Recent Submissions

  • The outcomes of emergency hospital admissions with non-malignant upper gastrointestinal bleeding in England between 2003 and 2015

    Rees, James; Evison, Felicity; Mytton, Jemma; Patel, Prashant; Trudgill, Nigel; Trudgill, Nigel; Sandwell West Birmingham NHS Trust; Medical and Dental; Sandwell and West Birmingham NHS Trust; Worcestershire Acute Hospitals NHS Trust; University Hospital Birmingham NHS Foundation Trust (Georg Thieme Verlag KGThieme Gruppe, 2021-02-18)
    Background: Upper gastrointestinal bleeding (UGIB) is a common medical emergency with significant mortality. Despite developments in endoscopic and clinical management, only minor improvements in outcomes have been reported. Methods: This was a retrospective cohort study of patients with non-malignant UGIB emergency admissions in England between 2003 and 2015, using Hospital Episode Statistics. Multilevel logistic regression analysis examined the associations with mortality. Results: 242 796 patients with an UGIB admission were identified (58.8 % men; median age 70 [interquartile range (IQR) 53 - 81]). Between 2003 and 2015, falls occurred in both 30-day mortality (7.5 % to 7.0 %; P < 0.001) and age-standardized mortality (odds ratio (OR) 0.74, 95 % confidence interval [CI] 0.69 - 0.80; P < 0.001), including from variceal bleeding (OR 0.63, 95 %CI 0.45 - 0.87; P < 0.005). Increasing co-morbidity (Charlson score > 5, OR 2.94, 95 %CI 2.85 - 3.04; P < 0.001), older age (> 83 years, OR 6.50, 95 %CI 6.09 - 6.94; P < 0.001), variceal bleeding (OR 2.03, 95 %CI 1.89 - 2.18; P < 0.001), and a weekend admission (Sunday, OR 1.18, 95 %CI 1.12 - 1.23; P < 0.001) were associated with 30-day mortality. Of deaths at 30 days, 8.9 % were from ischemic heart disease (IHD) and the cardiovascular age-standardized mortality rate following UGIB was high (IHD deaths within 1 year, 1188.4 [95 %CI 1036.8 - 1353.8] per 100 000 men in 2003). Conclusions: Between 2003 and 2015, 30-day mortality among emergency admissions with non-malignant UGIB fell by 0.5 % to 7.0 %. Mortality was higher among UGIB admissions at the weekend, with important implications for service provision. Patients with UGIB had a much greater risk of subsequently dying from cardiovascular disease and addressing this risk is a key management step in UGIB.
  • The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease

    King, Dominic; Chandan, Joht Singh; Thomas, Tom; Nirantharakumar, Krishnarajah; Reulen, Raoul C; Adderley, Nicola J; Trudgill, Nigel; King, Dominic; Trudgill, Nigel; Sandwell and West Birmingham NHS Trust; et al. (Oxford University Press, 2021-01-09)
    Background: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet's syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM. Methods: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis. Results: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn's disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86). Conclusions: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN. Keywords: Crohn’s disease; Sweet’s syndrome; aphthous stomatitis; dermatological; erythema nodosum; extra intestinal manifestations; inflammatory bowel disease; psoriasis; pyoderma gangrenosum; ulcerative colitis.
  • The diagnostic accuracy of colon capsule endoscopy in Inflammatory bowel disease - a systematic review and meta-analysis

