The effect of mesalazine therapy on quality of life in patients with mildly and moderately active ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) has a major impact on the quality of life (QoL) of affected patients. Patient-reported outcomes have not been thoroughly evaluated in patients with UC receiving oral mesalazine (mesalamine). AIM: To examine the effect of mesalazine on QoL of patients with mildly and moderately active UC and assess the time course of change, baseline disease severity, mesalazine dose and responder status on QoL parameters. METHODS: Inflammatory Bowel Disease Questionnaire (IBDQ) data were combined from two double-blind, randomized, multicentre, active-controlled trials assessing 2.4 and 4.8 g/day oral delayed-release mesalazine in 687 patients. Mean score changes from baseline were compared at 3 and 6 weeks and effects of baseline severity, mesalazine dose and response to therapy were examined. RESULTS: Mesalazine significantly improved IBDQ scores at 3 and 6 weeks (mean increase, 29.6 and 39.7 points, respectively; P < 0.0001 for both). Improvement was greater for patients with moderate disease. Greater week 6 changes occurred in clinical responders than nonresponders (50.1 vs. 23.6 points, respectively; P < 0.0001). CONCLUSIONS: Delayed-release oral mesalazine produces significant clinical and statistical improvements in QoL of patients with UC by 3 weeks, with further improvement at 6 weeks.

A comparison of autonomic function in patients with inflammatory bowel disease and in healthy controls.

We evaluated autonomic function, symptoms and psychological parameters in patients with ulcerative colitis (UC), Crohn's disease (CD) and matched controls to assess whether UC patients have greater basal sympathetic autonomic activity. Outpatients with UC (n = 15), CD (n = 13) and healthy controls (n = 28) underwent spectral analysis of heart rate variability to assess cardiac autonomic function, a methacholine challenge to assess cholinergic pulmonary responsiveness, and questionnaires assessing disease severity, anxiety and depression. UC but not CD patients had greater sympathetic activity than controls with increased absolute (6600 vs 5884; P = 0.04) and relative (62.8%vs 54.8%; P = 0.02) low frequency areas. This was not because of increased overall autonomic nervous system (ANS) activation and was independent of disease activity. In UC patients, trait (personality-related) anxiety correlated strongly with disease symptoms (R = 0.84; P < 0.001) and quality of life (R = -0.81; P < 0.001) while situational (state) anxiety did not. In CD patients, ANS measures were similar to controls and disease activity was unrelated to psychological measures. Cholinergic pulmonary responsiveness was normal in both UC and CD patients. UC patients have an increased sympathetic ANS activity which is independent of symptom severity. In these patients symptom severity is strongly associated with measures of personality related (but not current) anxiety.

Validation of the mainland Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) for ulcerative colitis and Crohn's disease.

BACKGROUND: Inflammatory bowel disease affects the quality of a patient's life in many ways, but no validated instrument for measuring disease-specific quality of life in these patients is available for use in Mainland China. The aim of our study was to develop and validate the Mainland Chinese translation of the Inflammatory Bowel Disease Questionnaire for ulcerative colitis (UC) and Crohn's disease (CD) by assessing its construct validity, discriminant ability, reliability, and sensitivity to change. METHODS: We administered a developed Mainland Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ). Ninety-two Mainland Chinese patients (52 with UC and 40 with CD) completed the Mainland Chinese version of the IBDQ, the Chinese version of SF-36, and the global scale for general well-being. A subgroup of 71 patients also completed the Mainland Chinese version of the IBDQ and the global scales for general well-being on a second occasion. Clinical activity was assessed by the Walmsley and Harvey-Bradshaw simple indices. RESULTS: The Mainland Chinese IBDQ scores correlated well with the related SF-36 dimensional scores for all 4 domains (r = 0.51-0.82), SF-36 total scores (r = 0.58-0.87), the colitis activity index (r = -0.56-0.74), and the CD activity index (r = -0.64-0.78) as well as with the global scales. The Mainland Chinese IBDQ was able to discriminate between active and inactive disease. Cronbach's alpha was 0.95 in UC and 0.94 in CD. Test-retest reliability was excellent (intraclass correlation coefficient 0.69-0.93) when it was repeated in patients whose clinical activity index was stable. In contrast, there was a significant difference between the baseline and follow-up measurements in patients whose clinical activity index was changed. CONCLUSIONS: The Mainland Chinese IBDQ proved to be a valid, discriminative, and reliable instrument for assessing health-related quality of life in patients with UC and CD in Mainland China.

