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Emergency admissions in England for alcohol-related liver disease (ArLD) have increased steadily for decades. Statistics based on administrative data typically focus on the ArLD-specific code as the primary diagnosis and are therefore at risk of excluding ArLD admissions defined by other coding combinations.To deploy the Liverpool ArLD Algorithm (LAA), which accounts for alternative coding patterns (e.g., ArLD secondary diagnosis with alcohol/liver-related primary diagnosis), to national and local datasets in the context of studying trends in ArLD admissions before and during the COVID-19 pandemic.We applied the standard approach and LAA to Hospital Episode Statistics for England (2013-21). The algorithm was also deployed at 28 hospitals to discharge coding for emergency admissions during a common 7-day period in 2019 and 2020, in which eligible patient records were reviewed manually to verify the diagnosis and extract data.Nationally, LAA identified approximately 100% more monthly emergency admissions from 2013 to 2021 than the standard method. The annual number of ArLD-specific admissions increased by 30.4%. Of 39,667 admissions in 2020/21, only 19,949 were identified with standard approach, an estimated admission cost of £70 million in under-recorded cases. Within 28 local hospital datasets, 233 admissions were identified using the standard approach and a further 250 locally verified cases using the LAA (107% uplift). There was an 18% absolute increase in ArLD admissions in the seven-day evaluation period in 2020 versus 2019. There were no differences in disease severity or mortality, or in the proportion of admissions with decompensation of cirrhosis or alcoholic hepatitis.The LAA can be applied successfully to local and national datasets. It consistently identifies approximately 100% more cases than the standard coding approach. The algorithm has revealed the true extent of ArLD admissions. The pandemic has compounded a long-term rise in ArLD admissions and mortality.

Background Patient-reported outcome measures (PROMs) are recommended for assessing patient-centered outcomes in inflammatory bowel disease (IBD). The main aims were to assess the level of participation in an electronic PROM (ePROM) data collection system among patients with IBD, and evaluate reliability and validity of the resulting scores. Methods Patients included in the IBD registry of Maccabi Healthcare Services, a state-mandated healthcare provider for over 2.6 million people in Israel, were invited to complete the IBD-Control measure and a general health item, with follow-up ePROMs at 3 and 6 months including a global rating of change item. Descriptive statistics were used to compare patient characteristics by participation rate, and assess survey completion time. Initial scores were assessed for internal consistency reliability using Cronbach's alpha. Test–retest reliability was assessed using the intraclass correlation coefficient from paired scores of patients identified as unchanged between the initial and first follow-up. Construct validity was assessed by the ability of IBD-control scores to discriminate between patient sub-groups in expected ways. Empirical validity was assessed using ePROM score correlations with laboratory markers of disease activity. Score coverage was also assessed. Results A total of 13,588 patients were invited to participate [Mean age = 49 years (SD = 17); females = 51%]. Participation rate was 31.5%. Participants compared to non-participants were slightly older, were more likely to be female, to have a history of biologic treatment, to have higher socio-economic status, and to be more experienced in the usage of the digital patient portal. Median survey completion time was approximately 1:30 min. Internal consistency and test–retest reliability were 0.86 and 0.98, respectively. Scores discriminated between patient sub-groups in clinically expected ways, with expected correlations to laboratory markers of disease activity. A notable ceiling effect was observed (> 15%) for IBD-Control scores. Conclusions Feasibility, reliability, and validity of the ePROM system was supported for measuring the level of perceived disease control in patients diagnosed with IBD in Israel. Additional research is needed to identify ways to increase patient participation, assess clinical implications of the identified measurement ceiling of the IBD-control, and evaluate the added value of the derived scores in support of clinical decision making.

Background Patient-reported outcome measures [PROMs] are key to documenting outcomes that matter most to patients and are increasingly important to commissioners of health care seeking value. We report the first series of the ICHOM Standard Set for Inflammatory Bowel Disease [IBD]. Methods Patients treated for ulcerative colitis [UC] or Crohn’s disease [CD] in our centre were offered enrolment into the web-based TrueColours-IBD programme. Through this programme, e-mail prompts linking to validated questionnaires were sent for symptoms, quality of life, and ICHOM IBD outcomes. Results The first 1299 consecutive patients enrolled [779 UC, 520 CD] were studied with median 270 days of follow-up (interquartile range [IQR] 116, 504). 671 [52%] were female, mean age 42 years (standard deviation [sd] 16), mean body mass index [BMI] 26 [sd 5.3]. At registration, 483 [37%] were using advanced therapies. Median adherence to fortnightly quality of life reporting and quarterly outcomes was 100% [IQR 48, 100%] and 100% [IQR 75, 100%], respectively. In the previous 12 months, prednisolone use was reported by 229 [29%] patients with UC vs 81 [16%] with CD, p 3 months. An IBD-related intervention was reported by 174 [13%] patients, and 80 [6%] reported an unplanned hospital admission. There were high rates of fatigue [50%] and mood disturbance [23%]. Conclusions Outcomes reported by patients illustrate the scale of the therapeutic deficit in current care. Proof of principle is demonstrated that PROM data can be collected continuously with little burden on health care professionals. This may become a metric for quality improvement programmes or to compare outcomes.

Regulatory approval of biosimilars often depends on extrapolating evidence from one clinical indication to all of those of the originator biologic. We aimed to develop a quantitative benefit-risk analysis to assess whether the resulting increase in the uncertainty in the clinical performance of biosimilars (i.e. risk) may be countered by their lower pricing (benefit). A 1-year decision-analytic model was developed for the biosimilar infliximab (Inflectra®) for Crohn’s disease. The perspective was that of the National Health Service in the UK and costs were valued to 2015/16. A hypothetical cohort of biologic-naive patients with moderate-to-severe Crohn’s disease was simulated through the model. Immunogenicity to infliximab was a key modifier, influencing rates of non-response and infusion reactions. Net health benefit was estimated based on quality-adjusted life-years. A range of sensitivity analyses tested the robustness of the results and explored how the biosimilar price must respond to varying immunogenicity to remain the preferred option. The base-case analysis predicted a positive incremental net health benefit of 0.04 (95% central range 0.00–0.09) favouring the biosimilar, based on 0.803 quality-adjusted life-years, and costs of £18,087 and £19,176 for the biosimilar and originator, respectively. Two-way sensitivity analyses suggested that if 50% of patients developed antibodies, the value-based price of £410 per vial must be lower than that of the originator (£420), but remain higher than the actual market price (£378). The model supports the use of Inflecta® for Crohn’s disease in the UK, and provides a framework for the quantitative evaluation of biosimilars in the context of a health technology assessment. Value-based pricing using this methodology could protect health systems from the potential risks of biosimilars where they are untested in the approved populations.