    Lei, Ian Io; Thorndal, Camilla; Manzoor, Muhammad Shoaib; Parsons, Nicholas; Noble, Charlie; Huhulea, Cristiana; Koulaouzidis, Anastasios; Arasaradnam, Ramesh P; Manzoor, Muhammad Shoaib; Gastroenterology; et al. (MDPI, 2024-09-16)
    Colon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of CCE for colonic inflammation, predominantly ulcerative colitis (UC) and Crohn's disease (CD). Methods: We systematically searched electronic databases (EMBASE, MEDLINE, PubMed Central, and Cochrane Library) for studies comparing the diagnostic accuracy between CCE and optical endoscopy as the standard reference. A bivariate random effect model was used for the meta-analysis. Results: From 3797 publications, 23 studies involving 1353 patients were included. Nine studies focused on UC, and ten focused on CD. For UC, CCE showed a pooled sensitivity of 92% (95% CI, 88-95%), a specificity of 71% (95% CI, 35-92%), and an AUC of 0.93 (95% CI, 0.89-0.97). For CD, the pooled sensitivity was 92% (95% CI, 89-95%), and the specificity was 88% (95% CI, 84-92%), with an AUC of 0.87 (95% CI, 0.76-0.98). Overall, for inflammatory bowel disease, the pooled sensitivity, specificity, and AUC were 90% (95% CI, 85-93%), 76% (95% CI, 56-90%), and 0.92 (95% CI, 0.94-0.97), respectively. Conclusions: Despite the challenges around standardised disease scoring and the lack of histological confirmation, CCE performs well in diagnosing inflammatory bowel disease. It demonstrates high sensitivity in both UC and Crohn's terminal ileitis and colitis and high specificity in Crohn's disease. Further studies are needed to evaluate the diagnostic accuracy of other colonic inflammatory conditions.
  • Impact of postoperative chemotherapy on survival for oesophagogastric adenocarcinoma after preoperative chemotherapy and surgery.

    Rahman, Saqib; Thomas, Betsan; Maynard, Nick; Park, Min Hae; Wahedally, Muhammad; Trudgill, Nigel; Crosby, Tom; Cromwell, David A; Underwood, Tim J; Trudgill, Nigel J.; et al. (Oxford University Press, 2022-02)
    Background: Perioperative chemotherapy is widely used in the treatment of oesophagogastric adenocarcinoma (OGAC) with a substantial survival benefit over surgery alone. However, the postoperative part of these regimens is given in less than half of patients, reflecting uncertainty among clinicians about its benefit and poor postoperative patient fitness. This study estimated the effect of postoperative chemotherapy after surgery for OGAC using a large population-based data set. Methods: Patients with adenocarcinoma of the oesophagus, gastro-oesophageal junction or stomach diagnosed between 2012 and 2018, who underwent preoperative chemotherapy followed by surgery, were identified from a national-level audit in England and Wales. Postoperative therapy was defined as the receipt of systemic chemotherapy within 90 days of surgery. The effectiveness of postoperative chemotherapy compared with observation was estimated using inverse propensity treatment weighting. Results: Postoperative chemotherapy was given to 1593 of 4139 patients (38.5 per cent) included in the study. Almost all patients received platinum-based triplet regimens (4004 patients, 96.7 per cent), with FLOT used in 3.3 per cent. Patients who received postoperative chemotherapy were younger, with a lower ASA grade, and were less likely to have surgical complications, with similar tumour characteristics. After weighting, the median survival time after postoperative chemotherapy was 62.7 months compared with 50.4 months without chemotherapy (hazard ratio 0.84, 95 per cent c.i. 0.77 to 0.94; P = 0.001). Conclusion: This study has shown that postoperative chemotherapy improves overall survival in patients with OGAC treated with preoperative chemotherapy and surgery.
  • Diagnostic yield from symptomatic gastroscopy in the UK : British Society of Gastroenterology analysis using data from the National Endoscopy Database

    Beaton, David Robert; Sharp, Linda; Lu, Liya; Trudgill, Nigel; Thoufeeq, Mo; Nicholson, Brian D; Rogers, Peter; Docherty, James; Jenkins, Anna; Morris, Allan John; et al. (BMJ Publishing Group, 2024-05-02)
    Objective: This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. Design: A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett's oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. Results: 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged <50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p<0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients <50).Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was <1%.The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p<0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms. Conclusions: Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was <1%, suggesting inefficient resource utilisation.
  • X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.