Review article: patients' fears and unmet needs in inflammatory bowel disease.

The management of chronic illness is becoming increasingly patient-centred. Although patients with inflammatory bowel disease have a normal life expectancy, most individuals experience an impact of inflammatory bowel disease on their daily lives as well as on their attitudes, fears and beliefs. Although currently available therapies for ulcerative colitis and Crohn's disease are becoming increasingly effective, there are still many unmet needs to address in this patient population. Physicians and patients' spouses or significant others underestimate the type and severity of problems reported by inflammatory bowel disease patients. Physical problems are frequently measured using disease activity indices. Emotional and social problems are reported using quality of life questionnaires and other specific measurement tools pertinent to the question of interest. Studies have indicated a poorer physical and emotional function in inflammatory bowel disease patients than in the general population. Effective therapies, both medical and surgical, produce significant improvements in the general and disease-specific quality of life. The quality of life is worse when the disease is more severe. Concomitant anxiety or depression appears to impair the quality of life even further. Common fears include the possibility of unanticipated flares, the need for surgery, poor energy levels and the side-effects of medication. Recent studies have suggested that more prominent patient participation in management has the potential for greater patient satisfaction, better outcomes and more efficient health resource utilization. Thus, future studies should focus not only on ensuring the wider availability of effective therapies, but on increasing access to health care that is tailored to individuals--more structure for some and more independence and self-management for others, with health provider supervision.

Quality of life assessment in gastro-oesophageal reflux disease.

Health related quality of life (HRQoL) is determined by both disease and non-disease related factors. Several studies have reported significant HRQoL impairment in GORD patients compared with the general population. Disease severity correlates strongly with HRQoL. Non-disease features, such as the presence of anxiety and comorbid conditions, also negatively impact on HRQoL. Combining a generic and disease specific instrument may avoid missing unexpected outcomes and ensure recognition of all clinically important changes. Full validation of assessment tools is critical. Long term, as well as short term, evaluation is important and is critical when undertaking comparative pharmacoeconomic evaluations.

Low molecular weight heparin (tinzaparin) vs. placebo in the treatment of mild to moderately active ulcerative colitis.

BACKGROUND: Heparin has anti-inflammatory and immunomodulatory activity which may be of therapeutic benefit in the treatment of ulcerative colitis. AIM: To test whether low molecular weight heparin, given subcutaneously, would provide a significant therapeutic response compared with placebo in the treatment of mild to moderate ulcerative colitis. STUDY DESIGN: A prospective, double-blind, randomized, placebo-controlled, multi-centre trial comparing tinzaparin 175 anti-Xa IU/kg/day (innohep, LEO Pharma) subcutaneously for 14 days followed by tinzaparin 4500 anti-Xa IU/day subcutaneously for 28 days with placebo, administered subcutaneously once daily for up to 42 days. The primary outcome measure was the mean change in colitis activity from baseline to the end of study treatment assessed by the sum of scores of stool frequency, rectal bleeding, sigmoidoscopic appearance and histology. Secondary outcome measures included changes in individual activity indices and laboratory parameters. Patients were assessed at weekly intervals for 6 weeks and within 1 week of completing treatment. RESULTS: One hundred patients with active ulcerative colitis (up to six bloody stools per day, no fever, no tachycardia or systemic disturbances) were randomized. Forty-eight received tinzaparin and 52 received placebo. The difference in the mean percentage change in colitis activity from baseline to end of treatment (tinzaparin-placebo) was not statistically significant (P = 0.84). There was no difference between tinzaparin and placebo in any secondary outcome measure. One major bleed (rectal), occurred in a patient receiving placebo. CONCLUSION: This is the largest trial to date of heparin in ulcerative colitis. The results show no benefit of low molecular weight heparin over placebo in mild to moderately active ulcerative colitis.

