bluuebunny/crossref_metadata_2025_split huggingface dataset:
P233 Sleep Disorders and Chronic Inflammatory Bowel Disease: What’s the Connection?
Authors: Hassine A , Hamami A , Dahmani W , Ben Ameur W , Elleuch N , Braham A , Bannour R , Jaziri H , Jmaa A 
Published: May 2021

Abstract

Background
The quality of sleep is a major determinant of quality of life, which has become a therapeutic target in the management of Chronic Inflammatory Bowel Diseases (IBD). The relationship between IBD and sleep disorders is still unclear. Although poor quality sleep is believed to be strongly linked to disruptions to clinical disease activity, IBD patients are reported to experience sleep disturbance even when the disease is clinically inactive. The objective of this work was to assess the prevalence and risk factors of sleep disorders as well as their impact on the quality of life of patients with IBD.

Methods
We conducted a cross-sectional study, including all patients followed for IBD, who presented to our consultation during the three months preceding our study. The quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI). The quality of sleep is impaired when the PSQI score&gt; 5. The activity of Crohn’s disease (CD) was evaluated by the Harvey-Bradshaw index (HBI), that of ulcerative colitis (UC), by the Clinical Mayo score. Quality of life was assessed by the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ).

Results
We included 100 patients, mean age 42.18 ± 15.71 years with a predominance of men (sex ratio M / F = 1.5). The mean course of IBD was 9.02 ± 6.57 years. Sixty eight patients (68%) had CD, the location was ileal in 32 patients (47%), ileocolonic in 22 patients (32.4%), and colonic in 14 cases (20.6%). Ano-perineal manifestations were present in 38.2% of cases. Severe disease activity was noted in 14 patients (20.6%). Thirty two patients (32%) had UC. Pancolitic involvement was noted in 14 patients (43.7%) UC activity was severe in 10 patients (31.3%). The mean PSQI score was 8.2 ± 4.42. A PSQI score&gt; 5 was noted in 68% of patients. There is a significant association between the PSQI score and disease activity in both patients with CD (p = 0.003) and those with UC (p = 0.026). The quality of sleep was altered in 44.4% of patients in remission vs. 81.25% of patients in relapse, with a statistically significant difference (p &lt;0.001). There was a strong negative correlation between the PSQI score and the S-IBDQ (p &lt;0.001, r = -0.61).

Conclusion
Our study showed that 68% of patients with IBD suffer from impaired quality of sleep. This disturbance was strongly correlated with the deterioration in the quality of life of these patients, requiring multidisciplinary management.
P235 Major Depression in patients with Crohn’s disease and its relationship with clinical activity and disease’s phenotype
Authors: Facanali C , Sousa Freitas Queiroz N , Facanali M R , Rodrigues Boarini L , Amuratti Gonçalves J L , Rodrigues Borba M , Nahas S C , Sobrado C W 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) has a considerable impact on quality of life and contributes to the onset of depressive symptoms¹. It has been demonstrated that depression is more prevalent in inflammatory bowel disease (IBD) patients compared to the general population². However, whether depression affects IBD course or the onset of IBD triggers psychological disorders remains to be elucidated. The aim of the study is to estimate the prevalence of major depression in patients with CD and to evaluate its relationship with the clinical activity and phenotype of the disease.

Methods
From November 2019 to February 2020, 283 patients with CD were evaluated using the Patient Heath Questionnaire-9 (PHQ-9). Major depression (MD) was defined by PHQ-9 ≥ 10 (0–4: absent depressive symptoms / 5–9: mild depressive symptoms / 10–14: moderate depressive symptoms / 14- 27: severe depressive symptoms). Data regarding socio-demographic characteristics, disease phenotype, clinical activity were prospective collected. Disease phenotype was characterized according to the Montreal classification and clinical activity was assessed using the Harvey-Bradshaw index (HBI). Statistical tests were performed with a 5% significance level.

