bluuebunny/crossref_metadata_2025 huggingface dataset:
P488 Trends in corticosteroid (CS) use over time and following diagnosis in patients with Inflammatory Bowel Disease (IBD), using IBM® MarketScan®
Authors: Raine T , Melmed G Y , Finney-Hayward T , Clark R , Chapman J C , Targownik L , Burisch J , Olen O
Published: January 2022

Background

As part of the IBD-DICE (Determinants, Incidence and Consequences of CS Excess) collaborative research programme, this study examined rates of CS use and excess use in patients with IBD over time and after initial diagnosis.

Methods

Using IBM® MarketScan®, a representative claims database including details of >200 million individuals annually in the United States (US), we conducted a retrospective analysis of CS use from 2007 to 2018 in adult patients with IBD. Patients with conditions commonly associated with high levels of CS use (other than IBD) were excluded. CS use and excess were examined over calendar time in all patients (prevalent cohort), and in relation to the time of first IBD diagnosis in a newly diagnosed subset (incident cohort). Both a restrictive and a broader definition of CS use were examined. The restrictive definition only included claims for oral budesonide or prednisolone/prednisone with a pre-defined minimum daily equivalent dose of ≥17.5 mg, based on a typical tapering CS prescription for IBD. Under the broader definition, CS use was considered as any claim for oral prednisolone, prednisone, budesonide or methylprednisolone. Excess CS use was defined as either ≥2 CS courses in a 12-month period or ≥3 months of continuous CS use.

Results

The prevalent cohort (restrictive definition) included a total of 338,837 patients with 1,051,213 observation years. Rates of CS use ranged from 23.7% in 2007 to 19.3% in 2009 and plateaued in subsequent years (18.4%–21.1%). Rates of CS excess were higher from 2007 to 2009 (8.9%–11.5%) than in later years, and remained relatively stable from 2010 to 2018 (7.9%–8.6%). Similar patterns were seen with the broad definition of CS use, with CS excess rates of 15.2% in 2007 and 10.9%–11.8% from 2010 to 2018 (Figure 1). The incident cohort included 106,875 patients with 320,295 observation years. CS use was highest in the first year after diagnosis (24.2% and 29.4% with the restrictive and broad definitions, respectively) and decreased and plateaued by the second year after diagnosis (range: 10.8%–14.8% and 16.8%–21.0%, respectively). Similarly, CS excess was highest in the first year after diagnosis (11.7% and 14.6% with the restrictive and broad definitions, respectively) and decreased and levelled off by the second year after diagnosis (range: 3.6%–6.2% and 5.6%–8.6%, respectively) (Figure 2).

Conclusion

Despite advances in IBD treatment over the past decade and the adverse effects associated with CS, use of CS has not decreased substantially in the US in recent years. Levels of CS excess remain a concern, and may represent an opportunity for more optimised treatment and education, especially for newly diagnosed patients.
P554 Vedolizumab Associated quality of Life and inflammatory bowel disease control Upon Entering a subcutaneous switching program (VALUE) – Results from a multi-centre UK study
Authors: Lim S , Gros Alcade B , Lehmann A , Lindsay J , Gaya D , Caulfield L , Dhar A , Ritchie S , Limdi J , Taylor J , Raine T , Balendran K , Shuttleworth E , Kwok J , Cococcia S , Murray C , Walker G , Aldridge R , George B , Colbert R , Dawson P , Jameson E , Irving P , Sharma E , Lees C , Samaa M
Published: January 2022

Background

Vedolizumab, a gut-selective monoclonal antibody targeting α4β7-integrin, was recently licenced as a subcutaneous (SC) preparation after demonstrating efficacy compared to placebo at maintaining remission in IBD patients who had a clinical response to intravenous (IV) induction therapy. We aimed to assess real-world experience of switching patients to SC administration.

Methods

Patients across 10 UK centres who had completed induction with IV vedolizumab were offered SC therapy. Demographic data and baseline disease characteristics (disease type and behaviour, medication history) were collected, alongside biochemical markers (C-reactive protein, faecal calprotectin), disease activity scores (SCCAI, partial Mayo or modified Harvey Bradshaw Index) and quality of life scores (IBD-Control-8) at baseline (defined as the first dose of SC medication), 8 and 24. Data was also collected on drug persistence, hospital admissions, steroid use and reported adverse events.

Results

351 patients were switched to SC dosing. All had data collected for weeks 0 and 8 and 164 had data at week 24. There were no statistically significant differences in biochemical markers, disease activity scores or quality of life at weeks 0, 8 or 24, nor were there statistically significant differences in rates of biochemical remission or clinical remission.

Subcutaneous vedolizumab persistence at week 24 was 86% (141/164), with discontinuation due to disease activity (n=9), adverse events (n=11), non-compliance (n=2) and pregnancy (n=1). Of the 23 who discontinued SC, 12 switched back to IV (4 of whom at an escalated dose), 4 changed to another biologic and 7 stopped/paused biologic therapy.

Within the 24-week study period, 7.9% (n=13) required steroids, 2.4% (n=4) had an IBD-related hospital admission and 8.5% (n=14) experienced an adverse reaction of which 7 were injection site-related. One patient experienced an anaphylactoid reaction upon restarting IV vedolizumab.

There were no statistically significant associations between baseline characteristics (including clinical or biochemical markers, duration of vedolizumab use or prior ant-TNF exposure) and week 32 outcomes.