    Asselta, Rosanna; Paraboschi, Elvezia M; Gerussi, Alessio; Cordell, Heather J; Mells, George F; Sandford, Richard N; Jones, David E; Nakamura, Minoru; Ueno, Kazuko; Hitomi, Yuki; et al. (Elsevier, 2021-03-04)
    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).
  • The time to Inflammatory Bowel Disease diagnosis for patients presenting with abdominal symptoms in primary care and its association with emergency hospital admissions and surgery : a retrospective cohort study

    Umar, Nosheen; Harvey, Phil; Adderley, Nicola J; Haroon, Shamil; Trudgill, Nigel; Trudgill, Nigel; Umar, Nosheen; Gastroenterology; Medical and Dental; Sandwell and West Birmingham NHS Trust; University of Birmingham; Royal Wolverhampton NHS Trust; National Institute for Health and Care Research Birmingham Biomedical Research Centre (Oxford University Press, 2024-04-02)
    Background: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes. Methods: A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively. Results: Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 μg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11). Conclusion: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.
  • National Institute for Health and Care Excellence (NICE) guidance on monitoring and management of Barrett's oesophagus and stage I oesophageal adenocarcinoma

    di Pietro, Massimiliano; Trudgill, Nigel; Vasileiou, Melina; Longcroft-Wheaton, Gaius; Phillips, Alexander W; Gossage, James; Kaye, Philip V; Foley, Kieran G; Crosby, Tom; Nelson, Sophie; et al. (BMJ Publishing Group, 2024-03-29)
    Barrett's oesophagus is the only known precursor to oesophageal adenocarcinoma, a cancer with very poor prognosis. The main risk factors for Barrett's oesophagus are a history of gastro-oesophageal acid reflux symptoms and obesity. Men, smokers and those with a family history are also at increased risk. Progression from Barrett's oesophagus to cancer occurs via an intermediate stage, known as dysplasia. However, dysplasia and early cancer usually develop without any clinical signs, often in individuals whose symptoms are well controlled by acid suppressant medications; therefore, endoscopic surveillance is recommended to allow for early diagnosis and timely clinical intervention. Individuals with Barrett's oesophagus need to be fully informed about the implications of this diagnosis and the benefits and risks of monitoring strategies. Pharmacological treatments are recommended for control of symptoms, but not for chemoprevention. Dysplasia and stage 1 oesophageal adenocarcinoma have excellent prognoses, since they can be cured with endoscopic or surgical therapies. Endoscopic resection is the most accurate staging technique for early Barrett's-related oesophageal adenocarcinoma. Endoscopic ablation is effective and indicated to eradicate Barrett's oesophagus in patients with dysplasia. Future research should focus on improved accuracy for dysplasia detection via new technologies and providing more robust evidence to support pathways for follow-up and treatment.
  • An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugs.

    Cordell, Heather J; Fryett, James J; Ueno, Kazuko; Darlay, Rebecca; Aiba, Yoshihiro; Hitomi, Yuki; Kawashima, Minae; Nishida, Nao; Khor, Seik-Soon; Gervais, Olivier; et al. (Elsevier, 2021-05-23)
    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.
  • Gut microbiota in celiac disease

    Yemula, Nehal; Yemula, Nehal; General Medicine; Medical and Dental; Sandwell and West Birmingham NHS Trust (Hellenic Society of Gastroenterology, 2024-02-09)
    Celiac disease (CD) is an autoimmune gastrointestinal disease triggered by dietary gluten, occurring in genetically predisposed individuals. Currently, a gluten-free diet is the only current evidenced-based treatment for CD. With the growing prevalence of this condition worldwide, adjuvant therapies are needed. We understand that there are several factors that influence the pathogenesis of the condition. There is a complex interplay between genetics, environmental triggers, the immune system and gut microbiota. Recently, there has been a growing focus on the significance of gut microbiota in several autoimmune-based conditions. In particular, there has been much research involving the role of microbial flora and CD. Here, in this mini-review, we highlight the importance of gut microbiota and the symbiotic relationship with the host, introduce key factors that influence the development of the intestinal flora in early colonization, and ultimately explore its role in the pathogenesis of CD.
  • Variation in proliferative and cell cycle markers in Barrett's esophagus in relation to circumferential and axial location in the esophagus

