Stress, coping and support needs of patients with ulcerative colitis or Crohn's disease: a qualitative descriptive study.

AIMS AND OBJECTIVES: To examine disease-related stress, coping strategies and the need for information and support in patients with inflammatory bowel disease (ulcerative colitis or Crohn's disease). BACKGROUND: Psychological stress is an important factor in ulcerative colitis and Crohn's disease, and therefore, coping strategies and support needs should be considered in routine clinical practice. DESIGN: This is a qualitative study using a descriptive interview-based approach. METHOD: Fifteen patients with ulcerative colitis (n = 7) or Crohn's disease (n = 8) were interviewed. The interviews were analysed with content analysis. RESULTS: The informants largely focused on disease-related stress (e.g. access to a toilet, symptoms and worries) and relations to other people (various reactions from others and social situations). Behavioural strategies (i.e. taking actions and the need for making plans, prepare and adapt), social strategies (seeking help and information and sharing feelings about the disease with others) and emotional strategies (distraction, positive attitude and acceptance) were adopted to cope with the stress associated with the disease. The need for information and support concerned instrumental support (disease-related information) and emotional support (to talk about disease management). CONCLUSION: Faecal urgency and the fear of losing bowel control are important stressors for patients with inflammatory bowel disease. The patients handle this problem using various coping strategies depending on the type of stressful events. Both instrumental and emotional support were requested which primarily occurred at the time of diagnosis and disease flare-ups. RELEVANCE TO CLINICAL PRACTICE: Patients with ulcerative colitis or Crohn's disease ask for information and psychosocial support that are tailored to their individual needs and at different stages in the disease trajectory to improve everyday life and strengthen self-management strategies.

[The willingness to pay for new drugs is based on ethical principles]. / Betalningsviljan för nya läkemedel bygger på etiska principer - NT-rådet tolkar riksdagens plattform för prioritering.

The County Council's board for new therapies (the NT Council) provides recommendations on the use of new drugs based on the ethical platform of priorities, founded by the Swedish parliament. The Council has formulated a policy that interprets the parliamentary ethical platform and operationalize its need and solidarity principle and cost effectiveness principle in four dimensions. The NT Council weighs the health economic evaluation of the drug and the four dimensions: the severity of the condition, the rarity of the condition, the effect size and the data reliability to determine the willingness to pay level and whether the platform allows a recommendation for using of the drug. The severity of the condition has a greater impact than the other dimensions. In the assessment of severity there is also a trade-off between prevention and treatment of manifest diseases and in prevention, the size of the risk of falling ill is of importance. A slightly higher willingness to pay level is reasonable for treatment of very rare conditions, but it is important that identified patients are not given priority over anonymous patient groups with equally strong needs.

Moderate hyperkalemia in hospitalized patients with cirrhotic ascites indicates a poor prognosis.

OBJECTIVE: Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis. MATERIAL AND METHODS: We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals. All patients had undergone at least one diagnostic ascites tap, and had initially been questioned about background factors and physically examined according to a standardized case record form, followed by sampling of blood, urine, and ascites. RESULTS: Death occurred within 1 year after inclusion in 53% of the cases, and was primarily liver-related in 70%. In a multivariable analysis, the two ordinary variables that showed the strongest correlation with risk of death were serum potassium and abdominal tenderness. All 22 patients with a serum potassium concentration of at least 4.8 mmol/L (maximum 5.8 mmol/L) died within 1 year after inclusion. Potassium concentration was related to renal function and potassium-saving drugs. CONCLUSION: This follow-up study of a prospectively recruited cohort of in-patients with cirrhotic ascites confirms their poor prognosis. Awareness of an elevated serum potassium value, which would reflect a threatened renal function, seems essential, because it may offer a simple way to identify cases with the worst prognosis. An area for further research should be to explore the significance of including serum potassium in prognostic models.

Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population.