Conclusion

Switching from IV to SC vedolizumab appears to maintain rates of remission with no significant changes in biochemical markers, clinical scores or quality of life, with SC administration persistence of 86% at week 24. Further long-term data on safety is required.
P603 INSPIRE: 6-month interim analysis from an observational post-marketing registry on the effectiveness and safety of darvadstrocel in patients with Crohn’s disease and complex perianal fistulas
Authors: Zmora O , Baumgart D C , Faubion W , Ferrante M , Gecse K , Genestin E , Geransar P , Hantsbarger G , Karki C , Tozer P , Panés J
Published: January 2022

Background

Darvadstrocel (DVS) is a suspension of expanded allogeneic adipose-derived mesenchymal (stromal) stem cells approved for the treatment of complex Crohn’s perianal fistulas (complex CPF). The INSPIRE (EUPAS24267) registry is a European observational, post-approval study designed to evaluate the real-world effectiveness and safety of DVS in patients with complex CPF for up to 36 months after DVS administration. Here we report clinical and safety outcomes from the first interim analysis at 6 months post treatment.

Methods

Patients with complex CPF treated with DVS according to local standard practice were eligible to enrol. Primary outcomes were clinical response (defined as closure despite gentle finger compression of ≥50% of external openings treated with DVS that were draining at baseline) and clinical remission (defined as closure despite gentle finger compression of all external openings treated with DVS that were draining at baseline). Outcomes were evaluated in the All Treated (AT) and Treated Per Protocol (PP) cohorts (Table 1) 6 months post treatment in patients who had received a single administration of DVS. The number and nature of adverse events (AEs), serious AEs (SAEs) are reported for the AT cohort.

Results

As of September 2021, 230 patients had enrolled, 225 met the inclusion criteria and 205 had complete treatment data and comprised the AT cohort, of these, 176 were treated per protocol. A total of 138 (AT) and 120 (PP) patients were 6 months post treatment, 66% (92/138) and 58% (69/120) had a 6-month visit, of which, 85% (78/92) and 100% (69/69) had evaluable data at Month 6, respectively. Baseline demographics and clinical and fistula characteristics are shown in Tables 1 and 2. In the AT and PP cohorts, respectively, 73% (57/78) and 74% (51/69) of patients had a clinical response, and 65% (51/78) and 65% (45/69) had clinical remission. Changes in Crohn’s disease (CD) activity (assessed with the Harvey–Bradshaw Index) post treatment were minimal, and most patients had no change in CD activity from baseline. In the AT cohort, 20% (41/205) of patients had ≥1 AE and 9.3% (19/205) had ≥1 SAE. There were no reports of ectopic tissue formation and no deaths.

Conclusion

This is the first real-world, multi-centre study reporting the effectiveness and safety data after DVS treatment for complex CPF. These interim analysis data are consistent with the pivotal ADMIRE-CD study in terms of effectiveness and safety. The ongoing status of the registry and small number of evaluable patients mean these data should be interpreted with caution, pending future analyses in larger numbers of patients with longer follow-up times.
P614 Proactive infliximab is superior to either conventional infliximab and vedolizumab in Inflammatory Bowel Disease
Authors: Rodrigues I , Serrazina J , Botto I , Fernandes S , Bernardo S , Gonçalves A R , Moura Santos P , Valente A , Correia L , Tato Marinho R
Published: January 2022

Background

Available evidence suggests that vedolizumab may be as effective as Infliximab (IFX) in patients with inflammatory bowel disease. However, it is unknown if proactive therapeutic drug monitoring may improve these results.

Methods

Retrospective study including consecutive patients under conventional management with IFX (n=108), vedolizumab (n=80) and proactive IFX (n=139) aiming at a trough level (IFXTL) between 5–10 µg/mL. We evaluated the rates of fecal calprotectin remission (<250 µg/g) at week 14 and 2 years, and clinical remission, treatment discontinuation, hospitalization, and surgery at 2 years. Primary non-responders were excluded.

Results

Proactive IFX was superior to vedolizumab in respect to Fc remission at week 14 (56.8% vs 34.2%; P=0.001) and at 2-years (74.8% vs 35.9%, P<0.001), clinical remission (79.9% vs 58.0%, P=0.001), and treatment discontinuation (24.5% vs 39.5%, P=0.015), without significance for other outcomes. These results remained significant after correcting for prior anti-TNF use (P=0.027, P<0.001, P=0.01, and P=0.03). Conventional IFX was superior to vedolizumab in respect to Fc remission at 2-years (51.9% vs 35.9%, P=0.022), and treatment discontinuation (15.7% vs 39.5%, P<0.001), without significance for other outcomes. However, these results were not significant after correcting for prior anti-TNF use (P=0.367 and P=0.065).

Conclusion

Our findings suggest that vedolizumab is as effective as conventional IFX. However, proactive IFX was superior to vedolizumab in most clinical outcomes.
P616 Safety of COVID-19 vaccines in patients with IBD
Authors: Dussias N , Carbone A , Melotti L , Privitera Hrustemovic H , Salice M , Scaioli E , Calabrese C , Rizzello F , Gionchetti P
Published: January 2022

Background

COVID-19 vaccines have demonstrated excellent efficacy and safety profiles among the general population. However, studies have shown that vaccine hesitancy remains a significant problem especially in patients with chronic diseases, in part because of a lack of data regarding vaccine safety in these special populations. With this in mind, we investigated rates of vaccine-related side effects and disease flares in patients with inflammatory bowel disease (IBD).

