bluuebunny/crossref_metadata_2025_split huggingface dataset:
P585 IBD Reference and Biosimilar adalimumab CroSS over Study (iBaSS): a mixed methods clinical trial of patients transitioning between originator and biosimilar adalimumab. Qualitative findings from an interim analysis presenting the patient perspective
Authors: Young D , Latter S , Harvey J , Addison J , Freudensprung U , Cummings F 
Published: May 2021

Abstract

Background
iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adults with Crohn’s disease. 112 participants have been recruited from patients attending the IBD clinic for routine treatment. Eligibility criteria included mHBI &lt; 8, stable on Humira™ or Imraldi™ with no expectation to discontinue or adjust adalimumab (ADA) dosing in the study period. The pragmatic study design mimics the optimal care pathway of patients transitioning between originator and biosimilar ADA, allowing all participants to experience both. Such transitions are part of routine clinical practice but with little understanding of the patient perspective. As part of iBaSS we capture the patient perspective and experience of transition, with the aim of informing future practice.

Methods
Purposive sampling was used to capture a wide range of perspectives from a subset of the participants treated with the originator ADA at enrolment. Interviews were semi-structured, using open-ended questions, facilitated by a topic guide developed with reference to published literature. Interviews were recorded, transcribed and analysed using thematic analysis. Thirty five participants were interviewed.

Results
Five themes were identified: (1) understanding and awareness of biosimilars, (2) motivation to undertake transition, (3) initial concerns, (4) reassuring factors and (5) reflection of experience.
Opinions expressed were often heterogeneous, but commonly-occurring experiences were also identified. Prior awareness of biosimilars and knowledge of the biosimilar concept was low indicating a disparity between healthcare professionals and patients. Patients accept a biosimilar transition to minimise drug expenditure. Prior to undertaking biosimilar transition away from the brand they had experienced, efficacy and adverse effects were common concerns for patients. Trust in the healthcare team is critical to patient acceptance of biosimilars and important reassurances include a point of contact, education about biosimilars and specific monitoring. When reflecting on the experience, participants noted little subjective difference in efficacy or tolerability (although 22 participants specifically mentioned injection pain) following brand transition and the majority feel comfortable with future transition to another ADA biosimilar. Injection experience is important in patient satisfaction.

Conclusion
While biosimilars have driven a reduction in drug acquisition costs, the majority of patients have little knowledge and some concerns about transitioning to a biosimilar but accept the principles and can be reassured. The wide-ranging views elucidated suggest that a tailored, patient-centred approach is key to successful implementation.
P594 Utilisation of anti-TNF agents in phlegmonous Crohn’s disease: an Australian tertiary referral centre experience
Authors: Chiu L , Digby-Bell J , Seah J , Melton S , Taylor K , Sparrow M 
Published: May 2021

Abstract

Background
Phlegmonous Crohn’s disease (CD) is a complication of penetrating disease where traditional management was surgical. There are a paucity of studies evaluating its medical management. The aim of our single-centre, retrospective case series was to evaluate the efficacy and safety of anti-TNF therapy in managing phlegmonous CD.

Methods
Cases were identified through searching patient records for CT, MRI and intestinal ultrasound reports containing the words “Crohn’s” and “phlegmon”. Patients were included if found to have CD-related phlegmon subsequently started on anti-TNF. Patients were excluded if they were already on an anti-TNF at diagnosis, or underwent surgery prior to starting anti-TNF. Electronic review of patient records was undertaken to determine demographics, current medication, length of disease and surgery.

Results
Of the 66 cases identified, 11 fulfilled inclusion criteria. 2 cases required surgery at 38 and 197 days post-phlegmon diagnosis, both of which had earlier ceased anti-TNF due to failed trial and severe depression respectively. 4 patients discontinued anti-TNF during follow up: 1 experienced severe anaphylaxis, 1 failed anti-TNF trial, and 2 ceased due to personal preference (severe depression, concern about adverse effects). 8 of 10 had complete resolution of the phlegmon with 1 patient awaiting imaging 6 months post-phlegmon diagnosis.