OBJECTIVE: The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected. PATIENTS AND METHODS: 373 patients with hemochromatosis detected through routine health check-ups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.9 ± 5.8 years. The degree of liver fibrosis and survival were analyzed. RESULTS: Overall survival among these patients was not significantly different from that of a matched normal population. The patients diagnosed through health check-ups and family screening were detected at an earlier age and had the highest rate of survival. Liver biopsy at the time of diagnosis revealed cirrhosis in 9% of those detected through the health check-ups and 5% in the case of family screening, compared with 13% for the group with arthralgia, 17% for other diseases/symptoms and 42% for liver disease. CONCLUSION: Health check-ups and family screening allow detection of hereditary hemochromatosis at an earlier age and with less advanced liver fibrosis, although a few of these patients have already developed cirrhosis. Our study indicates that iron indices should be included in health check-ups, and if abnormal, should lead to further investigation.

Increased mortality risk in patients with phenotypic hereditary hemochromatosis but not in their first-degree relatives.

BACKGROUND & AIMS: Hereditary hemochromatosis (HH) is an autosomal-recessive disorder characterized by iron overload. Relatives of HH patients were screened and those with HH-associated mutations and an increased iron load were identified. However, little is known about their mortality or strategies for their management. We assessed mortality among Swedish patients with HH and their first-degree relatives using health and census registers. METHODS: We performed a matched population-based cohort study of 3832 patients with HH and their 14,496 first-degree relatives using data collected from 1990 through 2007. Mortality data from these groups were compared with that of 38,969 population controls and their 143,349 first-degree relatives using Cox regression analyses. RESULTS: Patients identified on the basis of hospitalization with HH had an increased risk (relative risk [RR]) for death (RR, 2.45; 95% confidence interval [CI], 2.27-2.64; 857 deaths). Patients identified through other means had a mortality risk that was lower than those identified in the hospital but higher than controls (RR, 1.15; 95% CI, 1.00-1.33; 216 deaths). Their first-degree relatives had only a marginally increased mortality risk (RR, 1.05; 95% CI, 1.01-1.10); this RR was similar to that of patients' spouses (RR, 1.09; 95% CI, 0.86-1.38; 82 deaths). Patients with HH who also had a family history of HH did not have an increased mortality risk compared with other groups (RR, 1.05; 95% CI, 0.67-1.62; 21 deaths). CONCLUSIONS: Patients with HH have a modestly increased mortality risk compared with controls. The mortality of relatives is increased marginally compared with controls, and is similar among biological and nonbiological relatives.

Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience.

BACKGROUND: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival. AIMS: To investigate the epidemiology, clinical presentation and survival in patients with BCS. METHODS: Retrospective multicentre study in Sweden reviewing the medical records of all patients with BCS 1986-2003, identified from the computerised diagnosis database of 11 hospitals, including all university hospitals and liver transplantation centres. RESULTS: Forty-three patients with BCS were identified, of whom nine (21%) had concomitant portal vein thrombosis. The mean age-standardised incidence and prevalence rates in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. Myeloproliferative disorders (38%), thrombophilic factors (31%) and oral contraceptives (30%) were common aetiological factors. Two or more risk factors were present in 44%. In 23%, no risk factor was evident. The median follow-up time was 2.7 years. Seventy-two percent were on anticoagulant therapy during follow-up. Transjugular intrahepatic portosystemic shunting, surgical shunting procedures and liver transplantation were performed in 4, 6 and 18 patients respectively. Nineteen patients died. The overall transplantation-free survival at 1, 5 and 10 years was 47, 28 and 17% respectively. CONCLUSIONS: Budd-Chiari syndrome is a rare disorder; the mean age-standardised incidence and prevalence rates in Sweden in 1990-2001 were calculated to be 0.8 per million per year and 1.4 per million inhabitants respectively. The presence of a myeloproliferative disorder was a common aetiological factor in our cohort and about half of the patients had a multifactorial aetiology. The transplantation-free survival was poor.

Immunoreactivity against Goblet cells in patients with inflammatory bowel disease.

