The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom

OBJECTIVE: To determine whether the incidence of herpes zoster is elevated in patients with rheumatoid arthritis (RA) and whether herpes zoster is associated with use of disease-modifying antirheumatic drugs (DMARDs) in patients with RA. METHODS: Two retrospective cohort studies were conducted using data from a US integrated managed care database (PharMetrics claims database) from 1998-2002 and the UK General Practice Research Database (GPRD) between 1990-2001. Rates of herpes zoster among patients with RA and randomly sampled non-RA patients were compared. A nested case-control analysis was performed within each RA cohort to examine the effect of current treatment on herpes zoster risk. RESULTS: A total of 122,272 patients with RA from the PharMetrics database and 38,621 from the GPRD were included. The adjusted hazard ratios of herpes zoster for patients with RA compared with non-RA patients were 1.91 (95% confidence interval [95% CI] 1.80-2.03) in the PharMetrics database and 1.65 (95% CI 1.57-1.75) in the GPRD. In the PharMetrics database, current use of biologic DMARDs alone was associated with herpes zoster (odds ratio [OR] 1.54, 95% CI 1.04-2.29), as was current use of traditional DMARDs alone (OR 1.37, 95% CI 1.18-1.59). In the GPRD, current use of traditional DMARDs was associated with herpes zoster (OR 1.27, 95% CI 1.10-1.48). In both data sources, use of oral corticosteroids was associated with herpes zoster regardless of concomitant therapies. CONCLUSION: Data from 2 large databases suggested that patients with RA are at increased risk of herpes zoster. Among patients with RA, DMARDs and/or use of oral corticosteroids appeared to be associated with herpes zoster.     

The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease

BACKGROUND & AIMS: The pregnane X receptor (PXR) regulates an array of genes involved in the response to xenobiotics. Evidence from several studies suggests that xenobiotic metabolism may play a role in inflammatory bowel disease (IBD) and that low levels of PXR may be associated with disease expression. The aim of this study was to investigate the association of functional polymorphisms of the PXR encoding gene (NR1I2) with disease in IBD populations. METHODS: This was a case-control study examining 8 NR1I2 single nucleotide polymorphisms (SNPs) previously associated with altered activity of PXR-regulated genes in an Irish cohort including 422 patients with IBD and 350 ethnically matched controls. RESULTS: We showed significant associations of NR1I2 with IBD, Crohn's disease (CD), and ulcerative colitis (UC) groups compared with a control population for SNPs -23585 (IBD: P = .000008; odds ratio [OR], 1.62; 95% confidence interval [CI], 1.31-2.00) and -24381 (IBD: P = .0002; OR, 1.50; 95% CI, 1.21-1.84). SNPs 7635 (P = .0008) and 8055 (P = .007) were found to be associated with IBD and CD but not UC. Risk of IBD is strongly correlated to genotype at these sites, especially for the -25385CC genotype (P = .00001; OR, 2.92; 95% CI, 1.87-4.66). We also show specific correlations of IBD phenotype with genotypes and haplotypes in the patient group. CONCLUSIONS: These results show that genetic variation in the PXR encoding gene, which has been associated with altered activity of PXR, is strongly associated with susceptibility to IBD, CD, and UC.     

