Recent Submissions

  • Advance care planning in end-stage cirrhosis in a UK district general hospital.

    Poon, Dennis; Dunn, Lauren (Future Healthcare Journal, 2023-11)
    Advance care planning (ACP) has been shown to improve health-related quality of life (QoL) for patients with advanced liver disease and their caretakers.1,2 It is increasingly recognised that ACP alongside palliative input should be initiated in these patients early to help to address their needs as their disease progresses and facilitate completion of advance directives via discussion between healthcare professionals, patients and their carers.2 This study assessed the local practice of implementing ACP in patients with end-stage cirrhosis against international recommendations. We also explored quality of life (QoL), depression score, religious belief and spiritual needs in these patients using questionnaires. The findings of the study provide a better insight of our local patient cohort with advanced cirrhosis and allow us to improve our approach in delivering ACP to these patients.
  • Can an educational video improve the adequacy of bowel preparation for patients undergoing their first colonoscopy? Results of the EBOPS RCT.

    Foley, Stephen (Endoscopy International Open, 2024-03)
    Background and study aims The aim of this study was to assess the effect of an educational video on the quality of bowel preparation of patients from a UK population attending for their first colonoscopy. Patients and methods A prospective, endoscopist-blinded trial with 1:1 allocation was performed. Patients referred for their first colonoscopy were recruited between February 2019 and December 2019. All participants were prescribed Moviprep and received the trial site’s standard written bowel preparation instructions, with the intervention group also receiving a bespoke educational video. Adequacy of bowel preparation (defined as a Boston Bowel Preparation Scale of ≥2 in each segment of the bowel) and polyp detection rates (PDRs) were compared. Fisher’s chi squared test was utilized with P <0.05 as the threshold for significance. Results A total of 509 participants completed the trial from six centers; 251 were randomized to the intervention group. The mean age was 57 years and 52.3% were female. The primary endpoint was met with an adequacy rate of 216 of 251 (86.1%) in the intervention group, compared with 205 of 259 (79.1%) in the control group ( P <0.05, odds ratio [OR] 1.626, 95% CI 1.017–2.614). The PDR was significantly higher in the intervention group (39% vs 30%, OR 1.51, 95% CI 1.04–2.19, P <0.05). Conclusions An educational video leads to improved bowel preparation for patients attending for their first colonoscopy, and is also associated with greater detection of polyps. Widespread adoption of an educational video incurs minimal investment, but would reduce the number of inadequate procedures, missed pathology, and the cost that both these incur.
  • Budget Impact of RefluxStopTM as a Treatment for Patients with Refractory Gastro-oesophageal Reflux Disease in the United Kingdom

    Gemmill, Elizabeth (Journal of Health Economics and Outcomes Research, 2024-01)
    Background: Gastro-oesophageal reflux disease (GORD) is a common condition associated with heartburn and regurgitation. Standard of care for GORD patients in the UK involves initial treatment with proton pump inhibitors (PPIs) and laparoscopic antireflux surgery in patients unwilling to continue or intolerant of long-term PPI treatment. Recently, RefluxStop™, a novel, implantable medical device, has proven to be an efficacious and cost-effective treatment for patients with GORD. The current analysis aimed to describe the budget impact of introducing RefluxStop™ within National Health Service (NHS) England and Wales. Objectives: To estimate the more immediate, short-term clinical and economic effects of introducing RefluxStop™ as a therapeutic option for patients with GORD treated within NHS England and Wales. Methods: A model adherent to international best practice guidelines was developed to estimate the budget impact of introducing RefluxStop™ over a 5-year time horizon, from an NHS perspective. Two hypothetical scenarios were considered, one without RefluxStop™ (comprising PPI treatment, laparoscopic Nissen fundoplication, and magnetic sphincter augmentation using the LINX® system) and one with RefluxStop™ (adding RefluxStop™ to the aforementioned treatment options). Clinical benefits and costs associated with each intervention were included in the analysis. Results: Over 5 years, introducing RefluxStop™ allowed the avoidance of 347 surgical failures, 39 reoperations, and 239 endoscopic esophageal dilations. The financial impact of introducing RefluxStop™ was £3 029 702 in year 5, corresponding to a 1.68% increase in annual NHS spending on GORD treatment in England and Wales. Discussion: While the time horizon was too short to capture some of the adverse events of PPIs and complications of GORD, such as the development of Barrett’s esophagus or esophageal cancer, the use of RefluxStop™ was associated with a substantial reduction in surgical complications, including surgical failures, reoperations, and endoscopic esophageal dilations. This favorable clinical profile resulted in cost offsets for the NHS and contributed to the marginal budget impact of RefluxStop™ estimated in the current analysis. Conclusions: Introducing RefluxStop™ as a treatment option for patients with GORD in England and Wales may be associated with clinical benefits at the expense of a marginal budget impact on the NHS.
  • Cost-effectiveness of a novel, non-active implantable device as a treatment for refractory gastro-esophageal reflux disease.