BACKGROUND: A number of autoantibodies have been reported in inflammatory bowel disease (IBD). The aim of this study was to investigate to what extent sera from patients with IBD contain autoantibodies directed against normal human gastrointestinal mucosa. METHODS: Samples of sera from 50 patients with IBD and 50 healthy subjects were used for immunostaining of normal and affected human gastrointestinal tissues. RESULTS: Eighty-four percent of the sera from IBD patients showed immunoreactivity against goblet cells in the appendix compared with 8% of the sera from healthy subjects. Goblet cell reactivity of IBD patient sera varied between regions in the gastrointestinal tract. Sera from healthy subjects only reacted with goblet cells in the appendix. In the colon and the appendix, goblet cell reactivity of IBD sera was generally weak at the base of the crypts and gradually increased toward the lumen. Three IBD sera samples reacted with gastrin cells in the antrum. In colon biopsies from patients with ulcerative colitis, immunoreactivity against the remaining goblet cells showed an inverse correlation with inflammatory activity. CONCLUSIONS: These findings suggest that immunoreactivity against goblet cells may be of central importance in the pathogenesis of IBD. Identification of goblet cell antigens could lead to a better understanding of IBD and provide a new diagnostic tool.

Quality of life for patients with exacerbation in inflammatory bowel disease and how they cope with disease activity.

OBJECTIVE: Health-related quality of life (HRQoL) for patients with ulcerative colitis (UC) or Crohn's disease (CD) is influenced by symptoms and treatments. Periods with increased disease activity are specifically trying, but the knowledge of how patients manage this is sparse. The aim of this cross-sectional study was to examine (1) HRQoL for patients with UC or CD, (2) how patients cope with increased disease activity, and (3) if coping is associated with HRQoL. METHODS: A postal questionnaire was sent to patients with UC and CD who attended the gastroenterology and surgery department at a Swedish university hospital. Coping, HRQoL, and emotional well-being were assessed by Jalowiec Coping Scale, Short Form-36 Health survey, Short Health Scale, and the Hospital Anxiety and Depression Scale. RESULTS: Patients with increased disease activity reported impaired HRQoL and emotional distress. This was more prevalent among patients with CD, as compared to patients with UC. Optimistic, self-reliant and confrontive coping strategies were most frequently used to manage stressors, with no differences found between patients in exacerbation or remission or between patients with UC or CD. CONCLUSION: Impaired HRQoL and emotional distress is prevalent among patients with exacerbation in UC and CD. Thus, a complete evaluation of psychosocial status and management of psychosocial distress should be included in the clinical treatment of the patient. Patients use a variety of coping strategies in an effort to manage increased disease activity. However, these results did not support any associations between coping and HRQoL.

Fecal calprotectin: a quantitative marker of colonic inflammation in children with inflammatory bowel disease.

OBJECTIVES: The protein calprotectin (S100 A8/A9) is present in neutrophils, monocytes, and macrophages. Colorectal inflammation can be detected by increased excretion of fecal calprotectin (FC). The aim of this study was to evaluate FC as a quantitative marker of inflammatory activity in children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Thirty-nine children with IBD delivered a fecal spot sample and underwent colonoscopy. The samples were examined with an enzyme-linked immunosorbent assay for FC (Calprest, Eurospital, Trieste, Italy). The concentrations were correlated to macroscopic and microscopic assessments of extent and severity of inflammation in 8 colonic segments for each patient. RESULTS: FC correlated significantly to the macroscopic extent (Spearman rho = 0.61) and the severity (Spearman rho = 0.52) of colonic inflammation and to a macroscopic, combined extent and severity score (Spearman rho = 0.65). Significant correlations also were found to the microscopic extent (Spearman rho = 0.71) and severity (Spearman rho = 0.72) of colonic inflammation and to a microscopic, combined extent and severity score (Spearman rho = 0.75). The median FC was 392 mug/g (95% confidence interval [CI], 278-440) in children with clinical IBD symptoms (n = 23) and 32.9 mug/g (95% CI, 9.4-237) in asymptomatic IBD patients (n = 16). Of the asymptomatic children, 56% had a complete microscopic mucosal healing, and their median FC was 9.9 mug/g (95% CI, 5.9-41.9). CONCLUSIONS: FC can be used as a surrogate marker for estimation of colonic inflammation in pediatric IBD. Normalized FC concentration seems to indicate complete mucosal healing. FC is simple to obtain and analyze; this should facilitate objective assessment and monitoring of IBD activity.

