bluuebunny/crossref_metadata_2025_split huggingface dataset:
P724 Delaying an infliximab infusion by more than 3 days is associated with a significant reduction in trough levels
Authors: Ungar B , Ben-Shatach Z , Ziv-Baran T , Fudim E , Yavzori M , Picard O , Selinger L , Weiss B , Kopylov U , Eliakim R , Ben-Horin S 
Published: January 2020

Abstract

Background
An association between higher infliximab-trough-levels (TL) and better outcomes has been demonstrated among IBD patients. Although standard scheduled infliximab therapy regimen consists of infusions at pre-defined time-points (weeks 0, 2, 6 and every 8 weeks), short-period deviations from therapeutic schedule are common in ‘real life’, especially during maintenance period (due to weekends, holidays, concurrent illnesses, etc.). We aimed to determine whether short-period deviations from infusion-schedule affect infliximab-TL and therapy outcome.

Methods
This was a retrospective study, analysing sera from all IBD patients receiving infliximab maintenance-therapy every 8 weeks in a tertiary medical centre. Associations between time since last infusion and TL were analysed. Clinical scores were recorded prospectively on infusion days and baseline demographic parameters were derived from patients’ charts. Statistical analysis was performed using generalised estimating equations.

Results
In total, 2088 sera of 302 maintenance-period infliximab-therapy-patients were included (median TL 4.1 μg/ml, IQR 2.3–6.5 μg/ml). A delay beyond 3 days in infusion (n &gt; 59 days since last infusion) was demonstrated as significantly affecting TL (mean difference in TL 1 μg/ml, 95% CI 0.03–1.9 μg/ml, p &lt; 0.04). A sub-analysis was performed for 60 maintenance-period infliximab-therapy-patients with &gt;10 consecutive TL measurements (1226 measurements in total), with adjustment for background parameters (gender, infliximab dose, disease type, concomitant immunomodulator, age and weight). A delay of &gt;4 days from scheduled infusion resulted in a statistically significant decline in infliximab trough levels (mean difference in TL 1.45 μg/ml, 95% CI 0.61–2.2 μg/ml, p &lt; 0.001). Finally, deviation from infusion schedule was analysed in association with clinical remission status. Patients that were in clinical remission were more likely to arrive late, rather than early, for scheduled therapy, compared with patients with active disease (OR 2.92 CI 1.75–4.85, p &lt; 0.0001).

Conclusion
Real life delays of &lt;4 days from infusion protocol can probably be allowed. Delays beyond that would significantly decrease TL and might negatively affect therapy outcome. As patients arriving late for an infusion had higher rates of clinical remission than those arriving early, we assume clinical factors mainly drive patients to receive an earlier-then-scheduled infusion.
P740 Age determines the risk of familial IBD: A nationwide case–control study
Authors: Halfvarson J , Ludvigsson J , Sachs M , Askling J , Olén O 
Published: January 2020

Abstract

Background
A family history of inflammatory bowel disease (IBD) is a proxy for an individual’s genetic and, in part, environmental risk of developing IBD, and is one of the strongest known risk factors for developing IBD. Although a familial aggregation is a well-established concept, data on its strength and nature are sparse. Therefore, to provide precise estimates of the familial aggregation, we performed a nation-wide, case-control study and examined the relative risk for patients with IBD (vs. population controls) to have a first-degree relative (FDR) with IBD, by age of onset, type of family history, and IBD subtype.

Methods
Individuals diagnosed with IBD between 1 January 2003 and 31 December 2017 with at least one first degree relative (FDR) were identified from Swedish national registers and compared with non-IBD controls, with at least one FDR, from the general population. We used logistic regression to calculate odds ratios (ORs) as estimates of relative risk for IBD in FDRs taking age at IBD onset, sex, county, and year of IBD diagnosis into account.

Results
We identified 50,667 incident cases with IBD (CD, n = 14,927; UC, n = 27,221 and IBD-U, n = 8519) and 506,720 controls, matched for age, sex, birth year and county of residence. The overall familial relative risk estimate of IBD for siblings (OR 3.6 [95% CI 3.4–3.8]) was similar to that between generations (OR 3.5 [95% CI 3.3–3.7] for mothers and OR 3.5 [95% CI 3.3–3.7] for fathers). Half-siblings conferred a lower yet elevated relative risk (OR 2.0 [95% 1.8–2.2]). The familial relative risk estimates of IBD increased with number of affected FDRs (Figure 1). Pronounced differences were seen between subtypes of IBD in the index case and also across age of onset in the index case and in the FDR (Figure 2). Lowest odds ratios were seen for having an FDR with elderly onset IBD among cases who were diagnosed with elderly onset Crohn’s disease (OR 1.9 [95% CI 1.4–2.5]) or ulcerative colitis (OR 1.9 [95% CI 1.5–2.3]). Highest odds ratios were seen for having an FDR with paediatric onset IBD among cases who were diagnosed with paediatric Crohn’s disease (OR 10.6 [95% CI 8.2–13.5]) or paediatric ulcerative colitis (OR 8.4 [95% CI 6.4–10.9]).

