Colin John Crooks

Crohn’s disease (CD) is a chronic, relapsing inflammatory bowel disease characterised by heterogeneous clinical manifestations and a lifelong disease course. As therapeutic strategies have evolved ...

Background: Wales has the highest rate of colorectal cancer (CRC) in the UK. National guidelines recommend using the faecal immunochemical test (FIT) in patients presenting with symptoms of bowel cancer. FIT ≥ 10 μgHb/g in symptomatic patients is presumed to indicate a > 3% risk of CRC. However, evidence from England and Scotland has found that the risk is lower in certain demographic groups. Aims: To examine 1‐year risk of CRC in Welsh patients with symptoms of suspected bowel cancer by demographics, iron deficiency anaemia (IDA), and FIT. Methods: Cohort study of adults registered in the Welsh Longitudinal General Practice dataset with a FIT recorded from 01/01/2020–31/03/2024. Kaplan–Meier estimates were used to calculate 1‐year cumulative risks of CRC. Results: We included 166,863 patients with a FIT; 19.2% had a FIT ≥ 10 μgHb/g. Within 1 year, 2864 (1.72%) were diagnosed with CRC; 90.2% of which were following FIT ≥ 10μgHb/g. A FIT cut‐off of ≥ 10 μgHb/g in isolation identified a > 3% risk of CRC across all age groups. In those with FIT ≥ 10μgHb/g, IDA resulted in an increase in predicted risk across all age groups. IDA aided stratification further in women < 50 years; risk of CRC was 6.45% (95% CI: 3.52–9.29) with a FIT ≥ 10 μgHb/g and IDA compared to 2.20% (95% CI: 1.57–2.83) without IDA. Conclusions: In Wales, the risk of CRC following FIT ≥ 10 μgHb/g is higher than observed in English and Scottish cohorts. Stratification by demographics and blood results identified those at highest risk, but this did not fully explain the higher baseline risk observed in comparison to other UK nations.

Background: People with irritable bowel syndrome (IBS) often restrict their intake of FODMAPs because of associated gas and abdominal discomfort. Psyllium, a gel‐forming fibre, reduces colonic gas after inulin ingestion. Objective: We aimed to determine whether methylcellulose, a low‐cost, non‐fermentable gelling agent, widely used in food manufacture, could be formulated to match psyllium's physical properties and similarly moderate colonic fermentation of inulin. Methods: 3‐way randomised cross‐over study giving 15 g inulin with 15 g methylcellulose, psyllium or maltodextrin (placebo) in 22 healthy volunteers. Participants underwent hourly MRI scans for 6 h and serial breath hydrogen measurements for 24 h when a final MRI scan was performed. Results: Methylcellulose and psyllium gels did not significantly alter AUC _{0–360 min} , however, they were associated with less colonic gas after the gels reached the colon (AUC _{180–360 min} , p = 0.02). The gels increased AUC _{0–240 min} of small bowel free water ( p < 0.0001 and 0.048, respectively), methylcellulose effect>psyllium ( p = 0.0005). Both increased colon chyme wateriness (T1AC, AUC _{180–360 min} , p < 0.0001) and volume of hydrated fibre in colon (AUC _{180–360 min} , p < 0.0001 and 0.0009, respectively). Both parameters were greater after methylcellulose than psyllium ( p = 0.01 and 0.02, respectively). 24 h measurements of breath hydrogen were not different between groups (AUC _0–24 h , p = 1.0) but were reduced by psyllium in the 0–6‐h period p = 0.008. Conclusions: Methylcellulose and psyllium reduce colonic gas produced by inulin after the gels reach the colon. Methylcellulose increases the water content of both the small and large bowel more than psyllium. This additional effect may allow improved tolerance of FODMAPs, particularly in IBS patients with constipation. Trial Registration: ClinicalTrials.gov identifier: NCT06291272

