Perceptions and psychosocial impact of food, nutrition, eating and drinking in people with inflammatory bowel disease: a qualitative investigation of food-related quality of life.

INTRODUCTION: Extensive research has provided an important understanding of the impact of inflammatory bowel disease (IBD) on nutrient intake, requirements and metabolism. By contrast, there has been limited research examining the psychosocial aspects of food, eating and drinking in IBD. The present study aimed to address this unmet need. METHODS: Qualitative semi-structured interviews regarding the perceptions and psychosocial impact of food, eating and drinking were undertaken with 28 purposively selected people with IBD. Interviews were audio-recorded and transcribed verbatim. Colaizzi's framework was used to structure the data analysis. RESULTS: Five major themes were identified. IBD symptoms and both surgical and medical treatments were described as having a direct impact on eating and drinking, with participants also using different food-related strategies to control IBD symptoms. These included a process of experimentation to identify trigger foods, following a severely restricted and limited diet, eating small portions, and eating more frequently. However, their limited knowledge about if, and how, food affected their symptoms, often resulted in negative coping strategies that impacted on psychosocial functioning, including a lack of enjoyment of eating, being afraid to eat and finding social occasions stressful. Managing food and drinking also made food shopping and preparation more burdensome, creating problems with families, at work and for social life, as well as the need for careful preparation and advanced planning of activities. CONCLUSIONS: Inflammatory bowel disease has a profound impact on psychosocial aspects of food and nutrition, which impacts on 'food-related quality of life' (FRQoL). Further research is required to identify interventions that will improve FRQoL in patients with IBD.

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included.These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings;1. Patient populations involved in AYP transition. 2. Risks of failing transition or poor transition. 3. Models of AYP transition. 4. Patient and carer/parent perspective in AYP transition. 5. Surgical perspective.(AU)

Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease.

Type 1 interferon (IFN-1) promotes regulatory T-cell function to suppress inflammation in the mouse intestine, but little is known about IFN-1 in the human gut. We therefore assessed the influence of IFN-1 on CD4+ T-cells isolated from human colon tissue obtained from healthy controls or patients with inflammatory bowel disease (IBD). Immunofluorescent imaging revealed constitutive expression of IFNß in human intestinal tissue, and colonic T-cells were responsive to exogenous IFN-1 as assessed by phosphorylation of signal transduction and activator of transcription 1 (pSTAT1) and induction of interferon stimulated genes (ISGs). Unlike their blood counterparts, intestinal T-cells from non-inflamed regions of IBD colon displayed enhanced responsiveness to IFN-1, increased frequency of pSTAT1+ cells, and greater induction of ISGs upon IFN-1 exposure in vitro. In healthy tissue, antibody neutralization of IFNß selectively reduced T-cell production of the pro-regulatory cytokine interleukin-10 (IL-10) and increased IFNγ synthesis. In contrast, neutralization of IFNß in IBD tissue cultures increased the frequency of T-cells producing inflammatory cytokines but did not alter IL-10 expression. These data support a role for endogenous IFN-1 as a context-dependent modulator of T-cell function that promotes regulatory activity in healthy human intestine, but indicate that the IFN-1/STAT1 pathway is dysregulated in inflammatory bowel disease.

Systematic review: outcomes and post-operative complications following colectomy for ulcerative colitis.