Introduction Alcohol-related liver disease (ARLD) can present with neuropsychiatric complications. Epidemiological studies have not investigated the impact of confusional states on patient journeys. As part of the Connected Health Cities programme, we retrospectively investigated coding data from a regional administrative dataset to identify the burden of recognised cognitive impairment (CI) in a pre-identified cohort of patients during their index admission of ARLD (fiscal years 2014–18). Methodology Inpatient spells for a cohort of 3,887 index ARLD admissions were screened for ICD-10 codes indicative of acute and chronic CI. Descriptive analytics and stepwise multivariate logistic regression models were generated using Stata 15 (StataCorp, 2017) for predefined outcomes: inpatient mortality, length of stay, all-cause outpatient attendance and all-cause A&E attendance. These were casemix-adjusted for age, sex, co-morbidity, deprivation and variables associated with severity of liver decompensation. Results 20 codes corresponded to acute or chronic CI, most frequently encoding encephalopathy and alcohol-related amnesiac syndrome respectively. Codes for intoxication and withdrawal were excluded and adjusted for. 277 spells (7.1%) were coded with > 1 ICD code for acute CI, and 78 (2.0%) for chronic CI, with minimal overlap (0.6%). Comparisons were made with patients without relevant codes. Overall, these patients were older (mean age 57.5 and 64.1 respectively) with higher levels of co-morbidity (mean Charlson index 16.4 and 12.6 respectively) with median bed-days of 13 and 14. Multivariate logistic regression models demonstrated patients with acute CI had higher odds of inpatient mortality (OR 2.13) and long admission >21 days (OR 2.30). Patients coded with chronic CI had higher odds of long admission (OR 3.09) and A&E attendance within 90 days (OR 2.01), and were less likely to attend an outpatient clinic at 14-day (OR 0.28) and 30-day (OR 0.4) intervals post-discharge. CI did not predict risk of readmission. Conclusion In terms of mortality, acute CI is likely to reflect higher disease severity, particularly as encephalopathy is a poor prognosticator in this group of patients. The evidence suggests that chronic CI in patients with ARLD is under-detected in clinical practice. Our analysis demonstrates patients with recognised chronic CI experience extended admissions, are more likely to experience unplanned care and less likely to engage with outpatient care up to 90 days post-discharge. This suggests that current care models may not be appropriate for this subgroup, and alternative pathways integrating prompt identification and supported discharge mechanisms should be developed.

Introduction Oral corticosteroids continue to play a key role in inducing remission in inflammatory bowel disease (IBD) but are not effective as maintenance agents. Avoiding prolonged courses of treatment is an important strategy to minimise side effects. The UK IBD Registry has established an infrastructure capable of recording prescribing at point-of-care using a range of different local systems and software, including direct capture from local operational records. We investigated the feasibility of extracting data to undertake audit of steroid prescribing for hospitals participating in the Registry. Methods Data submitted to the UK IBD Registry were analysed over three consecutive fiscal years (2016/17, 2017/18 and 2018/19). All prescriptions for oral steroids (prednisolone or budesonide) with a record of both a start and stop date were extracted and linked to patient characteristics. We compared the mean duration of steroid courses initiated in each year and the proportion lasting eight weeks or less. Results There were 2,156 prescriptions (prednisolone 83%; budesonide 17%) with a start and stop date, relating to 1,591 patients treated at 42 hospitals. Three quarters (77.4%) of cases had a single steroid prescription recorded over the three year time period (5.8% had >2). Results are summarised in the table 1. There was a year-on-year reduction in the mean duration of recorded steroid courses from 13.0 to 8.4 weeks (p Conclusion IBD teams participating in the UK IBD Registry have achieved a reduction in the duration of steroid treatment courses, suggesting progress in efforts to avoid prolonged steroid exposure. The Registry has established an infrastructure capable of serving as a platform for future nationwide prospective steroid audit.

Introduction In-hospital mortality from alcohol-related liver disease (ARLD) remains high, with concern that some patients are dying during their first (index) emergency hospitalisation. However, the mortality rate during index ARLD admission in England is not well characterised. Nor do we know the relative proportion of fatalities that are genuinely ‘hidden’ to the system as opposed to having had prior contacts with primary or secondary care. Methods The CPRD dataset contains a nationally representative sample of the English population (approx. 13 million, 23.2%) with linked data from both primary and secondary care. We obtained data for all people with an alcohol or liver-related READ code in their primary care record or an alcohol-specific ICD-10 diagnosis in secondary care (n=496,762). We then selected all patients admitted as an emergency for index ARLD in fiscal year 2017/18 (applying our recently reported diagnostic algorithm for ARLD and screening the preceding 10 years), characterised their prior contacts with services across the decade before admission, their clinical characteristics and in-hospital mortality. Results Within the CPRD sample population for 2017/18, there were 2,423 patients with an index admission for ARLD (their first in last decade). In-hospital mortality for index admissions in England was 15.1% (n=366), with a mean age of 59 years, 60.7% male and mean Charlson index 18. Of the deaths, 28% had no record of an emergency admission for any cause in last 10 years – individuals who appear hidden to hospital services. However, 47% of those dying had at least one previous admission for an alcohol-specific diagnosis (other than liver disease) with a mean interval of 760 days between their first admission and fatal ARLD index. Of the deaths, 9% had no record of any primary care contact (seemingly unknown to GP services). However, 63.7% of those dying had a previous READ code for an alcohol-related problem in their GP record. Conclusion In England in 2017/18, fifteen percent of patients admitted for the first time with ARLD died during admission. Of patients who died, almost one in ten had had no contact with primary care, and over one in four had no record of a secondary care admission in the preceding 10 years. Patients lacking contact with both primary and secondary care represent a ‘hidden group’, with apparent lack of opportunity for healthcare intervention. However, a high proportion of patients who died are known to both primary and secondary care. There may be missed opportunities or ineffective healthcare intervention at both primary and secondary care levels. New, more effective strategies are needed to detect and help people at high risk of presenting acutely for the first time with fatal ARLD. Characteristics of survivors vs. those who died Number of deaths = 477 (13.91%); 141 (29.56%) had no previous GP contact; 16 (3.35%) had a GP liver flag only; 189 (39.62%) have an alcohol flag only and 131 (27.46%) both alcohol and liver codes. Number of survivors = 2,952 (86.09%); 868 (29.40%) had no previous GP contact; 43 (1.46) with a liver flag only; 1,309 (44.34%) with an alcohol flag only and 732 (24.80%) with both alcohol and liver codes. Mann-Whitney- comparison of the total number of days between the 2017/2018 index, and the date of first GP: alcohol, liver and combined alcohol + liver code. Showed no statistical significance between the length in time from GP code and index, within the died vs survived cohorts. Mortality cohort (n=477) Mean age = 59 (SD– 12.6) ARLD code in primary = 61.6% Short stay ( AKI= 64.8% Ascites = 51.2% Varices = 22.9 Survived cohort (n=2,952) Mean age = 53 (SD–11.9) ARLD code in primary = 46.3% Short stay ( AKI= 14.8% Ascites = 29.1% Varices = 16.9%

Background Anti-tumour necrosis factor (TNF) agents are effective in Crohn's disease but some patients lose response and require alternative biologic therapy. There are few data on comparative effectiveness of vedolizumab and ustekinumab in this setting. Aim To compare the effectiveness of ustekinumab and vedolizumab in anti-TNF-refractory Crohn's disease over 12 months. Methods Patients commencing ustekinumab or vedolizumab for anti-TNF-refractory Crohn's disease with minimum follow-up of 12 months were included. The primary outcome measure was the difference in steroid-free remission rates at end of induction (2 months) and at 12 months. We also assessed rates of clinical response and remission, treatment persistence, surgery and adverse events in both groups. We performed logistic regression analysis to assess factors associated with steroid-free remission and clinical response and remission. Results We included 85 patients commencing vedolizumab and 45 commencing ustekinumab. In an unadjusted model, rates of steroid-free and clinical remission were significantly higher among ustekinumab-treated patients. After adjusting for confounders, steroid-free remission was higher among ustekinumab-treated patients at 2 months (odds ratio, OR 2.79, 95% confidence interval, CI 1.06-7.39, P = 0.038) and 12 months (OR 2.01, 95% CI 0.89-4.56, P = 0.095). More patients treated with ustekinumab remained on therapy at the end of 12 months (84.4% vs 61.5%, P = 0.007). Conclusions Ustekinumab appeared more effective in treating anti-TNF-refractory Crohn's disease and more patients persisted with therapy.

