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Objective. The prevalence of anemia in inflammatory bowel disease (IBD) has been broadly described. The recurrence, type and burden of anemia remain unenlightened. The primary objective was to describe this. The secondary objective was to evaluate the implementation of European guidelines. Materials and methods. This longitudinal follow-up study included 300 IBD outpatients from six centers in Scandinavia. Patients were enrolled in a research cohort, in which each center included 5% of their IBD cohort. The study was prospectively planned, while data were retrospectively collected. The burden of anemia was calculated as number of months with anemia. A Markov model was used to calculate the probabilities of transitioning between stages. The European guidelines were used as the standard for anemia management. Results. Anemia affected andgt; 50% of IBD outpatients during the 2-year observation period. Totally, 20% of the total observation time was spent in anemia. Over the 7200 months of observation, anemia was found in 1410 months. The most frequent type was combined anemia (63%). Combined anemia covers both anemia of chronic disease (ACD) and iron-deficiency anemia (IDA). Pure ACD was present in 21% of burden time, while pure IDA was present in 16% of burden time. The European guidelines have mainly been implemented. Conclusion. Anemia affected a majority of the IBD outpatients. One in five months, the patients were anemic. Anemia related to inflammation dominated the different types of anemia. Pure IDA was found in for 16%. These findings, despite a fair implementation of guidelines., Funding Agencies|Vifor Pharma Nordiska AB, Kista, Sweden

Objective. Iron deficiency and anemia are being increasingly recognized as a complication of inflammatory bowel disease (IBD). The aim of this study was to observe, in a non-interventional way, how Swedish gastroenterologists adhere to guidelines in IBD outpatients treated with intravenous ferric carboxymaltose (FCM), and the result of treatment. Material and methods. Altogether 394 IBD patients (Crohns disease (CD) 60%, ulcerative colitis (UC) 40%) from 14 centers were included. Group A (n = 216) was observed from November 2008 and group B (n = 178) from March 2010. Time of observation ranged from 12 to 29 months. Results. S-Ferritin (mmol/l) and transferrin saturation (T-Sat; %) were recorded at baseline in 62% and 50% in group A. Median values for Hb, ferritin and T-Sat at baseline were 111 g/l, 10 mu mol/l and 10%, respectively, and 134 g/l, 121 mmol/l and 20% after iron treatment (p andlt; 0.001 for all three parameters). Similar results were found in group B. Approximately three-quarters of all patients had only one iron infusion during the study period. Median time to reinfusion was 6 (1-25) months. Only previously described infusion reactions occurred in 27 (7%) patients. Conclusions. Adherence to European guidelines was rather poor and needs to be improved. The effect on iron parameters of intravenous FCM was significant, and resulted in a ferritin level that indicates an effect on the iron stores. The effect was mostly sustained for a year since only one-quarter of the patients were given repeated iron infusions. No unforeseen safety concerns emerged during the observation period., Funding Agencies|Vifor Pharma Nordiska AB, Kista, Sweden

Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patients files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogrens syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Background similar to Patients with inflammatory bowel disease (IBD) often complain of fatigue. Aim similar to To investigate the prevalence and characteristics of fatigue among IBD out-patients in Scandinavia and to provide normative values for fatigue in IBD patients. Methods similar to A cross-sectional study was conducted on 425 IBD patients from six out-patient centres in Denmark, Norway and Sweden. Fatigue was measured using the Multidimensional Fatigue Inventory. The patients were also screened for anaemia and iron deficiency. Each centre included approximately 5% of their IBD cohort. The patients were enrolled consecutively from the out-patient clinics, regardless of disease activity and whether the visit was scheduled. The fatigue analysis was stratified for age and gender. Results similar to Using the 95th percentile of the score of the general population as a cut-off, approximately 44% of the patients were fatigued. When comparing the IBD patients with disease activity to the IBD patients in remission, all dimensions of fatigue were statistically significant (P less than 0.05). Being anaemic or iron deficient was not associated with increased fatigue. Being a male patient with ulcerative colitis treated with corticosteroids was a strong determinant for increased fatigue. The normative ranges for IBD fatigue were calculated. Conclusions similar to Fatigue in IBD is common regardless of anaemia or iron deficiency. Fatigue in IBD is most marked for patients less than60 years of age. Stratifying for gender and age is necessary when analysing fatigue, as fatigue is expressed differently between groups.