BACKGROUND: Colectomy for ulcerative colitis is associated with short- and long-term complications. Estimates of the frequency of such complications are variable and may have changed since the introduction of biological therapy. Understanding the true burden of surgical complications is important to clinicians in assessing risks and benefits of colectomy vs. continued medical therapy. AIM: To ascertain the outcomes of colectomy and ileal pouch surgery in patients with ulcerative colitis in the biologics era. METHODS: Embase, MEDLINE and The Cochrane Library were searched for studies (2002-2015) reporting the outcomes of colorectal procedures (total and subtotal colectomy, IPAA with J-, S-, W-pouch) in adults with ulcerative colitis. Conferences proceedings (2011-2015) were hand-searched. RESULTS: We identified 28 studies (20,801 patients) reporting outcomes from procedures conducted from 2002-2015. Early complications (≤30 days post-operatively), reported in 10 studies, occurred in 9-65% of patients with ulcerative colitis; late complications (>30 days post-operatively) occurred in 17-55% of patients. Most frequent short-term complications: infectious complications and ileus (mean incidence 20% and 18%). Most frequent long-term complications: pouchitis, faecal incontinence and small bowel obstruction (mean incidence 29%, 21% and 17%). Rates of early infection and late pouch failure decreased from 22% and 13% in 2002-2009 to 11% and 2% in 2010-2015. The mean incidence of post-operative mortality was 1.0% across 11 studies. CONCLUSIONS: Early and late complications arise in about one-third of patients undergoing surgery for ulcerative colitis. While colorectal surgical procedures are recommended for a specific group of patients, the post-operative complications associated with these procedures should not be underestimated.

Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.

BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109 /L) and faecal calprotectin (HR 2.95 for >50 µg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.

Systematic review: the financial burden of surgical complications in patients with ulcerative colitis.

BACKGROUND: Patients undergoing colectomy for ulcerative colitis (UC) may experience complications associated with reduced quality of life (QoL), and maybe a considerable economic burden to healthcare systems. Appreciation of these burdens is important to evaluate the cost effectiveness of newer interventions for UC vs. colectomy. AIM: To identify data representing resource utilisation or costs of complications arising from colorectal procedures in patients with UC, and data representing patient QoL, as reported by health state utility values (HSUVs). METHODS: Embase, MEDLINE and The Cochrane Library were searched for studies (1995-2014) reporting resource use/costs of surgical complications, and HSUVs data in adult patients with UC, undergoing colorectal procedures. Conference proceedings (January 2011-January 2014) were hand-searched. RESULTS: Twelve studies reported resource use/costs, and three reported HSUVs data in patients with UC experiencing surgical complications. Additional mean costs of postoperative complications ranged from $18 650/patient with complications at a 6-month follow-up (46% incidence) to $34 714/patient with complications over a 5-year period (49% incidence). Pouchitis, pouch failure and small bowel obstruction carried the greatest burden. Marked reductions in HSUVs were observed for patients with UC experiencing surgical complications, vs. patients with UC in a remission state. CONCLUSIONS: There is a paucity of well reported studies on resource use/cost, and QoL burden of surgical complications in patients with UC. However, surgical complications represent a substantial burden both in terms of cost and of quality of life, with reoperations, physician fees, additional in-patient hospital stays and infertility treatment being the main cost drivers.

Review article: selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases.

BACKGROUND: A link between histone deacetylases (HDACs) and intestinal inflammation has been established. HDAC inhibitors that target gut-selective inflammatory pathways represent a potential new therapeutic strategy in patients with refractory inflammatory bowel diseases (IBD). AIMS: To review the use of selective HDAC inhibitors to treat gut inflammation and to highlight potential improvements in selectivity/sensitivity by additional targeting of HDAC-regulating microRNAs (miRNAs). METHODS: Original articles and reviews have been identified using PubMed search terms: 'histone deacetylase', 'HDAC inhibitor', 'inflammatory bowel disease', 'gut inflammation,' and 'microRNA and HDAC'. RESULTS: The use of butyrate in distal colitis provided the first evidence that inhibition of HDACs decreases intestinal inflammation in IBD. HDAC inhibitors, such as valproic acid, vorinostat and givinostat, reduce inflammation and tissue damage in experimental murine colitis. Potential mechanisms of action for HDAC inhibitors include increased apoptosis, reduction of pro-inflammatory cytokine release, regulation of transcription factors and modulation of HDAC-regulatory miRNAs. HDAC2, HDAC3, HDAC6, HDAC9 and HDAC10 isoforms seem to be specifically involved in chronic intestinal inflammation, justifying the use of selective inhibitors as new therapeutic strategies in IBD. Controlling miRNAs for these isoforms can be identified. CONCLUSIONS: The pro-inflammatory influence of HDACs in the gut has been confirmed, but mostly in murine studies. Considerably more human data are required to permit development of selective HDAC inhibitors for IBD treatment. Inhibition of key HDAC isoforms in combination with modulation of HDAC-regulatory miRNAs has potential as a novel therapeutic approach.

