bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of the automatic control system of the blower motors of the diesel electric locomotive
Authors: Konovalova T G , Izotova I I , Astashkov N P , Olentsevich A A
Published: May 2021

The main tasks of the railway industry are focused on reducing the costs associated with the operation and repair of technological equipment. It is possible to solve them by the development of technical means that optimally take into account the natural and climatic, geographical and technical operating conditions. In these operating conditions, the development of locomotive traction involves the modernization of the existing fleet of traction rolling stock, improvement of the locomotives produced, the development of a paradigm-shifting platform of lines of innovative locomotives, the replacement of equipment by more reliable and modern one, and the automation of processes. Automation makes it easier to control the locomotive, reduce the risk of errors and ensure the most rational equipment operation modes. It was found that the damage to the electric parts of the electric motors accounted for more than 70 percent of the total number of faults. The purpose of this article is to develop a technical solution, the use of which will minimize the number of failures of auxiliary machines and locomotive equipment of this series. To implement this, it considers the main design features of electric motors, their connection diagram and the presence of protection elements to determine the trouble spots and justify the proposed technical solution.
Uncertainty quantification by ensemble learning for computational optical form measurements
Authors: Hoffmann Lara , Fortmeier Ines , Elster Clemens
Published: May 2021

Uncertainty quantification by ensemble learning is explored in terms of an application known from the field of computational optical form measurements. The application requires solving a large-scale, nonlinear inverse problem. Ensemble learning is used to extend the scope of a recently developed deep learning approach for this problem in order to provide an uncertainty quantification of the solution to the inverse problem predicted by the deep learning method. By systematically inserting out-of-distribution errors as well as noisy data, the reliability of the developed uncertainty quantification is explored. Results are encouraging and the proposed application exemplifies the ability of ensemble methods to make trustworthy predictions on the basis of high-dimensional data in a real-world context.
Likelihood-based tests for detecting circadian rhythmicity and differential circadian patterns in transcriptomic applications
Authors: Ding Haocheng , Meng Lingsong , Liu Andrew C , Gumz Michelle L , Bryant Andrew J , Mcclung Colleen A , Tseng George C , Esser Karyn A , Huo Zhiguang
Published: May 2021

Circadian rhythmicity in transcriptomic profiles has been shown in many physiological processes, and the disruption of circadian patterns has been found to associate with several diseases. In this paper, we developed a series of likelihood-based methods to detect (i) circadian rhythmicity (denoted as LR_rhythmicity) and (ii) differential circadian patterns comparing two experimental conditions (denoted as LR_diff). In terms of circadian rhythmicity detection, we demonstrated that our proposed LR_rhythmicity could better control the type I error rate compared to existing methods under a wide variety of simulation settings. In terms of differential circadian patterns, we developed methods in detecting differential amplitude, differential phase, differential basal level and differential fit, which also successfully controlled the type I error rate. In addition, we demonstrated that the proposed LR_diff could achieve higher statistical power in detecting differential fit, compared to existing methods. The superior performance of LR_rhythmicity and LR_diff was demonstrated in four real data applications, including a brain aging data (gene expression microarray data of human postmortem brain), a time-restricted feeding data (RNA sequencing data of human skeletal muscles) and a scRNAseq data (single cell RNA sequencing data of mouse suprachiasmatic nucleus). An R package for our methods is publicly available on GitHub https://github.com/diffCircadian/diffCircadian.
DOP28 Medical and Surgical Outcomes in Isolated Internal Penetrating Crohn’s Disease: A Multi-Centre Experience
Authors: Sebepos-Rogers G , Fragkos K , Shakweh E , Shah K , Lake L , Balarajah S , Chung Y , McGuire J , Al-Shakarchi N , Khetan T , Bottle J , Anandarajah C , Meade S , David L , Hicks L , Kok K , Joshi N , Samaan M , Patel K , Mehta S
Published: May 2021

Background

Isolated internal penetrating Crohn’s diseases (IIPCD) is the second most common fistulating phenotype yet remains poorly characterised in therapeutic trials. This study assessed long-term outcomes of IIPCD.

Methods

We performed a retrospective study on data collected from 6 IBD referral centres, screening imaging reports between January 2016 and April 2019, excluding perianal or enterocutaneous fistulation, resulting in 121 patients with IIPCD. Management was classified as no intervention, medical (new/optimised) or surgical. The primary endpoint was complete resolution (CR) of fistula at next two imaging reassessments, paired with symptom and nutrition status, as previously defined(Samimi et al., 2010). Secondary endpoint was combined CR and partial resolution (PR). Statistics: Fisher’s exact, Kaplan-Meier method (SPSS v.27).

Results

Of patients at IIPCD diagnosis, 21% had previous IBD-related surgery, 21% were on a current biologic, 41% immunomodulator and 41% no treatment. Fistulae were majority enteroenteric (55%) and enterocolonic (48%), minority genitourinary (7.4%), with median disease duration at IIPCD diagnosis of 64 months.

Outcomes of 118 patients with ≥1 interval imaging were analysed. Initial management was: 25.4% (n=30) no intervention, 49.2% (n=59) medical, 25.4% (n=30) surgical. Of fistula characteristics, only abscess predicted surgery over medical management (OR 5.30, 95% CI 1.60–15.48 p=0.0061), Figure 1.