Conclusion
The relative risk of familial IBD varies by IBD subtype as well as by age of onset in the index patient with IBD and the FDR, pointing to differences in genetic predisposition and environmental risks between different phenotypes of IBD.
P741 Incidence and clinical phenotype of inflammatory bowel disease in the north–west of Spain (Vigo) between 1991 and 2011
Authors: De Castro Parga M L , De Castro Luisa Hernández V , Pineda J R , Martinez Cadilla J , Figueira M , Sanromán L , Pereira S , Rodriguez-Prada J I 
Published: January 2020

Abstract

Background
The incidence of inflammatory bowel disease (IBD) seems to have stabilised in the last two decades in some western countries. Our aim was to analyse changes in the epidemiology of IBD between 1991 and 2011 in the area of Vigo (north–west of Spain).

Methods
Retrospective and descriptive study of two inception cohorts of IBD patients aged 15 years or more, that were enrolled in the area of Vigo in two European epidemiological studies: EC-IBD performed from 1991 to 1993 and EpiCom performed in 2010 and 2011. The population of Vigo at those moments was of 408.387 and 493.516 inhabitants, respectively.

Results
In 1991–1993, 102 new IBD cases were diagnosed: 65 ulcerative colitis (UC), 35 Crohn’s disease (CD) and 1 IBD unclassified (IBDU) that showed an incidence of 12.5 cases/100 000 inhabitants per year (8/100 000 inhabitants/year for UC, 4.3/100 000 inhabitants/year for CD and 0.1/100 000 inhabitants/year in IBDU). Regarding 2010–2011, there were 192 cases: 88 UC, 83 CD, 21 IBDU, which an incidence of 19.5 cases/100 000 inhabitants per year (8.9/100 000 inhabitants/year for UC, 8.4/100 000 inhabitants/ year for CD and 2/100 000 inhabitants/year for IBDU) (Figure 1). IBD patients in the second cohort were older: 43.5 (16.4) and 35.8 (16.2) years (p = 0.0005) than the first ones, and IBD diseases also differed in both cohorts (p = 0.001) with more CD (p = 0.03) and IBDU (p = 0.013) in 2010–2011. In 2010–2011 cohort UC patients were older: 39.2 (15.1) vs. 46.1 (16.4) years (p = 0.008) with no differences in gender or phenotype. CD patients were older as well: 29.1 (15.7) vs. 40.4 (15.8) year (p = 0.001), with more patients over their 40s (p = 0.005), and an increase in ileal vs. colonic location (53% vs. 20%, p = 0.006) (Table 1).

Conclusion
Between 1991 and 2011, an increase in the incidence of IBD in Vigo was demonstrated, mainly in CD and IBDU. The age at IBD diagnosis increased significatively, both in UC and CD.
P742 Morbidity and mortality outcomes of paediatric-onset inflammatory bowel disease in early adult life: A Scottish population-based, nested case–control study
Authors: Burgess C , Schnier C , Chalmers I , Russell R K , Hansen R , Henderson P , Wood R , Wilson D C 
Published: January 2020

Abstract

Background
The risk of morbidity and mortality related to paediatric-onset inflammatory bowel disease (PIBD) and its treatment is a major concern to both patients and clinicians, especially when this may affect early adult life. We aimed to determine whether PIBD patients are at increased risk of ischaemic heart disease (IHD), stroke, cancer and death in a nationwide population-based study using administrative health data research methodology.

Methods
All children diagnosed with PIBD in Scotland 1981–2017 were identified within the Scottish Morbidity Record inpatient and day-case dataset (SMR01). PIBD cases were defined as any inpatient International Classification of Diseases (ICD) coding for Crohn’s disease (CD; 555/K50) or ulcerative colitis (UC; 556/K51) until age 16; 10% of cases were individually validated. A nested case-control study (1:3 ratio) matched for sex, age, postcode sector and deprivation quintile within the Scottish population was performed. Data-linkage was applied to SMR01, SMR06 (Scottish Cancer Registry) and NRS deaths datasets to identify any diagnosis of IHD, acute stroke, cancer or mortality. Cancer diagnoses were classified into potential disease related (small bowel, colonic, rectal, anal, hepatobiliary) or treatment related (lymphoma, leukaemia, myeloma, PTLD) cancers. Hazard ratios (HR) were calculated for each outcome using mixed effects Cox regression and the potential effect of sex, year of diagnosis and age at diagnosis were explored.

