Øistein Hovde

Epidemiology and clinical course of Crohn's disease: Results from observational studies

The authors review the clinical outcome in patients with Crohns disease (CD) based on studies describing the natural course of the disease. Population-based studies have demonstrated that the incidence rates and prevalence rates for CD have increased since the mid-1970s. The authors search for English language articles from 1980 until 2011. Geographical variations, incidence, prevalence, smoking habits, sex, mortality and medications are investigated. An increasing incidence and prevalence of CD have been found over the last three decades. The disease seems to be most common in northern Europe and North America, but is probably increasing also in Asia and Africa. Smoking is associated with an increased risk of developing CD. Age < 40 at diagnosis, penetrating/stricturing complications, need for systemic steroids, and disease location in terminal ileum are factors associated with higher relapse rates. A slight predominance of women diagnosed with CD has been found. Ileocecal resection is the most commonly performed surgical procedure, and within the first five years after the diagnosis about one third of the patients have had intestinal surgery. Smoking is associated with a worse clinical course and with increased risk of flare-ups. In most studies the overall mortality is comparable to the background population. To date, the most effective treatment options in acute flares are glucocorticosteroids and tumor necrosis factor (TNF)-α-blockers. Azathioprine/methotrexate and TNF-α-blockers are effective in maintaining remission.

Patients with functional dyspepsia responding to omeprazole have a characteristic gastro-oesophageal reflux pattern.

BACKGROUND The effect of acid secretion inhibitors in patients with functional dyspepsia (FD) is equivocal. One previous trial showed an effect in patients with a characteristic gastro-oesophageal reflux pattern. This double-blind trial compares the number of reflux episodes in responders and non-responders to omeprazole. METHODS Twenty-four patients (men/women, 11:13; mean age, 49 years) with FD were included; those with reflux as the main symptom were excluded. An upper endoscopy and a 24-h oesophageal pH measurement were performed before randomization to treatment with 10-20 mg omeprazole or placebo for 4 weeks. Patients who at questioning considered themselves to have achieved sufficient relief of dyspeptic symptoms after 4 weeks were characterized as responders. RESULTS The number of responders in the omeprazole and placebo groups was 8 of 14 (57%) and 2 of 10 (20%), respectively (P = 0.07). The mean number of reflux episodes at the 24-h oesophageal pH measurement in responders and non-responders to omeprazole was 57 and 25, respectively (P < 0.003). In the omeprazole group the number of responders was 0 of 5 (0%) in those with < 32 reflux episodes and 8 of 9 (89%) in those with > 32 reflux episodes (P < 0.003). CONCLUSION Patients with FD responding to omeprazole were characterized by many reflux episodes.

A comparison of diagnostic tests for lactose malabsorption - which one is the best?

BackgroundPerceived milk intolerance is a common complaint, and tests for lactose malabsorption (LM) are unreliable. This study assesses the agreement between diagnostic tests for LM and describes the diagnostic properties of the tests.MethodsPatients above 18 years of age with suspected LM were included. After oral intake of 25 g lactose, a combined test with measurement of serum glucose (s-glucose) and hydrogen (H2) and methane (CH4) in expired air was performed and symptoms were recorded. In patients with discrepancies between the results, the combined test was repeated and a gene test for lactose non-persistence was added. The diagnosis of LM was based on an evaluation of all tests. The following tests were compared: Increase in H2, CH4, H2+CH4 and H2+CH4x2 in expired air, increase in s-glucose, and symptoms. The agreement was calculated and the diagnostic properties described.ResultsSixty patients were included, seven (12%) had LM. The agreement (kappa-values) between the methods varied from 0.25 to 0.91. The best test was the lactose breath test with measurement of the increase in H2 + CH4x2 in expired air. With a cut-off level < 18 ppm, the area under the ROC-curve was 0.967 and sensitivity was 100%. This shows that measurement of CH4 in addition to H2 improves the diagnostic properties of the breath test.ConclusionThe agreement between commonly used methods for the diagnosis of LM was unsatisfactory. A lactose breath test with measurement of H2 + CH4x2 in expired air had the best diagnostic properties.

