Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases

Socioeconomic differences in selection for liver resection in metastatic colorectal cancer and the impact on survival

Background Socioeconomic inequalities in colorectal cancer (CRC) survival are well recognised. The aim of this study was to describe the impact of socioeconomic deprivation on survival in patients with synchronous CRC liver-limited metastases, and to investigate if any survival inequalities are explained by differences in liver resection rates. Methods Patients in the National Bowel Cancer Audit diagnosed with CRC between 2010 and 2016 in the English National Health Service were included. Linked Hospital Episode Statistics data were used to identify the presence of liver metastases and whether a liver resection had been performed. Multivariable random-effects logistic regression was used to estimate the odds ratio (OR) of liver resection by Index of Multiple Deprivation (IMD) quintile. Cox-proportional hazards model was used to compare 3-year survival. Results 13,656 patients were included, of whom 2213 (16.2%) underwent liver resection. Patients in the least deprived IMD quintile were more likely to undergo liver resection than those in the most deprived quintile (adjusted OR 1.42, 95% confidence interval (CI) 1.18–1.70). Patients in the least deprived quintile had better 3-year survival (least deprived vs. most deprived quintile, 22.3% vs. 17.4%; adjusted hazard ratio (HR) 1.20, 1.11–1.30). Adjusting for liver resection attenuated, but did not remove, this effect. There was no difference in survival between IMD quintile when restricted to patients who underwent liver resection (adjusted HR 0.97, 0.76–1.23). Conclusions Deprived CRC patients with synchronous liver-limited metastases have worse survival than more affluent patients. Lower rates of liver resection in more deprived patients is a contributory factor

Including Health Economic Analysis in Pilot Studies: Lessons learned from a cost-utility analysis within the PROSPECTIV pilot study

Purpose To assess feasibility and health economic benefits and costs as part of a pilot study for a nurse-led, psychoeducational intervention (NPLI) for prostate cancer in order to understand the potential for cost effectiveness as well as contribute to the design of a larger scale trial. Methods Men with stable prostate cancer post-treatment were recruited from two cancer centres in the UK. Eighty-three men were randomised to the NLPI plus usual care or usual care alone (UCA) (42 NLPI and 41 UCA); the NLPI plus usual care was delivered in the primary-care setting (the intervention) and included an initial face-to-face consultation with a trained nurse, with follow-up tailored to individual needs. The study afforded the opportunity to undertake a short-term within pilot analysis. The primary outcome measure for the economic evaluation was quality of life, as measured by the EuroQol five dimensions questionnaire (EQ-5D) (EQ-5D-5L) instrument. Costs (£2014) assessed included health-service resource use, out-of-pocket expenses and losses from inability to undertake usual activities. Results Total and incremental costs varied across the different scenarios assessed, with mean cost differences ranging from £173 to £346; incremental effect, as measured by the change in utility scores over the duration of follow-up, exhibited wide confidence intervals highlighting inconclusive effectiveness (95% CI: -0.0226; 0.0438). The cost per patient of delivery of the intervention would be reduced if rolled out to a larger patient cohort. Conclusions The NLPI is potentially cost saving depending on the scale of delivery; however, the results presented are not considered generalisable

The health professionals’ perspectives of support needs of adult head and neck cancer survivors and their families: a Delphi study

Purpose: The aim was to identify the views of Australian and New Zealand health professionals regarding the support needs of people with head and neck cancer (HNC) and their families and current gaps in service delivery. Methods: A modified Delphi process assessed support needs of people with HNC following acute medical management. A systematic review of the literature was used to develop items relevant to seven key concepts underpinning the psychological experience of living with HNC. A panel of 105 health professionals was invited to participate in two questionnaire rounds. Results: Of the potential panellists, 50 (48%) completed round 1, and of these, 39 (78%) completed round 2. Following two rounds, there was consensus agreement on the concepts uncertainty and waiting, disruption to daily life and fear of recurrence. The concepts the diminished self, making sense of and managing the experience, sharing the burden and finding a path did not achieve consensus. There were no differences in responses according to gender, organization type or location. Medical professionals had significantly higher agreement for the concept uncertainty and waiting compared to allied health professionals, and professionals with five years’ or more experience had significantly higher agreement than those with less experience. Conclusions: Health professionals agreed that many psychosocial support needs of HNC survivors and families are not being met and that they experience difficulties in meeting these needs. Findings may inform evidence-based treatment programs for HNC survivors and their families to promote psychological resilience and quality of life in this vulnerable population

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods: This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings: After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10−78), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10−18). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10−4). Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time. Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list). </p