Immunosuppressant medications and mortality in inflammatory bowel disease

OBJECTIVE: This study examined whether treatment of Crohn's disease (CD) and ulcerative colitis (UC) with immunosuppressant medications was associated with an increased risk of death in the era prior to antitumor necrosis factor (TNF) therapies.
DESIGN: This retrospective cohort study used data from the General Practice Research Database from 1987 to 1997. CD and UC patients were matched to controls on age, sex, and primary care practice. CD and UC patients were stratified according to whether they used immunosuppressant medications during follow-up. Cox proportional hazards models adjusted for comorbidities were used to define the relative hazard of death. Additional models examined the relative hazard of death with current use of corticosteroids or thiopurines.
RESULTS: The cohort included 5,539 patients with CD, 8,910 patients with UC, and 41,624 controls. Patients with CD had an increased mortality (not immunosuppressant-treated CD hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.07–1.51; immunosuppressant-treated CD HR 2.44, 95% CI 1.84–3.25). Increased mortality was only observed among UC patients treated with immunosuppressant medications (HR 1.67, 95% CI 1.34–2.09). In both CD and UC, current corticosteroid therapy was associated with increased mortality (CD HR 2.48, 95% CI 1.85–3.31; UC HR 2.81, 95% CI 2.26–3.50). Current use of thiopurines was not associated with increased mortality (CD HR 0.83, 95% CI 0.37–1.86; UC HR 0.70, 95% CI 0.29–1.70).
CONCLUSIONS: Patients treated with corticosteroids, but not thiopurines, are at increased risk of death, although this study could not clarify whether this was as a result of the medication or the underlying disease severity.     

Health care resource utilization in inflammatory bowel disease.

BACKGROUND & AIMS: The aim of this study was to quantify temporal changes in health care utilization by a population-based cohort of IBD. METHODS: By using the University of Manitoba IBD Epidemiology Database we assessed utilization of outpatient and hospital services, estimating relative risk (RR) of utilization for IBD cases compared with a matched cohort of non-IBD controls and for CD versus UC. We tested differences in utilization between prevalence cohorts 1990-1991 and 2000-2001. Also, utilization of the 1987-1988 incidence cohort was followed forward 15 years from diagnosis. The probability, intensity, and volume of utilization were estimated. RESULTS: In 2000-2001, IBD patients compared with controls were more likely to have an outpatient visit (RR, 1.18; 95% confidence interval [CI], 1.17-1.19) and an overnight hospital stay (RR, 2.32; 95% CI, 2.16-2.49). CD cases were more likely than UC cases to be hospitalized (RR, 1.26; 95% CI, 1.11-1.43) and had a greater number of outpatient visits. From 1990-1991 to 2000-2001, IBD cases experienced a significant decrease in the likelihood of an outpatient surgical visit relative to non-IBD controls (P < .05), and for those cases who were hospitalized, CD cases tended to be less likely than UC cases to experience IBD-specific inpatient surgery (P < .07). Of the 1987-1988 incidence cohort, 80% of admissions that occurred during the follow-up period were during the first 5 years after diagnosis. CONCLUSIONS: In 2000-2001, health care utilization continued to be higher in IBD versus controls and CD versus UC; however, the gap in costly service utilization appeared to narrow between the latter pair.     

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark

BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.     

Trends in the epidemiology of inflammatory bowel disease in Colombia by demographics and region using a nationally representative claims database and characterization of inflammatory bowel disease phenotype in a case series of Colombian patients

The incidence of inflammatory bowel disease (IBD) is on the rise in Latin America. The aims of this study were to examine epidemiologic trends of IBD in Colombia by demographics, region, urbanicity, and to describe the IBD phenotype in a large well-characterized Colombian cohort.We used a national database of 33 million adults encompassing 97.6% of the Colombian population in order to obtain epidemiologic trends of IBD using International Classification of Diseases 10codes for adults with ulcerative colitis (UC) and Crohn disease (CD). We calculated the incidence and prevalence of UC and CD from 2010–2017 and examined epidemiologic trends by urbanicity, demographics, and region. We then examined the IBD phenotype (using Montreal Classification), prevalence of IBD-related surgeries, and types of IBD-medications prescribed to adult patients attending a regional IBD clinic in Medellin, Colombia between 2001 and 2017.The incidence of UC increased from 5.59/100,000 in 2010 to 6.3/100,000 in 2017 (relative risk [RR] 1.12, confidence interval (CI) (1.09–1.18), P < .0001). While CD incidence did not increase, the prevalence increased within this period. The Andes region had the highest incidence of IBD (5.56/100,000 in 2017). IBD was seen less in rural regions in Colombia (RR=.95, CI (0.92–0.97), p < .01). An increased risk of IBD was present in women, even after adjusting for age and diagnosis year (RR 1.06 (1.02–1.08), P = .0003). The highest IBD risk occurred in patients 40 to 59 years of age. In the clinic cohort, there were 649 IBD patients: 73.7% UC and 24.5% CD. Mean age of diagnosis in CD was 41.0 years and 39.9 years in UC. UC patients developed mostly pancolitis (43%). CD patients developed mostly ileocolonic disease and greater than a third of patients had an inflammatory, non-fistulizing phenotype (37.7%). A total of 16.7% of CD patients had perianal disease. CD patients received more biologics than UC patients (odds ratio: 3.20, 95% CI 2.19–4.69 P < .001).Using both a national representative sample and a regional clinic cohort, we find that UC is more common in Colombia and is on the rise in urban regions; especially occurring in an older age cohort when compared to Western countries. Future studies are warranted to understand evolving environmental factors explaining this rise.     

