Comparison of the Multiattribute Utility Instruments EQ-5D and SF-6D in a Europe-Wide Population-Based Cohort of Patients with Inflammatory Bowel Disease 10 Years after Diagnosis.

Background. The treatment of chronic inflammatory bowel disease (IBD) is costly, and limited resources call for analyses of the cost effectiveness of therapeutic interventions. The present study evaluated the equivalency of the Short Form 6D (SF-6D) and the Euro QoL (EQ-5D), two preference-based HRQoL instruments that are broadly used in cost-effectiveness analyses, in an unselected IBD patient population. Methods. IBD patients from seven European countries were invited to a follow-up visit ten years after their initial diagnosis. Clinical and demographic data were assessed, and the Short Form 36 (SF-36) was employed. Utility scores were obtained by calculating the SF-6D index values from the SF-36 data for comparison with the scores obtained with the EQ-5D questionnaire. Results. The SF-6D and EQ-5D provided good sensitivities for detecting disease activity-dependent utility differences. However, the single-measure intraclass correlation coefficient was 0.58, and the Bland-Altman plot indicated numerous values beyond the limits of agreement. Conclusions. There was poor agreement between the measures retrieved from the EQ-5D and the SF-6D utility instruments. Although both instruments may provide good sensitivity for the detection of disease activity-dependent utility differences, the instruments cannot be used interchangeably. Cost-utility analyses performed with only one utility instrument must be interpreted with caution.

Guidelines for the management of Helicobacter pylori infection in Italy: The III Working Group Consensus Report 2015.

Knowledge on the role of Helicobacter pylori (HP) infection is continually evolving, and treatment is becoming more challenging due to increasing bacterial resistance. Since the management of HP infection is changing, an update of the national Italian guidelines delivered in 2007 was needed. In the III Working Group Consensus Report 2015, a panel of 17 experts from several Italian regions reviewed current evidence on different topics relating to HP infection. Four working groups examined the following topics: (1) "open questions" on HP diagnosis and treatment (focusing on dyspepsia, gastro-oesophageal reflux disease, non-steroidal anti-inflammatory drugs or aspirin use and extra-gastric diseases); (2) non-invasive and invasive diagnostic tests; (3) treatment of HP infection; (4) role of HP in the prevention of gastric cancer. Statements and recommendations were discussed and a consensus reached in a final plenary session held in February 2015 in Bologna. Recommendations are based on the best current evidence to help physicians manage HP infection in Italy. The guidelines have been endorsed by the Italian Society of Gastroenterology and the Italian Society of Digestive Endoscopy.

Health-related quality of life in inflammatory bowel disease in a European-wide population-based cohort 10 years after diagnosis.

BACKGROUND: Chronic inflammatory bowel disease (IBD) negatively affects the patient's health-related quality of life (HRQoL). Only a few population-based studies have compared the HRQoL of patients with the background population. The aim of this study was to evaluate the HRQoL in a European cohort of patients with ulcerative colitis and Crohn's disease 10 years after diagnosis (European Collaborative study group of Inflammatory Bowel Disease) compared with the national background population in each country and to assess possible country-specific differences. METHODS: Patients with IBD from 7 European countries were invited to a follow-up visit 10 years after their diagnosis of IBD. We assessed their clinical and demographic data, including the generic HRQoL questionnaire short form health survey-36. Countrywise comparison with the background population was performed with z-scores using the Cohen's effect size index. RESULTS: Seven hundred sixty-nine patients were eligible for the study. We registered statistically significant and clinically relevant decreases in the short form health survey-36 dimensional scores in patients with symptoms at the time of follow-up and for patients reporting sick leave during the previous year or having received disablement pension. In the Netherlands and Norway, there was a moderate difference between the patients with IBD and the background population for the general health dimension. CONCLUSIONS: Overall, the HRQoL was not reduced in the IBD cohort compared with the background populations. However, in addition to older age and female gender, current symptoms at follow-up, disablement pension, and sick leave during the previous year were significantly associated with a reduced HRQoL in patients with IBD.

Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

BACKGROUND: In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. METHODS: IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. RESULTS: The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. CONCLUSION: In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

Thromboembolism in inflammatory bowel disease: results from a prospective, population-based European inception cohort.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have proven an increased risk of venous thromboembolism (VTE), particularly when hospitalized. The estimate of the true risk varies considerably between studies, primarily due to differences in methodology. We set out to determine the incidence of VTE in a population-based European inception cohort. METHODS: IBD patients were incepted into a cohort that was prospectively followed from the early 1990s to the early 2000s. A total of 1145 patients were followed for a total of 10,634 patient-years (p.y.). RESULTS: A total of 19 thromboembolic events were identified - 13 deep vein thrombosis and 6 with pulmonary embolism. The incidence rate of VTE was 1.8 per 1000 p.y. CONCLUSION: The risk of VTE was elevated in this IBD cohort but lower than previously reported. The highest risk was seen in hospitalized patients, but corticosteroids-requiring disease in outpatients also conferred some risk.