Objectives. The association between abdominal symptoms, disease severity of fecal incontinence (FI), and quality of life (QoL) is not yet clear. We hypothesized that it would become clearer by prospective diary data. We also aimed to compare QoL of FI patients with ulcerative colitis (UC) patients in relapse and remission. Material and methods. Sixty-five consecutive female patients with FI recorded bowel symptoms prospectively on diary cards. QoL was evaluated with the disease specific short health scale questionnaire (SHS). Patients with UC in remission and relapse were used as a reference group regarding SHS. Results. FI patients had median 3.5 leakage episodes/week. In all, 48% of bowel movements were associated with urgency. Urgency was correlated to decreased QoL according to SHS domains: symptoms (Rho = 0.54, p = 0.0002), function (Rho = 0.48, p = 0.0008), and disease related worry (Rho = 0.32, p = 0.027). Abdominal pain and bloating, reported by nearly half of patients, correlated to deceased QoL but not to number of leakages. QoL of patients with FI compared to UC in active phase (n = 35) was similar. FI patients had decreased QoL compared to UC in remission (n = 94) in all dimensions of SHS: symptoms (p < 0.0001), function (p < 0.0001), disease related worry (p < 0.0001), and general well being (p = 0.03). Conclusion. Urgency and irritable bowel syndrome (IBS)-like symptoms were associated with decreased QoL in FI. Therefore, IBS should be considered as an important confounding factor in FI QoL studies. QoL in patients with FI was considerably decreased, in a similar extent as in patients with UC in relapse.

Objective. The aim was to describe health-related quality of life (HRQL) and social factors, sickness and disability variables in a large population-based cohort of patients with Crohn’s disease (CD). Methods. HRQL was measured with SF-36 in 497 adult CD patients at three outpatient clinics. Comparisons were made with age-gender-matched background population and with ulcerative colitis (UC). Social factors, employment, sickness compensation, and disability pension for CD, were compared with national population registers. Results. CD had a greater negative effect on HRQL than did UC. This difference was more pronounced for women. Compared with background population, CD patients had lower educational level, and had a two-fold rise in long-term sickness and disability pension rate. CD women had higher rates of sickness and disability than CD men and were more often living single, though procreation was not affected. Conclusion. This study characterized the burden of CD in a large population-based cohort. CD had higher impact on HRQL, compared with UC. CD women had worse outcome in subjective health status, but not in objective assessment of disease activity. Women also had higher rates of sickness, disability pension, and single living. The mechanism underlying the gender-related inequalities in outcome for CD warrants further elucidation.

Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohns disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking inmicroscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55-73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p andlt; 0.001, odds ratio (OR) 2.95). In the age group 16-44 years, 75% of CC patients were smokers compared with 15% of controls (p andlt; 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers - at 42 years of age (median) compared with 56 years in non-smokers (p andlt; 0.003). Although the proportion with active disease did not differ between smokers and nonsmokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers., Funding Agencies|Kocks Foundation in Trelleborg||Orebro County Research Committee||Orebro University Hospital||County Council Ostergotland Research Foundation

Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p andlt; 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population.

Objective. To evaluate the prevalence of anemia and iron deficiency (ID) among patients with inflammatory bowel disease (IBD) in the Scandinavian countries. Material and methods. A cross-sectional study including 429 IBD patients from six centers in Denmark, Norway and Sweden. Patients were screened for anemia and ID. Each center included similar to 5% of their IBD cohort. Patients were consecutively seen in the outpatient clinic, regardless of disease activity and whether the visits were scheduled or not. Results. The overall prevalence of anemia was 19% (95% CI: 16--23%). The prevalence was higher among patients with Crohns disease than among patients with ulcerative colitis (p = 0.01). The etiology of anemia was as follows: iron deficiency anemia (20%), anemia of chronic disease (12%), and both conditions (68%). Less than 5% had folate acid or vitamin B12 deficiency. ID was found in 35% (CI: 31-40%) of the patients. Conclusions. Anemia was present in every fifth IBD patient and ID in every third IBD patient.