ATG16L1 and IL23R are associated with inflammatory bowel diseases but not with celiac disease in the Netherlands

BACKGROUND: Inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--and celiac disease are intestinal inflammatory disorders with a complex genetic background. Recently, two novel genes were found to be associated with IBD susceptibility. One, an uncommon coding variant (rs11209026) in the gene encoding for the interleukin-23 receptor (IL23R), conferred strong protection against CD. The other, rs2241880 in the autophagy-related 16-like 1 gene (ATG16L1), was associated with CD. We performed a case-control study for the association of IBD with IL23R and ATG16L1 in a Dutch cohort. We also looked at the association of IL23R and ATG16L1 with celiac disease. METHODS: Five hundred eighteen Dutch white IBD patients (311 CD and 207 UC, including 176 trios of patients with both parents), 508 celiac disease patients, and 893 healthy controls were studied for association with the rs11209026 (IL23R) and rs2241880 (ATG16L1) single nucleotide polymorphisms (SNP). RESULTS: The rs11209026 SNP in IL23R had a protective effect for IBD in the case-control analysis (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.10-0.37, P= 6.6E-09). Both CD (OR 0.14, CI 0.06-0.37, P= 3.9E-07) and UC (OR 0.33, CI 0.15-0.73, P= 1.4E-03) were associated with IL23R. For ATG16L1, the rs2241880 SNP was associated with CD susceptibility (OR 1.36, CI 1.12-1.66, P= 0.0017). The population-attributable risk of carrying allele G is 0.24 and is 0.19 for homozygosity for allele G in CD. No association was found between IL23R or ATG16L1 and celiac disease. CONCLUSIONS: We confirmed the association of IL23R and ATG16L1 with CD susceptibility and also the association of IL23R with UC. We found IL23R and ATG16L1 were not associated with celiac disease susceptibility.     

Risk factors for ulcerative colitis in a Chinese population: an age-matched and sex-matched case-control study

BACKGROUND AND AIMS: Cigarette smoking, alcohol use, appendectomy, and family history of inflammatory bowel disease (IBD) have all been shown to be associated with IBD, but there were no reports of risk factors for IBD in a Chinese population in which the incidence of IBD is increasing during the past decade. We conducted a case-control study to examine associations between previously reported environmental risk factors and development of ulcerative colitis (UC) in Wuhan city, central China. METHODS: A total of 177 patients with UC and 177 age-matched and sex-matched controls were prospectively studied in Wuhan city from January 2004 to December 2004. An age-matched and sex-matched case-control study was conducted to assess the role of smoking, alcohol use, appendectomy, and other potential risk factors in the development of UC by a detailed questionnaire. RESULTS: Smoking was a protective factor and exsmoking is a risk factor for UC [compared with nonsmokers, smokers: odds ratios (OR)=0.28, 95% confidence intervals (CI): 0.16-0.48, P=0.0001; exsmokers: OR=4.36, 95%CI: 1.46-13.04, P=0.008]. Positive family history of IBD was a risk factor (OR=4.35, 95%CI: 1.21-15.71, P=0.025) whereas appendectomy was a protective factor (OR=0.24, 95%CI: 0.07-0.86, P=0.028) for UC. There were no significant associations between UC and other factors examined. CONCLUSIONS: Although the incidence of UC in Chinese is relatively lower than that in white, the same risk factors for UC that were reported in white populations were associated with Chinese UC patients. Specifically, smoking was a protective factor for UC and exsmoking was associated with an increase risk of UC in a Chinese population. Family history of IBD was shown to be a risk for UC, whereas appendectomy was associated with a low risk for UC.     

