Fibre intake and the development of inflammatory bowel disease – a European prospective multi-centre cohort study (EPIC-IBD)

Background and Aims: Population-based prospective cohort studies investigating fibre intake and development of inflammatory bowel disease (IBD) are lacking. Our aim was to investigate the association between fibre intake and the development of Crohn’s disease (CD) and ulcerative colitis (UC) in a large European population. Methods: 401 326 participants, aged 20–80 years, were recruited in 8 countries in Europe between 1991 and 1998. At baseline, fibre intake (total fibres, fibres from fruit, vegetables and cereals) was recorded using food frequency questionnaires. The cohort was monitored for the development of IBD. Each case was matched with four controls and odds ratios (ORs) for the exposures were calculated using conditional logistic regression. Sensitivity analyses according to smoking status were computed. Results: In total, 104 and 221 participants developed incident CD and UC, respectively. For both CD and UC, there were no statistically significant associations with either quartiles, or trends across quartiles, for total fibre, or any of the individual sources. The associations were not affected by adjusting for smoking and energy intake. Stratification according to smoking status showed null findings apart from an inverse association with cereal fibre and CD in non-smokers (Quartile 4 vs 1 OR=0.12, 95% CI=0.02–0.75, P=0.023, OR trend across quartiles=0.50, 95% CI=0.29–0.86, P=0.017). Conclusion: The results do not support the hypothesis that dietary fibre is involved in the aetiology of UC, although future work should investigate whether there may be a protective effect of specific types of fibre according to smoking status in CD

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece

<p>Abstract</p> <p>Background</p> <p>Research has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece.</p> <p>Methods</p> <p>The current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GP's from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST).</p> <p>Results</p> <p>The crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; <it>p </it>= 0.029).</p> <p>Conclusions</p> <p>The implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.</p

GPA33 is expressed on multiple human blood cell types and distinguishes CD4(+) central memory T cells with and without effector function

The Ig superfamily protein glycoprotein A33 (GPA33) has been implicated in immune dysregulation, but little is known about its expression in the immune compartment. Here, we comprehensively determined GPA33 expression patterns on human blood leukocyte subsets, using mass and flow cytometry. We found that GPA33 was expressed on fractions of B, dendritic, natural killer and innate lymphoid cells. Most prominent expression was found in the CD4(+) T cell compartment. Naive and CXCR5(+) regulatory T cells were GPA33(high), and naive conventional CD4(+) T cells expressed intermediate GPA33 levels. The expression pattern of GPA33 identified functional heterogeneity within the CD4(+) central memory T cell (Tcm) population. GPA33(+) CD4(+) Tcm cells were fully undifferentiated, bona fide Tcm cells that lack immediate effector function, whereas GPA33(-) Tcm cells exhibited rapid effector functions and may represent an early stage of differentiation into effector/effector memory T cells before loss of CD62L. Expression of GPA33 in conventional CD4(+) T cells suggests a role in localization and/or preservation of an undifferentiated state. These results form a basis to study the function of GPA33 and show it to be a useful marker to discriminate between different cellular subsets, especially in the CD4(+) T cell lineage.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

Dietary Polyphenols in the Aetiology of Crohn's Disease and Ulcerative Colitis—A Multicenter European Prospective Cohort Study (EPIC)

Background: Oxidative stress may be involved in the aetiology of inflammatory bowel disease and whether dietary polyphenols, which possess antioxidants properties, prevent its development is unknown. Methods: A total of 401,326 men and women aged 20 to 80 years from 8 countries were recruited between 1991 and 1998 and at baseline completed validated food frequency questionnaires. Dietary polyphenol intake was measured using Phenol-Explorer, a database with information on the content of 502 polyphenols. Incident cases of Crohn's diseases (CD) and ulcerative colitis (UC) were identified during the follow-up period of up to December 2010. A nested case–control study using conditional logistic regression estimated the odds ratios (ORs), and 95% confidence intervals, for polyphenol intake (categories based on quartiles) and developing CD or UC. Results: In total, 110 CD (73% women) and 244 UC (57% women) cases were identified and matched to 440 and 976 controls, respectively. Total polyphenol intake was not associated with CD (P trend = 0.17) or UC (P trend = 0.16). For flavones and CD, there were reduced odds for all quartiles, which were statistically significant for the third (OR3rd versus 1st quartile = 0.33; 95% confidence interval, 0.15–0.69) and there was an inverse trend across quartiles (P = 0.03). Similarly, for resveratrol, there was an inverse association with CD (OR4th versus 1st quartile = 0.40; 95% confidence interval, 0.20–0.82) with an inverse trend across quartiles (P = 0.02). No significant associations between subtypes of polyphenols and UC were found. Effect modification by smoking in CD was documented with borderline statistical significance. Conclusions: The data supports a potential role of flavones and resveratrol in the risk of developing CD; future aetiological studies should investigate these dietary components and further examine the potential for residual confounding.Multiple funders including MRC and CRUK listed on paper

Prediagnostic Serum Vitamin D Levels and the Risk of Crohn’s Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study

Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn’s disease (CD) and ulcerative colitis (UC). Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC. Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83). Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings