Given the increasing burden of liver cancer in Europe, it is crucial to investigate how social determinants of health (SDoH) affect liver cancer risk factors and access to care in order to improve health outcomes equitably. This paper summarises the available evidence on the differential distribution of liver cancer risk factors, incidence, and health outcomes in the European Economic Area and the United Kingdom from an SDoH perspective. Vulnerable and marginalised populations have low socio-economic and educational levels and are the most affected by liver cancer risk factors. Reasons for this include varied access to hepatitis B virus vaccination and limited access to viral hepatitis B and C screening, harm reduction, and treatment. Additionally, alcohol -related liver disease remains highly prevalent among individuals with low education, insecure employment, economic instability, migrants, and deprived populations. Moreover, significant variation exists across Europe in the proportion of adults with steatotic liver disease, overweight/obesity, and diabetes, based on geographical area, gender, socio-economic and educational background, and density of ultra -processed food outlets. Inequities in cirrhosis mortality rates have been reported, with the highest death rates among individuals living in socio-economically disadvantaged areas and those with lower educational levels. Furthermore, insufficient healthcare access for key populations with primary liver cancer is influenced by complex healthcare systems, stigmatisation, discrimination, low education, language barriers, and fear of disclosure. These challenges contribute to inequities in liver cancer care pathways. Future studies are needed to explore the different SDoH-interlinked effects on liver cancer incidence and outcomes in European countries. The ultimate goal is to develop evidence -based multilevel public health interventions that reduce the SDoH impact in precipitating and perpetuating the disproportionate burden of liver cancer in specific populations. (c) 2024 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PDF file - 66K, Temporal protein profiles for HeLa cells.

PDF file - 52K, Systems modeling can act as a clinical tool to determine therapeutic windows and to assess adjuvant treatments.

PDF file - 237K, Supplementary Table 1: Translation of protein interactions into Ordinary Differential Equations. Supplementary Table 2: Pseudo-reactions for degradation and degradation rates as used in the model. Supplementary Table 3: Pseudo-reactions and kinetics for inhibition of BH3 only proteins and effectors BAK and BAX by anti-apoptotic proteins. Supplementary Table 4: BAK and BAX activation and BAK inhibition by VDAC2. Supplementary Table 5: Effector homo-oligomerization. Supplementary Table 6: Modeling apoptosis sensitizers ABT-737 and ApoG2. Supplementary Table 7 Two tBID chimeras were modeled to reproduce the findings of Llambi et al. Supplementary Table 8: BCL2 protein quantification of CRC cell lines. Supplementary Table 9: BCL2 protein quantification of CRC patient samples.

PDF file - 53K, Temporal protein profiles for HCT-116 cells.

The issue of doctor retention has been a challenge in Ireland for many years. Poor working conditions including poor supervision, cost of training, bullying, worsening mentoring experiences and speciality specific issues are a substantial challenge faced by doctors in Ireland, thus leading to a higher degree of emigration. While some changes have been introduced to the system and have some positive effects, the root causes of doctor emigration have not been addressed. This commentary reviews the publication by Brugha et al published in the IJHPM in April 2020 on "Doctor Retention: A Cross-sectional Study of How Ireland Has Been Losing the Battle" and explains why the current system needs to change for the benefit of patient safety, doctor well-being and better patient care. Ireland's Health Service Executive intends to take steps towards developing a new model of medical workforce to address the issue of recruitment and retention challenges within the healthcare system.

Background Sportspeople are more prone to binge drink than their peers. Aims We aimed to assess alcohol consumption, harms and behaviours in an elite Irish sporting population (Gaelic footballers and hurlers). Methods An anonymous web-based questionnaire (demographics, alcohol consumption, culture and related harms) was administered to all elite players. The AUDIT-C questionnaire (frequency, quantity of alcohol consumption and frequency of binge drinking) was used to assess for adverse alcohol use. Univariate and multivariate analyses assessed for predictors of adverse alcohol use. Results 717 players (mean age 24 years) were analysed. The majority of patients were male (75%), unmarried (93%) and had completed university (67%). 96% were current drinkers. Players consumed more alcohol during the off-season (median 20 versus 8 standard drinks in 28 days) compared to the elite season. Amongst current drinkers, 73% exhibit adverse alcohol use, 93% reported binge drinking and 65% an alcohol related harm in the past year. Most players would turn to family (36%) or friends (21%) for help. There were significant associations between monthly bingeing (OR 18.4), smoking (OR 3.3), generally drinking in public (OR 3.2), current gambling (OR 2.3), male gender (OR 2.1), an alcohol harm in the past year (OR 1.9) and adverse alcohol use. In contrast, co-habiting with a partner (OR 0.5) was protective. Conclusions Excess alcohol consumption, alcohol related harms and binge drinking are prevalent in an elite sporting population, particularly during the off-season. Specific strategies are required to reduce alcohol related harms, particularly amongst high-risk groups during the off-season.