Abdominal tenderness in ascites patients indicates spontaneous bacterial peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP), which has been reported to be present in 10-30% of patients with cirrhotic ascites, may easily be overlooked. An important aim of our study was to determine whether there are any clinical signs which, in clinical practice, may predict or exclude SBP. METHODS: We studied 133 patients with cirrhotic ascites from medical units at nine Swedish university hospitals where there had been at least one diagnostic ascites tap with analysis of polymorphonuclear leukocytes in the ascites fluid. The patients had initially been questioned about background factors and physically examined according to a standardized case record form. Samples of blood, urine, and ascites were then drawn for analysis according to a structured schedule. RESULTS: SBP could be excluded in 80% of all the cases and was confirmed in 8% of the 133 patients in the final analysis. Abdominal pain and abdominal tenderness were more common in patients with SBP (p<0.01), but no other physical sign or laboratory test could separate SBP cases from the others. CONCLUSIONS: SBP was present in about one-tenth of the hospitalized patients with cirrhotic ascites in this cohort. Performing repeated physical examinations and paying particular attention to abdominal tenderness may be the best way to become aware of the possible development of this complication.

Expression of cytochrome P450 and MDR1 in patients with proctitis.

BACKGROUND: The aim of this study was to investigate the effect of inflammation on the gene expression of three cytochrome P450's (CYP) and P-glycoprotein (P-gp) in the rectal and colonic mucosa in patients with proctitis. METHODS: Biopsies were obtained from inflamed and normal mucosa in association with routine sigmoidoscopy in patients with proctitis. The biopsies were snap-frozen in liquid nitrogen. Real time PCR (polymerase chain reaction) was used for quantitative analyses of mRNA specific for the CYP2E1, CYP3A4 and CYP3A5 gene and the MDR1 genes. Values were normalised based on gene expression of beta-actin to enable comparisons between samples. RESULTS: The gene expression of CYP2E1 and CYP3A4 was lower in mucosa with severe inflammation vs normal mucosa (p<0.05). For CYP3A5 and P-gp there was no significant difference when comparing normal and inflammatory changed mucosa. CONCLUSION: Our study suggests that at least for some of the CYP enzymes the expression decreases in response to the inflammatory process in the gastrointestinal tract.

Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients.

AIM: To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein (ECP), myeloperoxidase (MPO), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and albumin in patients with collagenous colitis (CC). METHODS: A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice (one and four weeks) after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum. RESULTS: Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective well-being at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant. CONCLUSION: Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.

High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study.

BACKGROUND & AIMS: There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease. METHODS: A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units. A total of 219 patients were randomized to 17 to 23 mg/kg body weight per day of ursodeoxycholic acid (n = 110) or placebo (n = 109) for 5 years. Follow-up data are available from 97 patients randomized to ursodeoxycholic acid and for 101 randomized to placebo. Quality of life was assessed by using the Medical Outcomes Study 36-item Short-Form Health Survey. RESULTS: The combined end point "death or liver transplantation" occurred in 7 of 97 (7.2%) patients in the ursodeoxycholic acid group vs 11 of 101 (10.9%) patients in the placebo group (P = .368; 95% confidence interval, -12.2% to 4.7%). The occurrence of liver transplantation as a single end point showed a similar positive trend for ursodeoxycholic acid treatment (5/97 [5.2%] vs 8/101 [7.9%]; 95% confidence interval, -10.4% to 4.6%). Three ursodeoxycholic acid and 4 placebo patients died from cholangiocarcinoma, and 1 placebo patient died from liver failure. Alkaline phosphatase and alanine aminotransferase tended to decrease during the first 6 months. There were no differences between the 2 groups in symptoms or quality of life. Analyses of serum ursodeoxycholic acid concentration gave no evidence that noncompliance may have influenced the results. CONCLUSIONS: This study found no statistically significant beneficial effect of a higher dose of ursodeoxycholic acid than previously used on survival or prevention of cholangiocarcinoma in primary sclerosing cholangitis.

Kinetics of mucosal granulocyte activation after gluten challenge in coeliac disease.