Methods

We conducted an online survey of patients with Crohn’s disease (CD) and ulcerative colitis (UC) who were vaccinated from January 23 to October 15, 2021 with COVID-19 vaccines approved in Europe. We collected data regarding patient demographics, disease type, treatment and activity at the time of vaccination, patient-reported systemic side effects, and rates of disease flares and outcomes within 15 days of both vaccine doses.

Results

A total of 329 (179 M, 150 F) patients participated in the survey, 162 with CD and 167 with UC. Mean age was 47.1 years (range 19–80). Patients were vaccinated with Pfizer-BioNTech (46.8%), Moderna (51.7%) or Oxford/AstraZeneca (1.5%). Three patients received only one dose because of recent prior infection, and one patient received a single dose dose due to infection before vaccine cycle completion. At the time of vaccination most patients (63.8%) reported disease remission, 22.8%= mild activity, 12.8%= moderate, 0.6%= severe. Mesalazine monotherapy was reported in 174 patients, 89 were on biologics, 8 were on azathioprine, and 58 were not undergoing treatment at the time of vaccination. Nineteen were on concomitant corticosteroid treatment.

After the first dose, the most common side effects were mild: fatigue (38.6%), arthromyalgia (16.7%), headache (14.3%), fever (6.7%) and nausea (1.8%). Side effects after the second dose were more frequent but similar in nature (fatigue= 54.8%, fever= 34.8%, arthromyalgia= 31.7%, headache= 22.8%, nausea= 2.5%).

Fourteen patients (4.3%) reported disease flare after the first dose and 26 patients (8%) after the second dose. Characteristiscs of these patients are summarized in Table 1. Most flares were self-limiting and did not require modification in treatment. In the five cases where treatment modification was required, two already had moderate/severe disease at the time of vaccination, one had suspended biologic treatment, and two patients had autonomously suspended maintenance therapy.

Conclusion

Disease flares are infrequent and generally self-limiting after COVID-19 vaccination in patients with IBD. Other side effects are mild and comparable to the general population. Vaccination is strongly recommended in patients with IBD, and patients should be reassured about their safety.
P617 Switching from an intensified regimen of infliximab to a subcutaneous standard dose in adults with Inflammatory Bowel Disease: our experience in a tertiary hospital
Authors: Chivato Martín Falquina I , Saiz Chumillas R M , Arias Garcia L , Vicente González B , Revilla Cuesta N , Alba Hernández L , Andrés Pascual L , Sicilia Aladrén B
Published: January 2022

Background

Intravenous (IV) infliximab is a first line treatment for moderate or severe flare of inflammatory bowel disease. Recently a new formulation of infliximab with subcutaneous (SC) administration has been developed and approved for this indication.

Methods

From March 2021, 14 patients diagnosed with inflammatory bowel disease (Crohn’s disease-CD- or ucerative colitis-UC), in clinical remission for at least 6 months with infliximab IV who had needed previous intensification, either because of a reactive therapeutic drug monitoring and loss of response, or because of a proactive drug monitoring (trough levels <3µg/ml), were switched to SC infliximab. We analized retrospectively from the start of SC infliximab until week 8 after switch, fecal calprotectin levels (FC), C reactive protein (CRP), concomitant treatment, trough levels, treatment adherence, need for intensification or relapse, and adverse events.

Results

Four patients (28,57%) were diagnosed with CD, 10(71,4%) were diagnosed with UC (Table 1). Median duration of IV treatment was 53 months (IQR 33–59). Reasons for starting infliximab were corticodependence in 6 patients (42,8%), corticorefractoriness in 6(42,8%) and topdown strategy in B2 phenotipe with Crohn’s disease in 2 (14,3%). Reasons for intensification were: loss of response in 5 patients (35,7%), intensified induction in one (7,1%), proactive therapeutic drug monitoring in 8 (57,14%) (graphic 1). Intensification regimens are shown in graphic 2. Eleven patients (78,57%) were still in an intensified regimen when switched. All patients were in clinical and biochemical remission (FC<200 µg/g and CRP<10 mg/dl) before switch. Median basal infliximab trough levels before switch were 6,98µg/ml (IQR 2,4-10,5); median trough levels 8 weeks after switch were 14,12 (IQR 12,22-22,7) (p=0,003) (graphic 3). Thirteen patients (92,8%) followed treatment and stayed in clinical remission. One patient, treated with original IV infliximab before switch, relapsed after third subcutaneous administration, and did not respond to reintroduction of original IV infliximab. There were no adverse events.

Conclusion

In our centre, switching from IV to standard dose SC infliximab maintained clinical and biochemical remission in patients that previously needed intensified regimen, improving trough levels without any adverse events. These findings provide potential therapeutic insights into SC infliximab as a monotherapy agent for inflammatory bowel disease.
P628 Processed and ultra-processed food and risk of Inflammatory Bowel Disease in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC-IBD)
Authors: Dong C , Casagrande C , Chan S , Huybrechts I , Nicolas G , Boutron-Ruault M C , Carbonnel F
Published: January 2022

Background

During the past decades, human diet has evolved towards higher intakes of processed and ultraprocessed food. We have investigated the association between these food groups and the risk of inflammatory bowel disease (IBD) in the European Prospective Investigation into Cancer and Nutrition.

Methods

413 590 participants from 8 European countries were included. Dietary data were collected at baseline from validated food frequency questionnaires. All EPIC food items were expressed as g/day and categorized according to the NOVA classification: “group 1—unprocessed or minimally processed foods”; “group 2—processed culinary ingredients”; “group 3—processed foods”; and “group 4—ultra-processed foods (UPFs)”. Because the EPIC dietary questionnaires were conceived before the NOVA classification, the food items were retrospectively categorized into this classification. Some food items collected in the EPIC questionnaires were difficult to categorize into group 3 or 4. We therefore merged them into a single category. We tested three scenarios for the estimation of the dietary content of this merged category: lower, middle and upper contents of groups 3 + 4. The association between the proportion of each NOVA group in the diet and IBD were estimated using Cox proportional hazard models to obtain Hazards Ratios (HRs) and 95% confidence intervals. We adjusted the HR for smoking status, educational level, physical activity, BMI, alcohol consumption and energy intake and stratified by centre, age at baseline (1-y interval), and sex.

Results

After a mean follow-up of 16 years, 179 Crohn’s disease (CD) and 431 ulcerative colitis (UC) cases were identified. NOVA group 1 was negatively associated with CD risk (adjusted HR for the fourth vs. the first quartile = 0.58; 95% CI = 0.35–0.95; P-trend = 0.03). Within group 1, fruit intake was the only food item to be negatively associated with the risk of IBD (adjusted HR for the fourth vs. the first quartile = 0.42; 95% CI = 0.24–0.73; P-trend = 0.003). We found numerical associations between group 3 + 4 and the risk of CD with the middle or upper scenarios (adjusted HRs for the fourth vs. the first quartile = 1.50; 95% CI = 0.92–2.46; P-trend = 0.12 and 1.41; 95% CI = 0.88–2.27; P-trend = 0.09 respectively). There was no association between any category of the NOVA classification and UC risk.

Conclusion

In the EPIC cohort, consumption of non-processed food was associated with a lower risk of CD while consumptions of processed or ultra-processed food were numerically associated with increased risk of CD. We found no association with UC.
P631 Impact of Covid-19 pandemic on initiation of immunosuppressive treatment in immune-mediated diseases. -A nationwide, retrospective study
Authors: Kutschera M , Ritschl V , Berthold R , Stamm T , Kiener H , Maier H , Reinisch W , Benka B , Novacek G
Published: January 2022

Background

Immunosuppressive and biological medications are a mainstay in the treatment of immune-mediated diseases, such as inflammatory bowel diseases (IBD), rheumatic diseases, and psoriasis. However, the COVID-19 pandemic caused concerns over the safety of these drugs pertaining to risk and severity of infection with SARS-CoV2. Moreover, pandemic mitigation strategies may negatively impacted treatment start with immunosuppressive and biological treatment fostering worse long-term disease outcomes. The aim of this study was to examine the impact of the COVID-19 pandemic on new starts of immunosuppressive and biological treatment in Austria.

Methods

We conducted a retrospective analysis with a 4-year observation period from 2017 to 2020 on real-world data on prescriptions for immune-mediated diseases of the Austrian health insurance funds covering 98% of the Austrian population. Data from all patients with incident biologic or conventional immunosuppressive treatment (Table 1) were included. Incidence of biologic (including small molecules) and immunosuppressive therapy was defined as all first prescriptions of one of the listed substances from 2017. The incidence rate for biologic and immunosuppressive treatments was recorded monthly in 2020 and compared with the three previous years (2017 – 2019).

Results

During the first lockdown in Austria in spring 2020 (week 12 – week 20), there was a significant decrease in the overall starts of biologic (including small molecules) and immunosuppressive treatments (both p<0.0001), especially in April (Figure 1 and 2). After that lockdown, new starts of immunosuppressive and biological treatments rapidly re-achieved pre-lockdown levels despite higher infection rates with SARS-CoV-2 and subsequent lockdown periods (Figure 3). Independent from the COVID-19 pandemic, we observed a continuous increase of biological medication (bDMARDs) and small molecules (p<0.0001) and a decrease of conventional immunosuppressive medications (cDMARDS) (p<0.0120) during all observed years (Figure 1 and 2)

Conclusion

In patients with immune-mediated diseases in Austria the COVID-19 pandemic led to a significant decrease of newly started immunosuppressive and biological treatments only during the first lock-down. Over the last four years, we can observe a continuous increase of small molecules and biological medication as well as a continuous decrease of conventional immunosuppressive medication.
P637 Risks of Development of COVID-19 among Patients with Inflammatory Bowel Disease
Authors: Kappelman M , Zhang X , Lewis J , Melmed G , Siegel C , Cerciello E , Dobes A , Weaver A , Weisbein L , Long M
Published: January 2022

Background

Patients with inflammatory bowel disease (IBD) may be at risk for development of COVID-19 infection due to innate immune dysfunction and/or immunosuppressive medication use. We sought to 1) evaluate the incidence of COVID-19 infection in a large, U.S. cohort of patients with IBD and 2) evaluate associations between demographic, clinical, and treatment-related factors and the development of COVID-19 infection.