Mortality and causes of death in Crohn's disease: results from 20 years of follow-up in the IBSEN study

Objective Population-based studies have shown a slightly decreased life expectancy in patients with Crohns disease (CD). The primary aim of the present study was to evaluate mortality and causes of death 20 years after the diagnosis in a well defined population-based cohort of CD patients in Norway. Design The Inflammatory Bowel South-Eastern Norway study has prospectively followed all patients diagnosed with CD in the period between 1 January 1990 and 31 December 1993 in four geographically well-defined areas. All patients (n=237) were age and sex matched with 25 persons from the same county selected at random from the general population. Data on death and causes of deaths were collected from the Norwegian Causes of Death Register. All causes and cause-specific mortality (gastrointestinal cancer, cancer and heart disease) were modelled with Cox regression model stratified by matched sets. Results are expressed as HRs with 95% CIs. Results There was no significant difference between CD patients and controls in overall mortality (HR=1.35, 95% CI 0.94 to 1.94, p=0.10). Furthermore, there were no marked differences in deaths from gastrointestinal cancer, other cancers or cardiovascular diseases in the CD group compared with the controls. In the CD group, 13.9% had died compared with 12.7% in the control group (p=0.578). Conclusions In our population-based inception cohort followed for 20 years, there was no increased mortality or more deaths from cancer compared with the general population.

Vitamin D deficiency in inflammatory bowel disease: prevalence and predictors in a Norwegian outpatient population

Abstract Background and aim: Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aims of the present study were to determine the prevalence of vitamin D deficiency and to identify clinical and epidemiological variables associated with vitamin D deficiency in an outpatient population with IBD. Methods: Participants were recruited from nine hospitals in the southeastern and western regions of Norway as part of an observational, multicentre study from March 2013 to April 2014. Clinical and epidemiological data were collected by interview and from medical records. All analyses of serum 25-hydroxyvitamin D (25-OH-D) were performed in the same laboratory. Results: In total, 49% (200/408) of the patients had a 25-OH-D concentration <50 nmol/L, including 53% (122/230) of the Crohn’s disease (CD) patients and 44% (78/178) of the ulcerative colitis (UC) patients. In CD patients, disease activity, measured as the HBI, was inversely associated with vitamin D deficiency. No such association was observed with the Simple Clinical Colitis Activity Index (SCCAI) scores in UC, but in UC patients, vitamin D deficiency was associated with elevated faecal calprotectin >100 mg/kg. In patients with CD, there were significantly more relapses during the previous year in patients with vitamin D deficiency. Conclusions: Vitamin D deficiency was common, especially in CD, and was associated with increased disease activity, a relapsing disease course and higher inflammatory activity.

Long-term outcome of palliative treatment with self-expanding metal stents for malignant obstructions of the GI tract

Abstract Background. Self-expanding metal stents (SEMS) are commonly used in the palliative treatment of malignant gastrointestinal (GI) obstructions with favorable short-term outcome. Data on long-term outcome are scarce, however. Aim. To evaluate long-term outcome after palliative stent treatment of malignant GI obstruction. Method. Between October 2006 and April 2008, nine Norwegian hospitals included patients treated with SEMS for malignant esophageal, gastroduodenal, biliary, and colonic obstructions. Patients were followed for at least 6 months with respect to stent patency, reinterventions, and readmissions. Results. Stent placement was technically successful in 229 of 231 (99%) and clinically successful after 1 week in 220 of 229 (96%) patients. Long-term follow-up was available for 219 patients. Of those, 72 (33%) needed reinterventions. Stent occlusions or migrations (92%) were the most common reasons. Esophageal stents required reinterventions most frequently (41%), and had a significantly (p = 0.02) shorter patency (median 152 days) compared to other locations (gastroduodenal, 256 days; colon, 276 days; biliary, 460 days). Eighty percent of reinterventions were repeated endoscopic procedures that successfully restored patency. Readmissions were required for 156 (72%) patients. Progression of the underlying cancer was the most common reason, whereas 24% were readmitted due to stent complications. Conclusions. Long-term outcome after palliative treatment with SEMS for malignant GI and biliary obstruction shows that 70% had a patent stent until death, and that most reobstructions could be solved endoscopically. Hospital readmissions were mainly related to progression of the underlying cancer disease.

Mortality and Causes of Death in Ulcerative Colitis: Results from 20 Years of Follow-up in the IBSEN Study.

Background:The best way to obtain knowledge about the natural history, including mortality, of ulcerative colitis (UC) is to conduct a longitudinal, population-based, prospective study. The aims of this study were to calculate the mortality rates and causes of death in patients with UC. Methods:A prospective, population-based, longitudinal cohort study was conducted in South-Eastern Norway. A total of 519 patients (51.4% men) with UC were included over a 4-year period. A gastroenterologist from a university hospital reviewed the clinical information of all of the patients. Mortality data were retrieved from the Cause of Death Registry and from Statistics Norway. Results:No statistically significant increases in total mortality or cause-specific mortality between the patients with UC and the controls were found. Conclusions:The present 20-year population-based cohort study revealed a good prognosis regarding the mortality, which partially might be explained by the patients′ coverage by a generally well-functioning health care system.