At first reassessment, CR and PR for the three management cohorts was 13.3%, 12.1%, 66.7% and 20.0%, 46.6%, 26.7%, respectively. The cumulative probability of CR was significantly greater for surgery compared with no intervention and medical management (log-rank p<0.001), Figure 2, and sustained when excluding pre-existing biologic (log-rank p=0.007), Figure 3, or previous surgery history (log-rank p<0.001).

As observed management was then adjusted, cohorts were re-stratified: 13.5% (n=16) no intervention only, 45.8% (n=54) any medical but no surgery, 40.7% (n=48) any surgery. At second reassessment, again surgery significantly predicted CR over other management (log-rank p<0.001), Figure 4, but this was lost using the less strict outcome of combined CR and PR (log-rank p=0.447). No baseline variables were predictive of CR by each management. 27.6% (16/58) and 6.7% (2/30) of initial medical and no intervention cohorts had subsequent surgery (median interval 6.7 and 50.1 months) but there was no significant difference in peri-operative parenteral nutrition or post-operative intra-abdominal septic complication rates between earlier or later surgery.

Conclusion

In this cohort, surgery increases the probability of resolution of IIPCD with medical therapy including biologics offering limited temporising effect.
DOP43 Impact of Inflammatory Bowel Diseases on the phenotype and severity of psoriasis and spondyloarthropathies
Authors: Attauabi M , Damsgaard Wewer M , Bendtsen F , Seidelin J B , Burisch J
Published: May 2021

Background

It is unclear whether inflammatory bowel diseases (IBD) affect the phenotype and severity of co-occurring axial spondyloarthropathies (axSpA) and psoriasis. Therefore, we aimed to investigate the characteristics of axSpA and psoriasis in relation to co-occurring IBD.

Methods

The systematic review and meta-analysis were conducted according to Cochrane’s recommendations. PubMed and EMBASE were searched from database inception till January 2020 for studies reporting disease phenotype and severity of axSpA and psoriasis in association with co-occurrence of IBD. Meta-analyses were performed using a random-effects model. Quality of the studies was assessed by the Newcastle-Ottawa Scale (NOS).

Results

The electronic search yielded 12,220 studies which were narrowed down to 152 after screening based on study titles and abstracts. Of these, a full-text review identified 20 eligible studies, including twelve and eight studies describing characteristics of axSpA and psoriasis, respectively, in relation to IBD.

AxSpA was identified among a total of 321 and 8,660 patients with and without a co-occurring IBD, respectively, and the studies’ mean NOS score was 6.8, including seven and five studies of moderate and high quality, respectively. The meta-analysis demonstrated that presence of co-occurring IBD was associated with an increased risk of dactylitis (risk ratio (RR)=2.06 (95%CI 1.24–3.42), I2=0%), but not enthesitis (RR=0.93 (95%CI 0.48–1.81), I2=86%). Furthermore, IBD was associated with a significantly lower Bath Ankylosing Spondylitis Radiology Index (mean difference (meandiff) -2.28 (95%CI -3.26-(-1.30)), p<0.01, I2=0%), better Schober’s test results (meandiff 0.80 (95%CI 0.64–1.49), p<0.01, I2=0%), and a lower finger to floor distance (meandiff -6.36 (95%CI -10.36-(-2.36)), p<0.01, I2=0%).

The phenotype of psoriasis was assessed among 680 and 222,279 patients with and without a co-occurring IBD. The mean NOS score was 7.4, including two studies of moderate methodological quality, while the remaining six studies were of high quality. The presence of IBD was associated with a significantly less frequent presentation of psoriasis in the nails (RR=0.14 (95%CI 0.05–0.42), I2=0%) but not psoriatic arthritis (RR=0.94 (95%CI 0.27–3.31), I2=75%). Finally, the presence of IBD was associated with a milder phenotype of psoriasis (RR=1.41 (95%CI 1.02–1.96), p=0.04, I2=70%).

Conclusion

This is the first systematic review with meta-analysis investigating the impact of IBD on the disease phenotype and severity of psoriasis and axSpA. Our data suggest that IBD modifies psoriasis and axSpA to be milder and emphasizes the importance of a multidisciplinary approach to patients with psoriasis or axSpA and co-occurring IBD.
DOP46 Sustainability rate of immunomodulators monotherapy in patients with Crohn’s Diseases: A population-based analysis from the epi-IIRN cohort
Authors: Atia O , Friss C , Mendelovici A , Shteyer E , Yogev D , Ledderman N , Greenfeld S , Kariv R , Loewenberg Weisband Y , Gabay H , Nevo D , Matz E , Dotan I , Turner D
Published: May 2021

Background

Immunomodulators (IMM), including thiopurines and methotrexate (MTX), have been long used to maintain remission in Crohn’s disease (CD), both associated with remission, but also with toxicity and therapeutic failure. We aim to compare the sustainability of thiopurines and MTX commenced as monotherapy in patients with CD, and to explore predictors of sustainability.

Methods

This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all biologic-naïve CD patients diagnosed after 2005 and treated with IMM monotherapy for at least three months. Sustainability was defined as continues IMM treatment without switching therapy, adding biologics or requiring surgery. In addition, at most one short steroid course was allowed. Cox regression model was used to explore estimated predictors to sustainability. To compare sustainability rate between thiopurines and MTX we used propensity score (PS) matching, and thereafter Cox regression model.