Results
The prevalence of MD in CD patients was 41.7% (Table 1). Female patients were more susceptible to MD (Table 2). Other socio-demographic characteristics did not increase the risk of MD. Disease activity was significantly associated with an increased risk of MD (Odds Ratio [OR] 795.97, 95% confidence interval [CI] 133.7–4738.78, p &lt;0.001) (Table 2). Regarding disease phenotype, the stenosing and penetrating behaviour were associated with a lower risk of MD (OR 0.8, 95%CI 0.01-.5 and OR 0.03, 95%CI 0.00–0.18), respectively, as compared with the inflammatory behaviour. No association was observed between location of the disease and MD.

Conclusion
Our study shows a high prevalence of MD among CD patients, which is significantly affected by disease phenotype and clinical activity. Given that the ultimate therapeutic goals for CD should include restoration of quality of life, this study shed light on the need of the inclusion of psychological assessment besides the objective measures of disease activity as an integral part of IBD care.
P239 A study to evaluate uptake of PROMS for IBD patients on Biologics: a sample United Kingdom district general hospital experience
Authors: Mahmood T , Muhammad Q 
Published: May 2021

Abstract

Background
In order to guide industry on medical product development, FDA developed an instrument to measure effectiveness as an endpoint of clinical trials. This patient oriented tool is called “Patient Related Outcomes Measures”. (PROMS). In 2009 NHS England adopted PROMS declaring that “the purpose is to collect information, from patients themselves, about how well the health service is treating them. Moreover “PROMs allows to understand the difference that healthcare interventions make to people’s quality of life”. Initially related to only certain surgical procedures, it eventually rolled out to many other conditions including IBD. This research looks at degree of success in implementation of PROMS for IBD patients on treatment with biologics in a sample district hospital of United Kingdom.

Methods
The IBD PROMs questionnaire is filled by patients themselves when treated with biologics. The questionnaire asks overall health status, treatment of bowel condition, effectiveness in controlling bowel condition, satisfaction with quality of treatment, Crohn’s and Colitis questionnaire CCQ12 and uses 12 dimensions: sleeping, appetite, energy level, rushing to the toilet, being bloated, incomplete emptying of bowels, blood in stool, generally unwell, faecal incontinence, nocturnal diarrhoea, passing wind and effect on leisure activity. It also has questions for patients with a stoma. We collected data from a sample district general hospital in United Kingdom for one year in retrospect and analysed the implementation of PROMS. We hoped at least 90% of patients would fill the PROMS questionnaire.

Results
45 patients with IBD who were on biologics were recruited in the study. They had repeated admissions for treatment and we kept check points at 3, 6 and 12 month follow up treatments. There were 21 patients on infliximab, 23 on vedolizumab, and 1 on ustekinumab with overall total number of infusions being 352 due to their recurrent admissions for biologic treatment. A minimum of 45 PROM responses could have been achieved and maximum of 352 for good implementation. In our data only 4 were filled (8.89% of minimum and 1.1 of maximum required). Thus PROMS for IBD was not implemented to any useful extent.

Conclusion
Our study did not look at the outcomes, but simply whether the PROMS was utilised sufficiently for IBD patients on biologics. We demonstrated low uptake by one sample district general hospital of United Kingdom. Further studies to evaluate practice of other IBD units in the country would help to understand the situation better. There can be various reasons for this low uptake including lack of resource, not knowing importance of PROMS or deficient motivation in staff.
P315 Population pharmacokinetics and pharmacodynamics of ozanimod in ulcerative colitis
Authors: Tatosian D , Shen J , Chen L , Lavigne J , Teuscher N , Harris S , Chitkara D , Tirucherai G S , Marta C 
Published: May 2021

Abstract

Background
Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and under development for ulcerative colitis (UC) and Crohn’s disease. Ozanimod and its major active metabolites CC112273 and CC1084037 block lymphocyte egress from lymphoid tissues, reducing the absolute lymphocyte count (ALC) in blood. To characterise the influence of patient characteristics on ALC response, a population PK/PD analysis was conducted.