Role of the PXR gene locus in inflammatory bowel diseases

BACKGROUND: The pregnane X receptor gene (PXR/NR1I2) has been recently associated with an increased risk for inflammatory bowel disease (IBD), although a subsequent case-control study failed to replicate the original association in an independent population. This nuclear receptor regulates genes involved in the detoxification process in the liver and intestine, like ABCB1/MDR1. PXR expression was significantly reduced in the colon of patients with ulcerative colitis (UC), but remained unaffected in Crohn's disease (CD) patients. Considering previous results, we aimed at investigating the impact of this locus on IBD predisposition in the Spanish population.METHODS: Three PXR polymorphisms, including the 1 more strongly correlated with IBD risk in the initial study at -25385C/T (rs3814055) and the 6 haplotypes conformed by them, were analyzed in 365 UC and 331 CD patients and compared with 550 ethnically matched controls.RESULTS: The overall haplotypic distribution showed a significant difference between UC and CD patients (P = 0.05; chi(2) = 10.84). Among UC patients a significant difference was seen between those with extensive colitis and controls (P = 0.004; chi(2) = 17.04), mainly due to the presence of a risk haplotype (rs3814055*T//rs6784598*C//rs2276707*C: P = 0.001; odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.20-2.30). Patients with extensive UC carrying the -25385T allele showed increased susceptibility compared with left-sided colitis patients and with healthy subjects. In patients with extensive UC a significantly different distribution of genotypes of the MDR1 G/A change located in intron 3 (rs3789243) was observed between carriers/noncarriers of the -25385T risk allele (P = 0.005).CONCLUSIONS: Our data seem to support the association of the PXR locus with extensive UC and the interaction between PXR and MDR1 genes.     

Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease

BACKGROUND: It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. METHODS: In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the C?te d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. RESULTS: In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients na?ve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. na?ve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). CONCLUSIONS: Patients with IBD have an increased risk of developing PILD. (Inflamm Bowel Dis 2012;).     

Environmental factors in inflammatory bowel disease: A case-control study based on a Danish inception cohort

Background

The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients.

Methods

A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003–2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression.

Results

Being breastfed > 6 months (OR, 0.50; 95% CI, 0.23–1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31–0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12–0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07–4.03) and polio (OR, 2.38; 95% CI, 1.04–5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15–10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC.

Conclusion

Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.     

Inflammatory bowel diseases increase future ischemic stroke risk: A Taiwanese population-based retrospective cohort study

Background and aimsThis cohort study assessed the association between inflammatory bowel disease (IBD) and the risk of future ischemic stroke.MethodsThe IBD cohort comprised adult patients (≥ 20 years old) who had received either ambulatory or inpatient care between 1998 and 2011 and IBD-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year (included 18,392 patients with IBD and 73,568 control patients). Both cohorts with ischemic stroke before the index date and the ischemic stroke cases diagnosed within one year after the index date were excluded. We observed the study patients until the incidence of ischemic stroke, death, withdrawal from the insurance program, or they were lost to follow-up, or the end of 2011.ResultsThe risk of ischemic stroke was 1.12-fold (95% CI, 1.02–1.23) higher among the IBD cohort than among the non-IBD cohort. Compared to the subjects without IBD, the adjusted HR of ischemic stroke was 1.15 (95% CI 1.04–1.28) in the Crohn's disease (CD) patients and 1.01 (95% CI 0.84–1.21) in the ulcerative colitis (UC) group. The risk of developing ischemic stroke significantly increased with the increased frequency of IBD exacerbation and hospitalization. Furthermore, the adjusted HR among the CD patients increased in conjunction with the number of medical visits, from 1.07 to 6.36 and the adjusted HR among the UC patients also increased in conjunction with the number of medical visits, from 1.11 to 2.10.ConclusionsIBD exhibited an increased risk of developing ischemic stroke.     

