Introduction

Celiac disease (CeD) is a chronic, immune-mediated, systemic disorder characterized by inflammation of the small intestine, antibody formation and villous damage in response to gluten ingestion. The only current management/treatment option for CeD is a gluten-free diet (GFD), which has major limitations, not least that patients following a GFD may still experience symptoms. The US Food and Drug Administration guidance ‘Celiac disease: developing drugs for adjunctive treatment to a GFD’ indicates that symptom monitoring should be a co-primary endpoint with histology for the assessment of disease improvement in clinical trials.

Aims & Methods

This US prospective observational study (Virtual Celiac Symptoms Study, NCT05309330) aimed to assess experience with a GFD and celiac-related symptoms in patients with CeD. Eligible participants were aged ≥12 years, had a CeD diagnosis for ≥1 year confirmed via self-reported biopsy (biopsy or serology for participants aged <18 years), were on a GFD for ≥6 months and reported CeD-related symptoms in the past 3 months. Participants were recruited with the assistance of the Celiac Disease Foundation via digital advertisements and data were collected using an electronic patient-reported outcomes platform. Study participants were followed up for 12 weeks and CeD-related symptoms and gluten exposure were assessed daily. Quality of life and healthcare resource utilization were also assessed. This analysis focuses on the gastrointestinal (GI) symptoms of diarrhea, abdominal pain, bloating, nausea and vomiting experienced by adults during the study.

Results

The study was conducted from July 25, 2022 to March 4, 2023. Adults comprised 338 of the 480 participants (88% female; 99% White) with a median age of 37 years (range 18–71). At baseline, 58% of adult participants reported CeD-related symptoms in the past week. All adult participants reported following a GFD; 21% reported “never eating gluten accidentally or on purpose” and 71% reported “rarely eating gluten accidentally”. The remaining 8% reported “rarely eating gluten on purpose”. During the 12-week study, all of the adults reported at least one GI symptom, with each GI symptom (with the exception of vomiting), occurring at least once in over 90% of adults (abdominal pain 99%, bloating 99%, diarrhea 95%, nausea 94% and vomiting 42%). Frequency of GI symptoms was high. For adults who experienced abdominal pain or bloating, these symptoms occurred on >50% of the follow-up days. For adults who experienced diarrhea and nausea, these symptoms occurred on >30% of days (Table 1).

Table 1. GI symptom occurrence among adult participants (N = 338)

Conclusion

Despite participants adhering to a GFD, symptom frequency in this adult population with CeD was high. GI symptoms such as diarrhea, nausea, bloating and abdominal pain may be appropriate endpoints for inclusion in clinical trials of potential CeD therapies. This study further highlights the unmet need for additional treatments for patients with CeD on a GFD.

Disclosure

LMM and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. JRM, SSe and SSu are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL and DA serve as consultants for Takeda Pharmaceuticals.
Funding statement: This study was sponsored by Takeda Development Center Americas, Inc. Medical writing support was provided by Christina Nikolakopoulou, PhD, of Oxford PharmaGenesis, Oxford, UK and was funded by Takeda Pharmaceuticals.

Introduction

Celiac disease (CD) has been associated with reduced quality of life and psychological disorders, among which the most common are anxiety and depression [1, 2]. Several reports have focused on the difficulties of living with CD, particularly regarding its impact on physical, social and emotional factors in adults.

Aims & Methods

The cross-sectional study evaluated the changes in the anxiety and depression of 48 patients with CD. The control group was consisted of 20 people without gastrointestinal diseases. Several validated questionnaires were administered to measure psychological symptoms (the Medical Outcomes Study Questionnaire Short Form 36 Health Survey (MOS SF-36), Hospital Anxiety and Depression Scale (HADS) and State-Trait Anxiety Inventory (STAI)) and adherence to a gluten-free diet (GFD). Based on the results GFD the patients divided into two groups. The first group patients have not been adhered to a GFD and the second group patients have been strictly following a GFD.

