Has the Incidence of Inflammatory Bowel Disease Peaked? Evidence From the Population-Based NorDIBD Cohort 1978-2020.

INTRODUCTION: While the incidence of inflammatory bowel disease (IBD) is rising globally, it has been suggested to stabilize in westernized countries, but this has not yet been shown in exhaustive and large cohorts. We generated an IBD cohort in North Denmark (NorDIBD) of 6,158 patients with IBD diagnosed from 1978 to 2020, based on all recorded and verified IBD diagnoses in the region. While describing the establishment of this cohort, we aimed to present the accurate incidence and prevalence of IBD over 4 decades. METHODS: The NorDIBD cohort covered all pediatric and adult patients with an IBD diagnosis dated between January 1, 1978, and December 31, 2020, and living in North Denmark, hence forming an unselected population-based patient cohort. IBD incidence rates between 1978 and 2020 and IBD point prevalences between 2003 and 2020 were calculated. RESULTS: We observed a 4-fold increase in the incidence of IBD from 11.5 per 100,000 persons (95% confidence interval [CI] 8.4-14.6) in the year 1978 to 51.3/100,000 (95% CI 45.5-57.1) in the year 2014, whereas in 2020, this rate stabilized. The overall prevalence of IBD more than doubled from 2003 to 2020, from 424 (95% CI 407-443) in 2003 to 872 (95% CI 849-896) IBD cases per 100,000 persons in 2020. DISCUSSION: Our population-based NorDIBD cohort suggests stabilizing of the incidence of IBD in Denmark, whereas the prevalence continues to rise. Because the data represent a 10% sample of the entire Danish IBD population, we believe that data can be extrapolated to the IBD population in general and used for healthcare planning.

Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease-a Case Series.

BACKGROUND AND AIM: Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP. METHODS: PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form. RESULTS: In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40-68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [n = 12], thiopurines [n = 10], infliximab [n = 4], ciclosporin [n = 2], methotrexate [n = 1], and tacrolimus [n = 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others. CONCLUSION: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy.

Premedication with corticosteroids does not impact the pharmacokinetics of infliximab in inflammatory bowel disease irrespective of azathioprine cotreatment.

OBJECTIVE: Loss of infliximab (IFX) effect is a clinical challenge in the management of patients with Crohn's disease (CD), but this can potentially be reduced with azathioprine (AZA) or with corticosteroids (CS). We aimed to study whether CS premedication with or without cotreatment with AZA could reduce antibody formation and affect the IFX elimination rate. PATIENTS AND METHODS: A cross-sectional observational study was conducted at two centers with CD patients receiving maintenance IFX therapy for 12-18 months. In addition to IFX, patients received either CS premedication or not, with or without concominant AZA. RESULTS: Fifty-seven patients were included in the study. Thirty-one patients received premedication with CSs, and 11 (35.5%) of these also received AZA, whereas this was the case for 22 of 26 (84.6%) patients in the non-CS group. No difference in IFX trough level (P=0.10) or halftime elimination (P=0.31) was observed with or without CS premedication. Concomitant AZA was associated with significantly longer mean half-life of IFX (P=0.04). Total IFX antibody concentrations were 15.8 and 12.9 with and without CS, respectively, in those not receiving AZA versus 4.3 and 6.1 AU/ml with and without CS, respectively, in those receiving AZA (P=0.004). Premedication with CS did not have any effect on the frequency of antibody formation (P=0.28). CONCLUSION: In patients with CD and in maintenance IFX therapy, premedication with CS did not influence antibody formation, IFX trough levels or IFX halftime elimination, irrespective of concomitant AZA use. However, the use of AZA was associated with higher IFX trough levels and lower total IFX antibody concentrations.

Changing Infliximab Prescription Patterns in Inflammatory Bowel Disease: A Population-Based Cohort Study, 1999-2014.