Results

A total of 4,891 (1,551 [32%] pediatric-onset and 3,340 [68%] adults) IMM-treated patients were included with 37,825 person-years of follow up, of whom 4,339 (89%) were treated with thiopurines and 552 (11%) with MTX. The median time from CD diagnosis to initiation of IMM was 6.1 months (IQR 1.7–19.7), and the median course duration was 11.9 months (6.1–25.3). Sustainability rate was recorded in 92% of patients after 6 months from initiation of IMM and 81%, 69% and 65% at one, three and five years, thereafter. The most common type of failure was escalation to biologics (67%), while 17% required repeated steroid courses and 15% underwent surgery. Sustainability was associated with earlier initiation of IMM during the disease course (HR 0.98 [95%CI 0.97–0.985]) and lack of steroids at initiation of IMM (HR 0.7 [95%CI 0.6–0.8]). A PS adjusted analysis that included 337 thiopurnes-treated patients individually matched with 337 MTX-treated patients, showed sustainability was significantly better with thiopurines (HR 0.7 [95%CI 0.5–0.8]).

Conclusion

Two thirds of biologic-naïve CD patients treated with IMM monotherapy sustain this treatment after five years, especially when initiated early during the disease course. Sustainability was more likely in those treated with thiopurines compared with MTX.
DOP71 Fungal and bacterial gut microbiota in paediatric onset Inflammatory Bowel Disease introduced to infliximab
Authors: Ventin-Holmberg R , Höyhtyä M , Saqib S , Korpela K , Nikkonen A , Salonen A , de Vos W M , Kolho K L
Published: May 2021

Background

Paediatric Inflammatory Bowel Disease (PIBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC) and IBD undefined (IBDU) is increasing worldwide and is characterized by an onset inflammation in the gastrointestinal tract. The patients may present severe symptoms such as abdominal pain, diarrhoea and bloody stool. No defined pathogenesis has been established for PIBD, but an imbalanced intestinal microbiota is strongly associated to the disease. Anti-tumour necrosis factor alpha (TNF-α) is an effective drug to treat inflammation in IBD, but up to half of the patients do not have a long-term response to the drug. Presently, there are no methods available to predict the TNF-α response. Here we have investigated the biomarkers of the gut fungal and bacterial microbiota, which are largely unexplored in paediatric patients, particularly for the fungal microbiota, with the aim to find possible predictors of drug response.

Methods

The gut microbiota composition of 30 PIBD (25 CD, 2 UC and 3 IBDU) patients at the Children′s Hospital, University of Helsinki receiving the anti-TNF-α drug infliximab (IFX) was studied by MiSeq sequencing targeting the bacterial 16S rRNA gene and fungal ITS region separately from faecal samples collected before the start of treatment and two and six weeks after treatment initiation. The response to IFX was evaluated by a faecal calprotectin value below 100 µg/g at week six after treatment initiation. The fungal MiSeq sequencing data was processed by using the DADA2 pipeline, annotated to the BLAST database and analysed using the package mare. The bacterial MiSeq sequencing data was analysed using mare and annotated to the SILVA database.

Results

Both the fungal and bacterial microbiota differed significantly between responders compared to non-responders to IFX, further validated by high predictive power (area under curve > 0.8) for therapy response. This difference was characterized by an increase in short-chain fatty acid producing bacteria, such as bacteria in the class Clostridia in the responders at baseline. This was observed as elevated Faecalibacterium and Subdoligranulum genera in particular of responders at baseline. Additionally, Candida was increased while Saccharomyces was decreased in non-responders at the end of the study. Finally, we observed that the interkingdom correlations differed between response groups to IFX.

Conclusion

Our results strengthen the proposal that the gut microbiota composition of PIBD patients could predict the response to anti-TNF-α treatment in the future.
P037 Nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion properties of MORF-057 support its clinical development as an oral selective α4β7 integrin inhibitor
Authors: Jones J , Lee D , Smukste I , Cui D , Bursavich M G , Troast D , Zhong C , Wong J E , Mangada M M , Bain G , Lippa B , Ray A S , Rogers B N
Published: May 2021

Background

MORF-057 is a potent and selective small molecule inhibitor of the α 4β 7 integrin. Using a receptor occupancy (RO) assay under physiologically relevant conditions, MORF-057 achieves 90% α 4β 7 RO at approximately 10 nM in human whole blood. The current studies evaluate nonclinical pharmacokinetics (PK) and properties of absorption, distribution, metabolism, and excretion (ADME) to enable dose/exposure projection to humans.

Methods

PK studies were conducted in mouse, rat, dog, and monkey following intravenous (IV) and oral administration. ADME studies were conducted in vitro and in rats using carbon-14 [14C] labeled MORF-057. MORF-057 levels were quantified using liquid chromatography coupled with tandem mass spectrometry. Human PK was predicted based on body weight allometry, well-stirred and semi-physiological models.

Results

MORF-057 exhibited low to moderate clearance (CL) in animals with species dependent volume of distribution (Vdss) resulting in half-lives of 1.1 to 2.7 hours (Table 1). Following an oral dose, absorption was high with bioavailability ranging from 15% to 49%. MORF-057 is highly protein bound and distribution of [14C]MORF-057 derived radioactivity in rat was predominantly in the small intestine wall, liver, and stomach wall. Rifampin, an inhibitor of organic anion transporting polypeptides, decreased MORF-057 clearance by 3-fold in monkeys suggesting MORF-057 elimination involves hepatic uptake transport. MORF-057 is further cleared via CYP3A metabolism followed by biliary/fecal elimination of metabolites. MORF-057 is predicted to have moderate bioavailability (40%) and CL (6.5 mL/min/kg) in humans. Wajima transformation shows good agreement of the normalized PK across animal species, with a predicted human concentration-time profile supporting >90% α 4β 7 RO at trough following 200 mg twice daily dose (Figure 1).

