BMJ Open Gastroenterology最新文献

Objectives: High-resolution anorectal manometry (HRAM) is the established investigation in faecal incontinence (FI). However, provocative tests (functional lumen imaging probe (FLIP) and anal acoustic reflectometry (AAR)) have been proposed as alternatives. This study uniquely explores all three methods in correlation with FI symptoms and subtypes.

Methods: This was a prospective observational study of patients with FI attending a tertiary pelvic floor unit between August 2022 and January 2024. Patients underwent HRAM, FLIP and AAR with the order randomised. FI severity was assessed with the Vaizey score and quality-of-life with the Manchester Health Questionnaire.

Results: 40 patients (39 women, median age: 62 (range: 38-85)) were recruited with 27 (67.5%) reporting urge FI, 8 (20%) mixed and 5 (12.5%) passive incontinence. FLIP squeeze measurements correlated with the Vaizey score, including incremental squeeze pressure at 40 mL (r_s=-0.412; p=0.008) and 50 mL (r_s=-0.414; p=0.009) and the pressure-diameter volume loop at 50 mL (r_s=-0.402; p=0.011). Incremental squeeze opening pressure with AAR correlated with the Vaizey score (r_s=-0.339; p=0.032). There was no correlation between symptom severity and HRAM parameters, or any parameter and quality-of-life scores. Resting parameters with all three modalities were lower in passive FI: mean resting pressure (HRAM; p=0.010), yield pressure (FLIP; p=0.031) and opening pressure (AAR; p=0.006). With FLIP, there was a trend towards reduced squeeze function in the urge group (pressure-diameter volume loop at 50 mL; p=0.295).

Conclusions: FLIP and AAR correlate better with FI symptoms compared with HRAM. Therefore, these provocative tests could be used to guide the management of FI in prospective studies.

Objective: Colorectal cancer (CRC) screening enables resection of polyp precursor lesions, preventing cancer or detecting it earlier. Post-polypectomy, people can remain at increased CRC risk, prompting surveillance colonoscopy. Less invasive faecal immunochemical tests (FIT) could reduce the burden of surveillance colonoscopy. We investigated whether changes in FIT values over multiple rounds were associated with advanced colorectal neoplasia (ACN) detection.

Methods: A cohort of men and women aged 60-72 years deemed intermediate risk by the 2002 UK adenoma surveillance guidelines and scheduled for three yearly colonoscopies were recruited (January 2012-December 2013) within the English Bowel Cancer Screening Programme and offered a quantitative FIT at 1, 2 and 3 years post-baseline colonoscopy for a prospective analysis within a diagnostic accuracy study. Participants positive (≥40 µg haemoglobin/g faeces) at 1 year or 2 years were offered early colonoscopy and excluded, otherwise, colonoscopy was offered at 3 years. Only those who completed three FIT rounds and attended the 3-year colonoscopy were included. Participants were grouped based on changes between FIT rounds, with changes defined as absolute differences ≥4 µg/g, and positivity at round 3.

Results: Among 4412 participants, the largest group (n=2773) was the no change category, which had the lowest ACN detection rate (4.7%, 95% CI: 3.9 to 5.5). The serial increase group with a positive round 3 value (n=46) had the highest ACN detection rate (32.6%, 95% CI: 19.5 to 48.0).

Conclusion: No change in FIT result across multiple rounds was associated with a low ACN detection rate, while a serial increase was associated with higher ACN detection rates. Further research should consider if sequential rounds of FIT could be used for stratifying individual risk.

Objective: To characterise gastrointestinal symptoms and bowel habits in healthy blood donors and explore symptom phenotypes and their associated factors.

Methods: Between November 2020 and March 2023, 53 046 participants in the nationwide Danish Blood Donor Study completed a questionnaire including 13 gastrointestinal symptoms, defaecation pattern regularity, stool frequency, and stool consistency. We used a data-driven approach to explore symptom phenotypes and investigated associated factors by multinomial logistic regression.