Conclusion
9 of 11 of our patient cohort avoided surgery after starting anti-TNF therapy for phlegmonous CD, out to a median follow up of 20 months. Our findings suggest anti-TNFs are generally well tolerated, and early commencement may be effective in preventing surgical intervention.
P605 Development and validation of an objective disability index for Inflammatory Bowel Disease patients (ODIBD)
Authors: Melcarne L , Vergara Gómez M , Villoria Ferrer A , Brunet Mas E , Garcìa Iglesias P , Llovet Soto L , Dosal Galguera A , Monllor Nunell T , Alforcea Alcaraz S , Calvet Calvo X 
Published: May 2021

Abstract

Background
Inflammatory Bowel Disease (IBD) can be a cause of disability. To date, the scores that evaluate disability in IBD patient use mainly subjective criteria. The aim of this study was to develop and validate an index of disability in IBD based on objective, measurable criteria.

Methods
IBD patients from the Catalan and Spanish Crohn and Colitis Associations volunteered to fulfill an online self-administered survey. Demographic, clinical, and therapeutic variables were collected. They also informed on whether they have a recognized disability and whether they receive a work disability pension.
Patients were divided into a training and validation set. In the training set, different multivariate analyses were carried out to evaluate objective variables related to having a recognized work disability, a general disability or a moderate or severe degree of disability.
The score was elaborated with the statistically or clinically significant variables present in the multivariate analyses.
The ROC curves for predicting general and work disability were calculated.

Results
981 valid surveys were included. Sixty six percent of the patients were women, mean age was 40.9 years and 59.3% had Crohn’s disease. Of these patients, 85 (9.1%) had a recognized work disability and 429 (45.9%) had a degree of recognized general disability. The results of the multivariate analyses are shown in table 1.
Eight variables were selected to develop the inflammatory bowel disease objective work disability index (ODIBD) (table 2). Each variable was scored one point to calculate the final index.
The AUROC of the index in the training group was 0.76 for work disability and 0.71 for general disability. The AUROC of the index in the validation group was 0.83 for work disability and 0.67 for general disability (fig1).

Conclusion
The ODIBD may be useful score to objectively assess of work disability in patients with IBD.
P607 The Faroese IBD Study: Update on incidence from 2015–2020 and prevalence from 1960–2020
Authors: Nielsen K R , Midjord J , Hammer T , Lophaven S , Burisch J 
Published: May 2021

Abstract

Background
Previous reports have found that the Faroe Islands has the highest reported incidence of inflammatory bowel disease (IBD) in the world.1,2 The purpose of this study was to update our previous work on the IBD incidence from 1960–20142 with data up until 2020 and to describe the prevalence of IBD over 60 years.

Methods
All cases of Crohn’s disease (CD), ulcerative colitis (UC) and IBD unclassified (IBDU) diagnosed between 1960 to 2020, including all age groups and year of death, were retrieved from the Medical Centre at the National Hospital of the Faroe Islands. Diagnoses were ascertained according to the Copenhagen Diagnostic Criteria. Population data from 1960–2020 were retrieved from Statistics Denmark and Statistics Faroe Islands. Point prevalence rates (per 100,000) were estimated as all IBD patients alive and living in the Faroe Islands by the end of 1960, 1970, 1980, 1990, 2000, 2010 and 2020, divided by the Faroese population (end of year).

Results
232 individuals have been diagnosed with IBD during the past 6 years in the Faroe Islands: 29 (12%) with CD, 111 (48%) with UC and 92 (40%) with IBDU, resulting in an increased age-standardised IBD incidence rate (European Standard Population, ESP) from 74 per 100,000 person-years (py) in 2010–14 to 80 in 2015–20. Figure 1 illustrates the updated IBD incidence rate integrated with results from our previous study.2 The point prevalence rate of IBD was 5,8 cases per 100,000 persons in 1960; 46,6 in 1970; 133,9 in 1980; 325,4 in 1990; 610,7 in 2000; 925,1 in 2010 and 1407,9 cases per 100,000 in 2020, corresponding to 1,4% of the Faroese population living with IBD in 2020 compared to 0,6% in 2000.

