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Background A faecal immunochemical test (FIT) result ≥ 10 µg/g is recommended in the UK to triage patients with symptoms of colorectal cancer (CRC) in primary care for urgent cancer investigation. The COLOFIT model combining FIT results with demographics and blood tests was developed to reduce the proportion of people referred without CRC. This study aims to externally validate the COLOFIT using data from Oxford University Hospitals (OUH). Methods FITs requested by GPs between January 2017 and February 2024 were extracted from the OUH Clinical Data warehouse. Adults with COLOFIT predictors and 180-day follow-up for CRC were included. External validation of the COLOFIT equation was conducted overall and for six independent time periods. Risk score thresholds where the model captured the same number of cancers as FIT ≥ 10 µg/g were estimated to understand the number of urgent referrals avoided. Results A total of 51,477 individuals (659 CRC) were included; 6194 (12%) had FIT ≥ 10 µg/g. FIT positivity and testing volume increased over time, associated with a gradual change from testing lower-risk patients to including those with higher-risk symptoms. COLOFIT was poorly calibrated overall (observed/expected [O/E] ratio 1.52 with calibration slope 1.05), but calibration improved over time (up to O/E ratio 1.09 with calibration slope 1.05). COLOFIT reduced referrals by 8% overall without missing colorectal cancers compared to FIT ≥ 10 µg/g, but this varied from 23% reduction to 2% increase depending on the period evaluated. Conclusions The potential benefit of COLOFIT varied depending on FIT testing rates, the proportion of FIT ≥ 10 µg/g, and the symptoms in the tested population. Adopting COLOFIT into current clinical practice demands, therefore, FIT positivity of at least 17% and CRC rates within 1.3–1.6%. Further validation in local and different populations would also be of significant value and help to maximise COLOFIT’s ability to improve diagnostic pathways.

Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic. We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention [PCI], PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs. Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020. Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses. UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.

Background Randomised trials are essential to reliably assess medical interventions. Nevertheless, interpretation of such studies, particularly when considering absolute effects, is enhanced by understanding how the trial population may differ from the populations it aims to represent. Methods We compared baseline characteristics and mortality of RECOVERY participants recruited in England ( n  = 38,510) with a reference population hospitalised with COVID-19 in England ( n  = 346,271) from March 2020 to November 2021. We used linked hospitalisation and mortality data for both cohorts to extract demographics, comorbidity/frailty scores, and crude and age- and sex-adjusted 28-day all-cause mortality. Results Demographics of RECOVERY participants were broadly similar to the reference population, but RECOVERY participants were younger (mean age [standard deviation]: RECOVERY 62.6 [15.3] vs reference 65.7 [18.5] years) and less frequently female (37% vs 45%). Comorbidity and frailty scores were lower in RECOVERY, but differences were attenuated after age stratification. Age- and sex-adjusted 28-day mortality declined over time but was similar between cohorts across the study period (RECOVERY 23.7% [95% confidence interval: 23.3–24.1%]; vs reference 24.8% [24.6–25.0%]), except during the first pandemic wave in the UK (March–May 2020) when adjusted mortality was lower in RECOVERY. Conclusions Adjusted 28-day mortality in RECOVERY was similar to a nationwide reference population of patients admitted with COVID-19 in England during the same period but varied substantially over time in both cohorts. Therefore, the absolute effect estimates from RECOVERY were broadly applicable to the target population at the time but should be interpreted in the light of current mortality estimates. Trial registration ISRCTN50189673- Feb. 04, 2020, NCT04381936- May 11, 2020.