    Umar, Nosheen; Alleyne, Lance; Cheung, Danny; Rees, James; Trudgill, Caitlin; Zanetto, Ulises; Muzaffar, Suhail; Trudgill, Nigel; Umar, Nosheen; Alleyne, Lance; et al. (Lippincott, Williams & Wilkins, 2024-01-22)
    Background: Adenocarcinoma in Barrett's esophagus (BE) occurs more frequently between 12 and 3 o'clock at the gastroesophageal junction (GEJ). Methods: BE patients were prospectively recruited from December 2013 to July 2016. Expression of p53, Ki-67, cyclin-D1, COX-2 and p21 was assessed in quadrantic biopsies from the proximal and distal margins of the BE segments. Cell cycle marker association with current or subsequent dysplasia or adenocarcinoma was examined. Results: 110 patients: median age 64 (IQR, 56-71) years; median BE segment length C4M6; and a median follow-up of 4.7 (IQR, 3.6-5.7) years. In total 13 (11.8%) had evidence of dysplasia or neoplasia (2.7% indefinite for dysplasia, 5.5% low grade, 1.8% high grade and 1.8% adenocarcinoma) at index endoscopy. Six (7%) developed dysplasia or neoplasia (1 low grade, 2 high grade and 3 adenocarcinoma) during follow-up. Ki-67 expression was highest at 3 o'clock, and overall was 49.6% higher in the 12-6 o'clock position compared to 6-12 o'clock [odds ratio (OR), 1.42 (95% confidence interval (CI), 1.00-2.12)]. A similar pattern was found with p21 [1.82 (1.00-3.47)]. There was increased expression of several markers in distal BE biopsies; cyclin-D1 [1.74 (1.29-2.34)]; Cyclo-oxygenase 2 [2.03 (1.48-2.78]) and p21 [2.06 (1.16-3.68)]. Expression of Ki-67 was lower in distal compared to proximal biopsies [0.58 (0.43-0.78)]. P53 expression had high specificity (93.8%) for subsequent low-grade dysplasia, high-grade dysplasia or adenocarcinoma. Conclusion: Increased cellular proliferation was seen at 12-6 o'clock at the GEJ. Cell-cycle marker expression was increased at the GEJ compared to the proximal BE segment. These findings mirror reflux esophagitis and suggest ongoing reflux contributes to the progression of dysplasia and malignancy in BE.
  • A Basic Intervention to Improve Compliance With Thromboprophylaxis in Patients With Neck of Femur Fracture.

    Gupta, Vinay; Gupta, Keshav Kumar; Sanghera, Ranjodh Singh; Gella, Sreenadh; Gupta, Vinay Kumar; Gupta, Keshav Kumar; Sanghera, Ranjodh Singh; Gella, Sreenadh; Gastroenterology; Ear, Nose and Throat; et al. (Ochsner Clinic Foundation, 2021)
    Background: Venous thromboembolism (VTE) is a significant complication following orthopedic intervention for neck of femur fracture. Our aim was to evaluate compliance with The National Institute for Health and Care Excellence guidance surrounding VTE prophylaxis before and after a brief intervention in an orthopedic department at a district general hospital. Methods: A 2-cycle quality improvement project was conducted. The primary outcome measure was whether adequate thromboprophylaxis was appropriately prescribed. For the intervention between the 2 cycles, posters were placed in key prescribing areas of all orthopedic wards. Results: In cycle 1, 63 (76.8%) patients were correctly prescribed enoxaparin, and 14 (17.1%) were prescribed other anticoagulants, leaving 5 patients (6.1%) who did not receive thromboprophylaxis for no apparent reason. In cycle 2, 56 (87.5%) patients were correctly prescribed enoxaparin, and the remaining patients were covered with alternative therapies. Conclusion: Small but basic interventions can lead to improvements in VTE prophylaxis prescribing. Future focus should be on implementing similar interventions across hospitals.
  • Complications of cholestasis : symptoms and extrahepatic manifestations

    Al-Shakhshir, Sarah; Trivedi, Palak J; Al-Shakhshir, Sarah; Gastroenterology; Medical and Dental; Sandwell and West Birmingham NHS Trust; Birmingham Biomedical Research Centre (Elsevier, 2023-06)
    Cholestasis is a state of impaired or reduced bile flow, resulting from intrahepatic disease, cholangiocellular disorders or large bile duct obstruction. Although disease-modifying treatments exist, not all provide the relief that patients seek. Pruritus and fatigue are the most commonly reported symptoms, and chronic cholestatic disorders can be complicated by hepatic osteodystrophy, dyslipidaemia and hypovitaminosis. Mechanistic insights into specific biological pathways have led to a revived interest in developing symptom-specific therapies, with a resurgence of clinical trial activity directed toward improving patients’ quality of life. However, with the exceptions of itch and metabolic bone disease, recommendations for managing the systemic complications of cholestasis currently lack an evidence base.
  • Complications of diagnostic upper Gastrointestinal endoscopy: common and rare - recognition, assessment and management.