Thiopurine withdrawal during sustained clinical remission in inflammatory bowel disease: relapse and recapture rates, with predictive factors in 237 patients.

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) remain integral to most medical strategies for maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC). Indefinite use of these drugs is tempered by long-term risks. While clinical relapse is noted frequently following drug withdrawal, there are few published data on predictive factors. AIM: To investigate the success of planned thiopurine withdrawal in patients in sustained clinical remission to identify rates and predictors of relapse. METHODS: This was a multicentre retrospective cohort study from 11 centres across the UK. Patients included had a definitive diagnosis of IBD, continuous thiopurine use ≥3 years and withdrawal when in sustained clinical remission. All patients had a minimum of 12 months follow-up post drug withdrawal. Primary and secondary end points were relapse at 12 and 24 months respectively. RESULTS: 237 patients were included in the study (129 CD; 108 UC). Median duration of thiopurine use prior to withdrawal was 6.0 years (interquartile range 4.4-8.4). At follow-up, moderate/severe relapse was observed in 23% CD and 12% UC patients at 12 months, 39% CD and 26% UC at 24 months. Relapse rate at 12 months was significantly higher in CD than UC (P = 0.035). Elevated CRP at withdrawal was associated with higher relapse rates at 12 months for CD (P = 0.005), while an elevated white cell count was predictive at 12 months for UC (P = 0.007). CONCLUSION: Thiopurine withdrawal in the context of sustained remission is associated with a 1-year moderate-to-severe relapse rate of 23% in Crohn's disease and 12% in ulcerative colitis.

Factors associated with thiopurine non-adherence in patients with inflammatory bowel disease.

BACKGROUND: Medication non-adherence seems to be a particular problem in younger patients with inflammatory bowel disease (IBD) and has a negative impact on disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine metabolite levels, is more common in young adults attending a transition clinic than adults with IBD and whether psychological co-morbidity is a contributing factor. We also determined the usefulness of the Modified Morisky 8-item Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co-morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the patients were non-adherent. Multivariate analysis [OR, (95% CI), P value] confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4), 0.01] were associated with non-adherence. Receiver operator curve analysis of MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P < 0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a specificity of 64% to predict thiopurine non-adherence. Non-adherence was associated with escalation in therapy, hospital admission and surgeries in the subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is more common in young adults with inflammatory bowel disease, and is associated with lower socio-economic status and depression. The high negative predictive value of MMAS-8 scores <6 suggests that it could be a useful screen for thiopurine non-adherence.

A UK retrospective observational study of clinical outcomes and healthcare resource utilisation of infliximab treatment in Crohn's disease.

BACKGROUND: Crohn's disease (CD) places a substantial burden on healthcare systems, with the majority of costs arising from hospitalisation and surgery. AIM: To evaluate the 'real-world' clinical effectiveness, impact on healthcare utilisation and cost of infliximab for the treatment of CD in UK practice. METHODS: A non-interventional, retrospective analysis of medical records from patients with CD treated with infliximab at 18 hospital centres across the UK. The primary objective was to compare cumulative clinical outcomes and healthcare resource utilisation for the 0- to 24-month post-infliximab period with the 12 months preceding infliximab treatment. Predefined outcomes included the number of elective surgical procedures, hospitalisations and healthcare provider consultations. Costs associated with healthcare utilisation were collected from the perspective of the UK National Health Service (NHS). RESULTS: The study involved 380 patients. Infliximab significantly reduced the mean number of elective (from 0.18 to 0.11; P = 0.0035) and non-elective (from 0.46 to 0.29; P < 0.0001) hospitalisations, and the number of consultations with gastroenterologists, gastrointestinal surgeons and radiologists (from 4.0 to 3.5, from 0.7 to 0.5 and from 0.5 to 0.2, respectively; all P < 0.001); all decreases were associated with significant cost reductions. The mean number of elective surgical procedures (including correction of severe anal fistulae and abscess drainage) was significantly reduced. CONCLUSIONS: The observed reductions in numbers of hospitalisations, surgical procedures and consultations with healthcare professionals are key indicators of the clinical effectiveness of infliximab for the treatment of CD. These benefits result in overall decreases in healthcare resource utilisation, which translate into cost savings for the NHS.