Alternative medicine use by Canadian ambulatory gastroenterology patients: secular trend or epidemic?

OBJECTIVES: To assess the prevalence and determinants of alternative medicine (AM) use in gastroenterology outpatients and those with inflammatory bowel disease (IBD). METHODS: An 80-item questionnaire, addressing symptoms, general health, quality of life, and AM use, was administered and analyzed using logistic regression. RESULTS: 52.5% of 341 participants used AM in the previous year. Most commonly used were herbal medicine (45.2% of users; 95% CI 35.4-52.5%), chiropractor (40.7%; 95% Cl 31.4-48.0%), and massage therapy (22.9%; 95% CI 15.9-29.1%). Reasons prompting AM use were ineffective medical therapy (39.5%; 95% CI 30.4-46.8%), a greater sense of self-control (29.1%; 95% CI 21.2-35.7%), agreement with personal beliefs (19.5%; 95% CI 13.1-25.4%), and conventional drug adverse-effects (17.3%; 95% CI 11.2-22.9%). AM use was predicted as follows: (1) higher education (odds ratio (OR) 2.10; 95% CI 1.22-3.60), (2) comorbid medical conditions (OR 1.80; 95% CI 1.08-3.00), 3) poor mental component summary score of the SF-12 health survey (OR 1.04; 95% CI 1.01-1.07), and (4) higher annual income (OR 1.17; 95% CI 1.001-1.36), but was not related to response to conventional medical therapy. AM practitioners had instructed 8.6% to change prescription medications. AM usage for gastrointestinal disease was greater in patients with IBD (44.6% vs 10.0%; p < 0.05), who were more likely to cite adverse drug effects as a reason for AM use (28.9 vs 14.4%; p = 0.03). CONCLUSIONS: AM was used by 52.5% of gastroenterology outpatients and its use was greater in those with a higher level of education, comorbid conditions, poorer mental health-related quality of life, and higher income. Drug-related side effects also led to increased AM use.

Health-related quality of life in functional GI disorders: focus on constipation and resource utilization.

OBJECTIVE: Functional GI disorders are common in the general population. However, their impact on health status and health resource use in Canada has not been well examined. We describe 1) health-related quality of life in Canadians with functional constipation or other functional GI disorders versus Canadian normative data or those without a functional GI disorder and 2) health resource utilization in subject's self-reporting of constipation. METHODS: An independent research firm was employed to conduct a randomly selected national survey examining GI symptoms and personal health. Household members 18 yr or older were recruited by a random-digit dial technique. Participants were then mailed a questionnaire and data were retrieved by a follow-up phone call. All functional GI disorders were defined using Rome II criteria, and constipation was further defined using self-report. Health-related quality of life was assessed using the Short Form 36. RESULTS: One thousand one hundred forty-nine subjects (49.3% male) with a mean age of 42.2 yr completed the survey. The prevalence of any Rome II functional GI disorder was 61.7%. The rate of functional constipation was 14.9%, whereas that of self-reported constipation was 27.2%. The mean physical and mental component summary and eight subscores of the Short Form 36 were significantly lower (p < 0.05) than Canadian norms for both self-reported constipation and Rome II functional constipation. Subjects with no GI disorder had significantly better Short Form 36 scores than the Canadian norms. The rate of physician visits for constipation was strongly predicted by the physical component of the Short Form 36. Most subjects (66.2%) were satisfied with their current constipation treatment. CONCLUSIONS: Constipation is common in the Canadian population and significantly impairs health-related quality of life. Poor quality of life is an important predictor of health care utilization in these subjects.