Conclusion

These data demonstrate that MORF-057 is well absorbed and PK properties in animals support the potential for achieving high α4β7 RO following oral administration in humans. These nonclinical results provided a basis for the progression of MORF-057 into a first-in-human Phase 1 clinical study assessing safety, pharmacokinetics, and receptor occupancy (results being reported separately).
P057 CRL4DCAF2 promotes cell proliferation and limits the development of colitis
Authors: Wang C , Yao L , Zhang Y , Cao Q
Published: May 2021

Background

Ulcerative colitis (UC) is an idiopathic intestinal inflammatory disease, which leads to chronic intestinal mucosal barrier damage. More and more evidences show that ubiquitination of proteins regulates the occurrence and development of intestinal inflammation. DCAF family proteins could form E3 ubiquitin ligase with CRL4-DDB1 to regulate cell growth, differentiation, apoptosis and other life activities. CRL4DCAF2 is a crucial regulator in cell cycle regulation, but there are few studies on its application in intestinal epithelium. This study aims to explore the specific mechanism of CRL4DCAF2 in regulating the proliferation and repairment of intestinal epithelial cells.

Methods

DSS - induced colitis in mice was used as the experimental model in vivo. HCT116 and SW480 cell lines were used as experimental models in vitro studies.The Cre-loxP system was used to construct a mouse model of intestinal epithelium-specific DCAF2 knockout. The intestinal mucosa biopsy specimens of 11 normal patients and 11 UC patients were collected. In addition, qRT-PCR, Western blot, RNA-seq and immunofluorescent staining were used to detect the expression levels of target genes in human colon biopsy specimens, mouse colon tissues, HCT116 or SW480 cells

Results

DCAF2 gene was highly expressed in the colon of mice. The occurrence and development of DSS-induced experimental colitis was accompanied by a significant down-regulation of DCAF2 protein expression in colon. DCAF2 mRNA level was significantly decreased in UC patients. Mouse with intestinal epithelial-specific knockout of DCAF2(i.e. DCAF2IEC-KO) suffered from embryonic death. Compared with wild-type adult C57BL/6J mice, DCAF2IEC-KD mouse showed more severe intestinal inflammation in DSS-induced colitis model. CCK-8 test, PI staining and EDU staining flow cytometry experiments showed that the proliferation of intestinal epithelial cells with DCAF2 overexpression was faster than that of the control (P < 0.05) in HCT116 and SW480 cell lines, while in knockdown of DCAF2 models, the opposite results were obtained. Its effect may be related to the ubiquitination of p21. At the same time, MLN4924 in vivo and in vitro experiments further verified our experimental results. Combined with RNA-seq and Western blot, we also found that DCAF2 may reduce the symptoms of colitis by maintaining the stability of autophagy.

Conclusion

DCAF2 is low expressed in patients with ulcerative colitis, which may promote the activation and proliferation of intestinal epithelial cells. It could maintain autophagy stability, and restore intestinal barrier, thus alleviate the development of ulcerative colitis
P144 Clock gene expression levels inversely correlate with disease activity in ulcerative colitis and Crohn’s disease
Authors: Weintraub Y , Cohen S , Chapnik N , Anafy A , Yerushalmy-Feler A , Ben-Tov A , Dotan I , Riva T , Froy O
Published: May 2021

Background

Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augment inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White Blood Cells (WBC). This reduction correlated with disease activity. Our aim in this study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC).

Methods

17 patients with CD and 13 with UC, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and fecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (< 250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC (20 samples).

Results

In UC, BMAL (p<0.008), CLOCK (p<0.02), CRY1 (p<0.002), CRY2 (p<0.0009), PER1 (p<0.003) and PER2 (p<0.003) showed decreased expression when Fcal levels were > 250 μg/mg. When compared with the clinical status and CRP levels, only BMAL1 showed reduced expression (p<0.003 and p<0.001, respectively). In CD, clinical status correlated with clock gene expression: CLOCK (p<0.035), PER1 (p<0.001) and CRY1 (p<0.028) were reduced in active disease. CRP and Fcal did not correlate with clock gene expression.

Conclusion

Altered levels of certain clock genes were demonstrated in young CD and UC patients in exacerbation vs. remission. In UC, Fcal levels inversely correlated with all major circadian genes and partially with clinical status and CRP levels. In CD patients clock gene expression inversely correlated with clinical status.
P214 Faecal S100A12 as a non-invasive marker of inflammatory activity in pediatric Inflammatory Bowel Disease
Authors: Casertano M , Cenni S , Caprio A M , Oglio F , Pacella D , Miele E , Martinelli M , Staiano A , Strisciuglio C
Published: May 2021

Background

Calgranulin-C (S100A12) is a new faecal marker of inflammation that is potentially more specific for Inflammatory Bowel Disease (IBD) than calprotectin, since it is only released by activated granulocytes. In recent years it has been confirmed that the S100A12 has comparable sensitivity and specificity to fecal calprotectin (FC) in adult patients with IBD. The aim of our study was to evaluate concentration of faecal S100A12 and calprotectin (FC) to see which of the two tests best correlated to inflammation in IBD children.