Review article: strategies for the management of chronic unremitting ulcerative colitis.

BACKGROUND: Chronic active ulcerative colitis (UC) is associated with significant morbidity, loss of productivity, increased colorectal cancer risk and cost. Up to 18% of patients suffer chronic active disease, with 30% requiring colectomy at 10 years. The management remains challenging given the relatively few clinical trials in this area. AIM: To summarise the evidence regarding optimal management strategies for patients with chronic active UC of differing disease extents and degrees of treatment refractoriness. METHOD: A literature search using the PubMed and Medline databases was performed. No time limit was set on article publication for inclusion. RESULTS: The principles of management should focus on confirming disease activity, exclusion of alternative diagnoses, adherence and treatment escalation. Infliximab and topical tacrolimus are options in refractory proctitis, although the evidence for these therapies is limited. Both infliximab and adalimumab are effective in corticosteroid-refractory disease, although the proportions of patients achieving corticosteroid-free remission remain modest (24% at 30 weeks and 16.9% at 8 weeks respectively). Alternatives include ciclosporin and tacrolimus, and possibly methotrexate. Colectomy often leads to an improved quality of life; medical strategies unlikely to provide durable corticosteroid-free remission should not be pursued. CONCLUSIONS: No current pharmacological treatment delivers mucosal healing in the majority of patients. Newer treatments such as vedolizumab and tofacitinib may represent valuable future therapies. Available medical options should be discussed with patients at every step of their management, with an honest appraisal of the evidence. Surgery should always be considered in patients with chronic refractory disease of any extent.

The phenotype and course of inflammatory bowel disease in UK patients of Bangladeshi descent.

BACKGROUND: We have tested the hypotheses that compared with local white Caucasians, UK-resident patients of Bangladeshi descent develop inflammatory bowel disease (IBD) at a younger age; more often have Crohn's disease than ulcerative colitis (UC); and have a more aggressive disease course. AIM: To test the hypotheses that compared to white Caucasian patients of English, Scottish or Welsh descent, patients of Bangladeshi descent develop IBD at a younger age; more often have Crohn's disease; and have a more aggressive disease course by screening case-records of these patients. METHODS: We screened the case-records of 132 Bangladeshi and 623 white Caucasian consecutive out-patients. We then matched each Bangladeshi to a patient of white Caucasian descent for age at diagnosis and disease duration. Data on migration status, phenotype, disease course, treatments and extra-intestinal manifestations and complications were obtained. RESULTS: No differences were seen in the adjusted age at diagnosis of IBD between Bangladeshi and white Caucasian patients. More Bangladeshis than white Caucasian patients (P < 0.01) were diagnosed with Crohn's disease than UC. Crohn's phenotype at diagnosis was similar in both groups. However, multivariate Cox logistic regression analyses showed that Bangladeshis developed perianal complications (HR [95% confidence interval CI] 8.6 [1.4, 53.1], P = 0.02), and received anti-TNFs (HR [95% CI] 3.0 [1.2, 7.7], P = 0.02) earlier and underwent surgery later (HR [95% CI] 0.4 [0.2, 0.9], P = 0.03) than white Caucasians. More Bangladeshis with UC had extensive disease (24/40 [60%]) than white Caucasians (16/49 [33%], P = 0.02). Overall, more Bangladeshis were anaemic and vitamin D deficient. CONCLUSIONS: Bangladeshi patients with IBD more frequently have Crohn's than UC. Bangladeshis with Crohn's more frequently develop perianal disease, have earlier medication escalation and undergo surgery later than white Caucasians. Bangladeshis have more extensive UC than white Caucasians. The relative contributions of genotype and environmental factors, including vitamin D, to these phenotypic differences require additional study.