Methods

Participants in 3 adult IBD studies sponsored by the Crohn’s & Colitis Foundation, IBD Partners, IBD QORUS (Improving the Quality of Care for Adults with Inflammatory Bowel Disease), and SPARC IBD (Study of a Prospective Adult Research Cohort with IBD), were invited to participate in a prospective, direct-to-patient cohort study about COVID-19 from April 23, 2020 until August 30, 2021. Each cohort received online surveys with questions on comorbidities, medication utilization and development of laboratory confirmed COVID-19 at times 0, 2, 4, 6, 8 weeks and then every 6 months. We calculated the incidence rate of COVID-19 and performed bivariate and multivariate analyses to describe associations between age, immunosuppression use, obesity, and race on the development of COVID-19.

Results

A total of 3953 patients with IBD were followed for a mean duration of 212 days (SD 157). Demographic, clinical and treatment factors are shown in Table 1. A total of 103 individuals developed COVID-19 during follow up (2.6%, rate of 45 per 1,000 person-years). Severity of infection was generally mild. Clinical characteristics were similar among those who developed COVID-19 as compared to not. African American race was associated with incident COVID-19 infection (OR 3.37, 95% CI 1.18–9.59). Immunosuppression use was not associated with development of COVID-19 (OR 1.19, 95% CI 0.72–1.75), nor was age (OR 1.00, 95% CI 0.99–1.02), nor obesity (OR 1.01, 95% CI 0.61–1.66).

Conclusion

The overall incidence of COVID-19 infection among this large U.S. cohort of IBD patients was relatively low. Immunosuppression use did not increase the risk of development of COVID-19. Therapeutic management of IBD should not be altered to prevent a risk of developing COVID-19.
P664 Bidirectional association between inflammatory bowel disease and psoriasis in a pediatric population: A nationwide insurance claim data analysis in South Korea
Authors: Kim D H , Cho S I
Published: January 2022

Background

Inflammatory bowel disease (IBD) and psoriasis are chronic inflammatory diseases and have been reported to have an association between them. However, most of the patients included in the previous reports were adults. As both diseases are related to each other, special consideration is required in managing each disease, as there is a high possibility of co-occurrence. In this regard, to figure out the association between the two diseases in childhood and adolescence is needed.

Methods

A nationwide population-based retrospective cohort study was performed using the Korean National Health Insurance claims database. A birth cohort from January 2002 to December 2006. Claim data related to IBD and psoriasis was evaluated up to December 2019 and was analyzed to figure the association between the two diseases.

Results

The datasets contained a total of 2,347,591 individuals. A total of 2,444 IBD patients and 5,165 psoriasis patients were identified. Thirteen patients had both IBD and psoriasis. Compared to the age and sex-matched control group, IBD patients showed a higher association of psoriasis (Odd ratios (ORs), 2.476; 95% confidence interval (CI), 1.240–4.945). In contrast, psoriasis patients did not show a statistically significant association compared to the control group (ORs, 1.857; 95% CI, 0.962–3.585). However, the proportion of patients with severe IBD was significantly higher (ORs, 6.000; 95% CI, 1.003–35.908).

Conclusion

The association between IBD and psoriasis is observed in pediatric patients. Recognizing and early diagnosis of related diseases in children with IBD and psoriasis is necessary for better clinical outcomes
P686 Outcomes of COVID-19 among patients with inflammatory bowel diseases and the influence of IBD-related medications– A Danish prospective population-based cohort study
Authors: Attauabi M , Dahlerup J F , Poulsen A , Rosager Hansen M , Vester-Andersen M K , Eraslan S , Prahm A P , Pedersen N , Larsen L , Jess T , Neumann A , Haderslev K V , Molazahi A , Lødrup A B , Glerup H , Oppfeldt A M , Jensen M D , Theede K , Kiszka-Kanowitz M , Seidelin J B , Burisch J
Published: January 2022

Background

Population-based data regarding outcomes of coronavirus disease 2019 (COVID-19) among patients with ulcerative colitis (UC) and Crohn’s disease (CD) remain limited.

Methods

We conducted a population-based study investigating the outcomes of COVID-19 among patients with UC and CD in Denmark. The Danish COVID-19 IBD Database is an extensive population-based database which prospectively monitors the disease course of laboratory-confirmed COVID-19 among patients with UC and CD. Severe COVID-19 was defined as COVID-19 necessitating intensive care unit admission, ventilator use, or death, while adverse COVID-19 was defined as requirement of COVID-19 related hospitalization. Regression analysis was adjusted for age, sex, disease type, disease activity, cardiovascular disease, and corticosteroids. Outcomes of COVID-19 among patients with UC and CD were compared with those among the background population covering all incidents of COVID-19 in Denmark.

Results

The study included 319 patients with UC and 197 patients with CD from January 28th, 2020, to April 1st, 2021. Baseline characteristics are presented in Table 1. A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N=46(14.4%), RR=2.49 (95%CI 1.91–3.26)) and CD (N=24(12.2%), RR=2.11 (95%CI 1.45–3.07)) as compared with the background population (N=13,306 (5.8%)). A similar pattern was observed for admission to intensive care (UC: N=8(2.51%), RR=27.88 (95%CI 13.88–56.00); CD: N=3 (1.52%), RR=16.92 (95%CI 5.46–52.46)) (Figure 1). The association between these outcomes and IBD-related clinical characteristics and treatments is presented in Tables 2–3. As shown, none of the IBD-related medications were associated with severe COVID-19 in univariate and multivariable analysis. However, systemic steroids were found to be associated with an increased risk of adverse COVID-19 among patients with CD (adjusted odds ratio (aOR)=13.62 (95% CI 1.98–17.77)).