Background: Long-term data on real life use of infliximab (IFX) for inflammatory bowel disease (IBD) are lacking. We studied prescription patterns during the first 16 years following marketing authorization. Methods: In a population-based cohort from the North Denmark Region, all IBD patients exposed to IFX during 1999 to 2014 were identified. Results: A total of 623 patients (210 with ulcerative colitis [UC] and 413 with Crohn's disease [CD]) were exposed to IFX. In patients with UC, age at first exposure decreased by 10 months per calendar year (P < 0.05) during the study period. In patients with CD, disease duration at time of first IFX exposure decreased by 7 months per calendar year (P < 0.001). From 2005-2009 to 2010-2014, the proportion of IFX-exposed patients with pancolitis (40% vs 24%, P = 0.04) and the proportion of patients with extensive CD (P = 0.002) decreased. The mean time to discontinuation of IFX remained stable in patients with CD during the study period (2.5-3.0 years) and increased from 0.34 years (2005-2009) to 1.11 years (2010-2015) in patients with UC (P = 0.04). Conclusion: During the first 16 years postmarketing, age at first exposure to IFX decreased in patients with UC, whereas disease duration at time of first exposure decreased in patients with CD. Also, a significant change toward less extensive disease in both UC and CD patients exposed to IFX was observed. Treatment duration in patients with UC increased during the study period, but did not reach the more constant and longer duration of treatment observed in patients with CD.

A cross-continental analysis of weight gain, psychiatric diagnoses and medication use during inpatient psychiatric treatment. The international study on physical illness in mentally ill.

Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment. 876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N = 265), Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466). There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change. In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.

High-dose fast infusion of parenteral iron isomaltoside is efficacious in inflammatory bowel disease patients with iron-deficiency anaemia without profound changes in phosphate or fibroblast growth factor 23.

OBJECTIVE: Iron isomaltoside (Monofer(®)) is a high-dose intravenous iron preparation with good tolerability and efficacy in inflammatory bowel disease (IBD) patients with iron deficiency anaemia (IDA). This trial evaluates the safety and efficacy, including effect on intact fibroblast growth factor 23 (iFGF23) of a high single dose and cumulative doses of iron isomaltoside in IBD patients with IDA. MATERIALS AND METHODS: The trial was a prospective, open-label, multi-centre trial conducted in IBD patients with IDA. Based upon haemoglobin (Hb) levels at baseline and weight, the patients received 1500, 2000, 2500 or 3000 mg of iron isomaltoside infused in single doses up to 2000 mg. The outcome measurements included adverse drug reactions (ADRs) and changes in haematology and biochemistry parameters. RESULTS: Twenty-one IBD patients with IDA were enrolled, receiving 1500 (seven patients), 2000 (eight patients), 2500 mg (four patients) or 3000 (two patients) mg of iron. No serious ADRs were observed. Four patients experienced nine mild to moderate ADRs (hypersensitivity, pyrexia, vomiting, constipation, abdominal pain, dyspepsia (two events) and eye allergy (two events)). In total, 15 (75%) patients had an increase in Hb of ≥2.0 g/dL during the trial, with normalisation of ferritin. No changes in iFGF23 or clinically significant hypophosphataemia were found. CONCLUSION: Rapid infusions of high-dose iron isomaltoside, administered as single doses up to 2000 mg and cumulative doses up to 3000 mg, were without safety concerns and were efficacious in increasing Hb levels in IBD patients. Iron isomaltoside did not induce profound phosphate wasting via increased iFGF23 levels.

Touch screens as a tool in patient care in the IBD outpatient clinic.

OBJECTIVE: We have introduced online touch screens in the waiting room for patients with ulcerative colitis (UC) or Crohn's disease (CD) for recording of symptoms before their consultation. This has made disease activity scores readily available to the physician in our newly established database, 'Gastrobio'. We wanted to validate the use of touch screens compared to paper questionnaires. MATERIAL AND METHODS: A total of 54 patients with UC and 74 patients with CD were included in the study. The UC patients filled out the Short Health Scale (SHS) and Simple Clinical Colitis Activity Index (SSCAI). The CD patients filled out the SHS and Harvey-Bradshaw Index (HBI). Paper questionnaires and touch screen versions were used in random order and comparison between the two modalities was made by Spearman correlation test, Bland-Altman plots, and Kappa-statistics. RESULTS: Among the 128 patients, the two SHS scores (SHS touch versus SHS paper) were found to be highly correlated (Spearman correlation; 0.92 for UC and 0.92 for CD). Also, on average, Bland-Altman plots demonstrated a difference close to zero between the two modalities. Agreement between paper version and touch screen version of SCCAI and HBI scores was also high (Kappa-statistics; 78% raw and 98% weighted for SCCAI; 65% raw and 97% weighted for HBI). CONCLUSIONS: It is feasible to introduce touch screens in the outpatient clinic and to have patients record their symptoms before the consultation. However, the study may not be representative for elderly patients.

Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding.

A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women < 40 years of age. Small intestine investigation (capsule endoscopy, CT, or MRI enterography) is not recommended routinely after negative bidirectional endoscopy but should be conducted if there are red flags indicating malignant or inflammatory small bowel disease (e.g., involuntary weight loss, abdominal pain or increased CRP). Targeted treatment of any cause of anemia with iron deficiency found on diagnostic assessment should be initiated. In addition, iron supplementation should be administered, with the goal of normalizing hemoglobin levels and replenishing iron stores. Oral treatment with a 100-200 mg daily dose of elemental iron is recommended (lower dose if side effects), but 3-6 months of oral iron therapy is often required to achieve therapeutic goals. Intravenous iron therapy is used if oral treatment lacks efficacy or causes side effects or in the presence of intestinal malabsorption or prolonged inflammation. Three algorithms are given for the following conditions: a) the paraclinical diagnosis of anemia with iron deficiency; b) the diagnostic work-up for unexplained anemia with iron deficiency without overt bleeding; and c) how to proceed after negative bidirectional endoscopy of the gastrointestinal tract.

Individualized Therapy Is a Long-Term Cost-Effective Method Compared to Dose Intensification in Crohn's Disease Patients Failing Infliximab.

BACKGROUND: In Crohn's disease patients failing infliximab therapy, interventions defined by an algorithm based on infliximab and anti-infliximab antibody measurements have proven more cost-effective than intensifying the infliximab regimen. AIM: This study investigated long-term economic outcomes at the week 20 follow-up study visit and after 1 year. Clinical outcomes were assessed at week 20. METHODS: Follow-up from a 12-week, single-blind, clinical trial where patients with infliximab treatment failure were randomized to infliximab intensification (5 mg/kg every 4 weeks) (n = 36), or algorithm-defined interventions (n = 33). Accumulated costs, expressed as mean costs per patient, were based on the Danish National Patient Registry. RESULTS: At the scheduled week 20 follow-up study visit, response and remission rates were similar in all study subpopulations between patients treated by the algorithm or by infliximab intensification. However, the sum of healthcare costs related to Crohn's disease was substantially lower (31 %) for patients randomized to algorithm-based interventions than infliximab intensification in the intention-to-treat population: $11,940 versus $17,236; p = 0.005. For per-protocol patients (n = 55), costs at the week 20 follow-up visit were even lower (49 %) in the algorithm group: $8,742 versus $17,236; p = 0.002. Figures were similar for patients having completed the 12-week trial as per protocol (50 % reduction in costs) (n = 45). Among patients continuing the allocated study intervention throughout the entire 20-week follow-up period (n = 29), costs were reduced by 60 % in algorithm-treated patients: $7,056 versus $17,776; p < 0.001. Cost-reduction percentages remained stable throughout one year. CONCLUSION: Economic benefit of algorithm-based interventions at infliximab failure is maintained throughout 1 year.

Where are patients who have co-occurring mental and physical diseases located?