Background A subcutaneous (SC) formulation of IFX has recently been shown to be as effective as intravenous (IV) IFX in a randomised trial but there are no real world data to support elective switching. We aimed to assess the effectiveness of an elective switching program from IV to SC IFX in patients with IBD. Methods Patients on maintenance IV IFX were included in this retrospective multi-centre cohort study across two sites. Disease activity was monitored serially with Harvey-Bradshaw Index (HBI) and simple clinical colitis activity index (SCCAI) at baseline, 3 and 6 months. Faecal calprotectin (FCP), C-reactive protein (CRP) and IFX levels were recorded at the same time points. Patients on 5mg/kg every 8 weeks were switched to SC IFX 120mg every other week (EOW), followed by those on 6 and 4 weekly IV IFX to either EOW or weekly SC IFX. A random selection of patients were surveyed for patient satisfaction using a likert scale. Criteria for switching were agreed within a standard operating procedure. Data was analysed using SPSS for Windows with p Results 172 patients (109 CD, 57 UC, 6 IBD-U) were switched to SC IFX since April 2020 (97 male vs. 75 female; mean age 39.7 years and weight 78.6kg). 57.6% patients (n=99) were on concurrent immunomodulators. 152 patients were switched to EOW dosing. From baseline to 6 months post switch, HBI, SCCAI, FCP and CRP remained stable (p>0.05, ns), but mean IFX levels significantly increased from baseline (baseline = 9.8ug/mL vs. 3 month = 14.6ug/mL; p0.05, ns). 8 patients (4.65%) had self-limiting skin injection site reactions, 1 UC patient (0.58%) required corticosteroids, and 2 patients (1.16%) developed perianal symptoms requiring examination under anaesthesia (EUA). Overall 4 patients (2.36%) discontinued SC treatment due to adverse events (2 perianal disease patients, 1 flaring UC patient requiring oral steroids and 1 patient with neurological symptoms) and 1 (0.58%) planned discontinuation for a patient in the 3rd trimester of pregnancy. 85.2% (75/88) of patients agreed they were happier on SC IFX compared to IV IFX, 88.6% (78/88) feeling at least the same or better on SC IFX, and 92% (81/88) and 86.4% (76/88) agreeing that SC IFX was easy to use and felt safe using it, respectively. Conclusion SC IFX is effective at maintaining remission in IBD patients switched from IV to SC IFX with no evidence of inferiority at 6 month follow up. There is a significant increase in IFX levels from baseline to 3 months which is maintained to 6 months post switch. SC IFX appears to be safe with low rates of adverse events and is well tolerated by patients.

Background and Aims: Success in delivering value-based healthcare involves measuring outcomes that matter most to patients. Our aim was to develop a minimum Standard Set of patient-centred outcome measures for inflammatory bowel disease (IBD), for use in different healthcare settings. Methods: An international working group (n=25) representing patients, patient associations, gastroenterologists, surgeons, specialist nurses, IBD registries and patient-reported outcome measure (PROM) methodologists participated in a series of teleconferences incorporating a modified Delphi process. Systematic review of existing literature, registry data, patient focus groups and open review periods were used to reach consensus on a minimum set of standard outcome measures and risk adjustment variables. Similar methodology has been used in 21 other disease areas (www.ichom.org). Results: A minimum Standard Set of outcomes was developed for patients (aged ≥16) with IBD. Outcome domains included survival and disease control (survival, disease activity/remission, colorectal cancer, anaemia), disutility of care (treatment-related complications), healthcare utilisation (IBD-related admissions, emergency room visits) and patient-reported outcomes (including quality of life, nutritional status and impact of fistulae) measured at baseline and at 6 or 12 month intervals. A single PROM (IBD-Control questionnaire) was recommended in the Standard Set and minimum risk adjustment data collected at baseline and annually were included: demographics, basic clinical information and treatment factors. Conclusions: A Standard Set of outcome measures for IBD has been developed based on evidence, patient input and specialist consensus. It provides an international template for meaningful, comparable and easy-to-interpret measures as a step towards achieving value-based healthcare in IBD. (248 words).

Background Variations in emergency care quality for alcohol‐related liver disease (ARLD) have been highlighted. Aim To determine whether introduction of a regional quality improvement (QI) programme was associated with a reduction in potentially avoidable inpatient mortality. Method Retrospective observational cohort study using hospital administrative data spanning a 1‐year period before (2014/2015) and 3 years after a QI initiative at seven acute hospitals in North West England. The intervention included serial audit of a bundle of process metrics. An algorithm was developed to identify index (“first”) emergency admissions for ARLD (n = 3887). We created a standardised mortality ratio (SMR) to compare relative mortality and regression models to examine risk‐adjusted odds of death. Results In 2014/2015, three of seven hospitals had an SMR above the upper control limit (“outliers”). Adjusted odds of death for patients admitted to outlier hospitals was higher than non‐outliers (OR 2.13, 95% CI 1.32‐3.44, P = 0.002). Following the QI programme there was a step‐wise reduction in outliers (none in 2017/2018). Odds of death was 67% lower in 2017/2018 compared to 2014/2015 at original outlier hospitals, but unchanged at other hospitals. Process audit performance of outliers was worse than non‐outliers at baseline, but improved after intervention. Conclusions There was a reduction in unexplained variation in hospital mortality following the QI intervention. This challenges the pessimism that is prevalent for achieving better outcomes for patients with ARLD. Notwithstanding the limitations of an uncontrolled observational study, these data provide hope that co‐ordinated efforts to drive adoption of evidence‐based practice can save lives.

Introduction Anti-tumour necrosis factor (TNF) agents are effective in Crohn’s disease (CD), but up to 30% of patients fail to respond or develop intolerance and require alternative biological therapy. Both vedolizumab and ustekinumab are licensed to treat anti-TNF refractory CD patients. Clinical trials of vedolizumab and ustekinumab in anti-TNF refractory patients seem to suggest comparable efficacy, but no real life data exist to enable clinicians to guide decision-making. We conducted a multi-centre retrospective cohort study to assess the comparative effectiveness of vedolizumab and ustekinumab in treating anti-TNF refractory CD. Methods CD patients who were commenced on vedolizumab or ustekinumab following exposure to anti-TNF therapy were included. Disease activity was monitored serially by calculation of Harvey-Bradshaw index (HBI) for up to 4 months. Faecal calprotectin (FC) at baseline and subsequent visits were recorded if available. Clinical response was defined as decrease in HBI ≥3 and remission by HBI Results After exclusion of patients without evaluable data, 51 patients commencing vedolizumab and 25 commencing ustekinumab therapy were included. Baseline characteristics (age, disease location, behaviour, smoking status and baseline FC) were comparable in both cohorts. Clinical response, remission and steroid-free remission rates were comparable between vedolizumab and ustekinumab at 2 and 4 months (see table 1). There was a significant reduction in HBI for vedolizumab at 2 months (1.8, 95% CI 0.50 to 3.13, p = 0.008) and ustekinumab at 4 months (3.4, 95% CI 1.84 to 4.96, p = 0.0001). Conclusions In a multi-centre cohort of anti-TNF refractory CD patients, vedolizumab and ustekinumab appear equally effective in the short-term. Our observations warrant longer-term follow up and further validation in independent cohorts.