Functional gastrointestinal disorders in Canada: first population-based survey using Rome II criteria with suggestions for improving the questionnaire.

The Rome II criteria and questionnaires developed to identify functional gastrointestinal disorders have not been evaluated. Our objectives were to determine the prevalence of functional gastrointestinal disorders in Canada, compare our results with data from other published studies, assess concordance of Rome I and Rome II criteria for irritable bowel syndrome, and suggest improvements in the Rome II questionnaire. An independent research firm was employed to conduct a random digit dial national survey, inviting household members > or = 18 years of age to participate in a study examining personal health issues. Subjects recruited by telephone, who agreed to participate, were mailed a questionnaire, and the data were retrieved by a follow-up phone call. The Rome II questionnaire and algorithms were used and where possible Rome I algorithms were also applied. At least one functional gastrointestinal disorder occurred in 61.7% of 1149 respondents (65.6% female versus 57.6% male; P < 0.05). The most prevalent were the functional bowel disorders at 41.6% followed by esophageal disorders at 28.9%. Irritable bowel syndrome prevalence by Rome II and I criteria were 12.1% and 13.5%, respectively (kappa = 0.76). Because the Rome II criteria have added exclusion items that are not present in the Rome I criteria, the prevalence of esophageal, gastroduodenal, and anorectal disorders is lower than the figures from a US market survey. In conclusion, functional gastrointestinal disorders are highly prevalent in Canada, with a significantly higher rate in women. There is substantial agreement between Rome I and Rome II criteria for irritable bowel syndrome. Rome criteria and questionnaire remain works in progress.

An epidemiological survey of constipation in canada: definitions, rates, demographics, and predictors of health care seeking.

OBJECTIVES: The prevalence of functional constipation is highly variable among epidemiological surveys and may relate to the definitions applied. We estimated the population prevalence of self-reported, Rome I-defined, and Rome II-defined constipation in Canada and determined the variables that best predicted health care seeking. METHODS: A research firm was employed to conduct a random digit dial national survey, inviting household members at least 18 yr of age to participate in a study assessing personal health issues. The sample was stratified to ensure that each region of Canada was represented. Data collection involved three stages: 1) recruitment of participants by phone, 2) mailing of the questionnaire, and 3) data retrieval through a follow-up phone call. The Rome II questionnaire was used to derive the prevalence of functional constipation using both Rome I and Rome II criteria. RESULTS: Of the 1149 participants, 27.2% self-reported constipation within the past 3 months, and 16.7% and 14.9% had functional constipation according to Rome I and II, criteria, respectively. For all three definitions, the rate for women was close to twice that for men. Approximately 34% of those with self-reported constipation had visited a physician for it, versus 26.3% of Rome II subjects. In a regression model, subjects self-reporting in the past 3 months were more likely to have seen a doctor for their constipation (odds ratio 2.47, p < 0.01) and significantly more women than men (35.6% vs 19.5%, p < 0.05). CONCLUSIONS: Functional constipation and related health care seeking are common in the Canadian population and are strongly determined by the definition used. The Rome II criteria for this disorder seem to be satisfactory, but modifications may be considered to allow for constipated subjects taking laxatives and to increase the number of qualifying symptoms.

Problems of HRQL assessment: how much is too much?