Conclusion

This Danish population-based study on COVID-19 outcomes among patients with UC and CD demonstrated severe COVID-19 among only a minority of patients, which was not associated with IBD-related medications. Apart from systemic steroids, this study encourages continued use of IBD therapy to prevent IBD relapse and complications.
P695 Attitudes and predictors of COVID-19 vaccine uptake in patients with Inflammatory Bowel Disease
Authors: Zhang E , Gupta A , Macrae F A , Christensen B
Published: January 2022

Background

Vaccination has proven to be an effective public health measure to combat the SARS-CoV-2 pandemic. However, vaccine “hesitancy” has limited uptake in some populations. We surveyed individuals with IBD to explore factors associated with vaccine uptake, concerns, and which sources of information were considered trustworthy surrounding vaccination.

Methods

Patients with IBD were recruited from a specialist IBD clinic at a tertiary hospital in Australia, and through a national IBD patient society (Crohn’s & Colitis Australia). Patients were invited to complete an anonymous survey between 31 October – 17 November 2021. Logistic regression was used to identify variables associated with vaccine uptake. Data was analysed using SPSS (Chicago, IL).

Results

There were a total of 441 respondents. Demographic and IBD characteristics are presented in Table 1. Most respondents 411 (93.2%) had received at least 1 dose of COVID-19 vaccination. Among 30 (6.8%) respondents who had not been vaccinated, concern about experiencing an IBD flare with vaccination and vaccine safety were most commonly identified. Of those who had not yet been vaccinated, the possibility of getting vaccinated in the future was likely in 3 (10.7%), unlikely in 12 (42.8%), whilst 13 (45.4%) were unsure about future vaccination. Multivariate analysis [Table 2] demonstrated past influenza vaccination (OR 3.28, 95% CI 1.34–8.9, p = 0.009) and self-perceived risk of being more unwell with COVID-19 infection due to IBD was positively associated with COVID-19 vaccine uptake (OR 5.25, 95% CI 1.96–14.04, p <0.001). Most agreed that that vaccination in general was safe 306 (90.1%). The perceived risk of COVID-19 vaccination causing an IBD flare, and concern that vaccination is unsafe in pregnancy were both negatively associated with vaccine uptake (OR 0.28, 95% CI 0.10–0.77, p = 0.01 and OR 0.22, 95% CI 0.08–0.65, p = 0.006) respectively. Trust in healthcare workers was high with 282 (73.7%) responders ranking them the most trusted source to obtain information surrounding vaccination [Figure 1]. Social media was ranked the least trusted source of information by 225 (58.6%).

Conclusion

Past influenza vaccination and self-perceived risk of being more unwell with COVID-19 due to IBD, were positive predictors of COVID-19 vaccine uptake in IBD patients. Concerns about an IBD flare with vaccination is a unique consideration in those vaccine hesitant and is a negative predictor of vaccine uptake. Among those not yet vaccinated, 45% were uncertain about future vaccination. Given healthcare providers were ranked the most trusted source surrounding this domain, this survey highlights the key role they have in exploring vaccination concerns and misconceptions in IBD patients
P714 Comparison of intestinal microbiota profiles of faecal samples, rectal swabs and mucosal biopsies in patients with Inflammatory Bowel Disease. A multicentre, observational study
Authors: Van Rossen T , van den Hoek K , Budding A , van Bodegraven A
Published: January 2022

Background

Since the gut microbiota is altered in patients with Inflammatory Bowel Disease (IBD), microbiome-based biomarkers may be useful for diagnosing and monitoring of IBD. Currently, endoscopy is the gold standard for diagnosis and monitoring disease activity, which can be a high burden for patients. This study aimed to compare intestinal microbiota profiles between three different sampling

methods

faecal samples, rectal swabs and colonic mucosal biopsies. This could provide more insight into the microbiota composition in different sample types and might contribute to the development of a less invasive biomarker for diagnosing and monitoring IBD.

Methods

Patients with IBD (Crohn’s Disease or Ulcerative Colitis) who were scheduled for endoscopy were asked to participate. Prior to bowel preparation, a fecal sample and rectal swab were collected. During colonoscopy, mucosal biopsies were derived 20 cm ab ano. Microbiota composition was analyzed by IS-pro, a PCR technique based on species-specific differences in the 16S-23S interspace region of the bacterial ribosomal DNA. Microbiota profiles of the three different sample types were compared within the same patient (for each patient: fecal sample vs. mucosal biopsy, fecal sample vs. rectal swab, rectal swab vs. mucosal biopsy), and between different patients (for each patient: fecal sample of one patient vs. mucosal biopsies of all patients, fecal sample of one patient vs. rectal swabs of all patients, etcetera).

Results

A total of 200 patients were included. For each patient, similarity of microbiota composition between two sample types was assessed by calculating the Pearson’s correlation (expressed as R2). R2 values of all patients were combined in boxplots. We found a significantly higher correlation between the microbiota profiles of different sample types within the same patient, than between microbiota profiles of different sample types of different patients (median R2 0.27–0.33 and 0.02–0.03 respectively, Figure 1). However, correlation between different sample types from the same patient was still relatively low. The highest correlation was found between microbiota profiles of faecal samples and rectal swabs (median R2 0.33, ICR 0.17–0.54). On phylum level, the highest correlation was found in the Bacteroidetes phylum (Figure 2). For a global analysis of all versus all samples, we generated a clustered heat map, which confirmed the previous finding that microbiota profiles from faecal samples and rectal swabs were most similar to each other.