    Gemmill, Liz (Journal of Medical Economics, 2023-01)
    Aims: Gastro-esophageal reflux disease (GERD) is a common, chronic gastrointestinal condition characterized by heartburn, chest pain, regurgitation, and bloating. The current standard of care includes chronic treatment with proton pump inhibitors (PPIs) or, in selected patients, laparoscopic anti-reflux surgery. RefluxStop is a novel implantable device indicated for GERD patients eligible for laparoscopic surgical treatment. The aim of this analysis was to assess the cost-effectiveness of RefluxStop against available treatment options for GERD. Material and methods: A Markov model was developed to assess the cost-effectiveness of RefluxStop compared with PPI-based medical management (MM) and two surgical management options, LNF and magnetic sphincter augmentation (MSA, LINX system), in people with GERD. Clinical outcomes and costs were estimated over a lifetime horizon from the UK National Health Service perspective and an annual discount rate of 3.5% was applied. Results: RefluxStop showed favorable surgical outcomes compared with both LNF and MSA. The base case incremental cost-effectiveness ratios compared with MM, LNF, and MSA were £4,156, £6,517, and £249 per QALY gained, respectively. At the UK cost-effectiveness threshold of £20,000 per QALY gained, the probability that RefluxStop was cost-effective against MM, LNF, and MSA was 100%, 93%, and 100%, respectively. Limitations: The model presented the results of a comparison, with evidence for RefluxStop derived from its single-arm CE mark trial and that for comparators from the literature. The varied clinical care pathway of individual GERD patients was necessarily simplified for modeling purposes, and necessary assumptions were made; however, the model results proved robust to sensitivity analyses. Conclusions: Introduction of RefluxStop was estimated to extend life expectancy and improve quality-of-life of GERD patients when compared with MM, LNF, and MSA. The results of the cost-effectiveness analysis demonstrated that RefluxStop is highly likely to be a cost-effective treatment option within NHS England.
  • Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study.

    Sagar, R; Jathana, N; Rothwell, L (BJA: British Journal of Anaesthesia, 2019-01)
    Background: Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods: This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results: Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51-19.97) than planned admissions (OR: 2.32, 95% CI: 1.43-3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8-51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions: After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies.
  • A colitis bundle initiative to improve the outcome of acute IBD colitis patients

    Bahrin, MHK; El Atrash, Malik Satea; Danish, Farheen; Ali, Ahmed
    Introduction Early detection and assessment of the severity are crucial in the management of an IBD flare-ups. This is so steroid therapy, the initial remission-inducing treatment can be administered at that right time. However, in those with severe colitis where steroid therapy is inadequate, often rescue therapy, either in the form of biologics or surgery is required. Simple measures during flare-ups would help to achieve this and potentially be life-saving. Methods This project aims to review the current performance against the IBD management NICE guideline and to introduce a trust-wide Colitis bundle to ensure junior doctors and consultants can make important decisions regarding colitis patient care. A retrospective audit was carried out on 40 In-patients with a diagnosis of an acute flare of ulcerative and Crohn’s colitis over the year 2021. A proforma was created based on the latest colitis management guidelines. This reviewed step-by-step management plans over the first 3 days period – which, if perfectly followed, will ensure deliverance of rescue therapy safely by day 3 or day 4. Results The results showed a delay in managing acute IBD flare-ups, in which the initial steroid therapy was given to only 82.8% and the VTE prophylaxis was commenced only on 65.7% of the cases. Recognition of colitis severity as defined by Truelove and Witt’s score was also poor as it happened in only 20% of the cases. This downplayed the urgency of acknowledging the need for an escalated treatment strategy, which subsequently resulted in a delay in pre-biologics screening test – this happened in 25.7% of cases only within the first 2 days of diagnosis. As this test was essential in those requiring rescue biologic therapies, this resulted in an overall delay in its initiation as demonstrated in Figure 1. Abstract P21 Figure 1 Time between the biologic therapy decision and its first dose administration Conclusions The quality improvement project has demonstrated poor recognition and assessment of acute IBD flare-ups as recommended by the NICE guideline. This subsequently led to a delay in initiation of the steroid therapy, pre-biologic screening test, and initiation of rescue biologic therapies in those with severe colitis. This is due to the lack of exposure among junior and senior doctors towards the guideline. As a response, a mass education at a Trust level for the doctors was recommended and a colitis bundle was constructed, which comprised of evidence-based action plans checklist divided into Day 1 to Day 3 to make sure that all the aspects are not missed.
  • Increased ERCP Volume Improves Cholangiogram Interpretation - A New Performance Measure for ERCP Training?