Introduction:Vedolizumab (VDZ) is a monoclonal antibody designed to inhibit alpha 4 beta 7 integrin and result in gut-selective anti-inflammatory activity. Real-world data are important in providing information to clinicians on the effectiveness and safety of this agent. Methods:A retrospective, multi-centre study was conducted across 9 Irish academic centres. Adult (>= 18 years) patients receiving VDZ for active IBD (ulcerative colitis [UC] or Crohn's disease [CD]) with at least 6 months follow-up were included in the study cohort. Primary study endpoints were defined as 3-month clinical response and 6-month corticosteroid-free remission. Secondary endpoints included 3-month corticosteroid-free clinical remission, 6-month clinical response, change from baseline in CRP, albumin and faecal calprotectin, and adverse events. Results:One hundred and twenty-nine patients were included in total (64 UC, 65 CD). In the UC cohort, baseline median PMCS was 7 [0 - 9] and 78.1% had prior anti-tumour necrosis factor alpha (anti-TNF alpha) exposure. Three-month and 6-month endpoints were achieved in 40% and 31%, respectively. Milder disease, CRP, albumin and prior anti-TNFa were associated with endpoints. One minor adverse event was documented. In the CD cohort, baseline HBI was 12 [0 - 29] and 94% previously received anti-TNFa therapy. Three-month and 6-month primary endpoints were achieved in 52% and 48%, respectively. Six-month remission was positively associated with Montreal B1 disease and negatively associated with perianal disease and baseline faecal calprotectin. Adverse events occurred in 11% of cases. Conclusion:These real-world data support the effectiveness and safety of vedolizumab in the treatment of IBD and give valuable insight into predictors of treatment outcomes. This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.Key Summary Vedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBD This study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Vedolizumab(VDZ) is an α4β7 integrin antagonist for the treatment of IBD. The role of VDZ therapeutic drug monitoring has not been clearly defined. We aimed to investigate the association between VDZ trough levels and therapy outcome in a cohort of patients with inflammatory bowel disease (IBD) and the association between VDZ trough levels and clinical and biochemical variables. IBD patients receiving VDZ were identified in a cross-sectional study where serum samples were not collected at a pre-specified time point. Ulcerative colitis(UC) and Crohn’s disease(CD) clinical activity was quantified using Mayo clinical subscore (MCS, remission MCS ≤ 1) and Harvey–Bradshaw Index (HBI, remission HBI < 5). VDZ and antibody-to-vedolizumab (AVA) concentrations determined by Prometheus® Anser® laboratories using non-radio-labelled liquid-phase mobility shift assays. p-values < 0.05 were considered significant. N = 35 IBD patients included (57% UC, 54% male, median age(range) 44.3 years(17.7–76.2), 9% receiving immunomodulators, 83% prior anti-TNF. 34/35 patients had trough VDZ level performed during maintenance therapy. Median(range) trough VDZ concentration 9.5 µg / ml(0 – 25). 0/35 subjects had detectable AVAs. No association between MCS or HBI defined remission and trough VDZ concentrations was observed p = 0.38 and p = 0.83, respectively. No difference in trough VDZ concentrations observed comparing by IBD phenotype(p = 0.50); prior biologic exposure(n = 0.37); or concomitant immunomodulator use(p = 0.68). CRP and albumin levels were not correlated with trough VDZ concentrations, correlation coefficient −2.2(p = 0.36) and 0.21(p = 0.36) respectively. In a real-world study of IBD patients receiving VDZ no clear association between VDZ trough levels and therapy outcome was observed. Significant immunogenicity was not observed supporting the use of VDZ monotherapy in uncomplicated patients. Further study is required to determine the utility of therapeutic drug monitoring in VDZ-treated patients.