Background: Inflammatory bowel disease (IBD) and colorectal cancer (CRC) share overlapping symptoms. Faecal immunochemical testing (FIT) is mandated in UK primary care to triage symptomatic patients suspected of having CRC, but the extent to which IBD is identified in these patients remains unclear. The aim of this study was to assess the 1-year IBD diagnosis rate in symptomatic patients after FIT for suspected CRC and how this varies with age, FIT level, and faecal calprotectin (FCP) result. Methods: A population-based cohort study of symptomatic patients who underwent FIT in the UK Clinical Practice Research Datalink (CPRD) (January 2019–June 2023) with 1-year follow-up was conducted. Kaplan–Meier estimates were used to assess cumulative 1-year IBD risk, stratified by age, FIT level, and FCP result. Results: Of 473 402 patients, 2762 patients (0.58%) were diagnosed with IBD within 1 year of FIT. Patients aged <50 years (110 501 patients) accounted for 53.6% of all IBD diagnoses (1481 patients), but only 6.9% of all CRC diagnoses (347 patients). Overall IBD risk was 2.3% with FIT ≥10 µg Hb/g compared with 0.1% with FIT <10 µg Hb/g. Among 63 469 patients with elevated FCP results and FIT levels, IBD risk in those aged 50 µg/g. The combined risk of CRC or IBD in those with FIT ≥10 µg Hb/g was 7.1%. This fell to 3.3% in the subset of patients who also had FCP ≤50 µg/g. Conclusion: IBD is more common than CRC in patients aged <50 years referred on symptomatic FIT pathways using FIT ≥10 µg Hb/g. In a selected cohort of dual-tested patients, FCP results provided additional risk stratification. Incorporating routine FCP testing into symptomatic FIT pathways may better target further investigations.

Dietary fibre is vital for a healthy diet, yet many people avoid it because of symptoms induced by colonic gas. Slowing rapid fermentation decreases colonic distention and reduces symptoms, allowing for better tolerance of prebiotics. Co-administration of inulin, a fermentable fibre, with psyllium, a gel-forming fibre, reduces gas production in irritable bowel syndrome patients compared to administering inulin alone, but the underlying mechanism is unclear. We hypothesise that psyllium polysaccharides’ physically cross-linked gel resists gastrointestinal shear forces and impairs microbial access to inulin, thereby delaying fermentation. Methylcellulose is another physically cross-linked fibre ingredient, widely used in food production for its tunability and affordability. Our aim was to develop a preparation of methylcellulose of comparable functionality to psyllium. A formulation of methylcellulose with comparable rheological and inulin release behaviour was developed in vitro. We subsequently performed a randomised, three-way, placebo-controlled non-inferiority study with healthy volunteers (n = 30), comparing the slowing of fermentation of inulin by co-administering with psyllium, methylcellulose or a control maltodextrin. Fermentation in vivo was assessed by breath hydrogen measurements for 24 hours after ingestion. While psyllium significantly reduced initial breath hydrogen production compared to the placebo, a non-inferior effect on reduction in initial breath hydrogen with methylcellulose was not demonstrated. Despite similar physicochemical properties, psyllium and methylcellulose hydrogels exhibited different transit behaviour based on the breath hydrogen time to rise >10 ppm and time to peak. We hypothesise that the fast reformation of psyllium's polysaccharide network or “self-healing” properties after deformation by intestinal pressure waves may underpin its effectiveness in slowing fermentation. The clinical trial registry number is NCT05911347 (https://clinicaltrials.gov).

Summary: Introduction: SARS‐CoV‐2 infection is associated with an increased risk of venous thromboembolism. Data are lacking on how this risk altered during the COVID‐19 pandemic and following vaccination. We aimed to evaluate the 90‐day risk of postoperative venous thromboembolism during the pandemic. Methods: We performed a retrospective cohort study of patients having abdominal, obstetric, orthopaedic, cardiac, thoracic or vascular surgical procedures using the OpenSAFELY‐TPP platform. Crude 90‐day risks of venous thromboembolism were calculated and crude and adjusted hazard ratios were derived from individual Cox proportional hazards models. Results: In total, 1,800,540 procedures were performed with 15,390 individual venous thromboembolic events recorded within 90 days. The highest crude absolute risk was in the Alpha wave at 1.2%. Postoperative SARS‐CoV‐2 infection was associated with a 4.4‐fold increase in relative risk of 90‐day venous thromboembolism (adjusted hazard ratio 4.42, 95%CI 4.21–4.64) compared with those without. Recent SARS‐CoV‐2 infection was associated with an increased risk of venous thromboembolism (adjusted hazard ratio 4.03, 95%CI 3.78–4.30) compared with those without. Patients who were unvaccinated had the highest relative risk for 90‐day venous thromboembolism. A single dose of vaccine was associated with a 20% relative risk reduction of venous thromboembolism (adjusted hazard ratio 0.80, 95%CI 0.76–0.84). Discussion: SARS‐CoV‐2 infection status and vaccination history were associated with 90‐day venous thromboembolism risk, with both recent and postoperative SARS‐CoV‐2 infection associated with an increased risk, whilst one dose of vaccine reduced the risk.