Results
The study population comprised 2484 children with PIBD and 7451 matched controls. Median age of PIBD diagnosis was 12 years (IQR 10–14) and age at end of follow-up 24 years (IQR 17–33) with 141,605 total person-years follow-up. Validation identified 242/261 true positive cases (positive predictive value 93%). 2 cases (0.08%) and 7 controls (0.09%) had an admission for IHD during follow-up (p = 0.845); 6 cases (0.24%) and 5 controls (0.07%) were admitted for stroke (p = 0.024). PIBD cases had a significantly higher risk of any cancer diagnosis (62 cases: 97 controls) HR 1.97 (p &lt; 0.001), including a 31.9 times higher risk of disease-related cancers (p &lt; 0.001) and a 6 times higher risk of treatment-related cancers (p = 0.011). The effect of PIBD on cancer risk was higher in males, but not related to year or age. PIBD cases had a greater risk of mortality (60 cases: 51 controls) HR 3.61 (p &lt; 0.001). The specific mortality risk from infection was 21.4 times higher in PIBD cases (p = 0.004); the risk of suicide was 2.4 times higher but not statistically significant (p = 0.085). The effect of PIBD on mortality risk was not modified by sex, year or age.

Conclusion
Cancer and mortality are meaningful, serious early adult life adverse sequelae of PIBD however IHD and stroke occur infrequently.
P760 Differences in persistence of oral mesalazine preparations as monotherapy in patients with ulcerative colitis
Authors: Fossmark R , Olaisen M , Martinsen T C , Melberg H O 
Published: January 2020

Abstract

Background
Oral mesalazine is the mainstay treatment of ulcerative colitis (UC). Mesalazine exerts its anti-inflammatory effect locally in the colonic mucosa. The mucosal mesalazine concentration is inversely correlated with the degree of inflammation and previous studies have found that mucosal drug concentrations differ between various oral mesalazine preparations. In the current study we have examined the drug persistence of oral mesalazine preparations in a national cohort of UC patients.

Methods
Patients with newly diagnosed UC from 2010 to 2014 using oral mesalazine as anti-inflammatory monotherapy 3 months after the time of diagnosis were identified by combining data from the Norwegian Patient Registry and the Norwegian Prescription Database. The patients were retrospectively followed through 2017, median follow-up time was 1029 days. Treatment failure was defined as start of topical mesalazine or glucocorticoid preparations, systemic glucocorticoids, immunomodulators and biologic treatment or a change to another oral mesalazine preparation. Drug persistence was defined as duration of oral mesalazine preparation in monotherapy. Disease was categorised as more severe in patients who had dispensed systemic glucocorticoids the first three months after diagnosis. Drug persistence at national and regional level was stratified by mesalazine preparation (Mezavant (MEZ), Asacol (ASA), Pentasa (PEN), Salofalk (SAL)) and disease severity. Consumption was estimated based on defined daily doses (DDD = 1.5 g) of mesalazine dispensed from pharmacies.

Results
A total of 3421 patients were identified. Overall median mesalazine drug persistence was 311 days. The persistence differed between the preparations in descending order: MEZ (398 days), SAL (374 days), PEN (273 days), ASA (266 days), and the order was similar in the four regions. Patients with more severe disease at diagnosis had shorter drug persistence (193 vs. 407 days). Systemic glucocorticoids were given to similar proportion of patients for ASA (0.60) and PEN (0.61), while this proportion of MEZ users was lower (0.52) and even lower for SAL users (0.43). The number of prescribed DDD the first year after diagnosis was slightly higher in MEZ users (MEZ 1.75, ASA 1.36, PEN 1.42, SAL 1.40).