BACKGROUND: Patients with a psychiatric illness have a higher prevalence of physical diseases and thus a higher morbidity and mortality. AIM: The main aim was to investigate where patients with co-occurring physical diseases and mental disorders (psychotic spectrum or mood) in the health and social service system are identified most frequently before admission into psychiatry. The second aim was to compare the differences in the treatment routes taken by the patients before entry into psychiatric services in all the participating countries (Denmark, Germany, Japan, Nigeria and Switzerland). METHODOLOGY: On admission to a psychiatric service, patients diagnosed with schizophrenia, schizotypal or delusional disorders (International Classification of Diseases-10 (ICD-10) group F2) or mood (affective) disorders (ICD-10 group F3) and a co-morbid physical condition (cardiovascular disease, diabetes mellitus and overweight) were asked with which institutions or persons they had been in contact with in the previous 6 months. RESULTS: Patients from Denmark, Germany and Switzerland with mental disorders had almost the same contact pattern. Their primary contact was to public or private psychiatry, with a contact percentage of 46%-91%; in addition, general practice was a common contact, with a margin of 41%-93%. Similar tendencies are seen in Japan despite the small sample size. With regard to general practice, this is also the case with Nigerian patients. However, religious guidance or healing was rarely sought by patients in Europe and Japan, while in Nigeria about 80% of patients with mental disorders had contacted this type of service. CONCLUSION: Promoting prophylactic work between psychiatry and the general practice sector may be beneficial in diminishing physical conditions such as cardiovascular disease, diabetes mellitus and overweight in patients with mental disorders in European countries and Japan. In Nigeria (a low-to-middle-income country), religious guides or healers, along with general practitioners, are the most frequently contacted, and they therefore seem to be the most obvious partner to collaborate with.

The incidence of ulcerative colitis (1995-2011) and Crohn's disease (1995-2012) - based on nationwide Danish registry data.

BACKGROUND AND AIMS: The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has increased during the 20th century in North America and Western Europe. However, there are conflicting reports whether the incidence has declined, stabilized or even continued to increase. No nationwide Danish data on the incidence of UC and CD exist after 1992, and therefore we studied the incidence of UC (1995 through 2011) and CD (1995 through 2012). METHODS: Based on data from the Danish National Patient Registry we identified patients recorded with a first time diagnosis of UC or CD in the study periods. Among these - patients were only included in the study as incident cases if they had at least one more discharge diagnosis of UC/CD or at least three subsequent outpatient visits. RESULTS: We identified 17,500 patients with UC and 7863 patients with CD. The mean incidence rate for UC in 1995-1998 was 14.4 per 100,000 per year for women and 13.8 for men, increasing to 23.2 per 100,000 per year for women and 23.4 for men in the period of 2009-2011. The mean incidence rate for CD in 1995-1998 was 7.8 per 100,000 per year for women and 5.6 for men, increasing to 10.3 per 100,000 per year for women and 8.9 for men in the period of 2009-2012. CONCLUSIONS: Based on nationwide Danish data from the last two decades, the incidence rates of UC and CD have continued to increase.

Individualised therapy is more cost-effective than dose intensification in patients with Crohn's disease who lose response to anti-TNF treatment: a randomised, controlled trial.

OBJECTIVE: Although the reasons for secondary loss of response to infliximab (IFX) maintenance therapy in Crohn's disease vary, dose intensification is usually recommended. This study investigated the cost-effectiveness of interventions defined by an algorithm designed to identify specific reasons for therapeutic failure. DESIGN: Randomised, controlled, single-blind, multicentre study. 69 patients with secondary IFX failure were randomised to IFX dose intensification (5 mg/kg every 4 weeks) (n=36) or interventions based on serum IFX and IFX antibody levels using the proposed algorithm (n=33). Predefined co-primary end points at week 12 were proportion of patients responding (Crohn's Disease Activity Index (CDAI) decrease ≥ 70, or ≥ 50% reduction in active fistulas) and accumulated costs related to treatment of Crohn's disease, expressed as mean cost per patient, based on the Danish National Patient Registry for all hospitalisation and outpatient costs in the Danish healthcare sector. RESULTS: Costs for intention-to-treat patients were substantially lower (34%) for those treated in accordance with the algorithm than by IFX dose intensification: € 6038 vs € 9178, p<0.001. However, disease control, as judged by response rates, was similar: 58% and 53%, respectively, p=0.81; difference 5% (-19% to 28%). For per-protocol patients, treatment costs were even lower (56%) in the algorithm-treated group (€ 4062 vs € 9178, p<0.001) and with similar response rates (47% vs 53%, p=0.78; difference -5% (-33% to 22%)). CONCLUSIONS: Treatment of secondary IFX failure using an algorithm based on combined IFX and IFX antibody measurements significantly reduces average treatment costs per patient compared with routine IFX dose escalation and without any apparent negative effect on clinical efficacy. TRIAL REGISTRATION NO: NCT00851565.