Methods

Between September 2019 and March 2020, we prospectively enrolled all IBD pediatric patients, both Crohn’s Disease (CD) and Ulcerative Colitis (UC). Blood and faecal samples were collected in order to evaluate serological markers of inflammation, faecal S100A12A and FC. S100A12 and FC were determined by enzyme-linked immunosorbent assay (ELISA).

Results

One hundred seventeen consecutive children, 46 (39%) with CD and 71 (61%) with UC were enrolled in the study. The mean age was 14.6 years (range:5–18), 44% female. Twenty three children were in clinical relapse (20%). No significant differences in S100 A12A levels were found between the UC and the CD groups (mean ±ds 25 ±32mcg/ml vs 34 ±27 mcg/ml respectively, p=0.22).In the UC group we found a statistically significant correlation of both calprotectin and S100A12 with CRP (r=0.253, p=0.044 and r=0.252, p=0.040, respectively). In CD group we found that both calprotectin and S100A12 correlated with hemoglobin (r= -0.343, p=0,024; r=-0.401, p 0.008 respectively), hematocrit (r=-0.361, p=0,046; r=-0.434, p=0.015, respectively), fibrinogen (r=0.499, p< 0,001; r=0.325, p =0.038, respectively), and white blood cells count (r=0.309, p=0.044; r=0.394, p=0.021, respectively). Moreover, in CD group, FC correlated with CRP (r=0.431, p=0.004) and erythrocyte sedimentation rate (r=0.430, p=0.004). Finally, S100A12 correlated with platelet count both in CD and UC group (r=0.351, p=0.021and r=0.254, p=0.038, respectively) IBD children in clinical relapse had higher values ​​of S100A12 and FC than patients in remission (66±47 mcg/ml vs 43±42 mcg/ml, p=0.05 and 260±192 mg/Kg vs 166±169 mg/Kg, p=0.046, respectively)

Conclusion

Our preliminary data show that both faecal S100A12 and FC are useful non-invasive biomarkers which reflect inflammatory activity of IBD children. Our future aim is to evaluate the correlation of S100A12 and endoscopic finding in order to further clarify its role in the diagnosis and the management of pediatric IBD.
P353 Pan-enteric capsule endoscopy enables assessment of mucosal healing after biologic treatment initiation in Crohn’s disease
Authors: Volkers A , Bosuyt P , de Jong J , D’Haens G , Löwenberg M
Published: May 2021

Background

Pan-enteric capsule endoscopy (pan-CE) visualizes the entire gastrointestinal tract and provides an attractive alternative to conventional ileocolonoscopy to evaluate luminal disease activity in Crohn’s disease (CD). An earlier study showed that pan-CE is feasible, safe and well tolerated by CD patients. The aim of the present study was to assess the Sensitivity TO measure Change (STOC) in mucosal disease activity using pan-CE in CD.

Methods

Patients with CD and active disease based on symptoms (i.e. Crohn’s disease activity index (CDAI) >150) and inflammatory biomarkers (i.e. C-reactive protein (CRP) >5 mg/L and/or fecal calprotectin (fCal) levels >250 mg/kg) underwent pan-CE, using the second-generation Pillcam colon capsule, prior to and 8-12 weeks after treatment initiation with infliximab, adalimumab or vedolizumab. Luminal disease activity was assessed using the Crohn’s disease endoscopic index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD), expanded with two segments for the jejunum and pre-terminal ileum. Sensitivity to detect mucosal change was assumed if the standardized effect size was >0.8. Correlations between the evolution in CDAI, CRP and fCal with endoscopic activity scores before and after treatment initiation were calculated.

Results

Twenty-eight patients underwent pan-CE of whom two withdrew consent and four did not start biologic therapy. Twenty-two patients (78.6%) started biologic treatment and underwent pan-CE twice. Median duration between treatment initiation and pan-CE was 11 weeks (IQR: 9.8-12 weeks). Half of patients (11/22) were female and the median age was 24 years (IQR=22-38 years). The standardized effect size was 1.11 for CDEIS and 1.36 for SES-CD. Median CDEIS scores decreased from 6.8 (IQR=4.6-11.2) to 3 (IQR=0.9-6.0, p=0.01). Median SES-CD scores decreased from 15.5 (IQR=9.8-22.5) to 6 (IQR=2.8-11.3, p=0.001). SES-CD score per segment decreased significantly for colon segments, not for small bowel segments (figure 1). The difference in CDAI, CRP and fCal outcomes before and after treatment did not correlate with the change in CDEIS and SES-CD.

Conclusion

Pan-CE is useful to assess luminal disease activity in CD patients who embark on biological treatment. Pan-CE is sensitive to monitor mucosal healing outcomes and might therefore replace ileocolonoscopy for this indication in CD patients.
P472 Payer addressable burden of Crohn’s disease in patients treated with ustekinumab and vedolizumab in the United States
Authors: Ghosh T , Smith I , Fehr J , Davidson J , Fan T , Candela N , Tsang C , Koch T
Published: May 2021

Background

Vedolizumab (VDZ) and ustekinumab (UST) are treatments for moderate-to-severe Crohn’s disease (CD). The payer addressable burden (PAB) is the total allowed cost of care of a national health plan based on an actuarial analysis of all members total cost burden, for a given disease, regardless of any other underlying conditions. We used an actuarial retrospective claims analysis of direct and indirect costs associated with payer allowed resource utilizations to understand the US payer cost burden of the biologic-treated CD population.