Results

To decrease of the level physical and mental components of the quality of life was determined in patients with CD in comparison with the control group (36.1 and 40.0, respectively; p < 0.01). The most of the patients with CD (72.8%) had anxiety reactions. According to HADS anxiety has reached clinically significant level in 43.7% patients with CD. STAI score state anxiety and trait anxiety have been elevated in patients with CD (p <0.01). Its haven`t been significant differences in the frequency and severity of anxiety in patients with CD without and with GFD. Symptoms of depression have been more frequently in patients with CD with GFD, however it’s have not been reached a clinically significant level.

Conclusion

The features of emotional disturbances in patients with CD include the prevalence of the frequency of anxiety over the depression. The results showed no correlation between anxiety and adherence to GFD. The severity of depression increased in patients with GFD. This finding is consistent with Barratt et al.'s finding that difficulty with GPA compliance is a major factor in reduced quality of life [3].

References

1. Zingone F, Swift GL, Card TR, Sanders DS, Ludvigsson JF, Bai JC. Psychological morbidity of celiac disease: A review of the literature. United European Gastroenterol J. 2015 Apr;3(2):136-45. doi: 10.1177/2050640614560786
2. Canova C, Rosato I, Marsilio I, Valiante F, Zorzetto V, Cataudella G, D'Odorico A, Zingone F. Quality of Life and Psychological Disorders in Coeliac Disease: A Prospective Multicentre Study. Nutrients. 2021 Sep 16;13(9):3233. doi: 10.3390/nu13093233
3. Barratt S.M., Leeds J.S., Sanders D.S. Quality of Life in Coeliac Disease is Determined by Perceived Degree of Difficulty Adhering to a Gluten-Free Diet, not the Level of Dietary Adherence Ultimately Achieved. J. Gastrointestin. Liver Dis. 2011;20:241–245

Introduction

Initial reports suggested a high mortality associated with peri-operative COVID-19 infection resulting in delayed surgery and a global change in surgical pathways. The impact of COVID-19 variants and vaccinations on surgical outcomes is yet to be described.

Aims & Methods

We aimed to define the risk of COVID-19 infection in the 30 days following surgery and the associated mortality. With the approval of NHS England we identified all registered adult patients in an OpenSAFELY-TPP primary care general practice within England whilst having an abdominal, obstetric, orthopaedic, thoracic or vascular procedure defined using OPCS codes between 01/02/2020 and 01/03/2022.COVID vaccinations and COVID waves were defined. Crude 30 day risks were calculated using Kaplan Meier curves. A competing risks Cox proportional survival analysis was used to adjust the cumulative risk of COVID-19 infection by the competing risk of death and subsequent non COVID-19 emergency readmissions.
Primary care records managed by the GP software provider TPP were linked to ONS death data, Hospital Episodes Statistics, and Second Generation Surveillance System Public Health England test data through OpenSAFELY. All data were linked, stored and analysed securely within the OpenSAFELY platform: https://opensafely.org/. Data include pseudonymised data such as coded diagnoses, medications and physiological parameters. No free text data are included. All code is shared openly for review and re-use under MIT open license https://github.com/opensafely/PostOpCovid. Detailed pseudonymised patient data is potentially re-identifiable and therefore not shared.
This study was approved by the Health Research Authority [REC reference 21/EE/0278] by the East of England Research Ethics Committee.

Results

We identified 1,213,890 patients within the study period who underwent at least one surgical procedure. Following surgery 11,950 (0.9%) patients developed COVID-19 infection within 30 days. Post-operative COVID infections were greatest in wave 4 with 2.5% of patients having a post-operative infection. Adjusting for all factors post-operative COVID infection risk was 4.9 (aHR 4.88 95% CI 4.65-5.12) fold greater in the fourth wave compared to the first wave.
Within 90 days of surgery there were 820 (0.06%) deaths. A recent COVID infection increased crude morality to 1.42%, and a post-operative COVID infection increased crude mortality to 1.82%. The risk of death reduced following a first and second vaccination (aHR 0.11 95% CI 0.09-0.13). A recent COVID infection (7-42 days prior to admission) increased mortality 4 fold (aHR 3.84 95% CI 3.31-4.45) and a post-operative COVID infection increased mortality 8 fold (aHR 8.49 95% CI 7.6-9.48) compared to those without a COVID-19 infection. This increased 90 day mortality risk was highest in the second wave following a post-operative COVID infection, but then decreased to the non-covid baseline for both emergency and elective procedures in the 3^rd and 4^th waves.