Conclusion
The increasing incidence of IBD from 2015–2020 is mainly driven by IBDU, accounting for 40% of all cases and has increased from 21 per 100,000 (ESP) in 2010–14 to 32 in 2015–2020. The age-standardised incidence rate of CD remains unchanged compared to our previous study, at 10 per 100,000 (ESP), while the incidence of UC has decreased from 44 to 39 per 100,000 (ESP). The prevalence of IBD has increased radically in accordance with the increasing incidence. Further investigations into the high proportion of IBDU and causes of the observed IBD pattern is currently ongoing.
1. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 2018;390:2769–78.et al.
2. The Faroese IBD Study: Incidence of Inflammatory Bowel Diseases Across 54 Years of Population-based Data. J Crohns Colitis 2016;10:934–42.
P615 Does smoking really influence the development and the outcomes of Inflammatory Bowel Disease in Asian population? Results from the Taiwanese patients
Authors: Chen B C , Weng M T , Chang C H , Huang L Y , Wei S C 
Published: May 2021

Abstract

Background
Smoking has been reported to be associated with increased risk of Crohn’s disease (CD) and protect against ulcerative colitis (UC) from the Western population. However, the association are not well studied and there is no report about smoking and disease outcomes in the Asian population. This study is to clarify the influence of smoking in the development and disease outcomes of inflammatory bowel disease (IBD) in Asian population.

Methods
This case-controlled study was conducted by cross section chart review for smoking status as well as clinical characteristics of IBD patients at the National Taiwan University Hospital (NTUH). Age, sex, co-morbidities (hypertension, diabetes, and hyperlipidemia) matched non-IBD control were identified by using the database from the National Health Interview Survey of Taiwan, with 4 to 1 ratio for IBD patients. Clinical characteristics including disease phenotype, medication usage, times of admissions, times of emergency room (ER) visits, surgery, development of new cancer, survival status, endoscopic severity, laboratory data were retrieved and analyzed.

Results
A total of 700 IBD patients (UC: 412; CD: 378) diagnosed from January 1963 to 2020 were identified and analyzed for the influence of smoking to outcomes. The median follow-up time of UC and CD was 104 and 85 months, respectively. Among them, 575 patients (UC: 297, CD: 278) with complete information of comorbidities and aged from 12 to 64 years old were enrolled for smocking prevalence analysis. The prevalence of smoking was significantly lower in UC compared to the matched control (20.88% vs 30.39%, p = 0.0003), but there was no difference between CD and the matched control (19.78% vs 22.12%, p = 0.595). UC smokers were associated with less times of admission (1.56 vs. 2.46, p = 0.017), but higher rate of new cancer development (16% vs. 6.67%, p = 0.01), and mortality (16% vs. 4.91%, p = 0.001), when compared to the non-smokers. CD smokers tended to have disease located in terminal ileum (L1) and ileocolon (L3) (p = 0.0067), higher rate of stricturing (B2) and penetrating (B3) disease (p = 0.0328), higher risk of surgery (60.32% vs. 38.27%, p = 0.001) than the non-smokers, but no difference on mortality.