Introduction Ensuring the safe, appropriate and effective use of costly biological agents presents a significant challenge for healthcare systems. Although no longer funded as a national audit programme, NHS England has identified audit of biologics for IBD as a priority area for QI activity for hospitals (Quality Accounts List). The UK IBD Registry provides a system for collecting, submitting and reporting data to support participation in biologics audit. Methods Participating centres submit quarterly extracts of standardised data collected via a range of software solutions, including demographics, clinical characteristics, infection screening, drug initiations, clinical review visits and disease activity scores. Eligible cases for audit require a record of drug start date and baseline visit. Algorithmic analysis identifies most relevant review visit and associated disease score if recorded (time-windows: post-induction, 8–16 wks; 12-month review, 44–60 wks). The rolling audit focuses on seven key performance indicators (KPIs). Cumulative results are presented, focused on each patient’s first biologic initiation (April 2016 – Present). Results 3,617 eligible cases (CD: 61%; UC: 35%; IBD-U: 3%). Humira 36%; Remsima 24%; Inflectra 18%; Vedolizumab 14%; Remicade 3%; Golimumab 2%; Ustekinumab 2%; Not specified 1%. Table 1 shows mean KPIs (%) across all sites, and sub-divided by eligible cases. Across the seven KPIs, 20–45% of hospitals had results below the registry-wide mean value (arbitrary benchmark). Conclusions The UK IBD Registry is supporting a growing network of hospitals with participation in continuous biologics audit, providing benchmarking reports to drive local and registry-wide quality improvement. Although incomplete case ascertainment and missing data are inevitable challenges, the biologics data is maturing as sites establish live registers. Results highlight an ongoing need for most centres to improve biologics monitoring through better-organised and documented review visits with objective recording of standardised outcomes.

Introduction Several global initiatives are seeking to standardise outcome assessment for IBD in clinical trials (Core Outcome Sets) and routine care (e.g. ICHOM). The UK IBD Biologics Audit found inconsistent use of clinical disease activity indices among UK clinicians. We aimed to explore variability in outcome assessment in routine practice, evaluating the range of individual outcomes elicited and extent of standardisation and quantification. Methods Ethnographic observations of 52 IBD clinic consultations by 17 IBD clinicians (8 consultants, 7 IBD nurses and 2 trainees) across four acute hospitals in the North West region of England. Consultations were observed, audio-recorded, transcribed and analysed for IBD outcomes elicited by clinicians (or volunteered by patients), including specific items required for Harvey-Bradshaw Index (HBI) and Simple Clinical Colitis Activity Index (SCCAI). Results Most commonly elicited outcomes are shown in the table 1. HBI or SCCAI were collected in only 4 (8%) of consultations. In the remainder, domains of HBI and SCCAI were discussed in variable detail. Complete HBI coverage: 5/29 (17%); symptom components of HBI (wellbeing, liquid stools, abdominal pain): 16/29 (55%). No Crohn’s disease consultation involved specific discussions about symptoms over past 24 hrs (including 2 where HBI was calculated). Complete SCCAI coverage: only 1 consultation. Partial coverage (5 out of 6 SCCAI domains): 8/21 (38%). Symptoms were never specifically defined over past 3 days. Certain symptoms were elicited significantly more often by nurses than doctors (p Conclusions There is high variability in breadth, depth and quantification of outcomes during routine clinical assessments. Most domains for activity indices were elicited but formal scoring and assessment for a fixed time period was rare. Standardised outcomes may be better-captured directly from patients (PROMs) than via clinician-generated indices.

Introduction Patients with Inflammatory Bowel Disease (IBD) often struggle with access to prompt advice regarding and place a heavy reliance on overstretched services. We have a track record in guided self-management of IBD so explored whether this could be built into a novel patient-centred portal with direct on line access to a fully personalised health record, integrating individualised plans of care and disease monitoring tools. Methods In a unique collaboration with local patients, the patient charity Crohn’s and Colitis UK, health care and IT teams, we developed, implemented and evaluated a web based portal at Salford Royal. At the outset, a user group of patients was established and their views and needs were central to each step of the development, refinement and evaluation of the portal. From this group it was clear that there was a particular demand by IBD patients to have access to their health records and reliable information. Results We have built and refined the ‘MY IBD’ portal, which is fully integrated with the electronic patient record and delivers: Access to personalised information: diagnosis, visual aids and links to CCUK information resources Immediate access to blood results, investigation results, clinic letters Disease activity assessment tools A personalised plan of care available online for the patient Improved communication with the IBD team: messaging facility and trigger emails when disease activity scores are high. 720 patients are now using the portal. Overall usability was scored as excellent, showing patients were helped with decision-making. Improvements were seen in perceived support (p=0.06) compared to non-users with a trend to improved disease related knowledge (p=0.14). An average of clinic 2.9 attendances per year (2014–15) reduced to 0.6 attendances for portal self-management users (2016–2017) releasing over 500 clinic appointments. Satisfaction with self-management remains high with 98% of patients rating the process as good/excellent. User group sessions have captured value to patients. They expressed it had ‘completely changed my care’, ‘having up to date information about your condition leads to less stress and better health’ and ‘puts patients back in control of their illness’. The portal has also been refined for integration with the IBD registry. Conclusions Patient experience and service have improved. Portal patients are more in control, with greater independence to self-manage through better understanding of their condition. Other Trusts are now seeking to adopt the portal and we welcome enquiries to establish it in other NHS sites. Acknowledgments funded by CCUK, ‘Living with IBD’.

Introduction Despite major progress in drug development for Crohn’s disease (CD) and advances in trial methodology, there is no internationally recognised core outcome set (COS). Poor standardisation in outcome reporting may impact negatively on translation of trials into practice. The suitability of traditional disease activity indices as primary end-points has been challenged, with growing interest in objective measures of inflammation. We undertook a systematic review to explore heterogeneity and time trends in the reporting of efficacy and safety outcomes in placebo-controlled randomised controlled trials (RCTs) of patients with CD. Methods We searched MEDLINE, EMBASE, CINAHL and Cochrane Library from their inception to November 2015, for RCTs of adult CD patients with treated with medical or surgical therapies. We extracted information on efficacy and safety outcomes, definitions of end-points, and measurement instruments. To explore temporal trends studies were stratified by publication date (pre-2009 and 2009-onwards). Results 181 RCTs comprising 23 850 patients. Trial focus: Induction of remission, 110 trials (60.8%), 104 medical and 6 surgical interventions. Maintenance of remission, 71 trials (39.2%). Biologics were intervention of interest in 33.7%, as either monotherapy or part of a combination therapy. 92.3% of trials reported clinical efficacy outcomes as a primary or secondary endpoint. CDAI was the dominant index, used to determine clinical response or remission in 63.5% of trials. However, there was heterogeneity, with 35 definitions of response or remission. CDAI Conclusions As expected, the CDAI was the dominant composite index reported but there was significant variation in the selection and definition of clinical trial end-points in RCTs for CD between studies, and over time. Despite growth in reporting of objective measures of inflammation and in PROMs, there is much heterogeneity and lack of standardisation. This highlights the need for international researchers and clinicians to develop a COS for comparative effectiveness research in CD.