Conclusion

The risk of post-operative COVID infection is low but has increased as strains have been become more transmissible. The absolute risk of death following peri-operative COVID-19 infection is greater than those who have not had infection however this risk has become attenuated during the latter waves of the pandemic.

Acknowledgements: We are very grateful for all the support received from the TPP Technical Operations team throughout this work, and for generous assistance from the information governance and database teams at NHS England and the NHS England Transformation Directorate.

Disclosure

None to declare

Introduction

Celiac disease (CeD) is a chronic, immune-mediated, systemic disorder characterized by inflammation of the small intestine and antibody formation in response to gluten ingestion. A gluten-free diet (GFD) has major limitations but is the only current treatment for CeD.

Aims & Methods

This US prospective observational study (Virtual Celiac Symptoms Study, NCT05309330) was conducted from July 25, 2022 to March 04, 2023 and aimed to assess experience with a GFD and celiac-related symptoms in patients with CeD. Eligible participants were aged ≥12 years, had a CeD diagnosis for ≥1 year confirmed via self-reported biopsy and serology (or serology only for participants diagnosed at age <18 years), were on a GFD for ≥6 months and reported CeD-related symptoms in the past 3 months. Participants were recruited with the assistance of the Celiac Disease Foundation via digital advertisements and data were collected using an electronic patient-reported outcomes platform. Study participants were followed up for 12 weeks and CeD-related symptoms and gluten exposure were assessed daily. Quality of life and healthcare resource utilization were also assessed. This analysis focuses on the adult participants’ perception of their disease experience at study initiation.

Results

The baseline questionnaires were completed by 338 adult participants. The median age was 37 years (range 18–71), 88% were female and 99% were White. CeD-related symptoms were reported by 58% of participants in the past week. When questioned about occurrence of CeD symptoms, 23% reported “Chronic/ongoing CeD symptoms even when I don't think I've been exposed to gluten”, 37% reported “CeD symptoms only while I am exposed to gluten or within a few days after exposure to gluten” and 36% reported “Chronic/ongoing CeD symptoms, but they are worse when I get exposed to gluten”. The most commonly reported symptoms were bloating (83%), tiredness (81%), abdominal pain (77%) and diarrhea (71%). All participants were following a GFD; 21% reported “never eating gluten accidentally or on purpose” and 71% reported “rarely eating gluten accidentally”. In total, 84% of participants reported that they were likely/extremely likely to experience CeD symptoms after gluten exposure. Symptom intensity was described as moderate or severe by 71% of participants, and 11% reported hospitalization or emergency department care due to CeD in the past year.

Conclusion

Despite high levels of reported adherence to a GFD, many patients still report CeD-related symptoms, especially in response to perceived gluten exposure. Symptoms were often reported as severe and over 10% reported a CeD-related hospitalization or emergency department visit in the past year. This ongoing study highlights the requirement for further understanding of persistent/recurrent symptoms and an unmet need for additional treatments for patients with CeD on a GFD.

Disclosure

LMM and DAL are employees of Takeda Development Center Americas, Inc. and receive stock or stock options. JRM, SSe and SSu are employees of Analysis Group, Inc., which received research support from Takeda Development Center Americas, Inc. MG is an employee of the Celiac Disease Foundation, which received financial support from Takeda Development Center Americas, Inc. EL and DA serve as consultants for Takeda Pharmaceuticals.
Funding statement: This study was sponsored by Takeda Development Center Americas, Inc. Medical writing support was provided by Christina Nikolakopoulou, PhD, of Oxford PharmaGenesis, Oxford, UK and was funded by Takeda Pharmaceuticals.

Introduction

There are no prediction models for a diagnosis of inflammatory bowel disease (IBD) in primary care. Our aim was to develop an IBD risk prediction tool to reduce the length of time patients have undiagnosed IBD symptoms and improve IBD clinical outcomes.