Conclusion

Microbiota composition in different sample types from the same patient were more similar to each other than to profiles from different patients. Microbiota profiles of faecal samples and rectal swabs were most identical.
P717 Faecal Microbiota Transplant in Ulcerative Colitis (FMTUC) – A randomised clinical trial feasibility study
Authors: Jitsumura M , Cunningham A , Hitchings M D , Wilkinson T , Kinross J , Row P , Davies A , Dean Anthony H
Published: January 2022

Background

Dysbiosis of the gut microbiota may be responsible for the pathogenesis of ulcerative colitis (UC). Restoration of gut microbiota diversity by means of faecal microbiota transplantation (FMT) is of increasing interest as a therapeutic option in the management of UC. The aims of this phase II feasibility study are to estimate the magnitude of treatment response to FMT in treatment-naïve patients with newly diagnosed UC, evaluate donor and patient recruitment rates and determine optimal study conditions for phase III study (ISRCTN 58082603).

Methods

Treatment-naïve patients with histologically confirmed UC below the sigmoid were recruited. Subjects were randomised to three arms; single FMT enema, five daily enemas and control. All groups received antibiotic for 10 days and bowel preparation 48 hours before the interventions. They were followed up for 12 weeks with quality of life (QOL) scores (IBDex, CUCQ-32) and 16S RNA study on faecal samples. Endoscopic (Mayo score) and histological assessments were performed at the baseline and week 12. The primary endpoints were endoscopic remission of UC and rate of persistent microbial engraftment at 12 weeks. Secondary endpoints included QoL and mucosal cytokine profiling with IL-10. Clinical remission was defined as Mayo score ≤ 2 with an endoscopic Mayo score of 0.

Results

Eighteen UC patients were recruited between July 2016 and February 2020 until the COVID-19 pandemic, of those five achieved Clinical remission. One subject from the control group withdrew at week 4 due to worsening symptoms. 72% improved Mayo and QOL scores, and 44% avoided medical treatment. Clinical remission was more observed among subjects with lower baseline QoL and mild-moderate disease, although this did not reach statistical significance (P=0.173). No correlation between FMT dose, frequency and clinical remission were observed. The 16S evaluation of the faecal samples demonstrated successful engraftment of FMT and showed a similar faecal microbiota profile amongst the intervention groups, which was markedly different from the control group. Coprococcus was found to be much more abundant amongst subjects who responded to the FMT intervention. This study also suggested an inverse correlation between IL-10 and the severity of UC.

Conclusion

FMT intervention protocols were well adhered and achieved 94% completion rate, though the recruitment period was much longer than the original plan due to unforeseen interruptions. Yet, this feasibility study demonstrated potential for employing this method for a larger multicentre RCT to further evaluate FMT dose and frequency effects. The correlation between IL-10 and IL-10 producing microorganisms should be sought in the future study.
N18 Introduction of inflammatory bowel disease specialized dietitian and nutritional status in a multidisciplinary IBD team
Authors: Hoekx S , Vanderstappen J , Wellens J , Verstockt B , Marc F , Vermeire S , Guedelha Sabino J
Published: January 2022

Background

Qualitative inflammatory bowel disease (IBD) care is marked by a multidisciplinary approach including physicians, nurses, psychologists and dietitians. Specialist IBD dietitians can address the specific needs of patients with IBD, with an emphasis on nutritional status, disease activity, and functional symptoms. We wanted to obtain a snapshot of the IBD population referred to the dietitian at our IBD clinic.

Methods

Since February 2021, two specialist IBD dietitians were hired at the multidisciplinary IBD-team of our tertiary referral centre. Data from all IBD patients seen by the IBD-dietitians were prospectively collected. Patients with IBD were referred to the IBD dietitians for dietary advice concerning optimization of nutritional status, modulation of diet-induced abdominal symptoms, and IBD-related problems (e.g. high output stoma, obstruction, enteral or parenteral nutrition). Malnutrition as reason for referral was defined as an abnormal body mass index (BMI <18.5 or >25 kg/m²).

Results

From 1 February 2021 until 16 November 2021, 219 IBD patients (58.4% women, median age 38 years, 127 Crohn’s disease, 92 ulcerative colitis) were seen by the IBD-dietitians. Patient characteristics are described in table 1. A total of 303 contacts were registered, including 82% in-hospital consultations (16% in-patient clinic, 66% outpatient clinic) and 18% remote consultations (via telephone or email). The median BMI at first consultation was 23.49 kg/m2. In this cohort, 46.6% of IBD patients had a normal BMI, 37% were obese or overweight, and 13.2% has underweight. Males had a significantly higher BMI than females (BMI 24.5 vs 22.5 kg/m2, p-value 0.048). The main reasons for referral were IBD-related symptoms or disease activity (46.6%), malnutrition (26%), functional symptoms (16.4%), and patient’s interest in receiving more information on diet (9%). Of note, none of the patients were being treated with enteral nutrition at time of referral, and only 5 patients were being treated with parenteral nutrition. Most patients received dietary advice (92%) and only 1 patient was started with enteral nutrition.

