bluuebunny/crossref_metadata_2025_split huggingface dataset:
P195 Cost-effectiveness of a 17-gene classifier to guide initial treatment choice in Crohn’s disease in the UK
Authors: Buchanan V , Griffin S , Lee J , Mckinney E , Kinnon P , HILLS K 
Published: January 2020

Abstract

Background
PredictSURE IBD™ is a CE-marked whole blood-based biomarker test that predicts long-term clinical outcomes in inflammatory bowel disease (Crohn’s disease, CD and ulcerative colitis, UC). PredictSURE IBD™ uses a 17-gene qPCR-based classifier to stratify patients into two prognostic subgroups, high and low risk. High-risk patients experience significantly more aggressive disease than low-risk patients, with the need for earlier and more frequent treatment escalation over time. Early stratification could enable personalised treatment strategies, such as ‘top-down’ use of biologics in high-risk patients. Our objective was to examine the cost-effectiveness of PredictSURE IBD™ in guiding the use of early biologic therapy in newly diagnosed CD patients in the UK.

Methods
A decision tree leading into a Markov state-transition model was constructed in MS Excel to compare two treatment approaches: (1) standard of care therapy following established UK clinical guidelines, consisting of sequences of immunomodulator followed by biologic upon relapse (‘step-up’ treatment), (2) targeted therapy guided by PredictSURE IBD™, whereby patients identified as high-risk receive sequences of anti-TNF biologic treatment followed by other biologic classes upon relapse (‘top-down’ treatment), Figure 1. Parameters were informed by patient data from PredictSURE IBD™ clinical studies and the literature.

Results
Top-down treatment guided by PredictSURE IBD™ resulted in an incremental cost-effectiveness ratio (ICER) of £7,179 per quality-adjusted life-year (QALY), with £1,852 incremental costs and 0.258 incremental QALYs vs. standard of care generated over a 15-year time horizon. Additional costs relating to earlier biologic use were offset by reductions in the costs of flares, hospitalisations and surgery. Incremental QALYs were driven by increased time spent in remission and improved quality of life from reduced flares and surgery. The model was most sensitive to the time horizon, rates of mucosal healing on top-down vs. step-up therapy, the costs of hospitalisation and the costs and quality of life in the severe disease health state.

Conclusion
Modelling shows that upfront use of biologic guided by PredictSURE IBD™ could substantially improve clinical outcomes for high-risk patients by increasing remission rates and reducing flares, surgery and treatment escalations. The ICER for PredictSURE IBD™ was well below the £20–£30k/QALY threshold used by the UK National Institute for Health and Care Excellence (NICE). Top-down treatment guided by PredictSURE IBD™ would not only represent a treatment paradigm shift for CD patients but would also be a highly cost-effective use of resources in the UK National Health Service.
P200 Risk of progression of preclinical ulcerative colitis
Authors: Rodríguez-Lago I , Merino O , Azagra I , Maiz A , Zapata E , Higuera R , Montalvo I , Fernández-Calderón M , Arreba P , Carrascosa J , Iriarte A , Muñoz-Navas M , Cabriada J L , Barreiro-de Acosta M 
Published: January 2020

Abstract

Background
The diagnosis of ulcerative colitis (UC) is usually established after the development of symptoms, but preclinical disease may be present even years before the final diagnosis. Around 25% of UC patients may show a proximal extension of the disease. The primary aim of the study was to define the main characteristics and the risk of progression of preclinical UC.

Methods
We performed a multicentric, retrospective study of all patients included in the colorectal cancer screening programme in 11 centres between 2009–2014. All subjects were initially assessed with a faecal occult blood test (OC-Sensor, Eiken Chemical Co., Tokyo, Japan) and, if this test was positive (cut-off 20 μg Hgb/g), a colonoscopy was performed. All patients were asymptomatic and had an incidental diagnosis of UC confirmed by histology during a screening colonoscopy. The main outcomes were the risk of developing symptomatic disease and proximal disease extension. A chi-square test was performed in order to assess the risk factors of proximal extension and symptomatic disease.