Introduction The UK IBD Registry (IBD-R) provides a standardised dataset and alternative methods for local teams to record structured electronic data in routine care. The infrastructure enables collection of data for local use and upload of anonymized data centrally (each quarter). Registry participation allows sites to demonstrate engagement with national audit (e.g. Biologics Audit, listed on the NHS Quality Accounts) and access to centrally-developed analytics and reporting. Methods To evaluate growth in establishment of local biologics registers using the IBD-R, we analysed three uploads of data (March, June and Sept 2017) with a focus on key data items required for producing site-level reports for patients treated with these agents (from a basic to more granular-level detail, using the ‘biologics events’ dataset). We generated Quarterly Reports and distributed to centres, seeking feedback to inform future iterations. Results Participating centres grew by 59% (32 to 51) and number of sites contributing biologics events more than doubled (16 to 37). Total registered patients in the IBD-R increased from 24 633 to 31 613. Biologics Events For adults with CD, submitted initiation events increased >6 fold (472 to 3126 patients), post-induction review ~3 fold (709 to 2,022) and 12 month review >19 fold (22 to 437). Agents used for adult CD [UC]: Remicade 1423 [450]; Humira 1675 [311]; Inflectra 345 [236]; Remsima 398 [225]; Vedolizumab 186 [201]; Ustekinumab 16 [0]. Data completeness varied by item, e.g. recording of ‘naive’ status (y or n) was static at ~50%; categorization of clinical indication consistently high at >80% of cases. Outcome measures By Sept 17, Physician Global Assessment (PGA) was reported at 1053 initiation events for CD (62%) and UC 940 (66%); and at 1537 (97%) and 1248 (80%) post-induction reviews showing rapid adoption, but data for disease activity indices (HBI or SCCAI) remained static at around 10%. The next upload (Feb 2018) contains almost 40 000 records from 63 sites and confirms continuing growth (analysis in progress). Conclusions There has been significant increase in participation and in the breadth and depth of data being submitted to the UK IBD-R, particularly for biological therapies. Patterns of outcome data collection suggest clinical teams favour simple global outcome measures to formal activity indices – likely reflecting the added burden of administering and recording the data. However, the feasibility of site-level reporting to support local biologics registries is now established. Funded by Crohn’s and Colitis UK

Common ile uct (CBD) stones 10%–20% of patients with gallstone disease. ndoscopic retrograde cholangio-pancreatography (ERCP) Methods All adult patients with diagnosis (ICD-10) codes for alculus of bile duct with cholangitisalculus of bile duct with cholecystitisalculusofbile duct without cholangitis were used to select results from HospitalEpisode Statistics (HES) data for the years 2013/14 – 2016/17. Episodes were excluded where there were episodes with one or moreof these codes for the previous 2 financial years to censor patients already on a CBD pathway. Results There were 1 40 890 patients identified, of which 91 178 (64.72%) were female Mean age at first admission was 70. Of the 1 40 890 individual patients, 1 02 072 (72%) had an emergency first admission. The incidence of cases in each year was 33,557, 35,053, 35 621 and 36 659 respectively. were performed on 48 306 patients in this cohort over the study period Of the 48 306 individuals who had an ERCP, 39 192 (65%) had only one procedure, 7105 (1%) had two procedures and 2009 (%) had three or more. For the identified CBD cohort 60 793 holecystectomies were performed over the study period with 17 063 patients having had both an ERCP and holecystectomy.

Introduction The rising burden and high mortality for alcohol-related liver disease (ARLD) is well-recognised in the UK. Efforts to plan adequate liver and alcohol services and to identify unwarranted variation are limited by lack of robust, actionable information about true workload and real-world risk-adjusted outcomes. We report an informatics programme (Connected Health Cities, Northwest Coast) that is generating new analytical resources to support services. Methods A healthcare data lab. team of data scientists is linked to a secure ‘data ark’ hosting regional commissioning datasets (Admitted Patient Care, A and E, Outpatients, fiscal years 14/15 to 16/17) and is working with clinical teams to construct novel ways to interrogate data (‘algorithmic approach’), model outcomes and unexplained variation and visualise data (small area mapping). Entire patient journeys were linked, to identify ARLD cases and their all-cause emergency admissions (categorised by diagnosis), capture phenotyping flags (e.g. first occurrence of codes for varices), pre-admission events and outcomes (e.g. in-hospital mortality; all-cause 30 day readmission). Maps were used to communicate catchment areas and identify admission ‘hot spots’. Site-level benchmarking reports were shared with teams at 7 hospitals. Results Compared to the standard approach for capturing cases (i.e. primary diagnosis at discharge; 6 specific ICD-10 codes; ‘ARLD-Primary’ Method), the algorithmic approach (ARLD-Alg) identified 9 other patterns of primary and secondary diagnoses with >60 primary ICD-10 codes consistent with emergency care for ARLD. Activity: Across 7 NHS Trusts, estimates of total 3 year activity for ARLD increased from 3185 (ARLD-Primary) to 5912 (ARLD-Alg) for admissions, 35 840 to 56 010 for bed days (equivalent to 50 extra in-patient beds), and 485 to 665 for in-hospital deaths. Case-mix for the 2 approaches was similar (mean age: 51.6 v 51.4; males 63.2 v 63.6%; Charlson Index: 1.6 v 1.7) but ARLD-Alg captured more shorter stays (median LoS: 7 v 6 days;% short stay [0–2 days]: 12.1 v 16.5). Varices cases account for 15%–20%. Outcomes Crude mortality across hospitals varied significantly by method ARLD-Primary: 13.0%–21.7%; ARLD-Alg: 10.2%–14.5%. All binary logistic models identified male patients were at lower risk of in-hospital death than females (Adj OR: 0.70). Treatment provider was a predictor of outcome. Conclusions Standard approaches to analysis of administrative data under-estimate the burden of unplanned care for ARLD (by up to 60%) and have dubious value for service planning or benchmarking. More sophisticated clinically-driven Methods can leverage greater value from routine data. These novel tools are scalable for nationwide deployment and have potential to inform policy and support data-driven service improvement. Funding Department of Health

Aim We examined whether roll out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period. Method This is a retrospective cohort study of 27,763 incident cases of CRC over a 1-year period during the roll-out of screening across parts of England. The primary outcome was the number of emergency (unplanned) hospital admissions during the diagnostic pathway. The primary exposure was to those living in an area where BCSP was active at the time of diagnosis. Patients were categorized into three exposure groups: BCSP not active (reference group), active