Objective. Disease-related worries constitute an important dimension of patient-reported perception of health status in inflammatory bowel disease (IBD). The Rating Form of IBD Patient Concerns (RFIPC) questionnaire is purported to measure IBD-related worries. This study evaluated the psychometric properties of a Swedish translation of RFIPC in an unselected population of Crohns disease (CD) patients. The degree and nature of the worries were characterized and predictive factors for outcome of RFIPC and underlying dimensions were identified. Material and Methods. The RFIPC was completed by 447 CD patients in conjunction with regular visits. A physician global assessment of disease activity and four other health-related quality of life (HRQL) questionnaires were used for construct validity. Reliability and responsiveness were evaluated with follow-up visits. Underlying dimension and predictive factors were identified with factor analysis and multiple linear regression analysis. Results. Test-retest reliability was 0.90, correlation with corresponding HRQL measures 0.60-0.80 and responsiveness ratio 0.84. Median RFIPC sum score was lower than in previous studies. Top three concerns were ostomy, energy level and bowel control. Four dimensions were identified in descending order of concern: disease-related complications, daily-life achievements, intimacy, and stigmatization. Predictors of RFIPC score were disease activity, gender, and BMI (p andlt; 0.001-0.008). Conclusions. The Swedish version of RFIPC exhibited an adequate psychometric performance in CD patients, but was less sensitive to change in disease activity. The patients were more concerned about complications and achievement than intimacy and stigmatization. The strongest predictors of more worry were active disease, female gender and higher BMI.

Crohn disease is a chronic inflammatory bowel disease of unknown etiology. The chronic, relapsing nature of Crohn disease produces physical, psychological, and social stress. The disease occurs early in life, and the effects of Crohn disease on daily life are associated with symptom burden; thus, managing their disease and coping with its impact is a lifelong process for sufferers. This study was undertaken to identify and describe the meaning of quality of life in patients with Crohn disease. Using a grounded theory methodology, 11 interviews were performed with 6 men and 5 women, 29–83 years of age, all suffering from Crohn disease. The experience of quality of life was associated with limitations in daily activity, the major theme that emerged from the analysis. Quality of life varied depending on how the patient managed limitations related to the symptoms of the disease. The categories of self-image, confirmatory relations, powerlessness, attitude toward life, and sense of well-being were conceptualized as the dominant themes derived from the data. When caring for these patients, it is important to identify limitations and provide support so that patients are able to maintain a daily life that can be perceived as normal and routine.

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Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety. Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times. Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80. Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.

Objective. Patients with inflammatory bowel disease (IBD) often have low iron stores or anaemia. There is controversy about whether iron should be supplemented orally or intravenously (i.v.). The purpose of this study was to investigate whether treatment with intravenous iron is superior to treatment with oral iron. The primary end-points were response and remaining anaemia at the end of treatment (EOT). Material and methods. Ninety-one patients with IBD and anaemia (B-Hb <115 g/L) were randomized to oral iron sulphate (n=46) or intravenous iron sucrose (n=45) treatment for 20 weeks. Results. Forty-three patients in the intravenous iron group completed the study compared to 35 patients in the oral iron group (p=0.0009). Only 22 patients (48%) tolerated the prescribed oral dose, and 52% reduced the dose or withdrew from treatment because of poor tolerance. At EOT, 47% patients in the oral iron group increased their B-Hb by ≥20 g/L, compared with 66% in the intravenous iron group (p=0.07). In the oral iron group, 41% still had anaemia versus 16% of the patients in the intravenous iron group (p=0.007), and 22% versus 42% reached their reference B-Hb level (p=0.04). Treatment with intravenous iron sucrose improved iron stores faster and more effectively than oral iron (p=0.002). Under treatment with intravenous iron, 74% of the patients had no anaemia and normal S-ferritin levels (>25 µg/L) at EOT compared with 48% of patients receiving oral iron (p=0.013). Conclusions. Treatment with intravenous iron sucrose is effective, safe, well tolerated and superior to oral iron in correcting haemoglobin and iron stores in patients with IBD.