Background and aims Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. Patients and methods Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. Results Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3–76.8); disease duration 6.6 years (0–29.9); follow-up 8.7 months (0.4–39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2–28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1–0.7), P =0.008, and hazard ratio (95% confidence interval) 2.8 (1.3–5.7), P =0.007, respectively. Adverse events occurred in 7% of patients ( n =5), all of which were minor and self-limiting. Conclusion These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Vedolizumab (VDZ) is a monoclonal antibody designed to inhibit α4β7 integrin and result in gut-selective anti-inflammatory activity. Randomised control trials have shown VDZ to be safe and effective in treating patients with ulcerative colitis (UC). However, real-world data describing the outcome of VDZ therapy in routine clinical practice are limited. We aimed to evaluate the safety and efficacy of VDZ in routine clinical practice. A multicentre, retrospective study across seven Irish academic hospitals in the INITIATIVE Network was conducted. N = 68 eligible UC patients were identified with n = 39 having at least 6 months of follow-up included in the final study cohort. Demographics and disease characteristics were collected at baseline, and 3 and 6 months following VDZ initiation. VDZ was administered as per standard protocol. Primary endpoints were 3-month clinical response and 6-month steroid-free remission. Clinical response was defined as a decrease from baseline in clinical Mayo subscore of ≥3 points, with ongoing receipt of VDZ. Clinical remission was defined as a clinical Mayo subscore of ≤1, the absence of corticosteroid use and continuing receipt of VDZ. Secondary endpoints were baseline variables associated with VDZ induction outcome and rates of adverse events. Thirty-nine patients were included in the final study cohort. Baseline characteristics included (median [range]): age 44 [17–79]; gender 58% male; 61% extensive and 39% left-sided colitis; median clinical Mayo subscore at initiation 6 [2–9]; CRP 8mg/l [0.8–85mg/l) and median albumin 37g/l (20–47g/l). At VDZ initiation proportions receiving 5-aminosalicylates; thiopurines and systemic corticosteroids were 67%, 48%, and 50%, respectively. 24%, 35%, and 41% had been exposed to no, 1 and 2 anti-TNF agents, respectively. Three-month clinical response and 6-month steroid-free clinical remission rates were 47% and 46% respectively. Comparing anti-TNF naïve and exposed individuals; 3 months response rates was similar (40% vs. 48% respectively, p = 0.73); however, there was a trend toward increased 6 months steroid-free remission rates (75% vs. 35%, respectively, p = 0.10). Regression analysis demonstrated no baseline clinical or biochemical variable to be associated with 3-month clinical response or 6-month steroid-free remission. The rate of adverse events was 6.1%, none requiring hospitalisation. These data support the efficacy and safety of VDZ as an induction and maintenance agent in UC. Consistent with published literature the long-term outcome of VDZ therapy appears improved in anti-TNF naïve cohorts.

Introduction As finite healthcare resources come under pressure, the value of physician activity is assuming increasing importance. The value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Even though some attempts have been made to quantify the value of clinician activity, there is little in the medical literature describing the importance of endoscopists’ activity. This study aimed to characterize the value of endoscopic retrograde cholangiopancreatography (ERCP) performance of five gastroenterologists. Patients and methods We carried out a retrospective–prospective cohort study using the databases of patients undergoing ERCP between September 2014 and March 2017. We collected data from 1070 patients who underwent ERCP comparing value among the ERCPists at index ERCP. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure, T is the duration of procedure and C is the adjusted for complexity level. Quality and complexity were derived on a 1–4 Likert scale on the basis of American Society for Gastrointestinal Endoscopy criteria; time was recorded (in min) from intubation to extubation. Endoscopist time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized. Results In total, 590 procedures were analysed: 465 retrospectively over 24 months and 125 prospectively over 6 months. There was a 32% variation in the value of endoscopist activity in a more substantial retrospective cohort, with an even more considerable 73% variation in a smaller prospective arm. Conclusion In an analysis of greater than 1000 ERCPs by a small cohort of experienced ERCPists, there was a wide variation in the value of endoscopist activity. Although the precision of estimating procedural costs needs further refinement, these findings show the ability to stratify ERCPists on the basis of the value their activity. As healthcare costs are scrutinized more closely, such value measurements are likely to become more relevant.