    Ahmad, Saqib
    Background/aims: Cholangiogram interpretation is not used as a key performance indicator (KPI) of endoscopic retrograde cholangiopancreatography (ERCP) training, and national societies recommend different minimum numbers per annum to maintain competence. This study aimed to determine the relationship between correct ERCP cholangiogram interpretation and experience. Methods: One hundred fifty ERCPists were surveyed to appropriately interpret ERCP cholangiographic findings. There were three groups of 50 participants each: "Trainees," "Consultants Group 1" (performed >75 ERCPs per year), and "Consultants Group 2" (performed >100 ERCPs per year). Results: Trainees was inferior to Consultants Groups 1 and 2 in identifying all findings except choledocholithiasis outside the intrahepatic duct on the initial or completion/occlusion cholangiogram. Consultants Group 1 was inferior to Consultants Group 2 in identifying Strasberg type A bile leaks (odd ratio [OR] 0.86, 95% confidence interval [CI] 0.77-0.96), Strasberg type B (OR 0.84, 95% CI 0.74-0.95), and Bismuth type 2 hilar strictures (OR 0.81, 95% CI 0.69-0.95). Conclusions: This investigation supports the notion that cholangiogram interpretation improves with increased annual ERCP case volumes. Thus, a higher annual volume of procedures performed may improve the ability to correctly interpret particularly difficult findings. Cholangiogram interpretation, in addition to bile duct cannulation, could be considered as another KPI of ERCP training.
  • An international genome-wide meta-analysis of primary biliary cholangitis: Novel risk loci and candidate drugs.

    Misra, Sharat (Journal of Hepatology, 2021-09)
    Backgrounds & aims: Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening. Methods: We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts. Results: We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders. Conclusions: This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders. Lay summary: Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
  • Clinicopathological Features and Outcomes of Gastrointestinal Stromal Tumours in Oman: A multi-centre study.

    Qureshi, A (Sultan Qaboos University Medical Journal, 2021-05)
    Objectives: This study aimed to report the clinicopathological features, management and long-term outcomes of patients with gastrointestinal stromal tumours (GISTs) in Oman. Methods: This retrospective study was conducted on patients treated for GIST between January 2003 and December 2017 at three tertiary referral centres in Muscat, Oman. All patients with confirmed histopathological diagnoses of GIST and followed-up at the centres during this period were included. Relevant information was retrieved from hospital records until April 2019. Results: A total of 44 patients were included in the study. The median age was 55.5 years and 56.8% were female. The most common primary site of disease was the stomach (63.6%) followed by the jejunum/ileum (18.2%). Two patients (4.5%) had c-Kit-negative, discovered on GIST-1-positive disease. A total of 24 patients (54.5%) presented with localised disease and eight (33.3%) were classified as being at high risk of relapse. Patients with metastatic disease received imatinib in a palliative setting, whereas those with completely resected disease in the intermediate and high-risk groups were treated with adjuvant imatinib. Of the six patients (13.6%) with progressive metastatic disease, of which four had mutations on exon 11 and one on exon 9, while one had wild-type disease. Overall, rates of progression-free survival and overall survival (OS) at 100 months were 77.4% and 80.4%, respectively. Rates of OS for patients with localised and metastatic disease were 89.9% and 80.2%, respectively. Conclusion: The presenting features and outcomes of patients with GISTs in Oman were comparable to those reported in the regional and international literature.
  • X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.