Methods

Mean annual allowed cost per member with CD in the commercial health plan population was examined from a health plan actuarial and financial perspective. Data were obtained from medical and prescription claims of commercial and Medicare health plan members from Optum’s proprietary de-identified Normative Health Information database. Administrative claims data for all commercial members with pharmacy and medical coverage were used to determine medical utilization and medication unit cost patterns for CD treatment for 2017–2019. PAB analysis includes resource utilizations and associated costs among CD patients (pts) whose last biologic agent received in a year was UST subcutaneous (SC) or VDZ intravenous (IV). Costs captured were the total paid by plan and pts for medical or pharmacy claims. ICD-10 diagnosis codes were used to identify prescriptions to be included based on CD diagnosis. Members with diagnostic codes for concomitant ulcerative colitis (UC) were included only if they had more claims for CD than UC. Allowed claims costs, the sum of all medical and pharmacy costs, were categorized as CD-specific PAB and all-cause PAB. Cost per member per month was estimated by dividing total costs by total member enrolled months.

Results

In this retrospective claims analysis, more members with CD were treated with VDZ IV than UST SC in 2017 and 2018. Total and CD-related costs were lower with VDZ IV than with UST SC in overall members with CD and biologic-naïve members with CD (Figure 1). Both CD-related and all-cause PAB were markedly lower for VDZ IV than UST SC (Figure 2).

Conclusion

PAB can help payers identify opportunities for cost-saving. For patients with CD, the payer cost burden was lower with VDZ IV than with UST SC. This analysis provides a cross-sectional view of financial burden for US payers in managing members with CD. The analysis did not include longitudinal follow-up of pts for cost difference or adjustment of confounders in biologic-treated pts. The results capture the real-world burden of all forms of clinical practice and resource utilization in treating pts with CD enrolled in a commercial national plan.
P503 Inflammatory bowel disease video-consulting: a satisfaction survey during the second wave of Covid-19 pandemics
Authors: Todeschini A
Published: May 2021

Background

During the SARS-CoV-2 pandemic there was a substantial change in providing medical care. National and international statements recommended avoiding face-to-face visit for treatment of patients especially for chronic disease. Also lockdown and social distancing cause a lot of concern among patients, which prefer avoid hospital facilities due to fear of contracting COVID-19. For these reason there was a reorganization of inflammatory bowel disease follow-up visit shifting from traditional visit to telemedicine whereas it’ was possible. Our survey aimed to evaluated satisfaction about follow up video-consulting in IBD patients.

Methods

From September to December 2020, 75 video-consults were made as follow up in patients with IBD. Video-consult wasn’t performed as first visit nor in patients with new clinical issue. Every consult lasted about 15 minutes. At the end of the visit, a questionnaire of satisfaction was e-mailed to each patient. This questionnaire evaluated several items: satisfaction, difficulty of connection, opportunity to repeat the video-consult even in post-Covid-19 era, safety compared to face-to-face visit, level of concern about Covid-19 disease and fear of in-hospital transmission

Results

70% of the patients indicated an high video-consult rating and in most of cases (88%) there were no connection problems. The majority (88%) would like to repeat the tele-visit even in the post-Covid 19 era (77%). Video-consult seemed to be perceived as safer than face-to-face visit even if, in case of urgent consultation, it was preferred a traditional visit. Moreover, Covid-19 infection and fear of in-hospital trasmission was a great concern in the 73% and 58% of the patients respectively.

Conclusion

In our survey, outpatients reported a very high degree of satisfaction with video consultations. It was an easy and safe tool that may become an integral part of clinical practice in the future.
P601 Are Inflammatory Bowel Disease patients’ expectations met by dietetic services?
Authors: McCarthy N , Schultz M , Wall C
Published: May 2021

Background

Guidelines recommend that Inflammatory Bowel Disease (IBD) patients should have access to specialised dietitian support. Literature suggests that patients are often dissatisfied with their access to reliable nutrition information and dietitian services. Our aim was to assess whether New Zealand (NZ) dietetic services were meeting the expectations of patients.

Methods

In early 2020 an electronic survey to explore experience of dietetic services was disseminated to approximately 2000 patients (and parents) by Crohn’s and Colitis NZ and IBD health professionals. Quantitative responses were analysed via non-parametric methods and qualitative responses were analysed via inductive analysis.

Results

Responses were received from 407 IBD patients. Participants were asked if it ‘is useful for patients diagnosed with IBD to have access to a dietitian for nutrition advice?’ with 86% responding ‘Yes’ and 12% ‘Maybe’. Almost all (95%) patients had nutrition topics that they would like to discuss with a dietitian but only 52% had seen a dietitian and 45% had never been referred. Patients were interested in various nutrition topics (Table 1). Most (65%) would like access to a dietitian whenever a new nutrition issue arises.

The most frequent nutrition advice received was to follow a specific diet, most commonly a low fermentable carbohydrate diet followed by a low residue diet, or general nutrition advice. Two-thirds (66%) of respondents found the dietitian advice at least moderately useful while 18% reported it was not at all useful. Patients who saw a dietitian in a private clinic were more likely to find the advice useful (p=0.0001), as were those who had received written advice (p<0.0001).

