45 research outputs found
Ethnic differences in success at application for consultant posts among United Kingdom physicians from 2011 to 2019: a retrospective cross-sectional observational study
OBJECTIVES: To identify associations between success following application for consultant physician posts and demographic factors. DESIGN: Logistic regression analysis of nationwide survey data. SETTING: United Kingdom (UK) physicians with a recent certificate of completion of training (CCT). PARTICIPANTS: All UK trainee physicians who received a CCT between 2010 and 2019 were surveyed. Respondents were excluded if they had not applied for a consultant post or if application data were incomplete. MAIN OUTCOME MEASURES: The primary outcome measure was success over the entire consultant application process, i.e. shortlisted and offered the post following the first application. Secondary outcomes were: shortlisted following first application and offered a consultant post at first interview. RESULTS: From 7037 CCT holders surveyed, 50.7% responded. While 1198 (59.7%) respondents were white, 760 (37.9%) were from minority ethnic groups and 50 (3.5%) were of unknown ethnicity. Primary medical qualification (PMQ) country was the UK in 75.3% (n = 1512). On multivariable logistic regression analysis the independent negative associations with success were: minority ethnicity (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.43-0.71); p < 0.001) vs. white; PMQ from Europe (OR 0.47, 95% CI 0.28-0.79; p = 0.004) or Asia (OR 0.68, 95% CI 0.49-0.96; p = 0.027) vs. UK PMQ; year of CCT 2012 (OR 0.40, 95% CI 0.24-0.68; p = 0.001), 2013 (OR 0.39, 95% CI 0.23-0.65; p < 0.001), and 2014 (OR 0.26, 95% CI 0.15-0.43; p < 0.001) vs. 2019. Specialties associated with lower success rates included Cardiology, Endocrinology, Genitourinary medicine, Palliative care, Renal and Respiratory, compared to Acute medicine. CONCLUSIONS: Minority ethnic group candidates for consultant physician posts had lower success rates compared to white candidates after correction for important variables including specialty, time from and country of PMQ. This finding requires further evaluation to identify the causes for this variation
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
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
Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial
Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms
include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and
loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years
as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit
and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D.
Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with
embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from
outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily)
or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool
frequency, and stool consistency on a daily basis.
The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA)
recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and
quality of life will also be assessed.
Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline
and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the
barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact
of ondansetron.
Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining
ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond
A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus.
Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma
Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study
This is the final version. Available from Elsevier via the DOI in this record. Background We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment
and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of
response.
Methods Personalised Anti-TNF therapy in Crohn’s disease (PANTS) is a UK-wide, multicentre, prospective
observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients
with active luminal Crohn’s disease aged 6 years and older. At the end of the first year, sites were invited to enrol
participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across
the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation
testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response
in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined
in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed
symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional
surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449,
and is now complete.
Findings Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and
209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age
32·5 years [IQR 22·1–46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of
patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7–43·7),
34·4% (29·9–39·0), and 34·7% (29·8–39·5), and for adalimumab 35·9% (95% CI 31·2–40·5), 32·9% (26·8–39·2),
and 28·9% (21·9–36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later
timepoints were 6·1–10·0 mg/L for infliximab and 10·1–12·0 mg/L for adalimumab. After excluding patients who
had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3
were, for infliximab 34·4% (95% CI 30·4–38·2), 54·5% (49·4–59·0), and 60·0% (54·1–65·2), and for adalimumab
32·1% (26·7–37·1), 47·2% (40·2–53·4), and 68·4% (50·9–79·7), respectively. In multivariable analysis, loss of
response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug
concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45
[95% CI 0·30–0·67], adalimumab: 0·39 [0·22–0·70]). For patients treated with infliximab, loss of response was
also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11–1·95]), obesity (vs not obese 1·62 [1·08–2·42]),
baseline white cell count (1·06 [1·02–1·11) per 1 × 10⁹ increase in cells per L), and thiopurine dose quartile. Among
patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response
(HR 1·95 [95% CI 1·17–3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug
antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1–49·4) among patients
treated with infliximab and 20·3% (13·8–26·2) among those treated with adalimumab. The development of antidrug antibodies associated with undetectable drug concentrations was significantly associated with treatment
without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40
[95% CI 0·31–0·52], adalimumab 0·42 [95% CI 0·24–0·75]), and with carriage of HLA-DQA1*05 risk variant for
infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13–1·88]) but not for adalimumab (HR 1·60
[0·92–2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated
with increased time without the development of anti-drug antibodies associated with undetectable drug
concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20–3·74]) or introduction of an
immunomodulator after anti-TNF initiation (1·70 [1·11–2·59]). In years 2 and 3, 16 (4%) of 389 patients treated
with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal.
Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections
in years 2 and 3.
Interpretation Only around a third of patients with active luminal Crohn’s disease treated with an anti-TNF drug were
in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict
loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment,
particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with
undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05
and mitigated by concomitant immunomodulator use for both drugs.Guts UKCrohn’s and Colitis UKCure Crohn’s ColitisAbbVieMerck Sharp and DohmeNapp PharmaceuticalsPfizerCelltrion Healthcar
Improving triage in upper gastrointestinal bleeding: insights from the UK National Endoscopy Database (NED)
\ua9 Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ. Background and aims: We aimed to analyse data from the UK National Endoscopy Database (NED) to investigate factors associated with endotherapy in patients with suspected upper gastrointestinal bleeding (UGIB). Methods: Analysis of oesophagogastroduodenoscopy (OGD) uploads to the NED from 1 March 2019 to 29 February 2020 was performed. UGIB was defined as procedures with indications of melaena and/or haematemesis. The proportion where endotherapy was performed was calculated. Mixed-effects logistic regression was performed with patient sex, patient age, type of admission (inpatient, outpatient, unclassified) and symptoms as fixed effects on the dependent variable (receipt of endotherapy). Results were presented as adjusted ORs (aORs) with 95% CIs. Results: 47 481 OGDs were performed for UGIB; endotherapy was performed in 14.8%, increasing to 20.0% when only inpatient OGDs were analysed. Patients aged 18-39 years were half as likely to undergo endotherapy than those aged 50-59 years (aOR 0.5, 95% CI 0.5 to 0.6), with male patients at higher risk than females (aOR 1.3, 95% CI 1.2 to 1.4). Patients with both melaena and haematemesis were nearly three times more likely to receive endotherapy (aOR 2.8, 95% CI 2.6 to 3.0) compared with those with melaena alone. Conversely, patients with only haematemesis had a lower risk than those with melaena alone (aOR 0.9, 95% CI 0.8 to 0.9). Conclusions: Younger and female patients were at lower risk of undergoing endotherapy, while patients with both melaena and haematemesis were at three times the risk as those with each symptom alone. Incorporating these findings into UGIB risk scores could improve patient triage