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Background and Aim: Celiac disease (CeD) is increasingly diagnosed but significant disparities exist in awareness, practices, resources, and legislation worldwide. We conducted a global online survey with CeD experts to assess this disparity internationally., Methods: A 55 questions survey encompassing nine domains relevant to CeD care (awareness, gluten-free [GF] foods availability/cost/quality, GF labeling, CeD dietician availability, insurance for CeD patients, medical training, research funding, patient support groups, and unmet needs) was generated and sent to CeD experts worldwide electronically. Countries were stratified based on per capita income as high-income (HIC) and lower-income countries (LIC) (including upper-middle-, lower-middle-, and low-income countries). Survey responses were summarized as a single score using principal component analysis., Results: Valid responses were obtained from 131(37.4%) [HIC: 71; LIC: 60] of contacted CeD experts from 63 countries. Compared with HIC, LIC experts perceived worse availability (HIC:80% vs LIC: 47%; P < 0.001), quality (52% vs 20%; P < 0.001), and legislation for labeling of GF foods (82% vs 37%; P < 0.001), with unfavorable reimbursement policies (27% vs 12%; P = 0.002), subsidies (32% vs 13%; P < 0.001), and insurance (76% vs 43%; P < 0.001) for CeD patients. LIC also lacked awareness about CeD among general physicians (69% vs 32%; P < 0.001), trained celiac dieticians (39% vs 12%; P = 0.002), and active CeD patient support groups (93% vs 50%; P < 0.001). All experts believed that GF foods were costly (94% vs 87%), frequently contaminated (27% vs 32%), and unfavorably taxed (97% and 93%). The experts agreed on key unmet needs and better research funding. Overall CeD preparedness score (median 58.3 vs 33.0; P < 0.001) was also associated with income., Conclusions: The present survey highlights the opinion of global experts on the challenges, opportunities, and preparedness related to CeD and differences worldwide by income., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease., Methods: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events., Results: A total of 114 patients (male 39%, Crohn's disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed., Conclusions: At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile., (© 2023 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Introduction: Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT., Methods: Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16-23 S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI., Results: 209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction., Conclusion: Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice., (© 2024. The Author(s).)

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that encompasses two major conditions: Crohn's disease (CD) and ulcerative colitis (UC). Historically, IBD has been primarily reported in western countries, but over the past decades, its prevalence is rapidly increasing, especially in lower and middle-income countries (LMICs) such as India and China and also in Sub-Saharan Africa. The prevalence of IBD in LMICs has been the subject of growing concern due to the impact of access to public healthcare and the burden it places on healthcare resources. The classical thiopurines face significant challenges due to cessation of therapy in approximately half of patients within one year due to side effects or ineffectiveness. In this article, we highlight innovating thiopurine treatment for IBD patients in downregulating side effects and improving efficacy., (© 2024. The Author(s).)

Drug rediscovery refers to the principle of using 'old' drugs outside the indications mentioned in the summary of product characteristics. In the past decades, several drugs were rediscovered in a wide variety of medical fields. One of the most recent examples is the unconditional registration of thioguanine (TG), a thiopurine derivative, in patients with inflammatory bowel disease in the Netherlands. In this paper, we aim to visualise potential hurdles that hamper drug rediscovery in general, emphasise the global need for optimal use and development of potentially useful drugs, and provide an overview of the registration process for TG in the Netherlands. With this summary, we aim to guide drug rediscovery trajectories in the near future., Competing Interests: Competing interests: NdB served as a speaker for AbbVie and MSD and as consultant and principal investigator for TEVA Pharma BV and Takeda; and received an unrestricted research grant from Dr Falk, TEVA Pharma BV, MLDS and Takeda. MS received unrestricted research grants from TEVA Pharma BV. BM has nothing to declare. MN served as an adviser to Boehringer, MSD, AbbVie, Celgene, Pentax, Takeda, Janssen, Giuliani and PPM. AAvB received speaker, consultancy or advisory board fees from AbbVie, BMS, Galapagos, Ferring, Janssen and TEVA Pharma BV. Galapagos, Ferring and Janssen supported educational programmes. TEVA Pharma BV and Pfizer supported research projects. CM served as an adviser to TEVA UK, Arega Belgium and Douglas Pharma NZ., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)