Results: Among the 53 046 participants (52% women), 68% (95% CI 67.5% to 68.3%) reported at least one of 13 gastrointestinal symptoms. The most frequent symptoms were bloating (40%), abdominal rumbling (40%), abdominal pain (17%), acid regurgitation (13%), heartburn (12%), diarrhoea (12%), nausea (12%), and constipation (10%). Half of the participants (50%) had a regular defaecation pattern (defined as generally the same stool consistency and stool frequency) consisting of Bristol Stool Form Scale 4 stools 1-3 times per day. Symptom phenotypes and their prevalence among 51 820 near-complete case participants were as follows: (1) no gastrointestinal symptoms (32%); (2) bloating and/or rumbling only (21%); (3) acid regurgitation and/or heartburn only (4%); (4) any other one or two symptoms (14%); (5) any three or four symptoms (18%); (6) any five or six symptoms (7%); (7) at least seven symptoms (3%). The acid regurgitation and/or heartburn only phenotype associated with obesity, and the remaining symptomatic phenotypes were associated with female sex, decreasing age, and an irregular defaecation pattern, even after excluding individuals with self-reported irritable bowel syndrome, lactose intolerance, or gluten intolerance.

Conclusion: Most healthy adults, especially women younger than 50 years, experience gastrointestinal symptoms. Symptom phenotypes strongly correlate with sex, age, and bowel habits.

Objectives: Patients have difficulties in understanding how to manage their liver cirrhosis. This highlights a need for support in comprehending health-related information, which remains largely lacking within liver cirrhosis care. Involvement of registered nurses (RNs) in outpatient liver cirrhosis care has potential to improve quality of care and reduce patient mortality. However, the benefits of nursing care on patients' health-related quality of life (HRQoL) are scarcely studied. This study compared HRQoL in patients receiving either standard medical outpatient care or adjunctive, nurse-led care. The risk of malnutrition, decompensation events and mortality were also compared between the two study groups.

Methods: This was a pragmatic, multicentre, randomised trial, which enrolled 167 patients with liver cirrhosis. The primary outcome measure, HRQoL, was assessed using the RAND-36 questionnaire. The physical component summary (PCS) and the mental component summary (MCS) scores of RAND-36 were compared, using linear mixed-effects models for repeated measures, at 12 and 24 months.

Results: 83 patients received standard medical care, and 84 patients received adjunctive, nurse-led care for 24 months. Due to unforeseen circumstances, the final study population of 167 participants was less than the intended 500. Group comparisons were non-significant of the PCS and MCS scores (-1.1, p=0.53 and -0.7, p=0.67, respectively), malnutrition (p=0.62) and decompensation events (p=0.46), after 24 months. However, mortality was three times higher in the control group compared with the intervention group (12 vs 4, p=0.04) after 24 months.

Conclusions: In this study, adjunctive nurse-led care was not superior to standard medical outpatient care regarding HRQoL, risk of developing malnutrition or decompensation. However, RN involvement contributed to early identification of decompensation and reduced mortality.

Trial registration number: NCT02957253.

Objective: To develop and validate a prognostic model for risk-stratified monitoring of 5-aminosalicylate nephrotoxicity.

Methods: This UK retrospective cohort study used data from the Clinical Practice Research Datalink Aurum and Gold for model development and validation respectively. It included adults newly diagnosed with inflammatory bowel disease and established on 5-aminosalicylic acid (5-ASA) treatment between 1 January 2007 and 31 December 2019. Drug discontinuation associated with 5-ASA nephrotoxicity defined as a prescription gap of ≥90 days with decline in kidney function was the outcome. Patients prescribed 5-ASAs for ≥6 months were followed-up for up to 5 years. Penalised Cox regression was used to develop the risk equation with bootstrapping for internal validation and optimism adjustment. Model performance was assessed in terms of calibration and discrimination.

Results: 13 728 and 7318 participants who contributed 40 378 and 20 679 person-years follow-up formed the development and validation cohorts with 170 (1.2%) and 98 (1.3%) outcome events respectively. Nine predictors were included in the final model, including chronic kidney disease stage 3 and hazardous alcohol use as strong predictors. Age and Body Mass Index were weak predictors. The optimism-adjusted calibration slope, C and D statistics in the development and validation data were 0.90, 0.64 and 0.98, and 1.01, 0.66 and 0.94 respectively.