Conclusion
In Asian IBD population, smoking is a protective factor for UC occurrence and associated with lower hospitalization rate but more cancer and higher mortality. In contrast, smoking has no effect for CD occurrence and mortality but related to more aggressive behavior which resulted in higher surgical rate.
Estimating Perceptual Range of Female Monarch Butterflies (Danaus plexippus) to Potted Vegetative Common Milkweed (Asclepias syriaca) and Blooming Nectar Resources
Authors: Fisher Kelsey E , Bradbury Steven P 
Published: May 2021

Abstract
Habitat loss in the summer breeding range contributes to eastern North American monarch (Lepidoptera: Nymphalidae) population decline. Habitat restoration efforts include increasing native prairie plants for adult forage and milkweed (Asclepias spp.) for oviposition and larval development. As the monarch is a vagile species, habitat establishment at a grain that matches the monarch perceptual range will facilitate efficient movement, decrease fitness costs of dispersal, and increase oviposition. We released 188 experimental monarch females 5, 25, 50, and 75 m downwind from potted milkweed and blooming forbs in 4–32 ha sod fields. Perceptual range was estimated from monarchs that flew towards and landed on the milkweed and forbs. Flight patterns of 49 non-experimental monarchs that landed on the resources were also observed. In our experimental, resource-devoid setting, wind-facilitated movement occurred most frequently. Monarchs performed direct displacement as evidenced by shallow turn angles and similarity of Euclidian and total distances traveled. We hypothesize similar monarch flight behavior when traveling over other resource-devoid areas, such as crop fields. Although the majority of experimental monarchs flew downwind, eight experimental and 49 non-experimental monarchs were observed flying upwind toward, and landing on, the potted resources from distances ranging from 3 to 125 m (mean = 30.98 m, median = 25 m, mode = 25 m). A conservative estimate of the perceptual range is 125 m, as longer distances cannot be precluded; however, the majority of observations were ≤50 m. Our findings suggest establishing habitat patches ~ 50 m apart would create functional connectivity across fragmented agricultural landscapes.
Response to Anti-α4β7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline
Authors: Gazouli Maria , Dovrolis Nikolas , Bourdakou Marilena M , Gizis Michalis , Kokkotis Georgios , Kolios George , Michalopoulos Georgios , Michopoulos Spyridon , Papaconstantinou Ioannis , Tzouvala Maria , Viazis Nikos , Xourafas Vasilleios , Zacharopoulou Eirini , Zampeli Evanthia , Mantzaris Gerasimos , Papatheodoridis George , Bamias Giorgos 
Published: May 2021

Abstract

Background
Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4β7, vedolizumab, in patients with active ulcerative colitis (UC).

Methods
Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly.

Results
In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a “core” mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade.

Conclusions
Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.
Foretelling the Flex—Vertebral Shape Predicts Behavior and Ecology of Fishes
Authors: Donatelli Cassandra M , Roberts Alexus S , Scott Eric , DeSmith Kylene , Summers Dexter , Abu-Bader Layanne , Baxter Dana , Standen Emily M , Porter Marianne E , Summers Adam P , Tytell Eric D 
Published: May 2021

Synopsis
One key evolutionary innovation that separates vertebrates from invertebrates is the notochord, a central element that provides the stiffness needed for powerful movements. Later, the notochord was further stiffened by the vertebrae, cartilaginous, and bony elements, surrounding the notochord. The ancestral notochord is retained in modern vertebrates as intervertebral material, but we know little about its mechanical interactions with surrounding vertebrae. In this study, the internal shape of the vertebrae—where this material is found—was quantified in 16 species of fishes with various body shapes, swimming modes, and habitats. We used micro-computed tomography to measure the internal shape. We then created and mechanically tested physical models of intervertebral joints. We also mechanically tested actual vertebrae of five species. Material testing shows that internal morphology of the centrum significantly affects bending and torsional stiffness. Finally, we performed swimming trials to gather kinematic data. Combining these data, we created a model that uses internal vertebral morphology to make predictions about swimming kinematics and mechanics. We used linear discriminant analysis (LDA) to assess the relationship between vertebral shape and our categorical traits. The analysis revealed that internal vertebral morphology is sufficient to predict habitat, body shape, and swimming mode in our fishes. This model can also be used to make predictions about swimming in fishes not easily studied in the laboratory, such as deep sea and extinct species, allowing the development of hypotheses about their natural behavior.
Impact of preoperative antithrombotic therapy in patients undergoing elective isolated coronary artery bypass grafting
Authors: van Steenbergen Gijs J , van Straten Albert H M , Kabak Serhat , van Veghel Dennis , Dekker Lukas , Soliman-Hamad Mohamed A 
Published: May 2021