Increased end-stage renal disease risk in patients with inflammatory bowel disease:A nationwide populationbased study

AIM To estimate the risk of end-stage renal disease(ESRD)in patients with inflammatory bowel disease(IBD).METHODS From January 2010 to December 2013, patients with Crohn's disease(CD) and ulcerative colitis(UC) were identified, based on both the International Classification of Diseases, 10 th revision(ICD-10) and the rare,intractable disease registration program codes from the National Health Insurance(NHI) database in South Korea. We compared 38812 patients with IBD to ageand sex-matched non-IBD controls with a ratio of 1:3.Patients newly diagnosed with ESRD were identified with the ICD-10 code.RESULTS During a mean follow-up of 4.9 years, ESRD was detected in 79(0.2%) patients with IBD and 166(0.1%)controls. The incidence of ESRD in patients with IBD was0.42 per 1000 person-years. Patients with IBD had a significantly higher risk of ESRD than controls [adjusted hazard ratio(HR) = 3.03; 95% confidence interval(CI):1.77-5.20; P 0.001]. The incidences(per 1000 personyears)of ESRD were 0.51 in patients with CD and 0.13 in controls, respectively(adjusted HR = 6.33; 95%CI:2.75-14.56; P 0.001). In contrast, the incidence of ESRD was similar between the UC and control groups(0.37 vs 0.37 per 1000 person-years; adjusted HR = 2.01;95%CI: 0.90-4.51; P = 0.089).CONCLUSION The risk of ESRD was elevated in patients with CD, but not UC. Patients with CD should be monitored carefully for signs of renal insufficiency.     

Increased Risk of Both Ulcerative Colitis and Crohn’s Disease in a Population Suffering from COPD

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways. In the majority of cases, the inflammation is triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting development of Crohn's disease (CD). The present study was undertaken to investigate occurrence of IBD among COPD patients, indicating common inflammatory pathways and shared vulnerability on a genetic basis. The study was designed as a population-based cohort study. All individuals discharged with a diagnosis of COPD from 1987 to 2002 were identified in the Swedish Inpatient Register (n=180,239). Controls and first-degree relatives of both cases and controls were identified using the Multi-Generation Register. Finally, all individuals (n=1,174,557) were compared with the Inpatient Register, identifying discharges with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox proportional hazards regression analysis. COPD patients had a significantly higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33-3.18). Among first-degree relatives of COPD patients, there was also an overall increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI 0.96-1.23). The kinship of first-degree relatives displayed an increased risk of both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12-1.89, respectively). The results suggest that COPD and IBD may have inflammatory pathways in common, including genetic variants of genes predisposing for disease.     

Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association

OBJECTIVES: Published association studies of the TLR4 Asp299Gly polymorphism and inflammatory bowel disease (IBD) in caucasian populations have inconsistent results. We tested two TLR4 variants for association with IBD in the New Zealand caucasian population and assessed the cumulative evidence for association of TLR4 Asp299Gly and IBD. METHODS: The TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped and tested for case-control frequency differences in a New Zealand white cohort of 389 Crohn's disease (CD) patients, 405 ulcerative colitis (UC) patients, and 416 population controls. Meta-analysis using a random effects model was performed to test whether 299Gly carriage was associated with UC, CD, or phenotypes of CD patients. RESULTS: There were no significant allele or genotype frequency differences between cases and controls or between CD phenotypes in our New Zealand data. Meta-analysis did not identify any significant associations between CD phenotypes and 299Gly carriage. However, meta-analysis demonstrated significantly higher 299Gly carrier frequencies in CD patients (odds ratio 1.45, 95% CI 1.11-1.90) and in IBD patients (odds ratio 1.36, 95% CI 1.01-1.84) compared to controls. CONCLUSIONS: The meta-analysis provides evidence that Asp299Gly is associated with CD and IBD in whites. Only the Asp299Gly polymorphism has been consistently genotyped in previous TLR4 studies with IBD patients, therefore other TLR4 variants with stronger associations with IBD may exist. Additional well-powered studies of Asp299Gly and other TLR4 variants are urgently needed.     

