clinical prediction score (the SCOPE score) to predict sedation outcomes in patients undergoing endoscopic procedures.

BACKGROUND: Use of anaesthesia services during endoscopy has increased, increasing cost of endoscopy. AIM: To identify risk factors for and develop a clinical prediction score to predict difficult conscious sedation. METHODS: We performed a retrospective cross-sectional study of all patients who underwent oesophagogastroduodenoscopy (OGD) and colonoscopy with endoscopist-administered conscious sedation. The endpoint of difficult sedation was a composite of receipt of high doses (top quintile) of benzodiazepines and opioids, or the documentation of agitation or discomfort. Univariate and multivariate analyses were performed to measure association of the outcome with: age, sex, body mass index (BMI), procedure indication, tobacco use, self-reported psychiatric history, chronic use of benzodiazepines, opioids or other psychoactive medications, admission status and participation of a trainee. A clinical prediction score was constructed using statistically significant variables. RESULTS: We identified 13,711 OGDs and 21,763 colonoscopies, 1704 (12.4%) and 2299 (10.6%) of which met the primary endpoint, respectively. On multivariate analysis, factors associated with difficulty during OGD were younger age, procedure indication, male sex, presence of a trainee, psychiatric history and benzodiazepine and opioid use. Factors associated with difficulty during colonoscopy were younger age, female sex, BMI <25, procedure indication, tobacco, benzodiazepine, opioid and other psychoactive medication use. A clinical prediction score was developed and validated that may be used to risk-stratify patients undergoing OGD and colonoscopy across five risk classes. CONCLUSIONS: Using the Stratifying Clinical Outcomes Prior to Endoscopy (SCOPE) score, patients may be risk stratified for difficult sedation/high sedation requirement during OGD and colonoscopy.

Predictors of persistent villous atrophy in coeliac disease: a population-based study.

BACKGROUND: Villous atrophy (VA) with intraepithelial lymphocytosis is the histological hallmark of coeliac disease (CD), but reported rates of mucosal recovery are variable. AIM: To determine the impact of age and other demographic variables on the probability of persistent VA on follow-up biopsy. METHODS: We identified patients with VA on duodenal histology at all 28 Swedish pathology departments during the years spanning 1969-2008. We examined age, gender, calendar period, duration of disease and educational attainment to determine predictors of persistent VA. RESULTS: Of 7648 patients with CD who underwent follow-up biopsy, persistent VA was present in 3317 (43%; 95% CI 42-44%). The effect of age on persistent VA varied according to time period; among those biopsied in the years spanning 2000-2008, the prevalence of persistent VA was 31%, and increasing age was associated with increasing rates of persistent VA (17% among those younger than 2 years compared to 56% among those ≥70 years). In contrast, persistent VA did not vary widely by age in earlier years. On multivariate analysis (restricted to the calendar period 2000-2008, 2-5 years after CD diagnosis), persistent VA was more common among males (OR 1.43; 95% CI 1.07-1.90) and less common among patients with higher educational attainment (OR for college degree vs. <2 years of high school 0.52, 95% CI 0.35-0.78). CONCLUSIONS: The prevalence of persistent villous atrophy has changed over time, with greater rates of healing in recent years. Social differences in persistent villous atrophy suggest that access and/or education regarding the gluten-free diet impact mucosal healing.

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.

Mucosal healing and mortality in coeliac disease.

BACKGROUND: Coeliac disease (CD), characterised by the presence of villous atrophy (VA) in the small intestine, is associated with increased mortality, but it is unknown if mortality is influenced by mucosal recovery. AIMS: To determine whether persistent VA is associated with mortality in CD. METHODS: Through biopsy reports from all pathology departments (n = 28) in Sweden, we identified 7648 individuals with CD (defined as VA) who had undergone a follow-up biopsy within 5 years following diagnosis. We used Cox regression to examine mortality according to follow-up biopsy. RESULTS: The mean age of CD diagnosis was 28.4; 63% were female; and the median follow-up after diagnosis was 11.5 years. The overall mortality rate of patients who underwent follow-up biopsy was lower than that of those who did not undergo follow-up biopsy (Hazard Ratio 0.88, 95% CI: 0.80-0.96). Of the 7648 patients who underwent follow-up biopsy, persistent VA was present in 3317 (43%). There were 606 (8%) deaths. Patients with persistent VA were not at increased risk of death compared with those with mucosal healing (HR: 1.01; 95% CI: 0.86-1.19). Mortality was not increased in children with persistent VA (HR: 1.09 95% CI: 0.37-3.16) or adults (HR 1.00 95% CI: 0.85-1.18), including adults older than age 50 years (HR: 0.96 95% CI: 0.80-1.14). CONCLUSIONS: Persistent villous atrophy is not associated with increased mortality in coeliac disease. While a follow-up biopsy will allow detection of refractory disease in symptomatic patients, in the select population of patients who undergo repeat biopsy, persistent villous atrophy is not useful in predicting future mortality.

Living with coeliac disease: survey results from the U.S.A.