Background A number of global initiatives have sought to standardise the assessment of outcomes for inflammatory bowel disease (IBD), both for clinical trials (Core Outcome Sets1) and routine practice (ICHOM2). Our aim was to explore variability in the assessment and recording of clinical IBD outcomes during routine practice in England, evaluating the range of individual outcomes elicited and the extent of objective quantification of symptoms. Methods We performed ethnographic observations of 102 IBD clinic consultations conducted by 24 IBD clinicians (10 consultants, 10 IBD nurses and 4 trainees) in six acute hospitals in the North West region of England. We analysed 909 retrospective clinic records from outpatient IBD clinic visits recorded for observed patients in routine electronic patient records (EPRs). Audio-recordings of observed consultations and clinic records were analysed for pre-defined IBD outcomes, including those items required for Crohn’s Disease Activity Index (CDAI), Harvey–Bradshaw Index (HBI), Mayo Clinic Score (MCS) and Simple Clinical Colitis Activity Index (SCCAI). In addition, we performed 24 semi-structured interviews with IBD clinicians to explore the barriers and facilitators to capturing structured IBD outcomes in EPRs. Results The most commonly elicited and recorded outcomes were general well-being (95% consultations [C] and 61% clinic records [R]), stool frequency [SF] (87% C, 68% R), abdominal pain [AP] (79% C, 46% R), blood in stool [BS] (71% C, 57% R) and loose stool (64% C, 51% R). Clinical disease activity indices (HBI and SCCAI) were collected in only 15 (14.7%) observed consultations and recorded in 51 (5.6%) clinic letters. There was marked variation in the quantification of individual symptom items of MCS, SCCAI, CDAI and HBI in analysed consultations and records. Both PRO2 Crohn’s disease outcomes [AP and SF] were collected in 29/50 (58%) observed consultations and recorded in 169/484 (35%) records. Both PRO2 ulcerative colitis outcomes [SF and BS] were collected in 42/52 (81%) consultations and 253/425 (60%) records. Selected outcomes were recorded significantly more frequently by IBD nurses compared with doctors. Clinicians reported a range of IT barriers and issues with psychometric properties of currently available clinical disease activity indices in practice. Conclusion There is significant variability in the breadth, depth and quantification of IBD clinical outcomes during routine clinical assessments. Although most domains of clinical disease activity indices were elicited in consultations, formal scoring and assessment over fixed time periods was rare. There is an urgent need for practical alternatives to clinician reported disease activity indices in routine care.

Background: Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or ‘spots') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed ‘abnormal' and the subject is referred for further investigation, usually colonoscopy. If 1–4 windows are positive, the result is initially ‘unclear' and up to two further kits are submitted, further positivity leads to colonoscopy (‘weak positive'). If no further blood is detected, the test is deemed ‘normal' and subjects are tested again in 2 years' time. We studied the association between spot positivity % (SP%) and neoplasia. Methods: Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named ‘SP%'. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored. The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2. Results: During Episode 2, 284 261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result. The proportion of cancers detected was positively correlated with SP%, with an R2 correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ∼4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%. Conclusions: This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern. Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ∼4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.

Aim UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. Method A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. Results A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P

Limited evidence is available on the economic burden of ulcerative colitis (UC) in the UK, particularly relating to the impact of relapse frequency on direct medical costs. This study identifies and assesses medical resource utilization (MRU) and associated direct costs in mild and moderate UC patients in the UK.A retrospective chart review of patients with mild-to-moderate UC diagnosed at least 1 year before the study was performed. From 33 general practitioner (GP) and 34 gastroenterologist sites, charts of the last three UC patients fulfilling the inclusion criteria were reviewed. Descriptive statistics were calculated for MRU and 2011 costs (GB£) by number of relapses.The study population included 201 patients with a mean age of 39.9 years; 44% were women and the mean disease duration was 7.4 years. UC-related costs of each MRU category increased with the number of relapses. Comparing patients without relapse with those with more than two relapses, the mean annual UC-related costs were £14 versus £2556 for hospitalizations; £218 versus £988 for visits (including nurse, GP, specialist, and other visits); £21 versus £1303 for procedures; £17 versus £188 for diagnostics; and £1168 versus £6660 for all-cause total costs. Age, sex, and site of data reporting (GP vs. gastroenterologist) were not associated with MRU or costs.Patients with mild-to-moderate UC incurred considerable costs that increased markedly with the number of relapses. These findings support the importance of maintenance therapies in UC that reduce or prevent relapses. Quantifying the relationship between relapse rate and costs will inform future health economic studies.

Introduction: Stricturing is a common complication of Crohn's disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. Methods: A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn's strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Results: Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1-11; median 2) were carried out on 93 strictures (range, 1-5; median 1) over a median duration of 12 months (range, 1-84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn's disease duration (P = 0.03) and high C-reactive protein (P = 0.008) were associated with an increased need for subsequent surgery. Conclusions: EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn's disease phenotype, and the role of concomitant medication to identify those best suited to EBD.

All-cause death within 30 days of ERCP is a candidate indicator of care, but institutional-level statistics require careful interpretation. National-scale, population-based outcome studies of unselected patients undergoing ERCP are needed to define expected levels of real-world mortality risk and the case-mix factors that predict poor outcome.To develop methods for analyzing administrative data for English hospitals with linkage to death registration to study all-cause mortality after first ERCPs and explore predictors of death and institutional variation.Hospital episode statistics for 2006 to 2007 and 2007 to 2008 were linked to the statutory death register. First ERCP episodes were extracted and analyzed for demographic characteristics, admission method, diagnoses, and comorbidities. Additional linkages identified the last-coded diagnosis before death. Factors associated with 30-day death were identified by univariate and multiple logistic analyses. Pilot data and a survey were sent to clinicians at each institution. Crude and case-mix adjusted mortality were analyzed at the institutional level.Death within 30 days of the first ERCP procedure.We analyzed 20,246 first ERCPs from 2006 to 2007 and 20,422 from 2007 to 2008. Diagnostic profile: gallstone related 57.3%; cancer 12.6%; gallstone and cancer 2%; others 28.1%. All-cause 30-day death was 5.3% (2.4% in non-cancer cases). Predictors of 30-day death (adjusted odds ratio [OR]) were as follows: age (OR 6.2, for ≥85 years vs55 years), male sex (OR 1.2 vs female), emergency admission (OR 2.0 vs elective), cancer (OR 8.6 vs no cancer), and non-cancer comorbidity (OR 1.5 vs none). A mortality risk estimator (look-up table) based on pooled data for40,000 first ERCPs is provided. Specific procedural complication codes were identified in 1.2% of deaths (0.06% of ERCPs). At the institutional level, analysis of mortality rates was within expected statistical funnel limits, and we found no correlation with ERCP volume (Pearson r = -0.05; P.05).The completeness and accuracy of coding may vary between different hospitals. Routine coding does not capture information about procedural complexity or severity of illness.Linkage analysis of hospital episode statistics data for England provides a powerful tool for studying mortality risk after ERCP on an unselected and truly nationwide scale. Institutional-level statistics suggest that the mortality risk for patients requiring ERCP was comparable across English hospitals.

To perform a cost-utility analysis of a new formulation of mesalazine (Mezavant XL, MMX mesalazine) versus an existing oral mesalazine (Asacol; mesalazine) from the UK National Health Service perspective.A 5-year Markov cohort model was developed. Costs were obtained from the literature and utilities from an independent study. Uncertainty was evaluated using one-way and probabilistic sensitivity analyses (PSA). The potential effect of dosing frequency on adherence and possible long-term effects of remission maintenance on colorectal cancer (CRC) rates were also investigated.The model suggested that 5-year therapy with MMX mesalazine was likely to generate gains when compared with mesalazine, including a gain of 0.011 QALYs per patient, 19 more remission days, and 12% fewer hospitalizations and surgical episodes. These gains came at an increase in total NHS direct cost of £8, resulting in an incremental cost-effectiveness ratio (ICER) of £749. The PSA suggested that MMX mesalazine had a 62% chance of resulting in cost savings, and a 74% chance of being cost-effective (£20,000 threshold). Extended analysis including adherence and CRC effects suggested further incremental benefit of MMX mesalazine over mesalazine could be expected. Limitations include uncertainty in extrapolation to a 5-year time horizon and impact of adherence and drug acquisition costs on outcomes.The pharmacoeconomic analysis suggested that MMX mesalazine is likely to produce small, but worthwhile, increases in total NHS direct cost while increasing time in remission and associated quality of life, when compared with mesalazine. Advantages in adherence to treatment with MMX mesalazine relative to mesalazine suggested that further health gains and cost savings can be obtained. Overall, these results suggest that MMX mesalazine is a cost-effective treatment for UC.