Research on digestive and liver diseases: a priority for Europe - the societal importance of gastrointestinal diseases and research.

On 18 September 2012, in the European Parliament in Brussels, a public meeting was held between Science and Technology Options Assessments of the Parliament and the United European Gastroenterology to review the position of gastrointestinal and liver research in the context of the European Union. The meeting reflected the past situation, the ongoing close collaboration as well as facts and options on the upcoming European Union research programme Horizon 2020 that is in planning and will cover the years from 2014 to 2020.

Isolated colorectal cancer screening or integrated cancer prevention? A provocative suggestion!

Colorectal cancer (CRC) screening is still not fully established in the European Union. Recently, the United European Gastroenterology Federation (UEGF) supported CRC screening with the publication of quality guidelines and a written declaration in the European Parliament in favor of European-wide monitored CRC screening and primary prevention of CRC, the latter particularly in young citizens. In this article, the need for population-based CRC screening is once again stressed. In addition, the value of opportunistic CRC screening is pointed out, either as a regional or nation-wide alternative (such as in the USA and Germany) or as a 'forerunner' activity in view of subsequent population-based CRC screening. With regard to other parallel organ-related screening activities in Europe (breast, uterus) and the increasing need for primary prevention of malignant and benign diseases, the question is raised as to whether preventive activities should not be recognized as an integrated and logical part of a 'healthcare chain' offered to all European citizens.

New European initiatives in colorectal cancer screening: Budapest Declaration. Official appeal during the Hungarian Presidency of the Council of the European Union under the Auspices of the United European Gastroenterology Federation, the European Association for Gastroenterology and Endoscopy and the Hungarian Society of Gastroenterology.

Colorectal cancer (CRC) is the second most common newly diagnosed cancer and the second most common cause of death in the European Union (EU). CRC is an enormous health and economic burden. Early detection and prevention have the possibility of reducing this burden significantly. Many cancer-associated deaths can be avoided through early detection by high-quality colorectal screening programs followed by appropriate treatment. Under the auspices of the United European Gastroenterology Federation (UEGF), the European Association for Gastroenterology and Endoscopy, the Hungarian Society of Gastroenterology and the Hungarian College of Gastroenterology, the 'Budapest Declaration' (2011) was an accepted official scientific program during the Hungarian Presidency of the Council of the European Union. The Budapest Declaration follows the Munich Declaration (2001), the Brussels Declaration (2007), the Transatlantic Declaration (2009), the Barcelona Declaration (2010), the written declaration of CRC screening, a joint initiative with European Parliamentarians coordinated by the UEGF, and finally, the 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis'. The 'Budapest Declaration' together with previous declarations aims to urge the national and supranational healthcare decision makers to launch new Europe-wide initiatives to establish high-quality CRC programs to achieve optimal efficiency in CRC screening. In case of implementation of the proposals, actions and conditions recommended, we can achieve that one of the basic principles of the EU - the chance of equal access - be realized in member states with respect to the prevention of CRC and reduction of cancer-related mortality. To better achieve this goal, we propose to establish an UEGF joint committee, with one participant representing each EU member state to coordinate and supervise the implementation of CRC screening.

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.

BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is ≥235 pmol/8×10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263 pmol/8×10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235 pmol/8×10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.

Cancer in inflammatory bowel disease 15 years after diagnosis in a population-based European Collaborative follow-up study.

AIM OF THE STUDY: To determine the occurrence of intestinal and extraintestinal cancers in the 1993-2009 prospective European Collaborative Inflammatory Bowel Disease (EC-IBD) Study Group cohort. PATIENTS-METHODS: A physician per patient form was completed for 681 inflammatory bowel disease patients (445UC/236CD) from 9 centers (7 countries) derived from the original EC-IBD cohort. For the 15-year follow up period, rates of detection of intestinal and extraintestinal cancers were computed. RESULTS: Patient follow-up time was fifteen years. In total 62/681 patients (9.1%) [41 with ulcerative colitis/21 with Crohn's disease, 36 males/26 females] were diagnosed with sixty-six cancers (four patients with double cancers). Colorectal cancer was diagnosed in 9/681 patients [1.3%] (1 Crohn's disease and 8 ulcerative colitis). The remaining 53 cancers were extraintestinal. There was a higher prevalence of intestinal cancer in the Northern centers compared to Southern centers [p=NS]. Southern centers had more cases of extraintestinal cancer compared to Northern centers [p=NS]. The frequency of all observed types of cancers in Northern and in Southern centers did not differ compared to the expected one in the background population. CONCLUSIONS: In the fifteen-year follow up of the EC-IBD Study Group cohort the prevalence of cancer was 9.1% with most patients having a single neoplasm and an extraintestinal neoplasm. In Northern centers there were more intestinal cancers while in Southern centers there were more extraintestinal cancers compared to Northern centers. In this IBD cohort the frequency of observed cancers was not different from that expected in the background population.