    Misra, Sharat (Gastroenterology, 2021-06)
    Background & Aims Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Results Single-marker association analyses found approximately 100 loci displaying P < 5 × 10–4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10–6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028–1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09–1.26; P = 9.93 × 10–8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10–9; OR, 1.33; 95% CI, 1.21–1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B, PQBP1, PIM2, SLC35A2, OTUD5, KCND1, and GRIPAP1, as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3, the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). Conclusions This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus.
  • Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma

    Jankowski, Janusz (Carcinogenisis, 2021-04)
    Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
  • The impact of reader fatigue on the accuracy of capsule endoscopy interpretation

    Shonde, Anthony; Lam, Ching; Mohammed, Nizamuddin; Baxter, Andrew (Digestive and Liver Disease, 2021-08)
    Background and aims: Capsule endoscopy (CE) interpretation requires the review of many thousands of images, with lesions often limited to just a few frames. In this study we aim to determine whether lesion detection declines according to the number of capsule videos read. Methods: 32 participants, 16 of which were novices (NR) and 16 experienced (ER) capsule readers took part in this prospective evaluation study. Participants read six capsule cases with a variety of lesions, in a randomly assigned order during a single sitting. Psychomotor Vigilance Tests and Fatigue Scores were recorded prior to commencing and then after every two capsules read. Changes in lesion detection and measures of fatigue were assessed across the duration of the study. Results: Mean agreement with the predefined lesions was 48.3% (SD:16.1), and 21.3% (SD:15.1) for the experienced and novice readers respectively. Lesion detection declined amongst experienced reader after the first study (p = 0.01), but remained stable after subsequent capsules read, while NR accuracy was unaffected by capsule numbers read. Objective measures of fatigue did not correlate with reading accuracy. Conclusion: This study demonstrates that reader accuracy declines after reading just one capsule study. Subjective and objective measures of fatigue were not sufficient to predict the onset of the effects of fatigue.
  • Attitudes to radiation safety and cholangiogram interpretation in endoscopic retrograde cholangiopancreatography (ERCP): A UK survey

    Ahmad, Saqib (Frontline Gastroenterology, 2021-12)
    Background Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) exposes staff and patients to potentially harmful ionizing radiation. We performed a UK survey to explore trainee and trainer attitudes to radiation protection and cholangiogram interpretation in ERCP. Methods An electronic 10-point survey was prospectively distributed to endoscopy unit leads, training programme directors between October and November 2019. Only UK-based ERCP trainees and trainers with hands-on procedural exposure were eligible for the survey. Results The survey was completed by 107 respondents (58 trainees and 49 trainers), with an estimated overall response rate of 46%. Overall, 49% of respondents were up to date with their radiation protection course, 38% were aware of European Basic safety standards directive (BSSD), 38% wore radiation protection goggles, and 40% were aware of the average radiation screening dose per ERCP procedure. Compared with trainers, trainees were less likely to routinely wear thyroid protection shields (76% vs 92%; p=0.028), have awareness of the BSSD (20% vs 49%; p=0.037) or know their average procedural radiation dosages (21% vs 63%; p<0.001). With regard to cholangiogram interpretation, only 26% had received formal training, with 97% of trainees expressing a desire for further training. Conclusion This survey highlights a relative complacency in safety attitudes to radiation protection during ERCP. These data provide impetus to improve training and quality assurance in radiation protection, which should be regarded as a mandatory safety aspect prior to commencing hands-on ERCP training.
  • Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway: a diagnostic accuracy study

    Foley, Stephen; NICE FIT Steering Group (2020-10)
    Objective: To assess whether a faecal immunochemical test (FIT) could be used to select patients with suspected colorectal cancer (CRC) symptoms for urgent investigation. Design: Multicentre, double-blinded diagnostic accuracy study in 50 National Health Service (NHS) hospitals across England between October 2017 and December 2019. Patients referred to secondary care with suspected CRC symptoms meeting NHS England criteria for urgent 2 weeks wait referral and triaged to investigation with colonoscopy were invited to perform a quantitative FIT. The sensitivity of FIT for CRC, and effect of relevant variables on its diagnostic accuracy was assessed. Results: 9822 patients were included in the final analysis. The prevalence of CRC at colonoscopy was 3.3%. The FIT positivity decreased from 37.2% to 19.0% and 7.6%, respectively, at cut-offs of 2, 10 and 150 µg haemoglobin/g faeces (µg/g). The positive predictive values of FIT for CRC at these cut-offs were 8.7% (95% CI, 7.8% to 9.7%), 16.1% (95% CI 14.4% to 17.8%) and 31.1% (95% CI 27.8% to 34.6%), respectively, and the negative predictive values were 99.8% (95% CI 99.7% to 99.9%), 99.6% (95% CI 99.5% to 99.7%) and 98.9% (95% CI 98.7% to 99.1%), respectively. The sensitivity of FIT for CRC decreased at the same cut-offs from 97.0% (95% CI 94.5% to 98.5%) to 90.9% (95% CI 87.2% to 93.8%) and 70.8% (95% CI 65.6% to 75.7%), respectively, while the specificity increased from 64.9% (95% CI 63.9% to 65.8%) to 83.5% (95% CI 82.8% to 84.3%) and 94.6% (95% CI 94.1% to 95.0%), respectively. The area under the receiver operating characteristic curve was 0.93 (95% CI 0.92 to 0.95). Conclusion: FIT sensitivity is maximised to 97.0% at the lowest cut-off (2 µg/g); a negative FIT result at this cut-off can effectively rule out CRC and a positive FIT result is better than symptoms to select patients for urgent investigations.
  • Shared genetic etiology of obesity-related traits and Barrett's esophagus/adenocarcinoma: Insights from genome-wide association studies.