High-quality rectal cancer surgery is known to improve patient outcome. We aimed to assess the quality of colon cancer surgery by studying the extent of variation in the plane of surgical resection, the amount of tissue removed, and its association with survival. All resections for primary colon adenocarcinoma done at Leeds General Infirmary (Leeds, UK) between Jan 1, 1997, and June 30, 2002, were identified. The specimens were photographed and graded according to the plane of mesocolic dissection. Tissue morphometry was done on 253 tumours. Univariate and multivariate models were used to ascertain whether there was an association with 5-year survival. The primary outcome measure was overall survival defined as death from any cause. 521 cancers were identified, 122 were excluded because of either no photographic images or insufficient images to allow retrospective grading, leaving 399 specimens for analysis. There was marked variation in the proportion of each plane of surgery: muscularis propria in 95 of 399 (24%) specimens, intramesocolic in 177 of 399 (44%) specimens, and mesocolic in 127 of 399 (32%) specimens. Mean cross-sectional tissue area outside the muscularis propria was significantly higher with mesocolic plane surgery (mean 2181 [SD 895] mm 2) compared with intramesocolic (mean 2109 [1273] mm 2) and muscularis propria plane (mean 1447 [913] mm 2) surgery (p=0·0003). There was also a significant increase in the distance from the muscularis propria to the mesocolic resection margin with mesocolic plane surgery (mean 44 [21] mm) compared with intramesocolic (mean 30 [16] mm) and muscularis propria plane (mean 21 [12] mm) surgery, which was independent of tumour site (all excisions p<0·0001). We noted a 15% (95% CI) overall survival advantage at 5 years with mesocolic plane surgery compared with surgery in the muscularis propria plane (HR 0·57 [0·38–0·85], p=0·006) in univariate analysis. However, this association was no longer significant in the multivariate model (HR 0·86 [95% CI 0·56–1·31], p=0·472), but was especially noted in patients with stage III cancers (HR 0·45 [95% CI 0·24–0·85], p=0·014; multivariate analysis). The plane of surgery and amount of mesocolon removed varied between the different sites with better planes in left-sided resections than right-sided ones, which were better than transverse resection (p<0·0001). As previously shown in the rectum, we have now shown there is marked variability in the plane of surgery achieved in colon cancer. Improving the plane of dissection might improve survival, especially in patients with stage III disease. If confirmed by clinical trial data, such as from the ongoing National Cancer Research Institute Fluoropyrimidine, Oxaliplatin and Targeted Receptor pre-Operative Therapy for colon cancer (FOxTROT) trial of neoadjuvant chemotherapy in advanced resectable colon cancer, improvement of the plane of dissection might be a new cost-effective method of decreasing morbidity and mortality in patients with colon cancer. National Institute for Health Research Academic Clinical Fellowship Programme, Experimental Cancer Medicine Centre programme (both Department of Health, London, UK), Yorkshire Cancer Research (Harrogate, UK), and the Pelican Trust (Basingstoke, UK).

Bariatric surgery-induced weight loss is associated with reduced overall cancer incidence; however, some data suggest that risk of colorectal cancer (CRC) actually increases. Here, we suggest a need to fully characterise CRC (and colorectal adenoma) risk after bariatric surgery given that preventive measures (early diagnosis and polypectomy) can mitigate risk.

ObjectiveStudies 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.MethodsData 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.ResultsEarly-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).ConclusionThis 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.

BackgroundIn observational studies, the risk of immortal-time bias (ITB) increases with the likelihood of early death, itself increasing with age. We investigated how age impacts the magnitude of ITB when estimating the effect of surgery on 1-year overall survival (OS) in patients with Stage IV colon cancer aged 50–74 and 75–84 in England.MethodsUsing simulations, we compared estimates from a time-fixed exposure model to three statistical methods addressing ITB: time-varying exposure, delayed entry and landmark methods. We then estimated the effect of surgery on OS using a population-based cohort of patients from the CORECT-R resource and conducted the analysis using the emulated target trial framework.ResultsIn simulations, the magnitude of ITB was larger among older patients when their probability of early death increased or treatment was delayed. The bias was corrected using the methods addressing ITB. When applied to CORECT-R data, these methods yielded a smaller effect of surgery than the time-fixed exposure approach but effects were similar in both age groups.ConclusionITB must be addressed in all longitudinal studies, particularly, when investigating the effect of exposure on an outcome in different groups of people (e.g., age groups) with different distributions of exposure and outcomes.