Results
During this period we performed 31 005 colonoscopies after 498 227 FIT. We included 79 patients with a new diagnosis of UC (age 58 years [IQR, 52–63], 37% non-smokers]). At baseline, disease extension was E1 in 32%, E2 in 33% and E3 in 35%. After a median follow-up of 29 months (IQR, 17–41), 76% received some treatment, and no patient showed proximal disease extension. In 45% (33% E3 and 12% E2) we observed a reduction of the disease extension. Among those subjects who were asymptomatic at diagnosis, 32% developed symptomatic disease after a median of 7.5 months (IQR, 1–14). Disease extent at diagnosis did not influence the risk of symptomatic disease during follow-up (p = 0.85). Those patients with left-sided or extensive UC were more frequently treated with mesalazine, systemic steroids or thiopurines, compared with those with proctitis (p = 0.001, 0.023 and 0.047, respectively).

Conclusion
Approximately one-third of patients with preclinical UC develop symptomatic disease, but there is no risk of proximal disease extension after 2 years of follow-up.
P203 FIT and FC as a surrogate non-invasive marker for mucosal healing in inflammatory bowel disease
Authors: ISMAIL M S , Murphy G , Kelly C , O’Riordan F , Semenov S , Sihag S , Breslin N , Anthony O , Ryan B , McNamara D 
Published: January 2020

Abstract

Background
Mucosal healing (MH) is one of the goals of IBD therapy. Currently, the only way to assess MH is by colonoscopy. Faecal calprotectin (FC) and faecal immunochemical test (FIT) which detect colonic inflammation and bleeding might be useful adjuncts.

Aim
To assess FIT and FC as surrogate markers of MH.

Methods
Following ethical approval, patients undergoing routine colonoscopy were prospectively recruited. Demographics and colonoscopy findings were documented. A FIT and FC were collected prior to colonoscopy. FIT and FC were processed in our laboratory and reported as µg/g of stool. MH was defined no visible activity on colonoscopy.

Results
Of 105 colonoscopies, FC and FIT results were available in 99 and 88 patients. Mean age 48.8, 52% (55) males, 34% (36) UC, 60% (63) Crohn’s, 0.05% (6) IBDU. In all, MH occurred in 12%, (n = 12). In MH, the mean FIT and FC were 1142 and 353, while in active cases were 750 and 819. Only FC was significantly lower in MH cases (353 vs. 819, p = 0.05). Using standard cut-offs of &gt;50; sensitivity, specificity, PPV and NPV for MH for FIT was poor; 59%, 33%, 89%, 9% and for FC was better at 74%, 73%, 91%, 44%. The overall correlation between the biomarkers was weak r = 0.2, p &lt; 0.01. FC ROC analysis gave a specificity and sensitivity of 75% and 67% for a cut-off of &lt;64µg/g, AUC = 0.65.

Conclusion
MH was uncommon (12%) reflecting our clinical practice. FIT was a poor predictor of MH. FC might be a useful marker albeit ongoing research is needed to set an appropriate cut-off.
P206 Demographic data and therapy before proctocolectomy with ileal pouch-anal anastomosis are associated with long-term pouch outcomes: A report from the epi-IIRN
Authors: Ollech J , Harel S , Yadgar K , Asayag N , Cahan A , Lederman N , Matz E , Balicer R , Feldman B , Brufman I , Haklai Z , Turner D , Dotan I 
Published: January 2020

Abstract

Background
Up to 25% of patients with ulcerative colitis (UC) may undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Pouchitis may occur in 50–70% of patients, and ~30% may develop chronic pouchitis (CP) or Crohn’s-like disease of the pouch (CLDP). We aimed to identify predictors for the development of CP or CLDP during a long follow-up period.

Methods
Patients followed prospectively at the pouch clinic at Rabin Medical Center, were cross-referenced with data from the validated epiIIRN cohort which includes all IBD patients in Israel (n = 45 074). All patients had at least one year of follow-up since ileal continuity (i.e., ileostomy closure after pouch formation). CP was defined as an active flare of pouchitis for &gt;4 weeks and being treated with antibiotics or anti-inflammatory therapy, or &gt;4 episodes of acute pouchitis/year. CLDP was defined as having one or more of the following: pouch-related fistula (&gt;1 year after ileostomy closure), inflammation of the afferent limb, or fibrostenotic disease of the pouch. For the analysis, the cohort was further categorised into favourable pouch outcomes (sustained normal pouch, acute pouchitis) vs. unfavourable pouch outcomes (CP, CLDP or pouch failure). Logistic regression included gender, age, previous therapies, disease duration before pouch surgery, surgical technique and number of previous non-IBD related abdominal operations.

