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Inspired by a 2019 conference, Moana Water of Life, and including real-life insights from a diverse range of participants, this book showcases the potential fruits of open dialogue between stakeholders to navigate the critical challenges to planetary health caused by the climate crisis.

ObjectiveThe Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

BackgroundWhile infliximab is used as rescue therapy for steroid refractory acute severe colitis (ASUC), between 30 and 40% of patients do not respond and undergo colectomy. Accelerated induction regimes of infliximab have been proposed to improve response rates. We aimed to evaluate colectomy rates in steroid refractory ASUC patients receiving standard induction (SI) vs. accelerated induction (AI) of infliximab.MethodsData collected on hospitalised patients receiving rescue therapy for steroid refractory ASUC. The choice of rescue therapy was at the discretion of the treating clinician. Accelerated induction (AI) was defined as receiving second dose of infliximab within 8 days of first rescue therapy or receiving front loading dose of 10 mg/kg. Our primary outcome was the short-term (in-patient, 30 days and 90 days) colectomy rate. Secondary outcomes were 12-month colectomy rates, length of hospital stay (LOS), and complication rates. We used a propensity score analysis with optimal calliper matching using a priori defined high-risk covariates at the start of rescue therapy (albumin, CRP, CRP–albumin ratio, haemoglobin nadir and pancolitis) to reduce potential provider selection bias.ResultsA total of 131 patients receiving infliximab rescue therapy were included, of whom 102 patients received SI and 29 received AI. There was no difference in age, duration of diagnosis, age at rescue therapy, Montreal class or use of steroids, 5ASAs or thiopurines prior to index admission. In the unmatched overall cohort, there was no difference in colectomy during index admission (13% vs. 20%, p = 0.26), 30-day colectomy (18% vs. 20%, p = 0.45), 90-day colectomy (20% vs. 24%, p = 0.38) or 6 month colectomy (25% vs. 27%, p = 0.49). The LOS was shorter in the SI group (14.87 ± 8.1 days vs. 19.31 ± 5.8 days, p = 0.007). In patients who underwent colectomy, there were no differences in complications or serious infection rates. In the propensity score-matched cohort of 52 patients, there was no difference in overall colectomy rates between SI and AI groups (57% vs. 31%, p = 0.09), but the index admission colectomy (53% vs. 23%, p = 0.045) and 30-day colectomy (57% vs. 27%, p = 0.048) rates were higher in those receiving SI. There was no significant difference in LOS between SI and AI groups (23.6 ± 4.3 vs. 18.2 ± 7.1 days, p = 0.09) or in overall complication and infection rates but there was a mortality in AI group.ConclusionIn this retrospective cohort study, there was no difference in overall colectomy rates in ASUC patients receiving different induction dosing regimens of infliximab. However, using propensity score matching, the short-term colectomy rates appear to be better in those receiving accelerated induction regime. A prospective study to confirm findings is planned.

IntroductionThe genetic variation HLA-DQA1*05 has been reported to be associated with anti-Infliximab antibody in CD. The relevance in UC patients receiving infliximab is uncertain.AimTo evaluate the association of HLA-DQA1*05 and infliximab antibody formation, treatment changes and infliximab persistence in a real world setting of single centre cohortMethodsInfliximab treated UC patients (n=94) were retrospectively screened for HLA-DQA1*05. The risk of anti-infliximab antibody formation, absent drug levels in presence of antibody, change in therapy from infliximab were assessed in variant carrying patients in comparison to those without the variants. The proportion of patients needing dose optimisation of infliximab also evaluated.ResultsAnti-infliximab antibodies were detected in 41.5% of patients in a median follow up of 14.75 (IQR 9-29) months. HLA-DQAI*05 was positive in 39.13% of patients. 52.2% of patients were on concomitant immunomodulators. Higher proportion of patients with HLA-DQA1*05 developed anti-Infliximab antibodies (59% Vs 24%, p=0.002). Eighty percent of patients who had anti Infliximab antibodies with absent drug levels were positive for HLA-DQA1*05 with Hazzard Ratio (HR) for development of anti-Infliximab antibodies of 4.54 (95% CI 1.73-11.89) and for antibodies with absent infliximab drug levels 9.86 (95% CI 2.43 -40.01). Higher proportion of HLA-DQA1*05 patients required dose escalation (78% vs 31%, p=0.001). After adjusting for age, initial infliximab dose and concomitant immunomodulator use, there was no difference anti TNF persistence in patients with HLA-DQA1*05 variant (HR 2.36, 95% CI 0.89-6.25, p=0.06).Abstract HMO-5 Figure 1Antibody formation in infliximab treated patientsAbstract HMO-5 Figure 2Infliximab persistenceConclusionsDetermination of HLA-DQA1*05 status may identify patients at higher risk of anti-infliximab antibodies in ulcerative colitis. Early intervention with dose optimisation and concomitant immunomodulation may avoid loss of response and facilitate treatment persistence.