Conclusion
There were significant differences in drug persistence between oral preparations that were not explained by differences in prescription at regional level, but could partially be related to differences in disease severity. These differences could have clinical implications and bear further investigations.
P768 Long-term prognosis of Crohn’s disease and its temporal changes between 1986 and 2015 in a population-based cohort in the Songpa-Kangdong district of Seoul, Korea
Authors: Ye B D , Park H , Kim S H , Hong S N , Yoon H , Kim Y J , Seo S I , Rhee K H , Kim Y H , Kim K H , Cha J M , Park S Y , Jeong S K , Kim J S , Im J P , Jang J , Kim J H , Suh S O , Kim Y K , Park S H , Yang S K 
Published: January 2020

Abstract

Background
No previous population-based study has evaluated the natural course of Crohn’s disease (CD) over three decades in non-Caucasians. We previously reported a 30-year trend in the epidemiology of inflammatory bowel disease (IBD) in the Songpa-Kangdong (SK) District of Seoul, Korea between 1986 and 2015 (1). In this study, we aimed to analyse the long-term natural course of Korean patients with CD in the SK-IBD population-based cohort.

Methods
All patients newly diagnosed with CD between 1986 and 2015 were enrolled in this study. To assess the temporal trends in treatment paradigms and in the prognosis of CD, patients were divided into two cohorts according to the year of CD diagnosis: cohort 1, 1986–2003 and cohort 2, 2004–2015 (the anti-tumour necrosis factor [anti-TNF] era). Disease characteristics at diagnosis, outcomes and their predictors were evaluated.

Results
A total of 418 patients were enrolled. There were 318 males (76.1%) and median age at CD diagnosis was 22 years (interquartile range [IQR], 18–29). Disease location at CD diagnosis was ileal in 104 patients (24.9%), colonic in 39 (9.3%), and ileocolonic in 275 (65.8%). Disease behaviour at CD diagnosis was inflammatory in 339 patients (81.1%), stricturing in 34 (8.1%), and penetrating in 45 (10.8%). Perianal fistula/abscess was present in 43.3% (n = 181) before or at CD diagnosis. During the median follow-up of 108.1 months, the overall use of systemic corticosteroids, thiopurines, and anti-TNF agents was 57.4%, 80.9%, and 34.2%, respectively. Compared with the cohort 1, the cumulative probability of commencing corticosteroids decreased (p = 0.001), whereas that of commencing thiopurines and anti-TNF agents increased (both p &lt; 0.001) in the cohort 2. A total of 113 patients (27.0%) underwent intestinal resection, demonstrating cumulative risks of intestinal resection at 1, 5, 10, 20, and 25 years after diagnosis of 12.5%, 16.5%, 25.6%, 49.7%, and 55.5%, respectively. Multivariate Cox regression analysis revealed that stricturing behaviour at diagnosis (hazard ratio [HR] 2.393, 95% confidence interval [CI] 1.234–4.641), penetrating behaviour at diagnosis (HR 4.514, 95% CI 1.752–11.629), and the cohort 2 (HR 0.530, 95% CI 0.297–0.945) were independent predictors of intestinal resection. The standardised mortality ratio was 1.867 (95% confidence interval, 0.502–4.780).

Conclusion
Korean patients showed a similar clinical course and intestinal resection rate compared with Western patients. The risk of intestinal resection has decreased in the anti-TNF era.

Reference
P778 Longitudinal trajectory of fatigue in inflammatory bowel disease patients: a prospective study
Authors: Borren N , Long M , van der Woude J , Sandler R , Ananthakrishnan A 
Published: January 2020

Abstract

Background
Fatigue is a commonly reported and sometimes disabling symptom in patients with inflammatory bowel disease (IBD). Its prevalence, mechanism, and impact remain poorly understood. Using a large cohort of patients with IBD, we aimed to prospectively determine the trajectory of fatigue and to identify determinants and impact of incident and prevalent fatigue on patients with IBD.

Methods
This prospective study was nested within the IBD partners cohort, a validated internet-based cohort of patients with IBD. Participants were invited to prospectively complete questionnaires assessing fatigue status at baseline and subsequently after 6 and 12 months. Fatigue was assessed using the validated Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score. A FACIT-F score of &lt; 43 was defined as significant fatigue. We examined the trajectory and predictors of different courses of fatigue including incident fatigue (not fatigued as baseline but fatigued at 6 months) and resolved fatigue (fatigue at baseline but resolved on follow-up).