Results
We included 182 patients (55% females; median age at IPAA: 32 years (IQR 23–45); median disease duration until pouch surgery 6 years (3–11); two-staged surgery 69%). The median follow up time was 14 years (IQR 7–22). Before surgery, 37% of patients had been exposed to immunomodulators (either thiopurines or methotrexate), 24% were exposed to anti-TNF therapy and 5% were previously treated with vedolizumab. An unfavourable pouch phenotype was noted in 48% of patients. On multivariate logistic regression, anti-TNF therapy and older age at pouch surgery were associated with decreased odds of an unfavourable pouch outcome (OR 0.3 95% CI 0.11–0.69, p = 0.007 and OR 0.96 95% CI 0.93–0.98, p = 0.005, respectively).

Conclusion
Therapy of UC with an anti-TNF and older age were associated with a favourable pouch outcome. These may be surrogates for patients with longer follow up as well as indication for IPAA. Such factors should be taken into consideration in clinical decision making.
P208 Correlation between physician and patient disease assessments in ulcerative colitis: 2-year UK data from the ICONIC study
Authors: Bhala N , Hart A , Watts D , Lewis S , Ghosh S , van Haaren S , Hansell C , Ahmad T 
Published: January 2020

Abstract

Background
ICONIC is the largest prospective multi-country (n = 33) observational study assessing burden in adult ulcerative colitis (UC) patients under routine care. Both patient and physician assessments of disease severity, activity and life impact were captured 6 monthly up to 2 years. This local subanalysis evaluates baseline (BL) characteristics and the extent of agreement between patients and physicians in measures of disease activity in UK patients.

Methods
Adults with early UC (diagnosed ≤36 months) were enrolled irrespective of disease severity or treatment. Patient self-assessments include disease severity, Pictorial Representation of Illness and Self-Measure (PRISM, a tool assessing perception of disease-associated suffering; lower scores indicate greater disease burden), Patient Health Questionnaire-9 (PHQ-9), Short inflammatory bowel disease Questionnaire (SIBDQ) and patient-modified Simple Clinical Colitis Activity Index (P-SCCAI). Physician assessments include clinical parameters, PRISM, SCCAI. Correlation between PRISM and SIBDQ, PHQ-9 and SCCAI were evaluated by Spearman correlation. BL characteristics are based on observed data.

Results
BL characteristics of 63 UK patients in ICONIC are shown in Table 1. From BL to 2-years, patient/physician PRISM was moderately/strongly correlated with SIBDQ, PHQ-9, P-SCCAI or SCCAI (Table 2). For 62 patients with self and physician assessments, the level of agreement on disease severity at BL (concordant pairs) was: mild 66.7%, moderate 27.8%, severe 45.5%, in remission 50.0%. The mean ± SD P-SCCAI and physician SCCAI values at 2 years were 2.6 ± 2.6 and 1.5 ± 1.5, respectively; the measures were strongly correlated (Table 2). For patient/physician PRISM assessments at 2 years, scores were 5.2 ± 2.6 and 5.2 ± 2.1, respectively, and were moderately/strongly correlated (Table 2).

Conclusion
Results from this subanalysis of ICONIC demonstrate persistently high UC disease burden over 2-years, despite treatment. EIMs were common and therefore awareness of potential EIM impact is essential. PRISM, used for the first time in UC, was moderately correlated with disease-specific measures (SIBDQ/SCCAI) and a general depression assessment (PHQ-9). Alignment between patients and physicians on disease activity/severity varied according to the instrument used but was greatest for SCCAI.
P211 Positivity of stool sampling for enteric pathogens during inflammatory bowel disease flares in paediatric patients and its impact on disease outcomes
Authors: Melnik P , Matar M , Shamir R , Assa A 
Published: January 2020

Abstract

Background
Enteric infections due to Clostridium difficile toxin (CDT) is more common in patients with inflammatory bowel disease (IBD). We aimed to assess the frequency and outcomes of CDT and non-CDT enteric infections in symptomatic paediatric patients with IBD.

Methods
Patients’ records were retrospectively searched for disease flares in which stool samples were collected. Each patient with a positive sample was matched with a patient with IBD flares and negative sample in order to analyse 1-year outcomes following sampling.