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.

The first 2 years of colorectal cancer screening in Ferrara, Italy.

We report on the first screening round in the District of Ferrara, a region of Emilia-Romagna, carried out between March 2005 and March 2007 to illustrate the effort of colorectal cancer (CRC) screening from administration and information to therapy and follow-up. After invitation of 38 344 persons aged 50-69 years (28.5%), 19 480 (50.8%) accepted the immunological faecal occult blood test, with 1 149 (6%) resulting positive. One thousand and one individuals (88.2%) who tested positive for immunological faecal occult blood test accepted examination by either colonoscopy (99.5%) or barium enema (0.5%). Out of 996 screenees having a colonoscopy, 231 had low-risk adenomas (23.2%) and 239 had high-risk adenomas (24%), and were treated endoscopically (96%) or surgically (4%). Ninety-one cancers were diagnosed in 9.1% of colonoscopies (Dukes stadia: A, 58.2%; B, 19.8%; C, 18.7%; D, 3.3%). Fourteen cancers (all in polyps) were treated endoscopically, and the remaining 77 were treated by surgery. One Dukes B patient and 13 of 17 Dukes C patients received adjuvant chemotherapy. Three Dukes D patients had chemotherapy only. During the 2-year study period, 87 screenees had a follow-up colonoscopy: no neoplasia was found in 35 patients initially diagnosed with cancer; low-risk adenomas were found in 31 of 52 patients with initial high-risk adenomas. In conclusion, the first CRC screening round in Ferrara was easy to organize, had a high acceptance, and detected 91 cancers (78% of which were in Dukes stages A and B, compared with only 40% in sporadic CRC in the same background population). Chemotherapy was necessary in 17 cases. This report may motivate other health authorities to initiate CRC screening campaigns.

Screenee perception and health-related quality of life in colorectal cancer screening: a review.

Screening for colorectal cancer (CRC) has become established to varying degrees in several Western countries for the past 30 years. Because of its effectiveness, screening has been adopted or is planned in a number of other countries. In most countries, the screening method (e.g., fecal occult blood test [FOBT], sigmoidoscopy) is followed by colonoscopy, for verification. In other countries (e.g., United States, Germany), colonoscopy is the preferred first-line investigation method. However, because colonoscopy is considered to be invasive, might be poorly tolerated, and can be associated with complications, the idea of adopting colonoscopy as the primary screening method suffers. Negative effects of screening methods can reduce participation in programs and thereby negate the desired effect on individual and societal health. At present, there is no generally accepted method either to assess the perception and satisfaction of patients screened or the outcome of the screening procedures in CRC. In this review, we discuss the past development and present availability of instruments to measure health-related quality of life (HRQoL), the scarce studies in which such instruments have been used in screening campaigns, and the findings. We suggest the creation of a specific instrument for the assessment of HRQoL in CRC screening.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond.

In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further.

Managing complex patients on a medical psychiatric unit: an observational study of university hospital costs associated with medical service use, length of stay, and psychiatric intervention.

OBJECTIVE: Although there is a suggestion that the medical psychiatric unit (MPU) may reduce length of hospital stay (LOS), little is known about costs in terms of medical service use and psychiatric interventions in MPU care. METHOD: A record linkage study was conducted, linking cost data of hospital medical service use, LOS, and hospital psychiatric interventions to patients admitted to the MPU of the Maastricht University Medical Centre (MUMC) between 1998 and 2004. The data set was analyzed to enable comparison between cost changes of the same complex patient population following either MPU index admission or index admissions to reference MUMC medical wards. RESULTS: Comparisons revealed lower costs of medical service use in favor of the MPU (-euro104; 95% CI -euro174 to -euro35; P<.01). However, cost of psychiatric intervention and cost of LOS were higher after MPU admission (respectively, +euro165; 95% CI +euro25 to +euro305; P<.05; and +euro202; 95% CI +euro170 to +euro235; P<.001). Total costs were higher after MPU admission compared to medical ward admission (+euro263; 95% CI +euro68 to +euro458; P<.05). These differences were not moderated by somatic diagnosis or previous pattern of admissions. CONCLUSION: The findings suggest that patients at the interface of psychiatric and somatic morbidity are diagnosed and treated adequately at the MPU, leading to a decrease in medical service use and an appropriate increase in exposure to psychiatric interventions. These results are specifically generalizable to MPUs with a focus on psychosomatic conditions, for instance, somatoform disorders or affective disorders with comorbid somatic diseases. However, failure to show cost savings in terms of LOS compared to medical wards outweighs cost-benefit derived from lower medical service use, suggesting that MPU activities may gain in cost-effectiveness if shifted more to outpatient psychosomatic care solutions.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

BACKGROUND: The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. METHODS: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. RESULTS: At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). CONCLUSIONS: In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.