Common themes in response to open-ended questions included: frustration at difficulty accessing dietetic services; desire for routine dietitian referral at diagnosis and ongoing access; the need for dietitians to have specialist knowledge of IBD; a perception that some medical staff believe nutrition is not relevant in IBD management.

Conclusion

Many patients have never been referred to a dietitian and a proportion of patients did not find dietitian advice useful. Dietitian advice appears to be on the topics most commonly of interest to patients. Access to dietetic services needs to improve and exploration is needed to elucidate why some aspects of services are not meeting patient expectations.
An unusual case report of stress-induced cardiomyopathy presenting as ventricular fibrillation cardiopulmonary arrest and third-degree atrioventricular block
Authors: Parekh Akarsh , Sengupta Vivek , Zainea Mark
Published: May 2021

Background

Takotsubo cardiomyopathy (TCM) can clinically present as an acute coronary syndrome; however, the former has regional wall motion abnormalities that extend beyond a single coronary vascular territory without any plaque rupture. Takotsubo cardiomyopathy classically involves apical ballooning of left ventricle (LV). It is uncommon for TCM to present as cardiopulmonary arrest (CPA) along with third-degree atrioventricular (AV) block.

Case summary

A 63-year-old female, underwent a ventricular fibrillation (VF) CPA. She was defibrillated three times and return of spontaneous circulation (ROSC) was achieved after 37 min. Her post-ROSC electrocardiogram showed non-specific ST-segment changes and T-wave inversions and soon progressed to third-degree AV block. Patient had a transvenous pacemaker placed to pace her heart. Echocardiogram showed an LV ejection fraction of 15–20% with akinesis of the apex and anteroseptum. An echocardiogram repeated 4 days after the cardiopulmonary arrests showed an ejection fraction of 60–65% with hypokinesis of mid anterior and antero-apical hypokinesis. However, the patient still continued to require a pacemaker and hence eventually received a dual-chamber pacemaker/implantable cardioverter-defibrillator for her AV block and ventricular arrhythmia.

Discussion

Most commonly TCM presents with chest pain and symptoms of acute myocardial infarction. We present a very rare presentation of TCM associated with VF and CPA along with third-degree AV block. There have handful of case reports documenting TCM causing CPA in some patients and other case reports showing TCM causing high degree AV block. In our patient, TCM was associated with both VF and CPA along with third-degree AV block.
May Measurement Month 2019: blood pressure screening results from Chile
Authors: Lanas Fernando , Garcia María Soledad , Paccot Melanie , Beaney Thomas , Xia Xin , Poulter Neil R
Published: May 2021

Hypertension is a major preventable cause of death worldwide. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high blood pressure (BP) and identifying individuals with increased BP. A cross-sectional survey of volunteers aged ≥18 years old was carried out in May 2019 in Chile. Participating sites were distributed across the country, most of them from the Public Health System outpatient clinics. In addition, clinical research sites, universities, and private clinics participated. Blood pressure measurement protocol, hypertension categories, and statistical analysis followed the MMM protocol. Hypertension was diagnosed as mean systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or receiving antihypertensive medication. Overall, 6876 individuals were screened. After multiple imputations, hypertension prevalence was 35.4%, of which 65.9% were aware of their condition. While 60.1% were on antihypertensive medication and 34.4% of the total number of hypertensives had their BP controlled. Of participants not receiving antihypertensive treatment, 17.9% were identified as hypertensive. The MMM 2019 survey demonstrated a high proportion of participants with hypertension, with only one-third of these individuals having controlled BP (systolic BP <140 mmHg and diastolic BP <90 mmHg). The high percentage of participants with hypertension who were either untreated (39.9%) or were treated but uncontrolled (57.2%) suggesting that such opportunistic screening programmes may be a useful tool to improve hypertension control in Chile.
May Measurement Month 2019: an analysis of blood pressure screening results from Ghana-Sub-Saharan Africa
Authors: Twumasi-Ankrah Betty , Poulter Neil R , Tannor Elliot K , Adu-Boakye Yaw , Nyarko Obed O , Opoku Gilder , Konadu Saabea O , Aniagyei Marian , Ogah Anita , Baidoo Timothy E , Mensah Clarence , Clarke Jonathan , Beaney Thomas , Myers-Hansen Gustavus A
Published: May 2021

Raised blood pressure (BP) remains the biggest single risk factor contributing to the global burden of disease and to global mortality. Although a substantial number of people who have hypertension are either oblivious of it, not treated, or being managed but remain uncontrolled. May Measurement Month (MMM) is a global initiative led by the International Society of Hypertension (ISH) with the goal of increasing awareness of high BP and serving as a spur to establish screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. Measurement of BP and collection of relevant health information were performed according to a standardized protocol for MMM. Screening sites were set up in churches, mosques, health facilities, pharmacies, recreational parks, sports facilities, shopping centres, marketplaces, universities, workplaces, and community centres across four regions of Ghana. A total of 7102 participants gave their consent and were screened during MMM 2019. After multiple imputation, of all 7102 participants 1836 (25.9%) had hypertension. Of all 1836 participants with hypertension, 36.5% were aware of their status and 30.0% were on anti-hypertensive medication. Of 550 participants on antihypertensive medications, 46.1% had controlled BP (systolic BP <140 mmHg and diastolic BP <90 mmHg). Also, of all 1836 participants with hypertension, 13.8% had their BP controlled. Again, the proportion of participants with hypertension of those not receiving anti-hypertensive treatment was 1286 (19.6%). Data obtained from this project demonstrates that there is still a significant number of people with hypertension who are unaware of having it, are untreated, or are on treatment but remain uncontrolled. It also highlights the significance of BP screening campaigns as a tool to identify persons with elevated BP.
May Measurement Month 2019: an analysis of blood pressure screening results from Jamaica
Authors: Nwokocha Magdalene , Beaney Thomas , Holder Cheryl , Thaxter Nesbeth Karen , Whylie Natalie , Leitch Joan , Ferguson Trevor , Hosang Mark , Riley Vincent , Soyibo Adedamola , Oshi Daniel , Brown Paul , Paul Tomlin , Wilks Rainford , Poulter Neil R , Nwokocha Chukwuemeka
Published: May 2021