OBJECTIVE: To elucidate the dynamics of the rectal inflammatory response to rectal gluten challenge in coeliac disease by measuring inflammatory mediators released by activated neutrophils, eosinophils and mast cells/basophils. MATERIAL AND METHODS: The release of myeloperoxidase (MPO), eosinophilic cationic protein (ECP) and histamine was measured continuously during the early challenge period (3-6 h after gluten challenge) in coeliac patients (n = 9) and healthy controls (n = 5). A segmental perfusion technique was used to carry out this part of the study. Another method, the mucosal patch technique, was used to enable studies of the late challenge period (5-48 h after gluten challenge) in coeliac patients (n = 10) and healthy controls (n = 15). RESULTS: During the early challenge period the MPO levels began to increase as early as 3 h after challenge and increased progressively (p < 0.001) during the next 3 h. A decline in MPO levels was seen 15 h after challenge and another phase of increasing levels at 24 h. The MPO values declined 48 h after challenge but still remained significantly increased (p < 0.05). The ECP levels started to increase 4 h after challenge and increased progressively during the next 2 h (p < 0.05). The ECP kinetics during the late challenge period was similar as for MPO but the relative increase in ECP was more modest. No increase in histamine was found except in one patient who had a transient, early increase of histamine (3-5 h after challenge). No signs of inflammatory reaction to gluten were seen in the controls. CONCLUSIONS: There is a pronounced neutrophil activation in coeliac patients after rectal gluten challenge. This activation is apparent 4 h after challenge and remains for at least 48 h. A more modest eosinophil activation defined by ECP levels starts 1-2 h later and also remains for at least 48 h. The biphasic pattern of MPO and ECP after challenge suggests a biphasic inflammatory reaction.

Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract.

AIM: The aim of this study was to quantify the mRNA expression of three cytochromes P450 (CYP) and P-glycoprotein (P-gp) in the human gastrointestinal (GI) tract. METHOD: Biopsies were obtained from gastric, duodenal, colonic and rectal mucosa during routine gastro-colonoscopy in 27 patients. The biopsies were snap-frozen in liquid nitrogen. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used for the quantitative analyses of mRNA expressed by the CYP2E1, CYP3A4 and CYP3A5 genes, and the MDR1 gene coding for P-gp protein. The mRNA expression of b-actin was used as an internal standard for comparisons between samples. RESULTS: All CYP genes were expressed at all locations throughout the GI tract, although all showed substantial interindividual variation. CYP2E1 had the highest expression at all locations (P < 0.05 to P < 0.0001), except in the right colon. CYP3A4 and CYP3A5 had their highest mRNA expression in the duodenum (P < 0.001 and P < 0.000 001, respectively) and CYP2E1 in the stomach (P < 0.01). MDR1 mRNA concentrations increased along the GI tract with the highest expression being in the left colon (P < 0.000001). CONCLUSION: Multiple sampling within the same individual enabled us to study the intraindividual variation in expression of CYP and MDR1 genes along the GI tract. We find that CYP2E1 mRNA expression is higher than that of the other CYPs. CYP3A expression is highest in the duodenum and that of MDR1 increases from stomach and duodenum to colon.

Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms.

OBJECTIVES: The protein calprotectin is mainly derived from neutrophils. Increased fecal excretion of calprotectin has been reported in inflammatory bowel disease. The recommended cut-off level in adults (<50 microg/g feces) seems to be applicable in children aged 4 to 17 years. The aim of this study was to evaluate the use of fecal calprotectin to detect colorectal inflammation in children with gastrointestinal symptoms. METHODS: We obtained stool samples on thirty-six children with gastrointestinal symptoms and suspected inflammation of the colon before they underwent colonoscopy. The samples were examined with an improved fecal calprotectin enzyme-linked immunosorbent assay method (Calprest, Eurospital). The results were correlated with the histopathologic findings in the colon. RESULTS: In children with colorectal inflammation (n = 22) the median fecal calprotectin concentration was 349 microg/g (range, 15.4-1860 microg/g). The most common diagnosis in this group was inflammatory bowel disease. Median fecal calprotectin was 16.5 microg/g (range, 5.0-65 microg/g) in children with no inflammation (n = 14). When <50 microg/g was used as upper reference limit the fecal calprotectin test had a sensitivity of 95%, specificity 93%, positive predictive value 95% and negative predictive value 93% to detect colorectal inflammation. CONCLUSIONS: The improved fecal calprotectin enzyme-linked immunosorbent assay is a simple test with potential use in children. Increased fecal calprotectin strongly predicted the presence of colorectal inflammation in children with gastrointestinal symptoms. Fecal calprotectin can be used to select patients who should undergo diagnostic colonoscopy for investigation of colorectal inflammation, including inflammatory bowel disease.