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.

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.

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.

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.

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.

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.

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.

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.