Methods
A nonlinear mixed-effects Emax model described the ALC time course and relationship to CC112273 concentrations in healthy subjects and patients with UC or RMS. The analysed data included 34,449 ALC values obtained from 4122 subjects enrolled in 11 Phase 1, 2, and 3 clinical studies. The effect of age, sex, smoking status, disease type, body weight, total bilirubin, and baseline ALC on the maximum ALC reduction (Emax) and half-maximal concentration (EC50) were investigated. Simulations of typical ALC reductions for healthy subjects and patients with UC or RMS receiving 0.5 or 1 mg ozanimod were conducted to explore the influence of smoking and assess the time for ALC recovery.

Results
Increasing CC112273 concentrations were associated with reductions in ALC to a maximum of 74% from baseline, with an estimated EC50 of 2.8 nM CC112273. Healthy subjects, females, and higher body weights were associated with larger ALC Emax (Figure 1), while healthy subjects, increased age, nonsmokers and higher baseline ALC were associated with an increased EC50 (Figure 2). UC patients receiving 0.5 mg and 1 mg ozanimod HCl are predicted to have mean ALC reductions of 46.1% and 57.2%, respectively, with similar reductions for RMS patients of 48.0% and 57.4%. Smoking was associated with a 27.2% reduction in the ALC EC50, which partially offsets the reduced plasma CC112273 concentrations in smokers. Simulations show that 1 mg ozanimod has comparable ALC reductions of 57.4% in nonsmokers and 52.7% in smokers. Upon discontinuing ozanimod 1 mg in UC patients, a mean recovery time to normal (1 x 109/L ALC count) of 32.8 days was predicted, with 90% of the population recovering in 3 months. Overall results were consistent with findings from clinical trials.

Conclusion
Population analysis demonstrated a similar PK/PD relationship for ALC reductions in patients with RMS and UC. Smoking was not associated with substantial difference in ALC, consistent with no loss of efficacy in smokers. Upon discontinuation of ozanimod treatment, the majority of UC and RMS patients will recover lymphocyte counts to normal within 3 months.
P410 Which patients with established Crohn’s disease benefit most from the use of the Patency capsule test prior to small bowel capsule endoscopy?
Authors: Elosua Gonzalez A , Rullan Iriarte M , Rubio Iturria S , Rodríguez Gutiérrez C , Vicuña Arregui M , Elizalde Apesteguía I , Aznárez Barrio M R , Juanmartiñena Fernández J F , Nantes Castillejo Ó , Fernández-Urién I 
Published: May 2021

Abstract

Background
An important factor that limits a wider utilization of small bowel capsule endoscopy (SBCE) in Crohn’s Disease (CD) is the potential risk of retention. The Patency® capsule (PC) lowers the risk of SBCE retention by assessing pre-procedure intestinal patency. Our aims were to evaluate the use of PC in patients with established CD in routine clinical practice and to identify predictive factors of intestinal patency in CD patients.

Methods
We included all patients with CD followed in the Inflammatory Bowel Disease Unit of the Complejo Hospitalario de Navarra in which a SBCE was performed from 01/01/2008 to 31/12/2019. An intact PC excreted in its original shape within 30 hours after swallowing was considered a positive patency test.

Results
A total of 465 SBCE were indicated in 333 patients. In 61.9% a previous patency test with PC was performed, with significant differences in its use according to the age at diagnosis according to the Montreal classification (A1 75.9%, A2 64.8%, A3 46.1%) and behaviour (B2 81.3%, B3 80%, B1 54.2%), the indication (postoperative recurrence monitoring 87.2%, flare 65.5%, staging small bowel disease 52.4%, assessing mucosal healing 44.8%) and the presence of previous CD surgery (68.6% vs. 55.6%). In 33 cases (7%) SBCE was contraindicated due to negative patency test.
Eleven SBCE were retained of the 432 procedures finally performed (incidence 2.5%; 95% CI 1.06%-4.02%). Retention occurred in 5.6% of procedures without prior PC compared to 0.4% with previous PC (p&lt;0.001). Stricturing disease (OR 2.94; 1.31-6.58), penetrating disease (OR 3.85; 1.59-9.31) and presence of elevated inflammatory markers (OR 3.73; 1.85-7.50) were identified as independent factors associated with retention (negative PC test or SBCE retention) in the multivariate analysis.

