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Background There is uncertainty regarding the prevalence of psychiatric illnesses in patients with celiac disease (CD) and people who avoid gluten (PWAG) without a diagnosis of CD. Participants and methods We obtained data from 22 274 participants from the 2009–2014 National Health and Nutrition Examination Survey to compare the prevalence of depression, insomnia, quality-of-life variables, and psychotropic medication use in CD participants and PWAGs to controls. We used multivariable logistic regression to assess for independent associations between CD/PWAG status and the outcomes of these variables. Results Depression was present in 8.2% of controls compared with 3.9% of participants with CD (P=0.18) and 2.9% of PWAGs (P=0.002). After adjustment for age, sex, race, income, and access to healthcare, PWAGs maintained lower odds of depression compared with controls (odds ratio=0.25; 95% confidence interval: 0.12–0.51; P=0.0001). The prevalence estimates of sleep difficulty among controls (27.3%) compared to participants with CD or PWAGs were 37.7% (P=0.15) and 34.1% (P=0.11). Those with diagnosed CD had increased odds of sleep difficulty (odds ratio=2.41; 95% confidence interval 1.04–5.60), but this was no longer significant after multivariable adjustment (P=0.17). Conclusion Among a nationally representative US sample, participants with CD overall showed no increased odds of depression or sleep difficulty. PWAGs showed lower odds of depression compared with controls. Future research should investigate the relationship between a diagnosis of CD and the development of psychiatric conditions.

BACKGROUNDOxaliplatin in combination with either 5‐fluorouracil or capecitabine is commonly used as first‐line therapy for patients with small bowel adenocarcinoma. The addition of irinotecan improves survival in other gastrointestinal tumors but at the cost of hematologic toxicity. The authors performed a phase 2 cooperative group study (North Central Cancer Treatment Group N0543, Alliance) using genotype‐dosed capecitabine, irinotecan, and oxaliplatin (gCAPIRINOX), with dosing assigned based on UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genotype to test: 1) whether the addition of irinotecan would improve outcomes; and 2) whether UGT1A1 genotype‐based dosing could optimize tolerability.METHODSPreviously untreated patients with advanced small bowel adenocarcinoma received irinotecan (day 1), oxaliplatin (day 1), and capecitabine (days 2‐15) in a 21‐day cycle and were dosed with gCAPIRINOX according to UGT1A1*28 genotypes (6/6, 6/7, and 7/7).RESULTSA total of 33 patients (17 with the 6/6 genotype, 10 with the 6/7 genotype, and 6 with the 7/7 genotype) were enrolled from October 2007 to November 2013; 73% were male, with a mean age of 64 years (range, 41‐77 years). Location of the primary tumor included the duodenum (58%), jejunum (30%), and ileum (9%). The regimen yielded a confirmed response rate of 37.5% (95% confidence interval, 21%‐56%), with a median progression‐free survival of 8.9 months and a median overall survival of 13.4 months. Neither hematologic toxicity (grade ≥3 in 52.9%, 30.0%, and 33.3%, respectively, of the 6/6, 6/7, and 7/7 genotype groups) nor tumor response rate (41.2%, 33%, and 33%, respectively) were found to differ significantly by UGT1A1 genotype.CONCLUSIONSUGT1A1 genotype‐directed dosing (gCAPIRINOX) appears to be feasible with favorable rates of hematologic toxicity compared with prior 3‐drug studies in unselected patients. Larger studies would be needed to determine the regimen's comparability to oxaliplatin and capecitabine (CapeOx) alone or if response/toxicity differs among patients with different UGT1A1 genotypes. Cancer 2017;123:3494‐501. © 2017 American Cancer Society.

Linked ContentThis article is linked to Mahadev et al and Braude, Newnham papers. To view these articles visit https://doi.org/10.1111/apt.13988 and https://doi.org/10.1111/apt.14055.