ERCP is a complex endoscopic procedure that typically requires higher doses of sedation and analgesia compared to standard endoscopy. Our unit, like many countries in Europe, perform most ERCPs under conscious sedation. While monitoring patient comfort is routine during colonoscopy, no validated model exists for ERCP. The objective of our study is to evaluate comfort scores of patients undergoing ERCPs with conscious sedation, using a scoring system based on the modified Gloucester score.

With the funding constraints on healthcare providers, there is increasing focus on value in colonoscopy, rather than just quality alone. In healthcare, value is defined as quality adjusted for cost. Colonoscopy quality metrics include adenoma detection rate (ADR), for which polyp detection rate (PDR) is often used as a convenient surrogate, and cecal intubation rate (CIR). The principal cost components of a colonoscopy procedure are the endoscopist professional charge, healthcare facility charge and pathology charges. Procedure quality indicators, procedure duration and number of specimens sent for histological analysis are known to vary between endoscopists. This study aimed to characterize the value of colonoscopy activity among a cohort of endoscopists in an academic medical center.

Colonoscopy remains the gold standard for detection of colorectal cancer. Known indicators of colonoscopy quality include adenoma detection rate (ADR) and cecal intubation rate (CIR); polyp detection rate (PDR) is often used as a more convenient surrogate for ADR as it does not require pathologic analysis. The aim of this study was to assess whether a composite colonoscopy quality score, based on readily available parameters (PDR, CIR), correlates more closely with ADR than the individual parameters themselves (PDR and CIR).

INTRODUCTION:The General Medical Council (GMC) of the UK states that doctors have a duty to train and contribute to the education of colleagues, and that those involved in formal clinical teaching should have a teaching qualification.OBJECTIVES:We sought to evaluate the current levels of engagement of surgical trainees and recently appointed surgical consultants in clinical teaching.METHODS:All trainees who commenced a basic or higher surgical training post during or after 2007 were invited to participate. The electronic questionnaire was administered using the survey tool GetFeedback, collecting information regarding subspecialty, current role, quantity of teaching that respondents engaged in and who they taught and teaching motivations and barriers.RESULTS:There were 128 respondents out of 358 invitations to participate (36% response rate). Less than half (39%) of respondents had attended formal courses on clinical education. Over 70% of respondents engaged in clinical teaching for two or more hours each week. A lack of time and resources were noted as barriers to engaging in teaching. We found a low number of those involved in teaching seeking feedback after teaching sessions.CONCLUSION:In surgery, the apprenticeship model is still the framework for developing the surgeons of the future. In attempting to produce a highly skilled workforce for the future, we rely on those in senior positions to train those coming through; higher surgical trainees are relied on to teach the core surgical trainees and so on. Our study shows a low level of formalisation of this model.

Background & Aim: In the mid-1990s, a group of Rh negative women was diagnosed with hepatitis C virus (HCV) genotype 1b infection, following administration of contaminated anti-D immunoglobulin in 1977-79. We aimed to describe their disease history and estimate the effect of selected host and treatment factors on disease progression. Methods: We conducted a cohort study on the women infected with HCV. Information was collected from records at seven HCV treatment centres on demographics, treatment and health outcomes up to the 31st December 2013. We calculated cumulative incidence, case fatality, and sub hazard ratios (SHR) for disease progression using competing risks regression. Results: Six hundred and eighty-two patients were included in the study. Among the chronically infected patients (n = 374), 35% completed interferon-based antiviral treatment; 42% of whom had a sustained virological response. At the end of 2013, 19%, 1.9%, and 4.9% of chronically infected patients had developed cirrhosis, hepatocellular carcinoma, and liver-related death, respectively, compared with 10%, 0.8%, and 2.4% at the end of 2008. At the end of 2013, 321 (86%) of the chronically infected patients remained alive, 247 (77%) of whom were still chronically infected. Factors associated with increased cirrhosis rates included high alcohol intake (aSHR = 4.9 [2.5-9.5]) and diabetes mellitus (aSHR = 5.0 [2.9-8.8]). Conclusions: Development of liver-related outcomes accelerated with time, with the risk of cirrhosis, hepatocellular carcinoma, and liver-related death doubling in the last five years of follow-up, particularly in women with high alcohol consumption and diabetes mellitus. We recommend that patients with chronic HCV infection be advised of the additive harmful effect of alcohol, and that data be collected on this cohort after a further five years to analyse the effect of subsequent antiviral treatment during this rapidly evolving period in HCV treatment history. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.