Background: The Crohns Disease Activity Index (CDAI) has become the gold standard for assessment of disease activity in CD. This study investigated the relationship between CDAI and the physicians global assessment of disease activity (PGA) and whether different demographic and disease-related factors predict the outcome. Methods: Multiple linear regression analysis was used to investigate the relationship between CDAI and PGA obtained from 405 CD patients. Predictors of the CDAI and the PGA outcome were identified. Results: The correlation between CDAI and PGA was moderate. In patients with CDAI greater than 150, 72% of the total score were derived froth the subjective variables. The regression coefficients were not significant for 3 of the CDAI variables. In regression analysis, C-reactive protein (CRP), stenosis, smoking, bowel resection, concomitant disease, and gender predicted the CDAI outcome. The PGA outcome was predicted only by CRP, stenosis, and fistula. Conclusions: The correlation between CDAI and PGA was moderate and the subjective variables had a high impact on CDAI. Factors with no obvious relation to inflammatory activity predicted the outcome of CDAI, but not PGA. In trials of CD therapies, separation of subjective (symptoms, well-being) from objective (endoscopy, inflammatory markers) variables should be considered in the assessment of disease activity.

Background: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL. Methods: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day. Results: Severity of bowel symptoms had a deleterious impact on patients HRQOL. Patients with a mean of greater than= 3 stools/day or a mean of greater than= 1 watery stool/day had a significantly impaired HRQOL compared to those with less than3 stools/day and less than 1 watery stool/day. Conclusions: We propose that clinical remission in collagenous colitis is defined as a mean of less than3 stools/day and a mean of less than 1 watery stool per clay and disease activity to be a daily mean of greater than= 3 stools or a mean of greater than= 1 watery stool.

[No abstract available]

Introduction Infliximab was launched for the treatment of Crohns disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. Aim To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA). Methods During 1999-2008, CD patients were monitored for disease activity by Harvey-Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies. Results A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey-Bradshaw index decreased with infusions during the first year of treatment (Pandlt;0.0001), whereas hemoglobin (Pandlt;0.01) and albumin (Pandlt;0.001) increased, C-reactive protein (Pandlt;0.01) decreased, platelets (Pandlt;0.001) increased, and leukocytes (Pandlt;0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (Pandlt;0.0001), and nitrite (Pandlt;0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found. Conclusion Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.

Objective. Peristomal bulging caused by hernia or prolapse is common in patients with a sigmoidostomy. It is not known whether and to what extent peristomal bulging influences various daily activities. The purpose of this study was to evaluate the effects of bulging by using a general and disease-specific health scale (Short Health Scale, SHS) and a stoma-specific quality of life (Stoma-QoL) questionnaire in patients with and without peristomal bulging. Material and methods. Seventy patients with sigmoidostomies were examined to identify peristomal bulging. The mean (SD) age was 71.7 (13.7) years and the patients had had their sigmoidostomies for a mean of 8.1 (7.9) years. Bulging was noticed in 46 patients (66%) while 24 had no bulging. Results. It was found that patients with bulging were at a disadvantage. In the SHS, patients with bulging reported significantly impaired QoL in 3 out of 4 scales regarding symptom load, worry and general sense of well-being. Also, in the Stoma-QoL questionnaire there was a significant difference between patients with and those without bulging. Conclusions. QoL evaluated with a general and disease-specific instrument (SHS) was significantly impaired in patients with bulging around a sigmoidostomy. The Stoma-QoL questionnaire showed a small but statistically significant difference between patients with and those without bulging but the clinical significance is uncertain. Further studies are required to evaluate the role of some of the individual items in the Stoma-QoL questionnaire. © 2008 Taylor & Francis.