Conclusion: This prognostic model used information from routine clinical care and performed well in an independent validation cohort. It can be used to risk-stratify blood test monitoring during established 5-ASA treatment. A key limitation is that the decline in kidney function could have been due to factors other than 5-ASA nephrotoxicity.

Objective: The emergence of resistance-associated substitutions (RASs) poses a significant challenge to the effective treatment of hepatitis C virus (HCV) infection using direct-acting antivirals. This study's objective was to observe the prevalence of HCV genotypes and RAS within the Former Soviet Union (FSU) countries.

Methods: We analysed 60 NS3, 313 NS5A and 1119 NS5B sequences of HCV deposited in open-access databases from 11 FSU countries for the prevalence of genotypes and the presence of RAS using the Geno2Pheno software.

Results: The following NS3 RASs were revealed through our analyses: 156P/S/T, 168del, 80K, 55A and 174S. The most prevalent NS5A RAS was 30K (12.69%) in genotype 3a, associated with resistance to daclatasvir, elbasvir and ledipasvir, followed by 62S (8.96% in genotype 3a), linked with resistance to daclatasvir, and 93H (3.95% and 6.72% in genotypes 1b and 3a, respectively), conferring resistance to daclatasvir, ombitasvir, elbasvir, ledipasvir and velpatasvir. The NS5B RASs found in this study were 451S and 556G, associated with resistance to dasabuvir.

Conclusion: The high prevalence of HCV genotypes 1b and 3a in the FSU region and the presence of specific RASs should be considered when determining the most effective treatment regimen for HCV-infected individuals in the FSU countries.

Objective: It is controversial whether rapid lowering of triglyceride (TG) levels is associated with clinical benefits in patients with hypertriglyceridaemia-associated acute pancreatitis (HTG-AP). In particular, patients with different severity of disease may respond differently to TG-lowering therapy. In this study, we aimed to explore the association between rapid decline in serum TG levels and organ failure in patients with different severities of HTG-AP.

Methods: This is a secondary analysis of data from a multicentre, prospective registry recruiting HTG-AP patients admitted within 72 hours from the onset of symptoms. Patients were dichotomised into either target reaching (TG≤5.65 mmol/L on study day 3) or not. The primary outcome was the presence of organ failure at day 14. The association between target-reaching and the primary outcome was modelled. Furthermore, subgroup analyses were conducted based on the disease severity of HTG-AP patients at enrolment.

Results: Overall, 413 patients were included for analysis, of whom 192 (46.5%) reached the target on day 3. For the overall study cohort, there was no significant difference in presence of organ failure at day 14 between patients reaching the target or not (3.1% vs 6.8%, p=0.091). In the subgroup of HTG-AP patients with organ failure at enrolment, compared with patients with TG>5.65 mmol/L on day 3, patients who reached the target had significantly lower presence of organ failure at day 14 (7.8% vs 22%, p=0.039) and lower incidence of infected pancreatic necrosis within 60 days (3.1% vs 11.9%, p=0.049). Similar findings were seen in the subgroup with more severe HTG-AP (APACHE II ≥8 at enrolment).

Conclusion: More rapid decline of serum TG levels was associated with decreased presence of organ failure at day 14 in patients with more severe HTG-AP.

Trial registration number: The Chinese Clinical Trial Registry, number ChiCTR2000039541.

Objective: The aetiology of pancreatic cancer is complex, and there is limited research on its incidence. We aimed to investigate the incidence trends of pancreatic cancer in 43 countries and predict trends up to 2030.

Methods: The annual incidence of pancreatic cancer was obtained from the Cancer Incidence in Five Continents database, which comprises 108 cancer registries from 43 countries. Based on available data, we calculated age-standardized incidence rates (ASRs) per 100 000 people for 1988-2012. A Bayesian age-period-cohort model was used to predict the number of new cases and incidence rates up to 2030.