Mangafodipir as a cytoprotective adjunct to chemotherapy - a case report

Johnson Syndrome. She developed severe leucopenia (0.1 10/L) and thrombocytopenia (10 10/ L) and was treated with filgrastim and thrombocytesubstitution, respectively. She became febrile and, despite empiric broad spectrum antibiotics, developed septic shock resistant to vaso-active agents. After a comatose state, she finally died on the 12th day of hospitalization, 3 weeks after onset of her first symptoms. Capecitabine is an oral 5-fluorouracil (5-FU) prodrug mainly used for the treatment of CRC and breast cancer. The drug is activated in a 3-step process, yielding the active agent 5-FU (Figure 1). The final step of activation into 5-FU occurs preferentially in malignant cells. Main adverse reactions of 5-FU are myelotoxicity, mucositis and a hand-footsyndrome. More than 80% of 5-FU is metabolized by dihydropyrimidine-dehydrogenase (DPD), the rate limiting step of 5-FU inactivation (Figure 1) [1]. Brivudine ((E)-5-(2-bromovinyl)-2?-deoxyuridine; BVDU) is a thymidine analogue for treatment of herpes zoster virus infections. Brivudine is hepatically converted to bromovinyluracil (BVU) and 2-deoxyribose-1-phosphate (Figure 1). Non-metabolized brivudine is phosphorylated by viral deoxythymidinekinase to BVDU monophosphate (BVDU-MP) and BVDU diphosphate (BVDU-DP). The latter is trapped in infected cells and is activated to BVDU triphosphate (BVDU-TP), inhibiting viral replication. Of note, BVU is an irreversible inhibitor of DPD, decreasing DPD activity by ]90, which normalizes only within 18 days. This inhibition is associated with a 5-15 fold increase in 5-FU-concentrations [2,3]. Due to enhanced 5-FU toxicity, the combination of these drugs is absolutely contraindicated. In 1993, fifteen fatal DDI with the antiviral sorivudine, another irreversible DPD-inhibitor, and the 5-FU-prodrug tegafur were reported in Japan [4]. In our patient, the combination of brivudine and capecitabine occurred despite clearly visible warning labels on the package. This is the first report of a fatal DDI between capecitabine and brivudine and the only case reported to the Swiss National Pharmacovigilance Center Swissmedic [6]. Alertness of the prescribers and optimal communication between health care providers are essential to prevent concomitant prescription of these drugs.

Predictive factors for a severe clinical course in ulcerative colitis: Results from population-based studies

Ulcerative colitis (UC) is characterized by chronic inflammation of the large bowel in genetically susceptible individuals exposed to environmental risk factors. The disease course can be difficult to predict, with symptoms ranging from mild to severe. There is no generally accepted definition of severe UC, and no single outcome is sufficient to classify a disease course as severe. There are several outcomes indicating a severe disease course, including progression of the diseases extension, a high relapse rate, the development of acute severe colitis, colectomy, the occurrence of colorectal cancer and UC-related mortality. When evaluating a patients prognosis, it is helpful to do so in relation to these outcomes. Using these outcomes also makes it easier to isolate factors predictive of severe disease. The aims of this article are to evaluate different disease outcomes and to present predictive factors for these outcomes.

Malignancies in Patients with Inflammatory Bowel Disease: Results from 20 Years of Follow-up in the IBSEN Study

Background and Aims Whether patients with inflammatory bowel diseases [IBDs] have increased risk of developing cancer has been debated. The aims of the study were to determine the prevalence of intestinal/extraintestinal cancers in an IBD cohort 20 years after diagnosis and to assess whether these patients had an increased cancer-specific risk compared with a matched control population. Methods Patients with ulcerative colitis [UC] and Crohns disease [CD] diagnosed 1990-1993 have been prospectively followed up for 20 years. Follow-up visits were carried out 1, 5, 10, and 20 years after inclusion. Data on all cancer cases, deaths, and causes of death were collected from the Cancer Registry of Norway and from the Norwegian Cause of Death Registry. Results In all, 756 patients [519 UC and 237 CD] were diagnosed with IBD. Increased risk of cancer was seen in UC patients (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.08-1.81, p < 0.01), but not in CD patients [HR = 1.23, 95% CI 0.80-2.03, p = 0.30]. Stratified by gender, our data revealed a statistically increased risk for all cancers only in male UC patients compared with the controls [HR = 1.51, 95% CI 1.08-2.11, p = 0.017]. In both groups breast cancer was seen more often than expected. Conclusions Male UC patients display an increased risk of development of colorectal cancer and, also all cancers combined, compared with the controls. In both UC and CD, standardized incidence ratio for breast cancer was increased.