Conclusion
A patency test prior to SBCE was performed in 61.9% of patients with known CD. The use of PC is associated with a lower risk of SBCE retention in a routine clinical setting. Patients with stricturing or penetrating disease or elevation of inflammatory markers have significantly higher risk of retention and would therefore benefit from a pre-SBCE PC.
P437 Hyperbaric oxygen therapy for Inflammatory Bowel Disease – a systematic review
Authors: Meima - van Praag E , Lansdorp C , Smeekes G , Gecse K , van Hulst R , Buskens C 
Published: May 2021

Abstract

Background
Inflammatory bowel disease (IBD) is a chronic, debilitating disease with suboptimal success rates after conventional treatments. A potential new, additional approach is hyperbaric oxygen therapy (HBOT). We aimed to evaluate the efficacy and safety of HBOT in patients with IBD.

Methods
A systematic review of the published literature regarding HBOT as treatment for IBD was conducted according to the PRISMA guidelines. MEDLINE, Web of Science, EMBASE and the Cochrane Library were systematically searched. Search terms included ‘Hyperbaric Oxygenation’, ‘Inflammatory Bowel Diseases’, ‘Crohn’ and ‘Colitis’. All human studies with ≥5 patients and animal studies evaluating HBOT for IBD were included. Primary outcome was clinical response rate to HBOT. Secondary outcomes were radiological and endoscopic response rate, laboratory findings, adverse events and quality of life (QoL).

Results
The literature search resulted in 948 publications of which 26 were included (Figure 1); 11 human studies (778 patients) and 15 animal studies (554-558 animals). Seventeen were randomised controlled trials, 8 prospective cohort studies and 1 was a retrospective cohort study. The overall clinical response rate after 5-86 HBOT sessions was 82.1% (88.1% for ulcerative colitis and 78.7% for Crohn’s disease (CD)). Perineal CD was described in 56 patients, with a clinical response rate of 75%. The endoscopic response rate ranged from 50-100% in 4 studies and the radiological response in 1 study was 100%. Only one study described quality of life (QoL) and showed no significant differences in QoL between the HBOT and control group. Adverse events were described in 6 studies and occurred in 9 out of 75 patients (0.12%).
Animal studies reported less weight loss after HBOT and a significantly decreased Disease Activity Index compared to controls. Furthermore, histopathological features and laboratory values including inflammatory markers (such as TNF-α and IL-1) and oxidative stress markers (such as myeloperoxidase and malondialdehyde) improved after HBOT.

Conclusion
HBOT is a promising IBD treatment with high clinical-, radiological- and endoscopic response rates and few adverse events. Animal studies support these findings. The challenge now is to identify the appropriate amount of HBOT sessions and timing in the IBD treatment process and to identify which IBD patients can benefit most from HBOT.
P453 The use of immunosuppresants is associated with high treatment persistence rates for infliximab and adalimumab as first or second line anti-TNF therapy in patients with inflammatory bowel disease
Authors: Theodoraki E , Orfanoudaki E , Foteinogiannopoulou K , Drygiannakis I , Koutroubakis I E 
Published: May 2021

Abstract

Background
The aim of this study was to investigate the factors associated with treatment persistence for infliximab and adalimumab, as 1st or 2nd line anti-TNF therapy, in patients with inflammatory bowel disease (IBD).

Methods
A retrospective study of patients with IBD from the registry of our department who received infliximab (IFX) or adalimumab (ADA), during the period of 2002–2019 was performed. The persistence rate of IFX and ADA at 1 and 3 years from treatment initiation as 1st and 2nd line anti-TNF therapy respectively was calculated. In addition, possible related factors were analyzed.