Background: COVID-19 is associated with higher rates of gastrointestinal diseases, though the duration of this effect, and the role of vaccination and COVID-19 severity remain uncertain. Objective: To investigate the relationship between COVID-19 and gastrointestinal diseases, by vaccination status in hospitalised and non-hospitalised patients. Design: With NHS England approval, OpenSAFELY-TPP was used to access linked data from 24 million English adults. We defined three cohorts: “Pre-vaccination” (January 2020-June 2021), “vaccinated” and “unvaccinated” (June-December 2021). We estimated adjusted hazard ratios (aHRs) comparing the incidence of 10 gastrointestinal diseases, including upper and lower gastrointestinal bleeding, after versus before or without a COVID-19 diagnosis overall and by COVID-19 severity. Results: COVID-19 diagnosis was associated with elevated incidence of gastrointestinal diseases, particularly after hospitalised disease. In the pre-vaccination cohort (n=18,422,781), the adjusted hazard ratios (aHRs) for upper gastrointestinal bleeding after hospitalised COVID-19 were 20.1 (95% CI 18.4–22.1) in weeks 1–4 and 1.90 (1.63–2.22) in weeks 53–102. The corresponding aHRs after non-hospitalised COVID-19 were 1.92 (1.74–2.11) and 1.34 (1.23– 1.45) respectively. Across time periods, aHRs for gastrointestinal diseases were lower in vaccinated (n=14,948,727) than in unvaccinated (n=3,479,043) individuals. These patterns were similar across gastrointestinal diseases. Conclusion: The incidence of gastrointestinal disease is elevated for up to two years among individuals hospitalised following a COVID-19 diagnosis. Increases in incidence are attenuated among vaccinated individuals. Monitoring for gastrointestinal diseases after severe COVID-19 and promotion of vaccination in vulnerable groups are key to reducing long-term burden. KEY MESSAGES: What is already known on this topic: Acute symptoms of COVID-19 include gastrointestinal problems, and there is existing evidence that those with a COVID-19 diagnosis are more likely to experience long-term gastrointestinal complications, especially if they were hospitalised. Previous studies were either limited in size, lacked representativeness of the population, or had short follow-up (e.g. during hospitalisation). The role of vaccination, COVID-19 severity or peoples’ characteristics (e.g. age or sex) were not considered. What this study adds: Based on population-wide data on 18.4 million individuals, rates of 10 gastrointestinal diseases are elevated after COVID-19, compared with rates before or without COVID-19 diagnosis. The elevation in rates of gastrointestinal diseases after COVID-19 diagnosis was less marked in people who were vaccinated before COVID-19 diagnosis. The elevation in rates was markedly higher, and persisted for up to two years, among individuals hospitalised with COVID-19, compared with those who were not hospitalised. How this study might affect research, practice or policy: We show for the first time that the incidence of both acute and chronic gastrointestinal diseases remains elevated for up to two years after severe COVID-19 leading to hospitalisation. Our findings highlight the protective role of COVID-19 vaccination in reducing severe COVID-19 and its subsequent long-term gastrointestinal complications, reinforcing the importance of vaccination as a public health measure. Individuals who had severe COVID-19, regardless of vaccination status, should be prioritised for clinical monitoring for gastrointestinal diseases.