Cancer risk in inflammatory bowel disease according to patient phenotype and treatment: a Danish population-based cohort study.

OBJECTIVES: Population-based studies of site-specific cancer risk in patients with inflammatory bowel disease (IBD) according to IBD phenotype and treatment are lacking. We studied cancer risk in a well-characterized population-based IBD cohort from North Jutland County, Denmark. METHODS: A total of 1,515 patients were diagnosed with ulcerative colitis (UC) and 810 with Crohn's disease (CD) during 1978-2002. Patients were followed until 31 December 2010 for occurrence of incident cancer, identified in the Danish Cancer Registry. Observed numbers of cancer were compared with expected numbers (based on age- and sex-specific background rates) and presented as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs). RESULTS: Patients with UC were not at increased risk of cancer overall (SIR, 1.12; 95% CI, 0.97-1.28) despite increased risk of prostate cancer (SIR, 1.82; 95% CI, 1.17-2.71). Patients with CD had a 55% increased risk of cancer overall (SIR, 1.55; 95% CI, 1.29-1.84) related to young age, colonic disease, smoking, and thiopurine exposure. Patients were at increased risk of small bowel cancer (SIR, 15.18; 95% CI, 1.84-54.78), lung cancer (SIR, 2.13; 95% CI, 1.19-3.52 (associated with female gender and smoking)), colorectal cancer in males (SIR, 2.43; 95% CI, 1.05-4.78), cervical dysplasia (SIR, 1.65; 95% CI, 1.10-2.37 (associated with young age at diagnosis, smoking, 5-aminosalicylic acid, and thiopurine exposure)), and non-Hodgkin lymphoma (SIR, 3.43; 95% CI, 1.38-7.07 (unrelated to thiopurine exposure)). CONCLUSIONS: Patients with CD, but not UC, have an overall excess risk of cancer. Clinical characteristics of IBD patients at excess risk differ by cancer subtype.

Physical illness in psychiatric inpatients: comparison of patients with and without substance use disorders.

BACKGROUND: Physical comorbidities and substance use are commonly reported in patients with mental disorders. AIM: To examine somatic comorbidity in patients with substance use disorders (SUD) compared to patients with mental disorders but no SUD. METHODS: Lifetime prevalence data on mental and physical health status were collected from inpatients in 12 mental health care facilities in five different countries. Differences in somatic comorbidity were examined by means of logistic regression analysis controlling for age and gender. RESULTS: Of 2,338 patients, 447 (19%) had a primary or secondary SUD diagnosis. In comparison to patients with other mental disorders, patients with SUD had a higher prevalence of infectious and digestive diseases but a lower prevalence of endocrine, nutritional and metabolic disorders. Patterns of physical comorbidities differed according to type of substance used (alcohol use - cardiovascular; tobacco use - respiratory, neoplasms; cannabinoid use - injuries; opioid use - infectious, digestive; benzodiazepine use - endocrine, nutritional, metabolic; stimulants - urogenital). CONCLUSIONS: SUD are related to specific somatic health risks while some of our findings point to potentially protective effects. The widespread prescription of benzodiazepines requires research on physical health effects. Early detection of SUD and their integration into programmes targeting physical comorbidity should be a priority in organizing mental health care.

Nutritional screening and risk factors in elderly hospitalized patients: association to clinical outcome?