Results
A total of 618 paediatric patients with IBD (Crohn’s disease, n = 439, 71%, mean age at diagnosis 12.99 ± 3.4, females, n = 264, 42.7%) had 1204 stool samples during the study period (2001–2018). Of these, 43 (3.6%) were positive for bacteria, and 32 (74.4%) of which positive for Campylobacter jejuni. Of 463 samples for CDT, 31 (6.7%) were positive while parasitic infection was rare, 11/765 (1.4%). Overall, 19 positive C. jejuni cases and 19 positive CDT cases with matching controls were examined. During 12 months of follow-up, the mean number of disease flares and ER visits was higher among patients with positive CDT (1.5 ± 1.4 vs. 0.5 ± 0.9, p = 0.019, 1.3 ± 1.5 vs. 0.4 ± 0.8, p = 0.05, respectively) with a numeric increase of surgical interventions (3 vs. 0). There were no significant differences in disease outcomes between patients with C. jejuni infections and matched controls.

Conclusion
Clostridium difficile and Campylobacter jejuni are the most common enteric infections among paediatric patients with IBD but only clostridial infection results in a more severe disease course within 12 months of infection.
P212 Deep learning video analysis for a fully automated per-frame grading of ulcerative colitis
Authors: GUTIERREZ BECKER B , Gamez Serna C , Thalhammer A , Oh Y , Drawnel F , Arcadu F , Prunotto M 
Published: January 2020

Abstract

Background
Several approaches have been proposed to use deep learning to automatically assess the severity of ulcerative colitis (UC) in terms of Mayo Clinic Endoscopic Subscore (MCES) from colonoscopy videos. These previous methods have been trained and evaluated on high-quality individual frames, carefully hand-picked by an expert gastroenterologist and without rigorous central endoscopy reading as an anchor. We investigate the use of a fully automated, end-to-end approach which takes as input raw endoscopic videos and returns the MCES values for individual colon sections.

Methods
Our method consisted of two stages: (1) a Quality Control Network (QCN) which took as input a raw endoscopic video and removed from the analysis frames with poor image quality and (2) a Severity Scoring Network (SSN) which took the high-quality frames extracted using the QCN and returned a severity score for each individual frame. To obtain an aggregate severity score for a full video or a colon section, the individual predictions were aggregated by averaging all individual predictions. Both the QCN and the SSN are convolutional neural networks (Resnet50) trained in a weakly supervised manner. The QCN was trained by providing the network examples of good quality vs. bad quality video segments and the SSN was trained by giving pairs of video segments extracted for a given colon subsection (rectum, sigmoid, descending colon) and its corresponding MCES. Manual annotations of quality were performed by non-experts while annotations for colon subsection and MCES were performed by expert gastroenterologists as part of the Hickory (NCT02100696) and Laurel (NCT02165215) clinical studies.

Results
We evaluated our method retrospectively in 104 sigmoidoscopy videos obtained from Hickory and Laurel. We measured the agreement between the per-section MCES generated as part of the studies and the MCES obtained by automatic grading. Evaluation was done in a binary setting, where grading was constrained to determining whether a colon section has an MCES above a certain threshold. We achieved an Area Under the receiving operating characteristic Curve (AUC) of 0.76 +−0.08 for the detection of MCES &gt;1 and an AUC of 0.81 +−0.06 for MCES &gt;3 after performing 5-fold cross-validation.

Conclusion
We have demonstrated that the use of deep learning for a fully automated assessment of the severity of ulcerative colitis in colonoscopy videos is feasible. Our approach achieves high accuracy even when training is performed using weak labels and a limited number of examples and paves the way towards a fully automated assessment of the severity of ulcerative colitis in full colonoscopy videos.
P217 The role of 7-alfa-hydroxy-4-cholesten-3-one (C4) as a biomarker for bile acid malabsorption in inflammatory bowel disease and microscopic colitis
Authors: Lyutakov I , Lozanov V , Sugareva P , Nakov R , Valkov H , Dimov A , Vladimirov B , Penchev P 
Published: January 2020

Abstract

Background
Bile acid diarrhoea (BAD) is a condition when excessive bile acids (BAs) enter the colon due to bile acid malabsorption (BAM). Impaired metabolism of BAs and BAM interaction are involved in the pathophysiology of microscopic colitis (MC) and inflammatory bowel disease (IBD), especially in Crohn’s disease (CD). Plasma levels of 7-alfa-hydroxy-4-cholesten-3-one (C4) is a new biomarker of BA synthesis. Little is known about the mechanisms of BAs dysregulation and levels of C4 in patients with IBD, irritable bowel syndrome (IBS-D) and microscopic colitis (MC).