Results
A total of 2429 patients (1605 CD, 824 UC) completed baseline assessment among whom 1057 completed a second assessment at 6 months. First, we identified three distinct patterns of fatigue. Episodic fatigue defined as fatigue at any one (but not both) time point was the most common, affecting 1182 patients (57.0%). Persistent fatigue (at both baseline and follow-up) affected 33.5% (n = 695) while only 196 patients (9.5%) reported no fatigue at any time point (n = 196) (Figure). Patients that reported persistent or intermittent fatigue were more likely to have active disease (p &lt; 0.001), be younger, (p &lt; 0.001), report anaemia (p = 0.002) and low vitamin B12 levels (p &lt; 0.001) and to have a prior diagnosis of depression, anxiety or sleep disorder (p &lt; 0.001). Among patients who were not fatigued at baseline, 26% developed new fatigue at 6 months defined as incident fatigue). The strongest predictor of this being presence of sleep disturbance at baseline (OR 2.45, 95% CI 0.24–1.55) (Table). In contrast, only 12.3% of those with fatigue at baseline had symptom resolution by month 6. Resolution of fatigue was more common in those with UC (p = 0.03), quiescent disease at baseline (p = 0.006), not receiving biologic therapy at baseline (p = 0.016) and no sleep disturbance (p &lt; 0.001), anxiety (p = 0.002) and depressive (p = 0.005) symptoms at baseline.

Conclusion
Our findings indicate three distinct trajectories of fatigue in patients with IBD with their distinct predictors. Importantly, 26% of patients developed new onset fatigue at 6 months demonstrating the substantial impact of this on patients with IBD.
P788 Gender differences in consumption of processed and ultra-processed foods in Crohn’s disease patients
Authors: Sarbagili Shabat C , Zelber-Sagi S , Fliss Isakov N , Ron Y , Hirsch A , Maharshak N 
Published: January 2020

Abstract

Background
Consumption of processed foods is thought to be associated with Crohn’s disease (CD) pathogenesis. In Israel, CD demonstrates higher prevalence rate among men. Our aim was to examine gender differences among CD patients in the consumption of processed foods.

Methods
A post hoc analysis of a prospective validation study of a novel processed food questionnaire (PFQ) was performed in adult CD patients followed at a tertiary center in Israel. The PFQ categorises food items according to the level of processing as unprocessed or minimally processed, processed and ultra-processed foods. Demographic and clinical data were collected. Linear regression, ANOVA, t-test were performed looking at the association between disease characteristics, age, education, gender and consumption of processed foods.

Results
Sixty patients (33 men, 27 women) were included in the analysis. Mean age of participants was 29.4 ± 8.6 for men and 31.7 ± 10.2 for women. Men consumed on average more portions of processed foods per day than women (3.09 ± 2.31 vs. 1.98 ± 1.32, p = 0.023, respectively). Similar association was found for ultra-processed foods consumption, where men consumed 1.63 ± 0.75 more portions per day than women (5.77 ± 2.90 vs. 4.14 ± 2.87, p = 0.034, respectively). Disease characteristics (duration, behaviour, and activity), age and education levels were not associated with consumption of processed foods.

Conclusion
Men with CD consumed significantly more processed and ultra-processed foods compared with women, emphasising a need for dietary intervention in men if these findings are consistent in larger studies.
P796 Annual prevalence and clinical outcomes of ulcerative colitis with primary sclerosing cholangitis in Korea over the last 10 years
Authors: Jung S H , Kim T O , Baek D H , Kim D B , Song G A , Kang H S , Goong H J , Bae J H , Hye Kyung S , Lee H S 
Published: January 2020

Abstract

Background
The prevalence of ulcerative colitis (UC) in Korea has recently increased significantly, but there is few data for the prevalence and clinical outcomes of primary sclerosing cholangitis (PSC) associated UC. Thus, we assessed the prevalence of primary sclerosing cholangitis (PSC)and analysed clinical outcomes in Korean UC patients.

Methods
National Health Insurance System (NHIS) claim data from 2008 to 2017 were used in this population-based study. UC patients and PSC patients were identified by codes for ulcerative colitis (UC: K51) and (PSC: K830) in the NHIS registration system. Clinical events were defined as emergency department visit, hospitalisation, colectomy and liver transplantation.

Results
The overall number of UC with PSC & without PSC patients has increased steadily (Table 1). The prevalence of PSC in UC patients has increased since 2008 and was 0.33%in 2017.Clinical events were more frequent in UC with PSC, but the incidence of clinical events has decreased since 2008 in both groups (Figure 1).In 2017, the number of UC with PSC was 189 (male;118 vs. female;71) and the mean age of UC with PSC was 50.82 years(vs. UC without PSC;49.74). The incidence was low in teenagers and there was no difference in prevalence by age group.

Conclusion
This study confirmed that the prevalence of PSC is increasing in Korea. Additionally, UC with PSC patients have poor clinical outcomes. Therefore, the prevalence of PSC in UC patients suggests the need for greater attention and effort in clinical practice.