Background: Health-related quality of life (HRQoL) is an essential part of inflammatory bowel disease (IBD) assessment. The Short Health Scale (SHS), an HRQoL questionnaire in which the patients rate the disease impact on 4 important aspects of subjective health (symptoms, function, worry, and general well-being) was demonstrated in a previous study to be valid, reliable, and responsive in patients with ulcerative colitis. The present study evaluates the SHS in patients with Crohn's disease (CD). Methods: In all, 367 CD patients completed the SHS and 4 other HRQoL questionnaires (IBDQ, SF-36, RFIPC, and PGWB) at their regular outpatient visits. Then 330 patients completed the questionnaires at a second visit 6 months later. In addition, reliability data were obtained from repeat measurements 4 weeks after the first visit in 40 patients stable in remission. Results: Patients in remission scored better on all 4 questions than those with active disease (P < 0.001). All 4 questions were strongly correlated with the corresponding dimensions of the other HRQoL questionnaires (rS = 0.74-0.83). Reliability was confirmed with strong test-retest correlations (rS = 0.69-0.82) and intraclass correlation coefficients (0.66-0.77). Patients who changed from remission to active disease or vice versa showed a significant change in all 4 SHS scores (P < 0.005). Conclusions: SHS is a valid, reliable and responsive HRQoL instrument also in patients with CD. It is easily completed by the patient and requires no further calculation by the investigator. SHS gives a comprehensive overview of the main aspects of the patient's subjective health perception and is a useful tool in both clinical practice and clinical studies. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

Anemia is a common complication of inflammatory bowel diseases. An international working party has formed and developed guidelines for evaluation and treatment of anemia and iron deficiency that should serve practicing gastroenterologists. Within a total of 16 statements, recommendations are made regarding diagnostic measures to screen for iron- and other anemia-related deficiencies regarding the triggers for medical intervention, treatment goals, and appropriate therapies. Anemia is a common cause of hospitalization, prevents physicians from discharging hospitalized patients, and is one of me most frequent comorbid conditions in patients with inflammatory bowel disease. It therefore needs appropriate attention and specific care. Copyright © 2007 Crohn's & Colitis Foundation of America, Inc.

The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3, 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol, 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35). Copyright © Taylor & Francis Group, LLC.

Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

Objective. Assessment of health-related quality of life (HRQOL) is important in both clinical practice and clinical trials, and several multi-item questionnaires are currently in use. We have devised and evaluated a simplified four-item questionnaire, the Short Health Scale (SHS), representing each of four health dimensions: (a) symptom burden, (b) social function, (c) disease-related worry and (d) general well-being. Material and methods. Three hundred patients with ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ, RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months – or earlier if disease activity changed. Test–retest reliability was derived from measurements of the SHS questions, 2 weeks apart, on 18 patients in remission. Results. Patients in relapse scored higher on each of the four SHS questions than patients in remission (p < 0.001). Each of the four SHS scores were associated with results of their corresponding health dimension obtained with the other three questionnaires (rs=0.57–0.78, p < 0.001) (validity). The results of the SHS proved stable on repeated measurement with a 2-week interval in patients in remission (rs=0.71–0.91, p < 0.01) (test–retest reliability). Patients with a change in disease activity had a significant change in their SHS scores (p < 0.05) (responsiveness). Conclusions. The SHS is a valid, reliable and responsive measure of subjective health in patients with ulcerative colitis. It is simple to administer, quickly completed and the results do not need further calculations. The SHS can be used in clinical trials and in clinical practice to identify the patient's main problems affecting health.

Objective. Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). Material and methods. Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns, Short Form-36, and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. Results. The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. Conclusions. Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items. © 2006 Taylor & Francis.