Factors associated with nonadherence to thiopurines in adolescent and adult patients with inflammatory bowel disease.

OBJECTIVES: We hypothesised that nonadherence to thiopurines is more common in adolescents than in adults with inflammatory bowel disease. METHODS: We sought factors associated with thiopurine nonadherence defined by thiopurine metabolite levels. RESULTS: Multivariate logistic regression confirmed that adolescents (odds ratio [OR] 4.6 [95% confidence interval [CI] 1.9-11.5]; P < 0.01) compared with adults, patients with Crohn disease (OR 3.3 [CI 1.1-10.5] P = 0.04) compared with ulcerative colitis, and patients living in more socially deprived areas (OR 1.03 [CI 1.0-1.1] P = 0.02) were more likely to be nonadherent to thiopurines. CONCLUSIONS: Adolescents are more frequently nonadherent than adults: prospective studies are required to determine the reasons for nonadherence in adolescents.

Adolescents with IBD: the importance of structured transition care.

Children and adolescents with inflammatory bowel disease (IBD) tend to have more extensive and severe disease than adults. IBD presenting in childhood interferes with growth, education and employment as well as psychosocial and sexual development, frequently delaying adolescent developmental milestones. Transition, in the context of healthcare, is the purposeful, planned movement of adolescents and young adults with chronic physical and medical conditions to adult-orientated healthcare systems. Although no single model has been widely adopted and despite a paucity of data, recent guidelines from Europe and the USA propose the formation of specialist transition clinics for adolescent patients with IBD. In order to develop a successful transition service, the barriers that arise because of differences between paediatric and adult IBD services need to be identified. In this article, we review the concept of transitional care for adolescents with IBD, highlighting the important differences in not only, paediatric and adult IBD, but also paediatric and adult IBD services. We consider the consequences of failed transition, and describe the limited published data reporting different approaches to transition in IBD, before outlining our own approach.

Relationship between human intestinal dendritic cells, gut microbiota, and disease activity in Crohn's disease.

BACKGROUND: Altered intestinal dendritic cell (DC) function underlies dysregulated T-cell responses to bacteria in Crohn's disease (CD) but it is unclear whether composition of the intestinal microbiota impacts local DC function. We assessed the relationship between DC function with disease activity and intestinal microbiota in patients with CD. METHODS: Surface expression of Toll-like receptor (TLR)-2, TLR-4, and spontaneous intracellular interleukin (IL)-10, IL-12p40, IL-6 production by freshly isolated DC were analyzed by multicolor flow cytometry of cells extracted from rectal tissue of 10 controls and 28 CD patients. Myeloid DC were identified as CD11c(+) HLA-DR(+lin-/dim) cells (lin = anti-CD3, CD14, CD16, CD19, CD34). Intestinal microbiota were analyzed by fluorescent in situ hybridization of fecal samples with oligonucleotide probes targeting 16S rRNA of bifidobacteria, bacteroides-prevotella, C. coccoides-E. rectale, and Faecalibacterium prausnitzii. RESULTS: DC from CD produced higher amounts of IL-12p40 and IL-6 than control DC. IL-6(+) DC were associated with the CD Activity Index (r = 0.425; P = 0.024) and serum C-reactive protein (CRP) (r = 0.643; P = 0.004). DC expression of TLR-4 correlated with disease activity. IL-12p40(+) DC correlated with ratio of bacteroides: bifidobacteria (r = 0.535, P = 0.003). IL-10(+) DC correlated with bifidobacteria, and IL-6(+) DC correlated negatively with F. prausnitzii (r = -0.50; P = 0.008). The amount of TLR-4 on DC correlated negatively with the concentration of F. prausnitzii. CONCLUSIONS: IL-6 production by intestinal DC is increased in CD and correlates with disease activity and CRP. Bacterially driven local IL-6 production by intestinal DC may overcome regulatory activity, resulting in unopposed effector function and tissue damage. Intestinal DC function may be influenced by the composition of the commensal microbiota.