Patients with inflammatory bowel diseases (IBDs) of the colon are at an increased risk of colorectal cancer (CRC). This study investigates the epidemiology of IBD-CRC and its outcomes. Using population data from the English National Health Service held in the CRC data repository, all CRCs with and without prior diagnosis of IBD (Crohn's, ulcerative colitis, IBD unclassified, and IBD with cholangitis) between 2005 and 2018 were identified. Descriptive analyses and logistic regression models were used to compare the characteristics of the 2 groups and their outcomes up to 2 years. Three hundred ninety thousand six hundred fourteen patients diagnosed with CRC were included, of whom 5,141 (1.3%) also had a previous diagnosis of IBD. IBD-CRC cases were younger (median age at CRC diagnosis [interquartile range] 66 [54-76] vs 72 [63-79] years [ P < 0.01]), more likely to be diagnosed with CRC as an emergency (25.1% vs 16.7% [ P < 0.01]), and more likely to have a right-sided colonic tumor (37.4% vs 31.5% [ P < 0.01]). Total colectomy was performed in 36.3% of those with IBD (15.4% of Crohn's, 44.1% of ulcerative colitis, 44.5% of IBD unclassified, and 67.7% of IBD with cholangitis). Synchronous (3.2% vs 1.6% P < 0.01) and metachronous tumors (1.7% vs 0.9% P < 0.01) occurred twice as frequently in patients with IBD compared with those without IBD. Stage-specific survival up to 2 years was worse for IBD-associated cancers. IBD-associated CRCs occur in younger patients and have worse outcomes than sporadic CRCs. There is an urgent need to find reasons for these differences to inform screening, surveillance, and treatment strategies for CRC and its precursors in this high-risk group.

ObjectiveTo explore the risk of a positive test result for the delta or omicron variant of the SARS-CoV-2 virus in different occupations and deprivation groups in the UK.DesignAnalysis of the longitudinal COVID-19 Infection Survey.SettingCOVID-19 Infection Survey, conducted by the Office for National Statistics and the University of Oxford, UK, a nationwide longitudinal survey to monitor SARS-CoV-2 infection in the community, 26 April 2020 to 31 January 2022.ParticipantsSurvey participants recruited from randomly selected households to reflect the UK population (England, Scotland, Wales, and Northern Ireland) were divided into the delta cohort (2 July 2020 to 19 December 2021) and the omicron variant (on or after 20 December 2021), the dominant variants during our study period.Main outcome measuresIncidence rate and incidence rate ratio for the presence of the delta and omicron variants by area level deprivation and occupation sector. Multivariable Poisson regression models were fitted to estimate the adjusted incidence rate ratio after adjusting for age, sex, ethnic group, comorbid conditions, urban or rural residence, household size, patient or client facing job, and time (as quarters of the year).Results329 356 participants were included in the delta cohort and 246 061 in the omicron cohort. The crude incidence rate for the presence of the delta and omicron variants of the SARS-CoV-2 virus were higher in the most deprived group (based on the index of multiple deprivation divided by deciles; delta cohort 4.33 per 1000 person months, 95% confidence interval 4.09 to 4.58; omicron cohort 76.67 per 1000 person months, 71.60 to 82.11) than in the least deprived group (3.18, 3.05 to 3.31 and 54.52, 51.93 to 57.24, respectively); the corresponding adjusted incidence rate ratios were 1.37 (95% confidence interval 1.29 to 1.47) and 1.34 (1.24 to 1.46) during the delta and omicron variant dominant periods, respectively. The adjusted incidence rate ratios for a positive test result in the most deprived group compared with the least deprived group in the delta cohort were 1.59 (95% confidence interval 1.25 to 2.02) and 1.50 (1.19 to 1.87) in the healthcare and manufacturing or construction sectors, respectively. Corresponding values in the omicron cohort were 1.50 (1.15 to 1.95) and 1.43 (1.09 to 1.86) in the healthcare and teaching and education sectors, respectively. Associations between SARS-CoV-2 infection and other employment sectors were not significant or were not tested because of small numbers.ConclusionIn this study, the risk of a positive test result for the SARS-CoV-2 virus in the delta and omicron cohorts was higher in the most deprived than in the least deprived group in the healthcare, manufacturing or construction, and teaching and education sectors.

There is variability in clinical outcome for patients with apparently the same stage colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) mapping to chromosomes 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and Xp22 have robustly been shown to be associated with the risk of developing CRC. Since germline variation can also influence patient outcome the relationship between these SNPs and patient survivorship from CRC was examined. All enrolled into the National Study of Colorectal Cancer Genetics (NSCCG) were genotyped for 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and xp22 SNPs. Linking this information to the National Cancer Data Repository allowed patient genotype to be related to survival. The linked dataset consisted of 4,327 individuals. 14q22.22 genotype defined by the SNP rs4444235 showed a significant association with overall survival. Specifically, the C allele was associated with poorer observed survival (per allele hazard ratio 1.13, 95% confidence interval 1.05-1.22, P = 0.0015). The CRC susceptibility SNP rs4444235 also appears to exert an influence in modulating patient survival and warrants further evaluation as a potential prognostic marker.