    Jankowski, Janusz (2020-02)
    Background: Obesity is a major risk factor for esophageal adenocarcinoma (EA) and its precursor Barrett's esophagus (BE). Research suggests that individuals with high genetic risk to obesity have a higher BE/EA risk. To facilitate understanding of biological factors that lead to progression from BE to EA, the present study investigated the shared genetic background of BE/EA and obesity-related traits. Methods: Cross-trait linkage disequilibrium score regression was applied to summary statistics from genome-wide association meta-analyses on BE/EA and on obesity traits. Body mass index (BMI) was used as a proxy for general obesity, and waist-to-hip ratio (WHR) for abdominal obesity. For single marker analyses, all genome-wide significant risk alleles for BMI and WHR were compared with summary statistics of the BE/EA meta-analyses. Results: Sex-combined analyses revealed a significant genetic correlation between BMI and BE/EA ( r g = 0.13, P = 2 × 10 -04 ) and a r g of 0.12 between WHR and BE/EA ( P = 1 × 10 -02 ). Sex-specific analyses revealed a pronounced genetic correlation between BMI and EA in females ( r g = 0.17, P = 1.2 × 10 -03 ), and WHR and EA in males ( r g = 0.18, P = 1.51 × 10 -02 ). On the single marker level, significant enrichment of concordant effects was observed for BMI and BE/EA risk variants ( P = 8.45 × 10 -03 ) and WHR and BE/EA risk variants ( P = 2 × 10 -02 ). Conclusions: Our study provides evidence for sex-specific genetic correlations that might reflect specific biological mecha-nisms. The data demonstrate that shared genetic factors are particularly relevant in progression from BE to EA. Impact: Our study quantifies the genetic correlation between BE/EA and obesity. Further research is now warranted to elucidate these effects and to understand the shared pathophysiology.
  • Gastroesophageal reflux disease and Barrett esophagus: an overview of evidence-based guidelines.

    Jankowski, Janusz (2019-08)
    Gastroesophageal reflux disease is an extremely common condition worldwide, with the published prevalence rates varying from 2.5% in China to 51.2% in Greece. Its economic and morbidity burden is vast, and optimizing care for this condition carries huge financial and patient‑related benefits. The disease can be complicated by progression to Barrett esophagus (BE), a precancerous condition that affects approximately 2% of the population and remains undiagnosed in many individuals. The National Institute of Clinical Excellence has produced guidelines on cost‑effective management of gastroesophageal reflux disease in patients in the United Kingdom, and the Benign Barrett's and Cancer Taskforce consensus was the largest international review of evidence known on the management of benign BE complications. This paper is a review of these guidelines with updates on new evidence. Areas for future development involve risk‑stratifying patients to surveillance, chemoprevention agents, and genetic biomarkers to help decide who will be at highest risk of malignant progression. Evidence supports the safety of proton pump inhibitors for symptom control in the medium term (ie, 9 years) and reducing the risk of progression of BE, while surgical options are cost‑effective treatments for certain patients. Barrett esophagus surveillance should be directed towards high‑risk groups, while those at lower risk may benefit from chemoprevention strategies.
  • Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands UK - a retrospective observational study.