The importance of a patient's experience of disease impact on daily life and well-being (health-related quality of life (HRQOL)) is broadly acknowledged. Scepticism still remains about how HRQOL should be measured and the usefulness of standardised HRQOL questionnaires in medical research and everyday clinical practice. The lack of definitions, and the unclear relationship between disease activity and HRQOL makes it difficult to interpret results. The main purpose of this thesis was to determine a strategy for health assessment that is useful in daily practise and meaningful for clinicians and patients. The results are based on measurements of HRQOL and disease activity in a total of 511 patients with ulcerative colitis. The first aim of this thesis was to identify the major health dimensions and study their relationship in order to determine a strategy for health assessment. Based on theoretical reasoning and the pattern of association between measures of different areas of health status, the health concept was arranged into two categories, disease activity and HRQOL. Disease activity was further divided into biological variables and symptoms, and HRQOL into fimction, disease-related worry, and general well being. There was a poor association between these health dimensions. Measurement of health status is therefore better understood if it is divided into and interpreted as separate dimensions. It is then possible to see which dimensions are impaired and changes that have occurred. The second aim was to evaluate two disease-specific HRQOL questionnaires, the RFIPC and the IBDQ in Swedish patients with ulcerative colitis. The RFIPC was found to be a valid, reliable and responsive measure of disease-related worry and concern. The IBDQ had external validity and was shown to be a reliable and responsive measure of HRQOL. There are however some concerns regarding the internal validity of the IBDQ. The use of an overall sum score was not supported and the original four I

Objective: The aims of this study were to analyse the health-related quality of life of patients with ulcerative colitis and to assess in what way demographic and disease-related factors influence patients' experiences of this, in order to interpret the results of health-related quality of life assessment more correctly. Patients and methods: We carried out a cross-sectional evaluation of 300 consecutive patients with ulcerative colitis from the catchment areas of Linköping University Hospital and Örebro University Hospital in Sweden. Health-related quality of life was measured using four questionnaires: the IBDQ, the RFIPC, the SF-36 and the PGWB. Disease activity was evaluated using a one-week symptom diary, blood tests and rigid sigmoidoscopy. Demographic factors (gender, age, civil status, educational level), disease-related factors (disease duration, disease extent, disease activity) and presence of co-morbidity were obtained. Results: Health-related quality of life was mainly impaired in the psychological and social areas and to a much lesser degree in physical areas. Patients with relapse had significantly more disease-related worries and concerns (the RFIPC), more impaired social functioning (the IBDQ and SF-36), and a lower feeling of well being (the IBDQ, the SF-36 and the PGWB). However, their physical function (SF-36) was no worse than patients in remission. Besides the symptom burden of the current disease, co-morbidity and female gender were associated with a lower health-related quality of life. Conclusion: To correctly interpret health-related quality of life assessments, it is necessary to consider co-morbidity and gender distribution in addition to the symptom burden of the disease studied.

Background: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a disease-specific health-related quality of life (HRQOL) questionnaire including four dimensions and a sum score. The aim of this study was to assess the internal and external validity, reliability, and sensitivity of a Swedish version of the IBDQ. Methods: Three hundred consecutive patients with ulcerative colitis completed the IBDQ and three other health-related quality of life questionnaires (the Rating Form of IBD Patient Concerns (RFIPC), the Short Form-36 (SF-36) and the Psychological General Well-Being (PGWB) index). Disease activity was evaluated using a 1-week symptom diary, blood tests and rigid sigmoidoscopy. One hundred and fourteen patients filled in the questionnaire a second time, of whom 75 had been in stable remission for over 6 months and 39 had a significant clinical change in disease activity. Results: Factor analysis of the 32 IBDQ items did not support the four dimensional scores. The dimensional scores had sufficient convergent validity, but low discriminative validity and homogeneity. The homogeneity was also low for the sum score. The inter-dimensional correlations were high. The concurrent validity was supported by correlations between the dimensional scores and other measures of disease activity and HRQOL. Patients in relapse scored significantly less on the sum score and the four dimensions compared to patients in remission. The test-retest correlations for the dimensional scores were 0.40-0.76. Patients with a change in disease activity during the 6-month follow-up period had a significant change in IBDQ scores not found in those who remained in remission. Conclusions: The Swedish version of the IBDQ had external validity and was shown to be a reliable and sensitive measure of HRQOL in ulcerative colitis, though there are some concerns regarding the internal validity. The use of a sum score was not supported and the questionnaire may benefit from a redivision of items in