Conclusion

The introduction of IBD-dietitians in our multidisciplinary IBD care program has allowed IBD-patients with or without malnutrition, to be assessed by a specialist IBD dietitian who can provide appropriate dietary advice. Of note was that despite an already expert IBD center with a multidisciplinary team in place, the prevalence of malnutrition in this selected IBD cohort was very high. Nevertheless, IBD disease activity and IBD-related symptoms were the main reason for referral to the IBD-dietitian, reflecting the need for tailored nutritional advice complementary to medical or surgical treatment.
Adaptive Diversification in the Cellular Circadian Behavior of Arabidopsis Leaf- and Root-Derived Cells
Authors: Nakamura Shunji , Oyama Tokitaka
Published: January 2022

The plant circadian system is based on self-sustained cellular oscillations and is utilized to adapt to daily and seasonal environmental changes. The cellular circadian clocks in the above- and belowground plant organs are subjected to diverse local environments. Individual cellular clocks are affected by other cells/tissues in plants, and the intrinsic circadian properties of individual cells remain to be elucidated. In this study, we monitored bioluminescence circadian rhythms of individual protoplast-derived cells from leaves and roots of a CCA1::LUC Arabidopsis transgenic plant. We analyzed the circadian properties of the leaf- and root-derived cells and demonstrated that the cells with no physical contact with other cells harbor a genuine circadian clock with ∼24-h periodicity, entrainability and temperature compensation of the period. The stability of rhythm was dependent on the cell density. High cell density resulted in an improved circadian rhythm of leaf-derived cells while this effect was observed irrespective of the phase relation between cellular rhythms. Quantitative and statistical analyses for individual cellular bioluminescence rhythms revealed a difference in amplitude and precision of light/dark entrainment between the leaf- and root-derived cells. Circadian systems in the leaves and roots are diversified to adapt to their local environments at the cellular level.
Digitalization and beyond: the effects of Covid-19 on post-pandemic educational policy and delivery in Europe
Authors: Zancajo Adrián , Verger Antoni , Bolea Pedro
Published: January 2022

Education has been extremely affected by the coronavirus disease crisis, with almost all countries temporarily closing their schools in 2020. After the first stage of the pandemic, in which national governments focused on guaranteeing the academic year’s continuity, key international organizations emphasized the need to adopt structural policy reforms to face the challenges posed by the crisis. Based on international and European countries’ policy documents, this paper analyzes long-term responses articulated in the education sector. The analysis has allowed us to identify three preponderant areas of response: the digitalization of the educational system, educational inequalities, and teachers’ development. The agendas and policy instruments that international organizations have so far pushed for in relation to each of these areas do not differ substantially from the agendas and instruments they promoted in the pre-pandemic era. It is still early to assess the deepness of the transformations in course, but in most cases, prevailing responses represent the intensification of change processes initiated before the pandemic. Nonetheless, the type and intensity of country responses vary among the European Union member states. Although the pandemic represents a common thread, countries have experienced the crisis differently according to the characteristics of their educational systems and the main problems the crisis has revealed.
Collagen X Longitudinal Fracture Biomarker Suggests Staged Fixation in Tibial Plateau Fractures Delays Rate of Endochondral Repair
Authors: Working Zachary M. , Peterson Danielle , Lawson Michelle , O'Hara Kelsey , Coghlan Ryan , Provencher Matthew T. , Friess Darin M. , Johnstone Brian , Miclau Theodore , Bahney Chelsea S.
Published: January 2022

Objectives:

To use a novel, validated bioassay to monitor serum concentrations of a breakdown product of collagen X in a prospective longitudinal study of patients sustaining isolated tibial plateau fractures. Collagen X is the hallmark extracellular matrix protein present during conversion of soft, cartilaginous callus to bone during endochondral repair. Previous preclinical and clinical studies demonstrated a distinct peak in collagen X biomarker (CXM) bioassay levels after long bone fractures.

Setting:

Level 1 academic trauma facility.

Patients/Participants:

Thirty-six patients; isolated tibial plateau fractures.

Intervention:

(3) Closed treatment, ex-fix (temporizing/definitive), and open reduction internal fixation.

Main Outcome Measurements:

Collagen X serum biomarker levels (CXM bioassay).

Results:

Twenty-two men and 14 women (average age: 46.3 y; 22.6–73.4, SD 13.3) enrolled (16 unicondylar and 20 bicondylar fractures). Twenty-five patients (72.2%) were treated operatively, including 12 (33.3%) provisionally or definitively treated by ex-fix. No difference was found in peak CXM values between sexes or age. Patients demonstrated peak expression near 1000 pg/mL (average: male—986.5 pg/mL, SD 369; female—953.2 pg/mL, SD 576). There was no difference in peak CXM by treatment protocol, external fixator use, or fracture severity (Schatzker). Patients treated with external fixation (P= 0.05) or staged open reduction internal fixation (P= 0.046) critically demonstrated delayed peaks.

Conclusions:

Pilot analysis demonstrates a strong CXM peak after fractures commensurate with previous preclinical and clinical studies, which was delayed with staged fixation. This may represent the consequence of delayed construct loading. Further validation requires larger cohorts and long-term follow-up. Collagen X may provide an opportunity to support prospective interventional studies testing novel orthobiologics or fixation techniques.

Level of Evidence:

Level II, prospective clinical observational study.