    Foley, Stephen; Alam, Mohammad Aftab (2020-07-11)
    Purpose: Clinical trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn's disease (CD). Further real-world data is needed to inform clinical practice. The primary outcome was to assess corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers, concomitant drug use, endoscopic remission, surgical intervention, hospital admissions and adverse events. Materials and methods: A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across seven UK hospitals 1/11/14-30/11/16. Clinical disease activity was assessed using the partial Mayo Scores (pMS) and Harvey Bradshaw Index (HBI). Clinical remission was defined as HBI ≤4 or pMS <2 with a combined stool frequency and rectal bleeding sub score of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. Results: One hundred ninety-two patients were included in the final analysis. 45% of UC and 10% of CD patients were anti-TNF naive. Over the observation period corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Time to corticosteroid free remission for UC and CD was 17.6 [IQR: 8.7-29.6] and 14.1 [QR: 6.0-21.7] weeks, respectively. Time to clinical response for UC was 9.4 [IQR: 5.7-15.4] and CD was 9.5 [IQR: 6.1-18.2] weeks. There was a substantial decrease in the concomitant use of immunomodulators and a similar decrease in concomitant corticosteroid use over the study period. Conclusions: Results in this predominately anti-TNF experienced population mirror other published real-world data, demonstrating good clinical effectiveness and a comparable safety profile.
  • P671 Experiences of using vedolizumab in the treatment of inflammatory bowel disease in the East Midlands: a retrospective observational study.

    Foley, Stephen (2019-03)
    Randomised controlled trials have demonstrated efficacy of vedolizumab in ulcerative colitis (UC) and Crohn’s disease (CD). Its use is increasing and data in the real-world setting is needed to inform future practice.A multi-centre retrospective observational study was conducted with patients initiated on vedolizumab across 7 UK hospitals between 1/11/14–30/11/16. The Health Research Authority approved the protocol (19/HRA/0008). Clinical disease activity was assessed at baseline, Week 14, 30 and 52 using the Harvey–Bradshaw Index (HBI) and partial Mayo Score (pMS). Clinical remission was defined as HBI ≤ 4 or pMS &lt; 2 with a combined stool frequency and rectal bleeding subscore of ≤1. Clinical response was defined as ≥2 point decrease from baseline in pMS and ≥3 point decrease from baseline in HBI. The primary aim of this study was to describe corticosteroid-free and clinical remission after vedolizumab initiation. Secondary outcomes included effect on disease activity scores, biochemical markers (C-reactive protein (CRP) and faecal calprotectin (FCP), concomitant drug use, mucosal healing, surgical intervention, hospital admissions and adverse effects.192 patients were included in the final analysis: 99 CD, 88 UC and 5 IBD unclassified (grouped with CD in this analysis). Forty-five per cent of UC and 10% of CD patients were anti-TNF naïve. Immunomodulator and corticosteroid use at baseline for UC and CD was 41%, 49%, 27% and 27%, respectively. The median age at exposure was 44 (range 18–79) years; 49% male and median BMI was 25.7 (range 15.3–44.6). Median exposure to vedolizumab was 38.4 (IQR 23.6–58.9) for UC and 31.0 (IQR 21.6–52.5) weeks for CD. Corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44%, respectively. Clinical response rate for UC was 49% and CD was 53%. The median time to corticosteroid-free remission for UC and CD was 17.6 (IQR 8.7–29.6) and 15.7 (IQR 6.0–21.7) weeks and clinical remission was 15.1 (IQR 7.4–24.9) and 10.1 (IQR 3.1–21.0) weeks, respectively. Time to clinical response for UC was 9.4 (IQR 5.3–16.4) and CD was 9.5 (IQR 6.1–18.2) weeks. Median disease activity scores decreased from baseline to 14 weeks: pMS 5 (IQR 0–9) vs. 3 (IQR 0–9), HBI 7(IQR 0–15) vs. 5 (IQR 1–14). CRP and FCP normalisation occurred by 52 weeks in CD and 14 weeks in UC. The overall rate of IBD-related hospital admissions per patient per year was 1.3 (0–18). Adverse events were reported in 6% of patients.Results in our vedolizumab patient population, predominately anti-TNF experienced, mirror other published real-world data and demonstrate very good clinical effectiveness and comparable safety profile. Takeda UK Ltd. sponsored this study.
  • Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study.

    Watson, Nicholas; STARSurg Collaborative (2017-01)
    Background: Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods: Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien-Dindo classification (Clavien-Dindo III-V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results: From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60-1.34, p = 0.560). Conclusions: Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery.

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