Methods
The aim was to evaluate the diagnostic accuracy of plasma levels of C4 for finding BAM in patients with IBD, IBS-D and MC. We enrolled 109 adult patients with chronic diarrhoea and 11 healthy controls who underwent standard laboratory tests, colonoscopy, serum C4 and faecal calprotectin (FC). Patients were split into six groups: 30 patients with active IBD, 21 patients with IBD in remission reporting a high number of bowel movements per day, 21 patients with IBD after surgery (ileal resection), 23 patients with IBS- D, 14 patients with MC and 11 healthy subjects (controls). Fasting serum C4 were measured by high-performance liquid chromatography (HPLC) analysis and FC by the quantitative immunochromatographic method.

Results
Based on cut-off levels of C4 (above 48.4 ng/ml) diagnosis of BAM was confirmed in 66 of 109 patients (60.5%) and excluded in 43 patients (39.4%) compare to healthy controls. Median levels of C4 in patients with IBD active were 53.1 ng/ml, IBD remission was 52.2 ng/ml, IBD after surgery was 85.7 ng/ml, IBS-D were 7.5 ng/ml, MC was 69.3 ng/ml and healthy controls were with 3.7 ng/ml. A cut-off concentration of C4 of 48.4 ng/ml or higher identified patients with MC and IBD with diarrhoea attributable to BAM with an AUROC 0.89 and sensitivity 79.8%, specificity 90.9%, positive predictive value (PPV) of 96.1% and negative predictive value (NPV) of 88.6% compared with healthy controls (p &lt; 0.001). IBD patients in remission (FC &lt; 100 µg/g) with up to 4 bowel movements daily was n = 16 (76.2%) and concentration of C4 above 48.4 ng/ml were found in n = 13 (61%) of the patients.

Conclusion
BAM in IBD and MC is a common and very under-diagnosed condition. Serum C4 could be used for screening biomarker for BAM in patients with IBD, IBD after surgery (ileal resection) and MC. We found that serum concentrations of C4 above 48.4 ng/ml identify patients with diarrhoea likely attributable to BAM with high diagnostic accuracy and IBD patients in remission with found bile acid diarrhoea can benefit from additional treatment with bile acid binders. Further bigger studies are needed to establish the efficacy of serum C4 in patients with suspected BAM in IBD and MC.
P222 Extraintestinal manifestations in paediatric-onset inflammatory bowel disease depending on disease location and activity
Authors: Grzybowska-Chlebowczyk U E , Buczyńska A , Niewiem M , Flak-Wancerz A , Kałużna-Czyż M , Więcek S 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) and its major forms, i.e. Crohn’s disease (CD) and ulcerative colitis (UC), have systemic implications, which, as suggested by Vavricka et al., can be divided into extraintestinal manifestations (EIM) directly related to immune mechanisms and non-immune extraintestinal complications resulting from malabsorption. Extraintestinal manifestations may develop prior to or after IBD diagnosis. The aim of the study was to determine the prevalence and types of extraintestinal manifestations (EIMs) in paediatric-onset inflammatory bowel diseases (IBD), i.e., Crohn’s disease (CD) and ulcerative colitis (UC), depending on disease activity and location, and to determine whether the presence of EIM is associated with a distinctive clinical course of IBD.

Methods
The medical records of 336 children with IBD with or without EIMs were retrospectively analysed, especially regarding the following characteristics: age at diagnosis, clinical symptoms, nutritional status, the Paris Classification, and IBD activity. The diagnosis was made based on the revised Porto criteria. The medical histories of patients and data obtained in physical examinations were analysed, especially the following: (a) anthropometric measurements for nutritional status assessment based on percentile charts of the OLAF study, (b) disease activity using the PCDAI and the PUCAI, disease location and type according to the Paris classification.

Results
The study population of 336 children comprised 175 patients with UC and 161 patients with CD. EIMs were diagnosed in 65 patients (19%). The most frequent immune-related EIM in UC patients was primary sclerosing cholangitis (PSC); the collective proportion of PSC and PSC/autoimmune hepatitis (AIH) was 13,7% of UC patients. Arthropathy was the most prevalent EIM in the subpopulation of CD participants (8,6%). Pancolitis was a risk factor for EIMs in the UC and especially for PSC and AIH/PSC. We also analysed the population for correlation in presented symptoms pattern in patients EIM(+) vs. EIM(-) as well as differences in age and sex distribution and IBD activity, location and behaviour.

Conclusion
EIMs are a significant issue in the population of children with IBD; they developed in 19% of our patients. Determination of the prevalence of these manifestations and related risk factors might raise awareness of the problem and facilitate diagnosis and therapy.