BACKGROUND: The only treatment for coeliac disease is lifelong adherence to a rigorous gluten-free diet. The present study aimed to evaluate the influence of coeliac disease on the social aspects of daily life of individuals in the U.S.A. METHODS: The present study used a self-administered survey including the standard Quality of Life questionnaire (12-item short-form) with validated disease-specific questions. sas statistical software 2010 (SAS Institute, Cary, NC, U.S.A.) was used to calculate the mean (SD). RESULTS: Individuals with coeliac disease overall had a low positive health perception. Validated diet and disease-specific questions revealed a significant negative impact on quality of life in social settings. Specifically, the areas of travel, dining out and family life are most affected. The negative impact of diet significantly decreased over time, although it did not resolve for the domains of dining out of the home and travel. Those diagnosed in childhood and maintained on the diet had less of an impact on the quality of life as an adult. CONCLUSIONS: Individuals with coeliac disease in the U.S.A. have a diminished quality of life, especially in the social aspects of life.

Risk of colorectal adenomas in patients with coeliac disease.

BACKGROUND: Coeliac disease is associated with an increased risk of lymphoma and small bowel malignancy, but most studies have found no increased risk of colorectal cancer. AIM: To compare the prevalence of colorectal adenomas in coeliac disease patients with that in non-coeliac disease controls. METHODS: We identified all coeliac disease patients who underwent colonoscopy at our institution during a 44-month period. We matched each patient with non-coeliac disease controls by age, gender and endoscopist. We compared the adenoma prevalence between these groups, and used multivariate analysis to assess the independent association of coeliac disease with adenomas. RESULTS: We identified 180 patients with coeliac disease and 346 controls. At least one adenoma was present in 13% of coeliac disease patients and 17% of controls (P = 0.20). On multivariate analysis, age (OR per year 1.04, 95% CI 1.02-1.07) and male gender (OR 2.33, 95% CI 1.36-3.98) were associated with adenomas, while the relationship between coeliac disease and adenomas remained null (OR 0.75, 95% CI 0.41-1.34). CONCLUSIONS: Coeliac disease is not associated with an increased risk of colorectal neoplasia. The lack of increased risk of colorectal cancer observed in population studies is related to a true average risk of colorectal neoplasia, rather than artifactually reflecting increased colonoscopy and associated polypectomies in the coeliac population.

The development and validation of a new coeliac disease quality of life survey (CD-QOL).

BACKGROUND: Previous studies on coeliac disease (CD)-related quality of life (QOL) have been limited by their use of a 'generic' rather than coeliac disease-specific assessment instruments. AIM: To develop and psychometrically validate a new coeliac disease-specific instrument, the CD-QOL. METHODS: Through a series of focus groups, we elicited items from patients that related to the specific nature of their disease and its impact on their basic needs. Through expert review, cognitive debriefing with patients and pilot testing, a scale was developed, refined and administered to 387 patients on a gluten-free diet from both community-based support groups and a tertiary care referral centre. Finally, a formal validation study was conducted to assess the psychometric properties of the CD-QOL. RESULTS: The final CD-QOL has 20 items across four clinically relevant subscales (Limitations, Dysphoria, Health Concerns, and Inadequate Treatment). The CD-QOL has high internal consistency, reliability, and psychometric validation indicates both convergent and discriminate validity. CONCLUSIONS: The CD-QOL is a reliable and valid measure of coeliac disease related QOL. As a new disease-specific instrument, it is likely to be a useful tool for evaluating patients with this disorder.

The effect of substituting alternative grains in the diet on the nutritional profile of the gluten-free diet.

BACKGROUND: The only treatment for coeliac disease is lifelong adherence to a gluten-free diet. Several studies have reported nutritional deficiencies in individuals on a gluten-free diet. The present study aimed to determine whether the nutritional profile of gluten-free diet could be improved through the use of alternative grains. METHODS: A retrospective review of diet history records by a celiac specialist dietitian were used to establish a 'standard' gluten-free dietary pattern. An 'alternative' gluten-free dietary pattern was developed that substituted naturally gluten-free grains or gluten-free products made from 'alternative' flours (oats, high fibre gluten-free bread and quinoa) in the standard pattern. A paired t-test was performed to identify statistical significance between the 'alternative' and standard gluten-free dietary pattern. RESULTS: Analysis of standard pattern indicated that 38% of meals and snacks contained no grain or starch choice. Of those meals that contained a grain or starch component, rice was the grain chosen 44% of the time. The inclusion of alternative grains or grain products provided a higher nutrient profile compared to the standard gluten-free dietary pattern (P = 0.002). Several nutrients; protein (20.6 g versus 11 g), iron (18.4 mg versus 1.4 mg), calcium (182 mg versus 0 mg) and fibre (12.7 g versus 5 g) were significantly increased by changing the grain or starch component in the dietary pattern. The B vitamin content (riboflavin, niacin and folate) was improved, although this was not statistically significant (P = 0.125). DISCUSSION: The inclusion of alternative grain-based products increased the nutrient profile of the gluten-free dietary pattern significantly.