Incidence of inflammatory bowel disease across Europe: is there a difference between north and south? Results of the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND: It has been suggested that the incidence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is three or more times higher in northern than in southern Europe. The aim of this EC funded study was to investigate this apparent variation by ascertaining the incidence of IBD across Europe. METHODS: For the period 1 October 1991 to 30 September 1993 all new patients diagnosed with IBD were prospectively identified in 20 European centres according to a standard protocol for case ascertainment and definition. FINDINGS: Altogether 2201 patients aged 15 years or more were identified, of whom 1379 were diagnosed as UC (including proctitis), 706 as CD, and 116 as indeterminate. The overall incidence per 100,000 at ages 15-64 years (standardised for age and sex) of UC was 10.4 (95% confidence interval (95% CI) 7.6 to 13.1) and that of CD was 5.6 (95% CI 2.8 to 8.3). Rates of UC in northern centres were 40% higher than those in the south (rate ratio (RR) = 1.4 (95% CI 1.2 to 1.5)) and for CD they were 80% higher (RR = 1.8 (95% CI 1.5 to 2.1)). For UC the highest reported incidence was in Iceland (24.5, 95% CI 17.4 to 31.5) and for CD, Maastricht (The Netherlands; 9.2, 95% CI 6.5 to 11.8) and Amiens (north west France; 9.2, 95% CI 6.3 to 12.2). The lowest incidence of UC was in Almada (southern Portugal) (1.6, 95% CI 0.0 to 3.2) and of CD in Ioannina (north west Greece) (0.9, 95% CI 0.0 to 2.2). An unexpected finding was a difference in the age specific incidence of UC in men and women with the incidence in women but not men declining with age. INTERPRETATION: The higher overall incidence rates in northern centres did not seem to be explained by differences in tobacco consumption or education. Nevertheless, the magnitude of the observed excess for both conditions is less than expected on the basis of previous studies. This may reflect recent increases in the incidence of IBD in southern Europe whereas those in the north may have stabilised.     

Abnormalities of uterine cervix in women with inflammatory bowel disease

INTRODUCTION Cervical cancer is responsible for almost 4000 deaths annually in the United States[1]. Due in large part to mass screening protocols with papanicolaou (Pap) smears, mortality from cervical cancer has declined by over 70% in the past 50 years…     

Inflammatory bowel disease and the risk of fracture

Although patients with inflammatory bowel disease (IBD) have reduced bone mass, there is controversy whether there is an increased risk of fracture. This study examines the risk of fracture and its predictors in patients with IBD. In a primary care- based nested case-control study, 231,778 fracture cases and 231,778 age- and sex-matched controls were recruited. A history of IBD was assessed from medical records. The prevalence of IBD was 156 and 282 per 100,000 for Crohn’s disease (CD) and ulcerative colitis (UC), respectively. Patients with IBD had an increased risk of vertebral fracture (odds ratio [OR], 1.72; 95% confidence interval [CI], 1.13-2.61) and hip fracture (OR, 1.59; 95% CI, 1.14-2.23). The risk of hip fracture was greater in patients with CD (OR, 1.86; 95% CI, 1.08-3.21) compared with UC (OR, 1.40; 95% CI, 0.92-2.13). Disease severity, assessed by the number of symptoms, predicted fracture even after adjusting for corticosteroid use (OR, 1.46; 95% CI, 1.04-2.04). Only 13% of patients with IBD who had already sustained a fracture were on any form of antifracture treatment. Patients with IBD have a higher risk of fracture due to both disease activity and use of oral corticosteroids. However, few of these patients are receiving optimal bone-sparing therapy, highlighting the importance of increasing awareness of osteoporosis in those managing these patients.