Abstract OBJECTIVESThe objective of this retrospective study was to assess differences in clinical outcomes between patients on acetylsalicylic acid (ASA) monotherapy and patients on other antithrombotic (AT) regimens undergoing elective coronary artery bypass grafting (CABG).METHODSPatients who underwent elective isolated CABG between 2017 and 2019 at the Catharina Hospital Eindhoven were eligible for this study. The primary end points were re-exploration for bleeding and postoperative blood product transfusion. Secondary end points included 30-day mortality, in-hospital stroke, in-hospital myocardial infarction and duration of hospitalization. Propensity matching was used to compare outcomes of the main study groups (ASA vs other AT therapy) and subgroups of AT therapy (guideline adherence vs non-adherence).RESULTSA total of 1068 patients were included: 710 patients on ASA monotherapy and 358 patients on other AT regimens. In the 256 matched patients in the main study groups, using AT regimens other than ASA monotherapy was associated with increased risk of re-exploration for bleeding [6.6% vs 2.0%, P = 0.017; odds ratio (OR) 3.57 (1.29–9.83)] and increased use of blood products [37.5% vs 20.3%, P &lt; 0.001; OR 2.35 (1.58–3.49)]. In 122 matched subgroup patients, non-adherence was associated with an increased risk of re-exploration [10.7% vs 3.3%, P = 0.044; OR 3.52 (1.11–11.12)] and increased blood product use [51.6% vs 25.4%, P &lt; 0.001; OR 3.13 (1.83–5.38)]. Secondary end points were not significantly different among the main study groups and subgroups.CONCLUSIONSPreoperative use of AT therapy other than ASA monotherapy in patients who elected CABG was associated with the increased postoperative use of blood products and risk of re-exploration for bleeding; this finding was even more pronounced in non-guideline-adherent patients.
Task-Dependent Effects of SKF83959 on Operant Behaviors Associated With Distinct Changes of CaMKII Signaling in Striatal Subareas
Authors: Liu Pei-Pei , Chao Chih-Chang , Liao Ruey-Ming 
Published: May 2021

Abstract

Background
SKF83959, an atypical dopamine (DA) D1 receptor agonist, has been used to test the functions of DA-related receptor complexes in vitro, but little is known about its impact on conditioned behavior. The present study examined the effects of SKF83959 on operant behaviors and assayed the neurochemical mechanisms involved.

Methods
Male rats were trained and maintained on either a fixed-interval 30-second (FI30) schedule or a differential reinforcement of low-rate response 10-second (DRL10) schedule of reinforcement. After drug treatment tests, western blotting assayed the protein expressions of the calcium-/calmodulin-dependent protein kinase II (CaMKII) and the transcription factor cyclic AMP response element binding protein (CREB) in tissues collected from 4 selected DA-related areas.

Results
SKF83959 disrupted the performance of FI30 and DRL10 behaviors in a dose-dependent manner by reducing the total number of responses in varying magnitudes. Moreover, the distinct profiles of the behavior altered by the drug were manifested by analyzing qualitative and quantitative measures on both tasks. Western-blot results showed that phospho-CaMKII levels decreased in the nucleus accumbens and the dorsal striatum of the drug-treated FI30 and DRL10 subjects, respectively, compared with their vehicle controls. The phospho-CREB levels decreased in the nucleus accumbens and the hippocampus of drug-treated FI30 subjects but increased in the nucleus accumbens of drug-treated DRL10 subjects.

Conclusions
Our results provide important insight into the neuropsychopharmacology of SKF83959, indicating that the drug-altered operant behavior is task dependent and related to regional-dependent changes of CaMKII-CREB signaling in the mesocorticolimbic DA systems.