Results: From 1988 to 2012, the global incidence rate of pancreatic cancer showed a continuously increasing trend, with the ASR increasing from 5.89 in 1988 to 6.78 in 2012, representing an overall average annual percentage change of 8.45%. This increasing trend is expected to persist in most selected countries, whereas a few countries are projected to exhibit a declining trend by 2030.

Conclusion: It appears that the future global incidence of pancreatic cancer is on the rise, but the rate of increase varies among different countries, with some showing a declining trend.

Objective: Studies in the USA examining the relationship between ethnicity and colorectal cancer (CRC) identified significant variation. This study sought to examine the relationship between ethnic group, route to diagnosis, early-onset CRC and stage at diagnosis in the English National Health Service.

Methods: Data from COloRECTal cancer data Repository for all individuals diagnosed with CRC (International Classification of Diseases version 10, C18-C20) between 2012 and 2017. A descriptive analysis of the characteristics of the study population was performed. Multivariable logistic regression models were used to assess the association between ethnicity, route to diagnosis, stage at diagnosis and early-onset CRC.

Results: Early-onset CRC was least common in those in the white ethnic group (5.5% diagnosed <50, vs 17.9% in the Asian, 15.5% in the black and 21.8% in the mixed and multiple ethnic groups, p<0.01). Diagnosis following a 2-week wait referral was significantly less common among individuals from the Asian, black, other and unknown ethnic groups than the white ethnic group (Asian OR 0.84, 95% CI 0.79 to 0.91, black OR 0.86, 95% CI 0.79 to 0.93, other OR 0.81, 95% CI 0.73 to 0.90 and unknown OR 0.70, 95% CI 0.66 to 0.73). The Asian ethnic group had significantly lower odds of emergency diagnosis than the white ethnic group (OR 0.90, 95% CI 0.83 to 0.97). Following adjustment, individuals from the Asian ethnic group were significantly less likely, than their white counterparts, to be diagnosed at stage IV (OR 0.82, 95% CI 0.76 to 0.88).

Conclusion: This study identified different demographic profiles of those diagnosed with CRC between broad ethnic groups, highlighting the need to consider access to diagnostic CRC services in the context of ethnicity.

Objective: Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)_1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). S1P₁ receptor expression on cardiac cells is involved in cardiac conduction. We report cardiovascular treatment-emergent adverse events (TEAEs) associated with S1P receptor modulators and other cardiovascular events in the etrasimod UC clinical programme.

Methods: Patients were analysed in the Placebo-controlled UC cohort and All UC cohort. Incidence rates (IRs, per 100 patient-years) of cardiovascular-related TEAEs associated with S1P receptor modulators, including bradycardia/atrioventricular (AV) block and hypertension, and other cardiovascular events, including coronary artery disease (CAD) and cerebrovascular disease (CVD), were analysed.

Results: In patients receiving etrasimod, cardiovascular-related TEAEs were infrequent (≤2.6% per AE). In the Placebo-controlled UC cohort, IRs (95% CIs) for cardiovascular-related TEAEs were higher for patients receiving etrasimod (n=577) vs placebo (n=314), respectively, for bradycardia/sinus bradycardia, 3.85 (1.58 to 6.13) vs 0 and AV block, 1.40 (0.03 to 2.76) vs 0; and numerically higher for hypertension, 5.31 (2.62 to 7.99) vs 3.40 (0.07 to 6.72). Most bradycardia/AV block events were reported on day 1. All bradycardia and hypertension TEAEs were non-serious. One serious second-degree AV block type 1 TEAE occurred in the etrasimod group; no events of second-degree AV block type 2 or higher were reported. One event each of CAD and CVD occurred in two patients receiving etrasimod.

Conclusions: In the etrasimod UC clinical programme, IRs of cardiovascular-related TEAEs and other cardiovascular events were low. Most cardiovascular-related TEAEs were non-serious.

Trial registration numbers: NCT02447302; NCT03945188; NCT03996369; NCT02536404; NCT03950232; NCT04176588.