IntroductionThe PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available.AimTo evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomesMethodsWe prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at 6 and 12 months. Secondary outcomes were steroid free remission at 6 and 12 months, use concomitant immunosuppression and proportion needing dose escalation.ResultsSeventy-six patients were included in analysis (UC= 32, CD=43, IBD-U =1). HLADQA1*05 was positive in 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in 44% of the whole cohort and in 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in 8 patients and secondary loss of response in 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in 10 (15.6%) patients with 7 out of 10 positive for HLADQA1*05. However, only 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at 6 months was recorded in 77.1% and 78% respectively. There was no significant difference in drug persistence rates at 6 months and 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure 2). Steroid free remission at 6 and 12 months was also similar irrespective of the variant status (Figure 3)Abstract PMO-41 Figure 1Initial Theraphy choiceAbstract PMO-41 Figure 2Treatment presistance with initial theraphy strategyAbstract PMO-41 Figure 3Steroid free remissionConclusionsChoice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.

IntroductionThe efficacy of ustekinumab in prior biologic exposed refractory patients with inflammatory bowel disease is significantly inferior to those who are bio naïve. The optimal therapeutic level and hence the optimal dosing strategy in this setting is uncertain. Whether early dose optimisation is beneficial in this group of patients has not been evaluated. We aimed to compare the effectiveness and safety of early dose optimisation for maintenance compared to conventional maintenance regime in a retrospective cohort of refractory IBD patients.MethodsAll patients initiated on ustekinumab following failure of one or more anti-TNF agents were included. Patients who received conventional maintenance regime (Q8W) was compared to those who received accelerated maintenance regime (Q4H). The primary end point was steroid free remission at 12 months or at last follow up. The secondary end points were ustekinumab persistence at 6 months and 12 months, need for surgery and drug related infectious or non-infectious complications.ResultsOne hundred and four patients were included (male: female 48:56). Median follow up was 11 months (IQR 5-14). Fifty-six patients received accelerated dosing regimen while 48 patients received standard dosing regime. Dose escalation was required in 18 patients (37.5%) of standard dosing regimen while four patients (7.1%) in the accelerated dosing regimen had dose de-escalation. Higher proportion patients in the accelerated dosing regimen were in steroid free remission 87.5% vs 68.8% (p=0.018). Proportion of patients requiring surgery was higher in the standard dosing regimen group (22.91 5 vs 7.14%, p = 0.02). Ustekinumab persistence in patient started on the accelerated regime and conventional dosing regime was not significantly different at 6 months (94.1% and 95.3%, p=0.58) and 12 months (84.4% and 95.3, p=0.1). No serious drug related complications observed in either group.ConclusionsEarly dose optimisation of Ustekinumab improves steroid free remission rates and reduces the need for surgery in patients with anti-TNF refractory patients with IBD.