    Waddingham, William; Kamran, Umair; Kumar, Bhaskar; Trudgill, Nigel; Tsiamoulos, Zacharias P; Banks, Matthew; Trudgill, Nigel; Kamran, Umair; Gastroenterology; Medical and Dental; University College London Hospitals NHS Foundation Trust; Sandwell and West Birmingham NHS Trust; Norfolk and Norwich University Hospitals NHS Foundation Trust; East Kent Hospitals NHS Trust (BMJ Publishing Group, 2022-12-09)
    A clear understanding of the potential complications or adverse events (AEs) of diagnostic endoscopy is an essential component of being an endoscopist. Creating a culture of safety and prevention of AEs should be part of routine endoscopy practice. Appropriate patient selection for procedures, informed consent, periprocedure risk assessments and a team approach, all contribute to reducing AEs. Early recognition, prompt management and transparent communication with patients are essential for the holistic and optimal management of AEs. In this review, we discuss the complications of diagnostic upper gastrointestinal endoscopy, including their recognition, treatment and prevention.
  • British Society of Gastroenterology (BSG) and British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) joint consensus guidelines on the diagnosis and management of eosinophilic oesophagitis in children and adults.

    Dhar, Anjan; Haboubi, Hasan N; Attwood, Stephen E; Auth, Marcus K H; Dunn, Jason M; Sweis, Rami; Morris, Danielle; Epstein, Jenny; Novelli, Marco R; Hunter, Hannah; et al. (BMJ Publishing Group, 2022-05-23)
    Background: Eosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE. Methods: The Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance. Results: Fifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research. Conclusions: These comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.
  • Venous Thromboembolism Following Discharge from Hospital in Patients Admitted for Inflammatory Bowel Disease.

    Harvey, Philip R; Coupland, Benjamin; Mytton, Jemma; de Silva, Shanika; Trudgill, Nigel J; Trudgill, Nigel J; Sandwell and West Birmingham NHS Trust; Medical and Dental; Royal Wolverhampton NHS Trust; University Hospital Birmingham NHS Foundation Trust; Dudley Group NHS Foundation Trust; Sandwell and West Birmingham NHS Trust (Oxford University Press, 2023-01)
    Background and aims: Patients admitted to hospital with inflammatory bowel disease[IBD] are at increased risk of venous thromboembolism[VTE]. This study aims to identify IBD patients at increased VTE risk on hospital discharge and to develop a risk scoring system to recognise them. Methods: Hospital episode statistics data were used to identify all patients admitted with IBD as an emergency or electively for surgery. All patients with VTE within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient- and admission-level factors associated with VTE. A scoring system to identify patients at higher risk for VTE was constructed. Results: A total of 201 779 admissions in 101 966 patients were included. The rate of VTE within 90 days was 17.2 per 1000 patient-years at risk and was highest in patients admitted as an emergency who underwent surgery[36.9]. VTE was associated with: female sex (odds ratio 0.65 [95% confidence interval 0.53-0.80], p <0.001); increasing age [49-60 years] (4.67 [3.36-6.49], p <0.001); increasing length of hospital stay [>10 days] (3.80 [2.80-5.15], p <0.001); more than two hospital admissions in previous 3 months (2.23 [1.60-3.10], p <0.001); ulcerative colitis (1.48 [1.21-1.82], p <0.001); and emergency admission including surgery (1.59 [1.12-2.27], p = 0.010); or emergency admission not including surgery (1.59 [1.08-2.35], p = 0.019) compared with elective surgery. A score >12 in the VTE scoring system gave a positive predictive value [PPV] of VTE of 1%. The area under the curve [AUC] was 0.714 [95% CI 0.70-0.73]. Conclusion: IBD patients admitted to hospital with a prolonged length of stay, increasing age, male sex, or as an emergency were at increased risk of VTE following discharge. Higher-risk patients were identifiable by a VTE risk scoring system. Keywords: Deep vein thrombosis; inflammatory bowel disease; pulmonary embolism.
  • UK-wide study of the opinions of gastroenterology trainees: COVID-19, Shape of Training and the future workforce.