Results
We included 185 patients with IBD, naive to biologics, who initiated with anti-TNF treatment [105 men (57%), mean age (± SD) 44.5 ± 14.7 years, Crohn’s disease 144 (78%), median disease duration (IQR) 13 (7–20) years, 120 (65%) under IFX, 100 (55%) in combination with immunosuppressive therapy for at least 6 months]. In 59 patients [Crohn’s disease 47 (80%)] IFX or ADA was used as 2nd line anti-TNF therapy. The duration of administration and persistence rate of IFX and ADA as 1st and 2nd line treatment are shown in Table 1.
In univariate analysis statistically significant associations between the persistence rates of anti-TNF therapy as first-line therapy, with the use of immunosuppressants (P = 0.04) and treatment intensification (P = 0.01) in both 1st and 3rd year (P = 0.01 and 0.04 respectively) were found. No other significant association between demographic, disease type and clinical parameters and treatment persistence was found. Regarding the 2nd line anti-TNF treatment, persistence of therapy in the 1st year was associated with treatment intensification (P = 0.02) and in the 3rd year of administration with the combination with immunosuppressants (P = 0.05). In multivariate analysis only the use of immunosuppresants remained statistically significant associated both in 1st and 3rd year of treatment in 1st line therapy (P=0.05 and P=0.003 respectively). This was also the case in 2nd line therapy but only in the 3rd year of treatment (P=0.05).

Conclusion
The persistence rates of IFX and ADA used both as a 1st and 2nd line therapy in IBD patients are significantly associated with the combined use of immunosuppressants.
P456 Ig glycosylation in ulcerative colitis: it’s time for new biomarkers
Authors: Capecchi R , Migliorini P , Zanzi F , Maltinti S , Puxeddu I , De Bortoli N , Bellini M , Costa F , Marchi S , Bertani L 
Published: May 2021

Abstract

Background
Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.

Methods
We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- &lt;2) and mucosal healing (Mayo Endoscopic Score &lt;2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched.

Results
Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p=0,04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p=0,04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p&lt;0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2= 0,2211; p=0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p= 0,0135 and p=0,0089 , respectively).

Conclusion
Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.
P460 Biomarkers reflecting extracellular matrix turnover and inflammation can be used to monitor disease activity and treatment response in patients with Crohn’s disease undergoing infliximab induction therapy
Authors: Sorokina Alexdóttir M , Bourgonje A R , Asser Karsdal M , Bay-Jensen A C , Faber K N , Loveikyte R , van Dullemen H M , Visschedijk M C , Festen E A M , Weersma R K , Dijkstra G , Mortensen J H 
Published: May 2021

Abstract

Background
Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by high protease activity and increased extracellular matrix (ECM) turnover. Although immunotherapeutic drugs such as anti-TNFα have shown great promise in the treatment of CD, still up to 20–40% of patients do not respond to therapy. Failure to establish effective treatment may lead to further disease progression and potential disease complications. The aim of this study was to investigate whether biomarkers of ECM turnover and intestinal inflammation could serve as non-invasive tools for monitoring treatment response to anti-TNFα in patients with CD.

Methods
Serum biomarkers of matrix metalloproteinase (MMP)-related type I collagen degradation (reC1M), intestinal inflammation (VICM [macrophage activity], CPa9-HNE [serum calprotectin, neutrophil activity]) and type III collagen formation (PRO-C3) were measured using competitive ELISA in patients with CD (n=54) undergoing infliximab (IFX) induction therapy. Disease activity was defined by composite assessment of the Harvey-Bradshaw Index (HBI) together with physician’s global assessments (PGA). Clinical remission (HBI &lt;5) was assessed at week 14. Wilcoxon signed-rank tests were applied for pairwise comparisons of biomarker levels between baseline and week 14.
Table 1. Differences in biomarker levels between baseline and week 14 in CD patients receiving IFX treatment stratified by response. Biomarker concentrations presented as median [IQR].

Results
In patients responding to IFX treatment (n=50), serum levels of reC1M, VICM, and CPa9-HNE (all P&lt;0.05) were significantly lower at week 14 compared to baseline. However, serum levels of PRO-C3 (P&lt;0.01) were significantly elevated in responders at week 14 compared to baseline. No significant changes were observed in the biomarkers between baseline and week 14 in those not responding to IFX treatment (n=4).

Conclusion
Serum biomarkers for type I collagen degradation (reC1M), intestinal inflammation (VICM, CPa9-HNE) and type III collagen formation (PRO-C3) are linked to the pathology of CD, reflecting treatment response. Together, these biomarkers could be used as surrogate markers for disease monitoring during IFX treatment in CD to further improve disease management.