IntroductionTherapeutic Drug and antibody monitoring (TDM) is now an established strategy to manage patients with Inflammatory Bowel disease being treated with Biologic agents. Biosimilar switching of Originator Infliximab (IFX) is recommended by ECCO and BSG. The role of TDM during biosimilar infliximab switch is not well studied. This study aimed to analyse and compare IFX drug and antibody levels before and after switch.AimsTo study the impact of TDM on Biosilimar infliximab switching by detecting the proportion of patients who have sub-therapeutic drug levels and/or anti-IFX antibodies either before or 3 months after the switch, who would be considered as secondary loss of response (LOR).MethodsAll patients with either Crohn’s disease (CD) or Ulcerative Colitis(UC) who were switched to Remsima, a biosimilar Infliximab in 2017 at the two hospital sites were included. Disease activity was assessed using Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index(SCAI). The most recent colonoscopy/radiological imaging and faecal calprotectin (FCP) was recorded. Pre and post- switch Infliximab and antibody levels were obtained. Concomitant use of immunomodulators (Azathioprine, Mercaptopurine or Methotrexate) was noted.Results119 patients had IFX Remicade switch to Biosimilar Inflectra or Remsima. 86 pts had CD and 32 had UC. 110 patients had pre-switch therapeutic drug and antibody monitoring, and 115 had post switch monitoring as well within 3 months. 67 pts had sub-therapeutic but detectable IFX drug levels prior to the switch with either mild or inactive clinical scores for both CD and UC. 19 patients had undetectable IFX drug levels, and post switch continued to have undetectable levels. 16 of these 19 patients had high anti-IFX antibodies suggesting that these patients were secondary loss of response who needed a change of their biologic to another agent. 11/86 patients had dose escalation to 10 mg/kg and then attained therapeutic levels. SCAI ranged between 0–9, mean 1.433, and HBI ranged between 0–12, mean 2, indicating that majority of patients were in remission. Post switch matched FCP showed 60 pts in remission with FCP <200 ug/g and 22 pts with FCP >250 ug/g.ConclusionsTherapeutic drug and antibody monitoring before and 3 months after Biosimilar switch detects secondary loss of response in patients maintained on scheduled IFX treatment in clinical and biochemical remission. It should be recommended over blanket switching as it may prevent un-necessary switching for some patients who are no longer responding the IFX or those who may merit a drug withdrawal.

Healthcare organisations have had to make adaptations to reduce the impact of the Coronavirus 2019 (COVID-19) pandemic. This has necessitated urgent reconfiguration within inflammatory bowel disease (IBD) services to ensure safety of patients and staff and seamless continuity of care provision. To describe the adaptations made by a large inflammatory bowel disease service, caring for over 3,500 IBD patients, in response to the COVID-19 pandemic. A diary record of responses to the pandemic were logged, and meeting minutes were reviewed. Data were recorded from IBD advice lines, multidisciplinary team (MDT) meeting minutes, infusion unit attendances, and electronic referral systems for the 8-week period from 9 March 2020 until 2 May 2020. Descriptive analysis was performed. The IBD service at Hull University Teaching Hospitals NHS Trust (IBD Hull) instituted rapid structural and functional changes to the service. Outpatient services were suspended and substituted by virtual consultations, and inpatient services were reduced and moved to ambulatory care where possible. The delivery of biologic and immunomodulatory therapies was significantly modified to ensure patient and staff safety. There was a substantial increase in IBD advice line calls. The rapidly evolving COVID-19 pandemic required a prompt response, regular reassessment and planning, and continues to do so. We share our experience in of the successful adaptations made to our IBD service.

Abstract This chapter offers an analysis of the different voices and perspectives comprising the book. It explores the main themes that have emerged from the chapters and conversations, offering an overview of areas of difference, but also of surprising fundamental agreement, not just on the ‘what’ but also the ‘how’ of what needs to happen next.

This case-control study evaluated the mortality and morbidity in patients with end-stage renal disease (ESRD) who underwent open heart surgery, as compared with matched control patients. Outcome measures included length of use of ventilators, vasopressor agents, number of blood units transfused, chest tube output, and length of stay. Hospital length of stay was longer in patients with renal failure, but overall morbidity and mortality were not statistically different. Conclusions include that elective open heart surgery can be performed safely in ESRD patients using routine perioperative management.