    Raju, Suneil A; Harris, Rebecca; Cook, Charlotte; Harvey, Philip; Ratcliffe, Elizabeth; Harvey, Philip; Sandwell and West Birmingham NHS Trust; Medical and Dental; The University of Sheffield; Digestive Diseases Centre, NIHR Nottingham Biomedical Research Centre; Sandwell and West Birmingham NHS Trust (BMJ Publishing Group, 2021-12-20)
    Introduction: The COVID-19 pandemic has disrupted training. Gastroenterology higher specialty training is soon to be reduced from 5 years to 4. The British Society of Gastroenterology Trainees Section biennial survey aims to delineate the impact of COVID-19 on training and the opinions on changes to training. Methods: An electronic survey allowing for anonymised responses at the point of completion was distributed to all gastroenterology trainees from September to November 2020. Results: During the first wave of the COVID-19 pandemic, 71.0% of the respondents stated that more than 50% of their clinical time was mostly within general internal medicine. Trainees reported a significant impact on all aspects of their gastroenterology training due to lost training opportunities and increasing service commitments. During the first wave, 88.5% of the respondents reported no access to endoscopy training lists. Since this time, 66.2% of the respondents stated that their endoscopy training lists had restarted. This has resulted in fewer respondents achieving endoscopy accreditation. The COVID-19 pandemic has caused 42.2% of the respondents to consider extending their training to obtain the skills required to complete training. Furthermore, 10.0% of the respondents reported concerns of a delay to completion of training. The majority of respondents (84.2%) reported that they would not feel ready to be a consultant after 4 years of training. Conclusions: Reductions in all aspects of gastroenterology training were reported. This is mirrored in anticipated concerns about completion of training in a shorter training programme as proposed in the new curriculum. Work is now required to ensure training is restored following the pandemic.
  • UK endoscopy workload and workforce patterns: is there potential to increase capacity? A BSG analysis of the National Endoscopy Database.

    Beaton, David; Sharp, Linda; Trudgill, Nigel John; Thoufeeq, Mo; Nicholson, Brian D; Rogers, Peter; Docherty, James; Penman, Ian D; Rutter, Matt; Trudgill, Nigel J; et al. (BMJ Publishing Group, 2022-06-20)
    Background: The lack of comprehensive national data on endoscopy activity and workforce hampers strategic planning. The National Endoscopy Database (NED) provides a unique opportunity to address this in the UK. We evaluated NED to inform service planning, exploring opportunities to expand capacity to meet service demands. Design: Data on all procedures between 1 March 2019 and 29 February 2020 were extracted from NED. Endoscopy activity and endoscopist workforce were analysed. Results: 1 639 640 procedures were analysed (oesophagogastroduodenoscopy (OGD) 693 663, colonoscopy 586 464, flexible sigmoidoscopy 335 439 and endoscopic retrograde cholangiopancreatography 23 074) from 407 sites by 4990 endoscopists. 89% of procedures were performed in NHS sites. 17% took place each weekday, 10% on Saturdays and 6% on Sundays. Training procedures accounted for 6% of total activity, over 99% of which took place in NHS sites. Median patient age was younger in the independent sector (IS) (51 vs 60 years, p<0.001). 74% of endoscopists were male. Gastroenterologists and surgeons each comprised one-third of the endoscopist workforce; non-medical endoscopists (NMEs) comprised 12% yet undertook 23% of procedures. Approximately half of endoscopists performing OGD (52%) or colonoscopies (48%) did not meet minimum annual procedure numbers. Conclusion: This comprehensive analysis reveals endoscopy workload and workforce patterns for the first time across both the NHS and the IS in all four UK nations. Half of all endoscopists perform fewer than the recommended minimum annual procedure numbers: a national strategy to address this, along with expansion of the NME workforce, would increase endoscopy capacity, which could be used to exploit latent weekend capacity.
  • The association between inflammatory bowel disease and mental ill health: a retrospective cohort study using data from UK primary care.