The aim of this study was to test the intervalidity of three different nutrition screening tools towards a broad population of elderly hospitalized patients. The association with risk factors and mortality was investigated. This is a prospective cohort study in three medical, surgical and geriatric settings, in Denmark and Sweden. Patients >65 years were consecutively included. Patients were screened by mini-nutritional assessment (MNA), malnutrition universal screening tool (MUST) and nutritional risk screening (NRS-2002). Anthropometrics, cognitive test (SPMSQ), as well as a questionnaire investigation regarding eating problems and life situation, were performed. Mortality within 12 months was investigated. In total, 233 patients mean (SD) age 81(7.64) years were included. A large variation in prevalence of nutritional risk was determined between the screening tools, MNA was 68% vs. MUST, 47% and NRS 54%, p < 0.0001. An overall agreement of 67% was seen (κ 0.52-0.55). Risk factors were associated with nutritional risk, including depressive mood. Only handgrip strength, fungus in mouth, serum albumin, CRP and cognitive function were associated with mortality. Fungus had the strongest association (OR 3.7; CI 1.19-11.30). The overall mortality rate was 27% during 12 months. However, none of the three screening tools predicted 12-month mortality. The findings show great variation in the prevalence of nutritional risk of under nutrition both between the tools and the settings. The level of agreement between the tools was moderate, and none of the three tools were capable of predicting 12-month mortality. A functional and psychological evaluation including oral health seems recommendable in elderly patients at nutritional risk.

Cultural diversity in physical diseases among patients with mental illnesses.

OBJECTIVE: People with psychiatric diseases have a severely increased risk for physical morbidity and premature death from physical diseases. The aims of the study were to investigate the occurrence of cardiovascular diseases (CVD), diabetes (DM) and obesity in schizophrenia and depression in three different geographical areas - Asia (Japan), Africa (Nigeria) and Western Europe (Switzerland, Germany and Denmark) - and to search for possible transcultural differences in these correlations, which would also reflect the differences between low-income areas in Africa (Nigeria) and high-income areas in Europe and Japan. METHOD: Patients with International Classification of Diseases (ICD-10) F2 diseases (schizophrenia spectrum disorders) and F3 diseases (affective disorders) admitted to one Nigerian, one Japanese, two Swiss, two German and six Danish centres during 1 year were included. Physical diseases in accordance with ICD-10 were also registered. Psychiatric and physical comorbidity were calculated and standardized rate ratio incidences of background populations were our primary measures. RESULTS: Incidence rate ratios were increased for both CVD, DM and overweight in both F2 and F3 in all cultures (Western Europe, Nigeria and Japan) within the same ranges (however, the Japanese results should be interpreted conservatively owing to the limited sample size). Overweight among the mentally ill were marked in Nigeria. A parallelism of the incidence of overweight, CVD and diabetes with the occurrence in background populations was seen and was most marked in overweight. CONCLUSIONS: Overweight, CVD and DM were increased in schizophrenia spectrum disorders and affective disorders in all three cultures investigated (Western Europe, Nigeria and Japan). Lifestyle diseases were also seen in Nigeria and Japan. The results from this study indicate that cultural background might be seen as an important factor in dealing with lifestyle diseases among people with a severe mental illness, as it is in the general population.

Diagnosis and treatment of fistulising Crohn's disease.

A fistula is defined as a pathological connection between the intestine and an inner (bladder or other intestine) or outer (vagina or skin) epithelial surface. Fistulas are discovered in up to 25% of all Crohn's disease patients during long-term follow-up examinations. Most are perianal fistulas, and these may be classified as simple or complex. The initial investigation of perianal fistulas includes imaging (MRI of the pelvis and rectum), examination under anaesthesia (EUA) with digital imaging, endoscopy, probing and anal ultrasound. Non-perianal fistulas require contrast imaging and/or CT/MRI for complete anatomical definition. Any abscess should be drained, and the disease extent throughout the entire gastrointestinal tract should be evaluated. Treatment goals for perianal fistulas include reduced fistula secretion or none, evaluated by clinical examination; the absence of abscesses; and patient satisfaction. MR imaging is required to demonstrate definitive fistula closure. Fistulotomy is considered for simple perianal fistulas. In complex perianal fistulas, antibiotics and azathioprine or 6-mercaptopurine, which are often combined with a loose seton, constitute the first-line medical therapy. In cases with persistent secretion, infliximab at 5 mg/kg is given at weeks 0, 2, and 6 and subsequently every 8 weeks. Adalimumab may improve fistula response in both infliximab-naïve patients and following infliximab treatment failure. Local therapy with fibrin glue or fistula plugs is rarely effective. Definitive surgical closure of perianal fistulas using an advancement flap may be attempted, but this procedure is associated with a high risk of relapse. Colostomy and proctectomy are the ultimate surgical treatment options for fistulas. Intestinal resection is almost always needed for the closure of symptomatic non-perianal fistulas.

Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

BACKGROUND: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. METHODS: Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. RESULTS: The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome-wide significance in the combined analyses of all the panels. CONCLUSIONS: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between the Nordic and the other European populations.

Polymorphisms in NF-κB, PXR, LXR, PPARγ and risk of inflammatory bowel disease.

AIM: To investigate the contribution of polymorphisms in nuclear receptors to risk of inflammatory bowel disease (IBD). METHODS: Genotypes of nuclear factor (NF)-κB (NFKB1) NFκB -94ins/del (rs28362491); peroxisome proliferator-activated receptor (PPAR)-γ (PPARγ) PPARγ Pro12Ala (rs 1801282) and C1431T (rs 3856806); pregnane X receptor (PXR) (NR1I2) PXR A-24381C (rs1523127), C8055T (2276707), and A7635G (rs 6785049); and liver X receptor (LXR) (NR1H2) LXR T-rs1405655-C and T-rs2695121-C were assessed in a Danish case-control study of 327 Crohn's disease patients, 495 ulcerative colitis (UC) patients, and 779 healthy controls. Odds ratio (OR) and 95% CI were estimated by logistic regression models. RESULTS: The PXR A7635G variant, the PPARγ Pro12Ala and LXR T-rs2695121-C homozygous variant genotypes were associated with risk of UC (OR: 1.31, 95% CI: 1.03-1.66, P = 0.03, OR: 2.30, 95% CI: 1.04-5.08, P = 0.04, and OR: 1.41, 95% CI: 1.00-1.98, P = 0.05, respectively) compared to the corresponding homozygous wild-type genotypes. Among never smokers, PXR A7635G and the LXR T-rs1405655-C and T-rs2695121-C variant genotypes were associated with risk of IBD (OR: 1.41, 95% CI: 1.05-1.91, P = 0.02, OR: 1.63, 95% CI: 1.21-2.20, P = 0.001, and OR: 2.02, 95% CI: 1.36-2.99, P = 0.0005, respectively) compared to the respective homozygous variant genotypes. PXR A7635G (rs6785049) variant genotype was associated with a higher risk of UC diagnosis before the age of 40 years and with a higher risk of extensive disease (OR: 1.34, 95% CI: 1.03-1.75 and OR: 2.49, 95% CI: 1.24-5.03, respectively). CONCLUSION: Common PXR and LXR polymorphisms may contribute to risk of IBD, especially among never smokers.

Common polymorphisms in the microsomal epoxide hydrolase and N-acetyltransferase 2 genes in association with inflammatory bowel disease in the Danish population.

INTRODUCTION: Chronic inflammatory bowel disease (IBD) is characterized by recurrent inflammation of the intestinal mucosa. Reactive molecules play a central role in altering the intestinal permeability, which may induce or sustain an immune response. Changes in detoxification of substances that causes epithelial damage may confer susceptibility to IBD. Hence, polymorphic enzymes involved in the detoxification processes may be risk factors of IBD. METHODS: The two biotransformation enzymes microsomal epoxide hydrolase and N-acetyltransferase 2 were genotyped using TaqMan based real-time PCR in 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls. RESULTS: No association was found between the genotypes of low microsomal epoxide hydrolase activity or slow N-acetyltransferase 2 acetylator status and IBD. An association was found between microsomal epoxide hydrolase and less than 40 years of age at diagnosis of Crohn's disease and microsomal epoxide hydrolase and azathiporine use in patients with ulcerative colitis. No other evident phenotypic associations were found for the two enzymes and either ulcerative colitis or Crohn's disease. A possible modification of smoking on microsomal epoxide hydrolase genotypes was found. CONCLUSION: Microsomal epoxide hydrolase and N-acetyltransferase 2 genotypes appear not to be individual risk factors of IBD, or to be important in relation to phenotypic characteristics of IBD.