There is evidence of an elevated risk of hypertension in populations that are primarily of African origin. Hypertension is predominantly asymptomatic, necessitating increased awareness. May Measurement Month was a descriptive, population-based, cross-sectional study of blood pressure (BP) screening and awareness campaign conducted in 2019 in a sample of 2550 participants (≥18 years) in Jamaica. In total, 1791 (70.2%) of the participants were female, 756 (29.6%) were male, with an average age of 49.3 years, and a body mass index (kg/m2) of 28.5 (6.2). Of all participants, 2289 (89.8%) were black and 154 (6.0%) were of mixed races. Twenty-two (0.9%) had never had their BP measured, whereas 354 (13.9%) had their measurements more than a year ago, and 2129 (83.5%) had measured within the year. Of all 2550 participants, 1055 (41.4%) had hypertension, 69.9% of our subjects with hypertension were aware, whereas only 62.5% were on antihypertensive medication and 27.8% had controlled BP (systolic <140 mmHg and diastolic BP <90 mmHg). Of 660 participants on antihypertensive medication, 44.4% had controlled BP. Two hundred and seventy-six (15.4%) of women reported hypertension in a previous pregnancy. Hypertension with previous pregnancy was positively correlated with current elevation. These results suggest a high rate of raised BP among community dwellers whose hypertension had not been previously diagnosed by a health professional and warrant proactive approaches that promote community-based awareness, and regular measurements.
May Measurement Month 2019: an analysis of blood pressure screening results from Angola
Authors: Victória Pereira Savarino , Neto Marisa , Feijão Ana , Lutucuta Eurico , Mbala Claudio , Muela Henrique , Soito Ermelinda , Matias Altino , Mundombe Leonardo , Beaney Thomas , Partington Giles , Poulter Neil R , Fernandes Mário
Published: May 2021

Raised blood pressure (BP) is the biggest risk factor that contributes to the global burden of disease and mortality. May Measurement Month (MMM) is a global initiative aimed to improved awareness of BP and has been a temporary solution to the lack of screening programmes. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2019. Blood pressure measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. In total, 7112 individuals were screened (mean age 41.3 years; 50.4% female; 99.5% black) in 6 of the 18 Angolan provinces. In total, 99.6% of screenees provided three BP readings with an average BP of the 2nd and 3rd readings of 126/81 mmHg. After imputation, 2745 (38.6%) had hypertension of whom 1389 (59.8%) were aware of their diagnosis and 50.6% were on antihypertensive medication. Of those 1389 treated participants, 41.2% were controlled (<140/90 mmHg) and of all hypertensive individuals, 20.8% were controlled. Also, 1356 individuals had untreated hypertension and 817 were inadequately treated. Angolan MMM19 follows on from the MMM17 (n = 17481) and MMM18 (n = 14433) studies, which were the largest BP screening campaigns undertaken in Angola. The 2019 results showed a high percentage of hypertensive individuals and almost 2200 adults had either untreated or inadequately treated hypertension, demonstrating that there is work to do but also that the Angolan MMM is being effective at raising awareness at least among these individuals.
May Measurement Month 2019: an analysis of blood pressure screening results from Malawi
Authors: Ndhlovu Henry L L , Chirwa Maureen L , Mbeba Mary K , Nyirenda Nancy M , Mbulaje Lucia D , Beaney Thomas , Xia Xin , Poulter Neil R
Published: May 2021

May Measurement Month (MMM) is a global initiative that aims at raising awareness and screening people for high blood pressure (BP). Malawi has participated in MMM since 2017. A 2017 STEPwise Survey conducted in Malawi among 4187 participants found that 65.2% had never had their BP measured before, 26.8% had their BPs measured but not diagnosed, 3.9% were diagnosed but not within the last 12 months, and 4.1% were diagnosed within the last 12 months. An opportunistic cross-sectional survey of volunteers aged 18 and above was carried out in May and June 2019. All BP measurements, definition of hypertension and statistical analysis followed the standard MMM protocol. The screening took place in Nkhatabay, Lilongwe, and Blantyre. A total number of 9723 participants were screened with a mean age of 42.0 (SD 16.6) years. Of these 8444 (86.8%) had never had their BP measured within the last 12 months, 2559 (26.3%) had raised BP, 2169 (23.2%) of those with raised BP were not on treatment whereas 390 (4.0%) were on treatment. The results showed that many of the participants had not had their BP checked in the past year. There is a significant need to expand BP screening opportunities within Malawi for early detection of hypertension.