Background Patients with celiac disease (CD) are at increased risk of certain infections, but it is unknown if mucosal healing influences this risk. Methods We collected data on 29,096 individuals with CD (equal to villous atrophy) through Sweden’s 28 pathology departments undergoing biopsy 1969–2008. Through the Swedish Patient Register we obtained information on any infection and specifically sepsis, streptococcal infection, influenza, Clostridium difficile, herpes zoster and pneumococcal infection up until December 2009. We used Cox regression to calculate hazard ratios (HRs) for the risk of future diagnosis of infection according to mucosal healing on follow-up biopsy (persistent villous atrophy vs mucosal healing). Results Of 5598 CD individuals with no record of any infections before follow-up biopsy, 45% had persistent villous atrophy, 619 (24%) of them had a later infection, compared to 579 (19%) in those with mucosal healing ( p < 0.01); the yearly incidence was 2.1% in both groups. Adjusting for age, sex, calendar period, time between biopsies and education, persistent villous atrophy was however not associated with later infection overall (HR = 0.99; 95% CI = 0.88–1.11) or with any of the specific infections. Conclusions In CD, mucosal healing does not influence the risk of serious infection requiring hospital-based medical attention.

SummaryBackgroundDuodenal injury persists in some coeliac disease patients despite gluten‐free diet, and is associated with adverse outcomes.AimTo determine the prevalence and clinical risk factors for persistent villus atrophy among symptomatic coeliac disease patients.MethodsA 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.ResultsOf 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.ConclusionsA 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.

ABSTRACTObjectives:Celiac disease (CD) is a common immune‐mediated disorder that affects up to 1% of the general population. Recent reports suggest that the incidence of CD has reached a plateau in many countries. We aim to study the incidence and altered presentation of childhood CD in a well‐defined population.Methods:Using the Rochester Epidemiology Project, we retrospectively reviewed Mayo Clinic and Olmsted Medical Center medical records from January 1994 to December 2014. We identified all CD cases of patients ages 18 years or younger at the time of diagnosis. Incidence rates were calculated by adjusting for age, sex, and calendar year and standardizing to the 2010 US white population.Results:We identified 100 patients with CD. Incidence of CD has increased from 8.1 per 100,000 person‐years (2000–2002) to 21.5 per 100,000 person‐years (2011–2014). There was an increase in CD prevalence in children from 2010 (0.10%) to 2014 (0.17%). Thirty‐four patients (34%) presented with classical CD symptoms, 43 (43%) had nonclassical CD, and 23 (23%) were diagnosed by screening asymptomatic high‐risk patients. Thirty‐six patients (36%) had complete villous atrophy, 51 (51%) had partial atrophy, and 11 (11%) had increased intraepithelial lymphocytes. Two patients were diagnosed without biopsy. Most patients (67%) had a normal body mass index, 17% were overweight/obese, and only 9% were underweight.Conclusions:Both incidence and prevalence of CD have continued to increase in children during the past 15 years in Olmsted County, Minnesota. Clinical and pathologic presentations of CD are changing over time (more nonclassical and asymptomatic cases are emerging).

SummaryBackgroundTherapy for coeliac disease (CD) mainly relies on following a gluten‐free diet (GFD); however, a serum marker for gluten intake has yet to be established.AimTo evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse.MethodsAlkylresorcinol concentrations were compared among treated patients with coeliac disease (n = 34), untreated coeliac disease patients (n = 36) and controls (n = 33). Furthermore, seven additional coeliac disease patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of five mice fed a regular chow and 10 mice fed lifelong with a gluten‐free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated.ResultsTotal alkylresorcinol concentrations were significantly lower in treated with coeliac disease [median (IQR), 3 (2–8) nmol/L], compared to untreated patients [median (IQR), 32 (11–74) nmol/L; P < 0.0001] or healthy controls [median (IQR), 54 (23–112) nmol/L; P < 0.0001]. Moreover, alkylresorcinol concentrations in coeliac disease patients significantly decreased after introduction of a GFD (median, 34 nmol/L at diagnosis vs. 5 nmol/L after GFD, P = 0.02). In the mice, median (IQR) total alkylresorcinol concentrations in serum samples of mice fed lifelong with a gluten‐free chow was 1.8 (1.6–2.3) nmol/L, which was further significantly increased to 16 (11–22) nmol/L after 8 days of feeding with the gluten‐free chow that had gluten added to it. (P = 0.008).ConclusionSerum alkylresorcinol concentrations could be a useful marker for dietary gluten in coeliac disease.