Background: Peptic ulcers in patients on aspirin are associated with Helicobacter pylori infection. We investigated whether H. pylori eradication would protect against aspirin-associated ulcer bleeding. Methods: The Helicobacter Eradication Aspirin Trial was a randomised placebo-controlled trial (European Union Drug Regulating Authorities Clinical Trials 2011-003425-96), conducted in United Kingdom primary care using routinely collected clinical data. Consenting participants aged ≥ 60 years prescribed aspirin ≤ 325 mg but not ulcerogenic or gastroprotective medication underwent C13 urea breath testing for H. pylori. Those with a positive test were randomised to receive either a combination of clarithromycin 500 mg, metronidazole 400 mg and lansoprazole 30 mg, or placebos twice daily for 7 days. The primary outcome, time to death or hospitalisation due to peptic ulcer bleeding, was analysed using a Cox proportional hazards model. Findings: Between 14 September 2012 and 22 November 2017, 30,166 participants underwent H. pylori breath testing, 5367 had a positive result, 5352 were randomised to an intention-to-treat population of 2677 (eradication) and 2675 (placebo) and followed up for a median of 5.0 years (interquartile range 3.9–6.4). Statistical analysis of the primary outcome showed an overall hazard ratio of 0.69 [95% confidence interval 0.38 to 1.25; p = 0.22], but there was a significant departure from the proportional hazards assumption (p = 0.0068), requiring analysis split at the median time to event: 2.5 years. There was a significant reduction in the primary outcome in the eradication treatment group in the first 2.5 years (hazard ratio 0.35, 95% confidence interval 0.14 to 0.89; p = 0.028) but not the second period (hazard ratio 1.31, 95% confidence interval 0.55 to 3.11). The number needed to treat (first period) was 238 (95% confidence interval 184 to 1661). Results in the first 2.5 years remained significant when accounting for the competing risk of death (p = 0.028). During the study period, 657 participants died (306 in the eradication group and 351 in the controls group; hazard ratio 0.86, 95% confidence interval 0.74 to 1.01; p = 0.058). Malignancy was the most common cause of death and largely accounted for the numerical difference between the treatment groups. A health economic analysis found proactive screening not cost-effective, since the monetised benefits of the intervention in preventing a peptic ulcer bleed failed to outweigh the costs. Interpretation: Helicobacter pylori eradication protects against aspirin-associated peptic ulcer bleeding, but this may not be sustained or cost-effective when applied non-selectively to our study population. The possibility that H. pylori eradication, on a background of aspirin use, might affect death from malignancies warrants further evaluation. Limitations and future work: Studying subjects already established on aspirin probably contributed to the low event rate. A future study should investigate subjects starting on aspirin when the event rate is higher. Trial registration: This trial is registered as ISRCTN10134725; ClinicalTrials.gov number NCT01506986. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 09/55/52) and is published in full in Health Technology Assessment; Vol. 29, No. 42. See the NIHR Funding and Awards website for further award information.

Background/Objectives: Faecal Immunochemical Testing (FIT) is recommended for patients presenting to primary care with symptoms suggestive of colorectal cancer. This study quantified variations in use across England. Methods: Retrospective cohort of English patients (≥ 18 years) with a FIT result reported in routinely collected primary care records, 2019– 2023. Rates of FIT testing by age, sex, year and region were adjusted using Poisson regression. Multivariate logistic regression compared the effect of factors on the proportion of results exceeding the recommended referral threshold (10μgHb/g). Results: Between 01/01/2019 and 05/06/2023 there were 531,735 FIT results among 495,121 patients. Rates of testing increased from 0.69 per thousand person-years in 2019 (95% CI 0.68– 0.71) to 27.70 in 2023 (95% CI 27.56– 27.85). There were large variations in testing between regions, with rates > 3-fold higher in the Northeast than the West Midlands: 17.05 (95% CI 16.87– 17.23) versus 4.72 (95% CI 4.67– 4.76) per thousand person-years. About 20.4% of FIT results were ≥ 10μgHb/g. Despite increased testing, this did not change over time. The proportion of FIT ≥ 10μgHb/g was lower in regions with higher rates of testing, from 16.7% (Southwest) to 25.3% (Southeast; rates of testing 14.62 and 8.00 per thousand person-years respectively). This difference in proportion of FIT ≥ 10μgHb/g persisted after adjusting for year, sex and age (OR 0.57, 95% CI 0.55– 0.58). Conclusion: Rapid increases in FIT testing in primary care show large, persistent variations between English regions, which correlate with the proportion of results meeting the criteria for onward referral. Differences in the population tested and FIT’s implementation between regions are likely to explain these variations. Plain Language Summary: 1) Why was this study done?A simple test for blood in the poo, called FIT, can help decide whether a person with bowel symptoms seeing their primary care doctor should be referred to a hospital for further bowel investigations.Currently, a FIT result of 10 μgHb/g faeces or more is recommended to guide referral for bowel tests.No study has reported how FIT use, or results, differs across England. 2) What did the researchers find?This is the first study on national patterns of FIT testing, showing a rapid but unequal increase across England.There is large variation in the proportion of FIT results exceeding the referral criteria of 10 μgHb/g faeces between English regions that is associated with the rate of testing in each region. 3) What do these results mean?Using a single FIT value as a threshold for onwards referral may work differently in different regions of England. As FIT is adopted more widely and rates of testing increase, primary care services may see a decrease in the proportion of patients with a FIT result reported over the referral threshold.