Summary Background Anti-TNF-alpha agents for Crohn's disease (CD) have good clinical efficacy but high acquisition cost compared to rival drugs. Aim To assess the cost-effectiveness of infliximab and adalimumab for Crohn’s disease from the perspective of the UK NHS, incorporating recent trial and observational data. Methods Lifetime Markov analyses constructed to simulate quality-adjusted life-years (QALYs) and costs. CD was represented by four health-states representing: Full response, partial response, nonresponse, surgery and death. The course of CD under standard care was based on the Olmsted county cohort. Systematic review identified ACCENT I (infliximab) and CHARM (adalimumab) as sources for efficacy data. We modelled an intention-to-treat strategy for biologics including surgical rates based on observational data, cost estimates from our UK dataset and utilities from an algorithm converting CDAI to EQ-5D utilities. Results The incremental cost-effectiveness ratios (ICERs) compared to standard care for 1-year of treatment with infliximab or adalimumab were £19 050 and £7190 per QALY gained, respectively. Lifetime therapy was dominated by standard care. Analyses over shorter time horizons, matched to treatment duration, resulted in unfavourable ICERs. Conclusion The model suggests acceptable ICERs for biological agents when considering a lifetime horizon with periods of up to 4 years continuous therapy. As with all economic evaluations, the results may not be generalizable beyond the perspective of analysis.

Introduction Although the literature surrounding sedation practice and endoscopic outcomes remains sparse and controversial, there have been a number of stringent guidelines issued regarding sedation use in endoscopy. Aims To assess the impact of changes to enhance safer sedation practice on endoscopic outcomes. Methods Sedation practice was audited in 7234 consecutive gastrointestinal endoscopic procedures in 2004 and protocols for enhancing safer sedation practice were introduced. These included; introduction of a unit sedation policy, exchange of midazolam 10 mg vials to 5 mg repacked syringes, adverse events recording of midazolam use of greater than 5 mg and reversal agents, more stringent patient monitoring procedures and endoscopists education and feedback. A reaudit of 7071 procedures was performed in 2006. Outcomes audited the included midazolam doses, patient intolerance, 30-day postprocedure mortality, reversal agent use and total adverse events. Results Sedation doses were reduced substantially after intervention [mean midazolam dose (SD): 4.9 mg (2.5) in 2004 vs. 2.9 mg (1.2) in 2006; P

Summary Background Mesalazine (mesalamine) is standard first line treatment for moderately active ulcerative colitis (UC). Recently, doubling the mesalazine dose (Asacol 4.8 g/day) was shown to improve efficacy with no increase in adverse events. The cost-effectiveness of this strategy remains unknown. Aim To assess the cost-utility of high dose (HD) mesalazine (Asacol 4.8 g/day) compared with standard dose (SD) mesalazine (Asacol 2.4 g/day) as first line treatment for moderately active UC. Methods The costs and benefits associated with a treatment pathway beginning with HD or SD mesalazine were determined over 12 weeks using a decision tree analytical model. Results A 12-week treatment pathway starting with HD mesalazine cost an average of £2382 per patient compared with £2474 for SD mesalazine and generated 0.0016 more quality adjusted life years (QALYs). HD mesalazine dominated SD mesalazine, being both more effective and less costly. HD mesalazine treatment resulted in fewer patients requiring surgery or hospitalization for intensive pharmacological treatment. Probabilistic sensitivity analysis indicated a 72% chance that HD mesalazine was cost effective, based on a cost/QALY threshold of £30 000. Conclusions This study suggests that HD mesalazine represents a cost-effective alternative to SD mesalazine for moderately active UC, while potentially reducing the need for hospitalization.

Background: Matrix metalloproteinases (MMPs) have roles in inflammation and other processes relevant to the architectural disturbances seen in the gastric mucosa in response to Helicobacter pylori infection. Upregulation of MMPs has been reported in H pylori infection, but there are no detailed reports regarding altered production of their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Aims: To investigate changes in the abundance of TIMPs in human gastric corpus mucosa and murine stomach in Helicobacter infection, and to study cellular sources in man. Methods: Gastric corpus biopsy samples were assessed for abundance of mRNA or protein for TIMP-1 to -4 by real-time quantitative PCR or western blotting, respectively. Antral and corpus biopsies were processed for histology, H pylori status and inflammatory scoring. Cellular sources of TIMP-1, -3 and -4 were examined by indirect immunohistochemistry. Circulating gastrin was measured by radioimmunoassay. Also, abundance of TIMP-1, -3 and -4 mRNA in the stomach of Helicobacter felis infected mice post-infection was compared with that of uninfected control animals. Results: Compared with uninfected patients, mRNA and protein for TIMP-1, -3 and -4 were significantly more abundant in the gastric corpus of H pylori infected subjects. Gastric TIMP expression did not differ significantly between hyper- and normogastrinaemic subjects within the H pylori negative and positive groups. There was no difference in mRNA abundance for MMP-3 or -8. Immunohistochemistry showed TIMP proteins localised to gastric epithelial, stromal cells and inflammatory cells. Murine H felis infection was associated with upregulation of TIMP-1 and -3 mRNA. Conclusions: Helicobacter infection is associated with upregulation of specific TIMPs (TIMP-1 and -3) in glandular epithelium and stroma. It is suggested that increased expression of specific protease inhibitors in the corpus mucosa may exert important effects on extracellular matrix remodelling and influence the outcome of H pylori infection.

Healthcare metrics have been used to drive improvement in outcome and delivery in UK hospital stroke and cardiac care. This model is attractive for chronic obstructive pulmonary disease (COPD) care because of disease frequency and the burden it places on primary, secondary and integrated care services.Using 'hospital episode statistics' (UK 'coding'), we examined hospital 'bed days/1000 population' in 150 UK Primary Care Trusts (PCTs) during 2006-07 and 2007-08. Data were adjusted for COPD prevalence. We looked at year-on-year consistency and factors which influenced variation.There were 248 996 COPD admissions during 2006-08. 'Bed days/1000 PCT population' was consistent between years (r = 0.87; P0.001). There was a2-fold difference in bed days between the best and worst performing PCTs which was primarily a consequence of variation in emergency admission rate (P0.001) and proportion of emergency admissions due to COPD (P0.001) and to only a lesser extent length of hospital stay (P0.001).Bed days/1000 population appears a useful annual metric of COPD care quality. Good COPD care keeps patients active and out of hospital and requires co-ordinated action from both hospital and community services, with an important role for integrated care. This metric demonstrates that current care is highly variable and offers a measurable target to commission against.