    Umar, Nosheen; King, Dominic; Chandan, Joht Singh; Bhala, Neeraj; Nirantharakumar, Krish; Adderley, Nicola; Zemedikun, Dawit T; Harvey, Phil; Trudgill, Nigel; Umar, Nosheen; et al. (Wiley, 2022-06-30)
    Background: Patients with active inflammatory bowel disease (IBD) and mental illnesses experience worse IBD outcomes. Aim: To describe the incidence of mental illnesses, including deliberate self-harm, in IBD patients. Methods: A population-based retrospective cohort study using IQVIA medical research data of a primary care database covering the whole UK, between January 1995 and January 2021. IBD patients of all ages were matched 4:1 by demographics and primary care practice to unexposed controls. Following exclusion of patients with mental ill health at study entry, adjusted hazard ratios (HR) of developing depression, anxiety, deliberate self-harm, severe mental illness and insomnia were calculated using a Cox proportional hazards model. Results: We included 48,799 incident IBD patients: 28,352 with ulcerative colitis and 20,447 with Crohn's disease. Incidence rate ratios of mental illness were higher in IBD patients than controls (all p < 0.001): deliberate self-harm 1.31 (95% CI 1.16-1.47), anxiety 1.17 (1.11-1.24), depression 1.36 (1.31-1.42) and insomnia 1.62 (1.54-1.69). Patients with Crohn's disease were more likely to develop deliberate self-harm HR 1.51 (95% CI 1.28-1.78), anxiety 1.38 (1.16-1.65), depression 1.36 (1.26-1.47) and insomnia 1.74 (1.62-1.86). Patients with IBD are at increased risk of deliberate self-harm (HR 1.20 [1.07-1.35]). The incidence rate ratios of mental illnesses were particularly high during the first year following IBD diagnosis: anxiety 1.28 (1.13-1.46), depression 1.62 (1.48-1.77) and insomnia 1.99 (1.78-2.21).
  • Diagnosis and treatment for gastro-oesophageal cancer in England and Wales : analysis of the National Oesophago-Gastric Cancer Audit (NOGCA) database 2012-2020

    Pucher, Philip H; Park, Min Hae; Cromwell, David A; Crosby, Tom C; Thomas, Betsan; Trudgill, Nigel; Wahedally, Muhammad; Maynard, Nick; Gossage, James A; Trudgill, Nigel; et al. (Oxford University Press, 2023-05-16)
    Background: The National Oesophago-Gastric Cancer Audit (NOGCA) captures patient data from diagnosis to end of primary treatment for all patients with oesophagogastric (OG) cancer in England and Wales. This study assessed changes in patient characteristics, treatments received, and outcomes for OG cancer surgery for the period 2012-2020, and examined which factors may have led to changes in clinical outcomes over this time. Methods: Patients diagnosed with OG cancer between April 2012 and March 2020 were included. Descriptive statistics were used to summarize patient demographics, disease site, type, and stage, patterns of care, and outcomes over time. The treatment variables of unit case volume, surgical approach, and neoadjuvant therapy were included. Regression models were used to examine associations between surgical outcomes (duration of stay and mortality), and patient and treatment variables. Results: In total, 83 393 patients diagnosed with OG cancer during the study period were included. Patient demographics and cancer stage at diagnosis showed little change over time. Altogether, 17 650 patients underwent surgery as part of radical treatment. These patients had increasingly more advanced cancers, and a greater likelihood of pre-existing comorbidity in more recent years. Significant decreases in mortality rates and duration of stay were noted, along with improvements in oncological outcomes (nodal yields and margin positivity rates). Following adjustment for patient and treatment variables, increasing audit year and trust volume were associated, respectively, with improved postoperative outcomes: lower 30-day mortality (odds ratio (OR) 0.93 (95 per cent c.i. 0.88 to 0.98) and OR 0.99 (95 per cent c.i. 0.99-0.99)) and lower 90-day mortality (OR 0.94 (95 per cent c.i. 0.91 to 0.98) and OR 0.99 (95 per cent c.i. 0.99-0.99)), and a reduction in duration of postoperative stay (incidence rate ratio (IRR) 0.98 (95 per cent c.i. 0.97 to 0.98) and IRR 0.99 (95 per cent c.i. 0.99 to 0.99)). Conclusion: Outcomes of OG cancer surgery have improved over time, despite little evidence of improvements in early diagnosis. The underlying drivers for improvements in outcome are multifactorial.

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