Aims & Methods

We developed and internally validated a risk prediction tool for the diagnosis of IBD, ulcerative colitis (UC) and Crohn’s disease (CD).
A population-based retrospective open cohort study using Clinical Practice Research Datalink (CPRD) database was undertaken between 1st January 2010 and 31st December 2019 of all the patients aged 18 years or older. Patients were followed from first presentation with lower gastrointestinal (GI) symptoms potentially related to IBD to IBD diagnosis. Candidate predictors were chosen based on clinical and substantive knowledge. Cox proportional hazards regression with backward elimination was used for model development of IBD, UC and CD risk prediction models. The predictive performance of the models was assessed using discrimination (C-statistic). Internal validation using 1000 bootstrap sampling repetitions was used to estimate the optimism-corrected measures of predictive performance.

Results

Of 2,056,398 patients with lower GI symptoms: 11,192 patients had an IBD diagnosis (7033 UC (62.8%) and 4138 CD (37.0%)). The final IBD model included demographic factors (age, sex, ethnicity, smoking, index of multiple deprivation, body mass index, Charlson comorbidity index, loperamide use) co-existing conditions (anxiety, depression, irritable bowel syndrome (IBS), haemorrhoids), extraintestinal (EIM) manifestations (mouth ulcers, ophthalmic, primary sclerosing cholangitis, dermatological), laboratory investigations (low haemoglobin (Hb), low Mean Corpuscular volume (MCV), low albumin, low ferritin, raised C-reactive protein (CRP), raised Erythrocyte Sedimentation Rate (ESR), raised calprotectin level). The UC model included all above except mouth ulcers, IBS, ophthalmic EIM. Depression and ferritin were excluded in the CD model though low vitamin B12 level was included. The risk score for each patient was the sum of individual risk factors. In the development dataset, models showed moderate discrimination. For the IBD prediction tool: C-statistic 0.71 (95% CI 0.70-0.71),UC prediction tool: C-statistic 0.70 (95% CI 0.69-0.70) and CD prediction tool: C-statistic 0.75 (95% CI 0.74-0.76). The C-statistics of the models showed that the IBD, UC and CD prediction tools reliably differentiated patients with and without IBD,UC and CD respectively.

Conclusion

A risk score of patient demographics, symptoms and investigations performs well for IBD,UC and CD and may help in prioritising suspected IBD referrals in symptomatic subjects in primary care.

Disclosure

No conflict of interest to declare

Introduction

Glucagon-like-peptide-1 receptors agonists (GLP1-RA) are approved for treatment of diabetes mellitus (DM) and weight reduction.

Aims & Methods

We aimed to investigate the association between GLP1-RA use and poor preparation of colon.
Methods: A multicenter, retrospective study was conducted, including all colonoscopies performed across seven gastroenterology departments from 2016 to 2022. Patients who had undergone colon surgery or had conditions such as Parkinson's disease, cerebrovascular accidents (CVA), scleroderma, amyloidosis, gastroparesis, or those taking narcotic or anti-cholinergic drugs, as well as those with incomplete preparation data, were excluded from the study. The rates of "poor preparation" were collected.

Results

4,104 patients treated with GLP-1 receptor agonists (GLP-1 RA) (age 60 ± 0.2 years, 55.6% females) to 294,643 patients not treated with GLP1 RA (age 56.06 ± 13 years, 52.6% females), these patients were undergoing their first colonoscopy. The study found that 409 (10%) of GLP1 RA patients had poor colonic preparation, compared to 16,811 (5.7%) of patients not treated with GLP1 RA. Subgroup analysis revealed that 173 (8.3%) non-diabetic patients treated with GLP1 RA had poor colonic preparation, compared to 14,810 (5.4%) non-diabetic patients not treated with GLP1 RA (p<0.001). Among diabetic patients, 236 (11.7%) treated with GLP1 RA had poor colonic preparation, compared to 2,001 (9.7%) diabetic patients not treated with GLP1 RA (p=0.004). Multivariate analysis showed that both diabetes mellitus (DM) and treatment with GLP-1 RA were independent risk factors for poor colonic preparation, with odds ratios of 1.7 (p<0.001) and 1.3 (p<0.001), respectively.

Conclusion

GLP-1 RA among diabetes and non-diabetic have an impact on colonic preparation, indicating that these patients may require special consideration and tailored recommendations for their colonoscopy preparation. To establish the most effective approach for these patients, prospective studies are needed.