Background & Aims: Interactions between epithelial and stromal cells are important determinants of mucosal organization, but the signaling mechanisms are understood incompletely. Matrix metalloproteinase (MMP)-7 is produced uniquely in epithelia, may act on growth factors and matrix proteins, and in the stomach is increased with Helicobacter pylori infection. We have studied the role of MMP-7 in signaling between epithelial cells and a key stromal cell type, the myofibroblast. Methods: Immunohistochemistry and Western blotting were applied to gastric corpus biopsy specimens; primary cultures of human gastric glands and myofibroblasts were used to study the role of MMP-7 in regulating proliferation and migration of the latter, and MMP-7 substrates were identified by proteomic methods. Results: Increased abundance of the myofibroblast marker α-smooth muscle actin was identified in H pylori –positive biopsy specimens. Media from H pylori –infected gastric epithelial cultures stimulated proliferation and migration of primary human gastric myofibroblasts and antisense oligonucleotide treatment indicated a role for MMP-7. Proteomic methods identified insulin-like growth factor binding protein (IGFBP)-5 as a substrate for MMP-7 in medium from gastric myofibroblasts. Knockdown of IGFBP-5 by small interfering RNA or immunoneutralization of IGF-II, abolished myofibroblast responses to MMP-7. Proliferation of gastric epithelial cells also was stimulated by MMP-7–treated myofibroblasts via IGF-II. Conclusions: MMP-7 acts as an epithelial-derived signal increasing the bioavailability of IGF-II released from myofibroblasts. Because IGF-II acts on both stromal and epithelial cells, the findings suggest that increased MMP-7 expression contributes to redefining the niche occupied by dividing cells and leading to hyperproliferation in H pylori infection.

Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose beta1, 3 N-acetylgalactosamine alpha-), among the same IBD twins.Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor kappaB (NFkappaB) activation with investigators blinded to the diagnosis.Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFkappaB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFkappaB.Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFkappaB activation.

Aims: (i) To determine the value of individual alarm features for predicting cancer in subjects referred to a rapid access upper gastrointestinal cancer service; and (ii) to develop a clinical prediction model for cancer and to prospectively validate this model in a further patient cohort. Methods: Patient demographics, referral indications, and subsequent diagnosis were recorded prospectively. Logistic regression analyses were employed to determine the predictive value of individual alarm features in an evaluation cohort of 1852 consecutive cases. The potential impact of applying a modified set of referral criteria was then examined in a validation cohort of 1785 patients. Results: Evaluation cohort: mean age was 59 years; cancer prevalence 3.8%; and serious benign pathology 12.8%. Dysphagia (odds ratio (OR) 3.1), weight loss (OR 2.6), and age >55 years (OR 9.5) were found to be significant predictive factors for cancer but the value of other accepted alarm features was more limited. In particular, uncomplicated dyspepsia in those over 55 years was a negative predictive factor for cancer within this high risk cohort (OR 0.1). Validation cohort: the clinical prediction model would have selected 92% of cancer patients for fast track investigation while reducing the “two week rule” workload by 572 cases (31%). Conclusions: Fast track endoscopy in subjects fulfilling current criteria for suspected upper gastrointestinal malignancy results in a significant yield of cancer (∼4%) and serious benign diseases such as peptic ulceration, strictures, and severe oesophagitis (13%). However, the predictive value of individual features for cancer varies widely. Uncomplicated dyspepsia in older subjects was a poor predictor of cancer. Application of narrower referral criteria for accessing fast track services may reduce pressures while retaining high sensitivity for cancer.

Crohn's disease is a chronic inflammatory bowel disease of unknown aetiology which affects around 35,000 people in the UK (population 56.8 million). The potential for onset in early adult life, disease chronicity and a need for hospitalisation and surgery mean that the disease can be associated with substantial healthcare costs. Cost-of-illness studies focusing on direct medical costs have identified that over half the average costs associated with the disease relate to hospital costs. Estimates of the contribution of drug costs to the total direct economic burden have varied between 4.6 and 25%. Figures for average annual direct costs per patient in the US have been put at between US dollars 6561 (1990 values) and US dollars 12,417 (1994 values), whereas European studies have given much lower cost estimates (US dollars 655, 1994 values). However, all studies have highlighted that much of the total cost of illness relates to extensive interventions required by a small proportion of severely affected individuals. Indirect costs associated with reduced productivity in Crohn's disease can be high, with long periods of absenteeism and early disability. However, most patients (90%) remain in the workforce and life expectancy is relatively normal. A variety of drugs are employed for the treatment of Crohn's disease, both in an attempt to induce clinical remission in active disease and to maintain remission once this has been achieved. Comparative data on cost effectiveness is lacking, though crude estimates based on randomised trials suggest that the frequently prescribed aminosalicylates, which have only modest efficacy, are a relatively costly drug option. The costs associated with adverse drug effects, particularly for corticosteroids, have not been formally quantified. Despite high costs, new drug therapies for more severe disease, such as anti-tumour necrosis factor (TNF-alpha) antibodies, may prove a cost-effective option if the need for hospitalisation is reduced. In a modelling exercise, a US group estimated that if a theoretical new drug was introduced which was capable of reducing non-drug costs (including hospitalisation) by a fifth despite doubling the overall drugs bill, there would still be a reduction in the overall costs of Crohn's disease by 13%. Although surgical therapy is costly, there may be prolonged post-surgical remission following resection of localised disease and early surgery may represent a cost-effective option for selected patients. Without formal cost-effectiveness analyses, or (better still) clinical trials incorporating cost data, decisions about the relative efficiency of treatment alternatives for Crohn's disease remain subjective and more research is clearly required in this area.

Background. It has long been recognised that specific patterns of gastritis are linked with different gastroduodenal diseases and that serum pepsinogens vary with the histological state of the gastric mucosa. With the discovery of the role of Helicobacter pylori in chronic gastritis and the availability of noninvasive tests for H. pylori infection, individuals with H. pylori gastritis can now be identified without endoscopic biopsy. However, without a knowledge of the pattern and severity of gastritis it is impossible to predict the likelihood of significant associated gastroduodenal pathology. Aims. The aim of this study was to evaluate the diagnostic potential of serum pepsinogens I and II in predicting the topography and severity of gastritis in H. pylori-infected dyspeptic patients attending for endoscopy. Methods. Fasting serum was obtained from consecutive dyspeptic patients attending for endoscopy, and pairs of gastric biopsies obtained from the mid-body and antrum. Gastritis was graded according to the Sydney System, and serum pepsinogen levels determined by radio-immunoassay. Results. Sixty-nine dyspeptic patients were studied (mean age: 49.6 years) of whom 34 had H. pylori-associated chronic gastritis (Hp-gastritis) – antral predominant gastritis (APG) in 41.2%, pangastritis (PAN) in 52.9%, and corpus predominant (CPG) in 5.9%. Serum pepsinogen II levels were significantly higher, and the serum pepsinogen I : II ratio significantly lower, in the H. pylori positive group than in other groups. Within the Hp-gastritis group, there was a step-wise decrease in serum pepsinogen I levels with progression from APG through PAN to CPG pattern (a cut-off value of ≥ 100 ng/ml would have identified APG with a positive predictive value of 77%, though with low sensitivity). Within the Hp-gastritis group, serum pepsinogen I and II levels were correlated with antral chronic inflammation score and serum pepsinogen II levels also with antral activity score. Serum pepsinogen I and the pepsinogen I : II ratio were lowest in severe gastric corpus atrophy. Conclusion. In dyspeptic patients known to be infected with H. pylori, serum pepsinogen values provide an assessment of the overall topography of gastritis, the severity of antral inflammation and the presence of severe corpus atrophy.