OBJECTIVE: Health is a complex and multi-dimensional entity and is neither easily determined nor easily conveyed to others. Publications have often combined various variables of disease activity and health-related quality of life (HRQoL), used the variables interchangeably or utilized summation indices to compare health assessment. The aim of this study is to investigate the relationship between measurements of disease activity and HRQoL. STUDY: design Cross-sectional evaluation of disease activity and HRQoL. STUDY POPULATION: Two hundred and eleven consecutive patients with ulcerative colitis. SETTING: The catchment area of Linköping University Hospital. MEASUREMENTS: HRQoL was measured using two questionnaires, the Sickness Impact Profile (SIP) and the Rating Form of IBD Patient Concerns (RFIPC). Patients were also asked if they were 'feeling fit and well', as a measurement of general health perception. Disease activity was measured by means of symptom cards, laboratory tests and sigmoidoscopy. RESULTS: The correlations (Spearman's r (r5)) between variables of disease activity and HRQoL were low. 'Feeling fit and well' was best correlated to worries and concerns (the RFIPC, rs 0.32, P < 0.05), while there was a decreasing association with subjective functional status (the SIP, rs 0.31, P < 0.05), symptoms (stools per day, rs 0.15, not significant) and biological variables (endoscopy score, rs 0.04, not significant). CONCLUSION: The correlations between traditional measurements of disease activity and various measures of HRQoL are low. We therefore propose a system whereby the process is conceptualized using a 'network strategy', ordering the measurements of disease activity and HRQoL into five dimensions: biological variables, symptoms, functional status, worries and concerns, and health perceptions. We feel that this method of interpretation more accurately reflects the overall health of a group of patients with IBD than more traditional summation indices.

Objective: The aim of this study was to characterize the health-related quality of life (HRQOL) in a Swedish population of patients with ulcerative colitis. Methods: A total of 211 patients with ulcerative colitis were studied. Demographic and disease-related factors were noted. HRQOL was measured by one disease specific questionnaire, the Rating Form of IBD Patient Concerns (RFIPC) and one generic, The Sickness Impact Profile (SIP). Additional questions regarding information needs, medication, and well-being were asked. Disease activity was measured by symptom cards, laboratory samples, endoscopy, and two indices of disease activity. The influence of additional concomitant disease was also evaluated. Results: Functional impairment as measured by the SIP was primarily in psychological and social areas and to a lesser extent in the physical areas. The highest scores for individual items of the RFIPC were those related to potential complications, e.g., needing an ostomy appliance, needing surgery, developing cancer, losing bowel control, and uncertainty about the disease and effects of medication. Patients with active disease scored higher on both SIP and RFIPC when compared to patients in remission. Presence of coexisting disease weighted heavily on HRQOL. Conclusion: Ulcerative colitis has a negative influence on the subjective functional status and seems to cause many worries and concerns. Patients in relapse had greater concerns, more impairment of functional status, and a reduced subjective sense of well-being than patients in clinical remission. Nevertheless, the patients in this Swedish study scored a much better HRQOL than has previously been reported using these questionnaires in patients with ulcerative colitis from the US, France, and Austria.

Background: We wanted to characterize a Swedish version of the Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) with regard to validity, reliability, and responsiveness. Methods: Two hundred and three consecutive patients with ulcerative colitis were studied. Health-related quality of life (HRQOL) was measured with the disease-specific questionnaire, the RFIPC, and a general questionnaire, the Sickness Impact Profile (SIP). Concerns about general well-being were also reported. Disease activity was measured by means of symptom cards, laboratory tests, and two clinical indices for disease activity. Results: Test-retest reliability using Spearman's r (rs) was 0.79, and internal consistency measured with Cronbach's alpha was 0.95. RFIPC had a fair correlation with concerns about general well-being (rs = 0.69, P < 0.001). There was also a stronger correlation with another measure of HRQOL, the overall SIP score (rs = 0.43), than with measures of disease activity such as stool frequency (rs = 0.28) and sigmoidoscopic grading (NS). The group of patients in relapse had a higher RFIPC sum score than patients in remission (P = 0.001). Measures of HRQOL had a low correlation with disease activity and did not respond to changes in disease activity. Conclusion: The Swedish version of the RFIPC is a valid and reliable measure of HRQOL. The SIP and the RFIPC have a good discriminative ability between groups of patients in remission and in relapse. However, they do not seem to be useful in predicting the disease activity or change in disease activity over time in the individual patient.