Few investigations have explored the extent to which a number of less serious problems contribute to health-related quality of life (HRQL) impairment beyond a smaller number of more serious problems. Our study examined the relative impact of the number and severity of patient problems on HRQL. This study analyzed results from 100 patients with irritable bowel syndrome (IBS) and 100 women with polycystic ovary syndrome (PCOS). We compared an aggregation method that generated scores using all items that could affect HRQL as the denominator (all items) to a second method that considered only items that patients experienced as problems (problem items). For each IBS and PCOS questionnaire domain, we used regression analysis to examine the relative contribution of scores from the all-items and problem-items approaches to prediction of scores on the other instruments. Of 57 correlations between IBS domains and scores on the other questionnaires, the all-items method explained a statistically significant additional proportion of the variance beyond the problem items in 29 cases and the problem items a significant additional proportion of the variance between the all items in 7 (p < 0.001). Of the 28 correlations between the PCOS and the other questionnaires, the all-items approach explained a significant additional proportion of the variance in 21 cases and the problem items approach in 5 (p < 0.001). With IBS and PCOS, including all potential items in calculating a domain score provided a more accurate portrayal of HRQL than a selected approach focusing on problem items

Monocyte/macrophage activation by normal bacteria and bacterial products: implications for altered epithelial function in Crohn's disease.

Intestinal immune cells are less reactive than those in the peripheral blood; however, such cells from patients with Crohn's disease may be more responsive to bacterial products. Our study examined if nonpathogenic bacteria or lipopolysaccharide (LPS), can affect epithelial function in the presence of monocytes/macrophages. Lamina propria mononuclear cells (LPMCs) and peripheral blood monocytes (PBMs) were obtained from patients with Crohn's disease and control patients. Filter-grown T84 epithelial monolayers were co-cultured with nonactivated or LPS-activated LPMCs or PBMs for 48 hours. Epithelial secretory [baseline short-circuit current (Isc) and DeltaIsc to forskolin] and barrier (transepithelial electrical resistance) parameters were measured in Ussing chambers. LPS-activated PBMs from both controls and patients with Crohn's disease significantly increased Isc ( approximately 300%) and reduced transepithelial electrical resistance ( approximately 40%). Epithelial function was not altered after co-culture with control LPMCs +/- LPS. However, LPMCs from patients with Crohn's disease spontaneously secreted tumor necrosis factor-alpha, and induced epithelial changes similar to those produced by LPS-activated PBMs. Co-culture with control Escherichia coli and PBMs induced comparable changes in epithelial physiology, which were abrogated by anti-tumor necrosis factor-alpha antibody. We conclude that LPMCs of patients with Crohn's disease are spontaneously activated, possibly by gram-negative luminal bacteria, and can directly cause significant alterations in epithelial ion transport and barrier functions.

Low mortality in ulcerative colitis and Crohn's disease in three regional centers in England.

OBJECTIVES: Recent epidemiological studies suggest that mortality rates for inflammatory bowel disease (IBD) are similar to those of the general population. However, most of this work has been done in referred populations or larger urban centers. We intended to estimate mortality rates for ulcerative colitis (UC) and Crohn's disease (CD) in three British district general hospital practices in Wolverhampton, Salisbury, and Swindon. METHODS: Consecutive patients with CD or UC were identified from 1978 to 1986 and followed prospectively. Demographic data, date and cause of death or health status at December 31, 1993 were used to estimate standardized mortality ratios (SMRs) and 95% confidence intervals. RESULTS: Sixty-four deaths occurred in 552 patients (UC 41 of 356; CD 23 of 196). The overall SMRs were 103 [95% confidence interval (CI): 79-140] for UC and 94 (95% CI: 59-140) for CD. The respective SMRs were higher only in the first year after diagnosis at 223 (95% CI: 99-439; p = 0.02) and 229 (74-535; p = 0.056), and even then, most subjects died from non-IBD causes (5 of 13). Nonsurvivors were significantly older than survivors in both UC and CD (p < 0.01). The SMR was also significantly greater during a severe first attack of UC at 310 (95% CI: 84-793; p = 0.04). Patients with perianal or colonic CD had an increased SMR [396 (95% CI: 108-335; p = 0.02) and 164 (95% CI: 82-335; p = 0.02)] respectively, partly related to the older mean age (52 vs 32 yr, p < 0.001). CONCLUSIONS: Mortality rates are not increased in IBD compared with the general population. However, older patients may be at increased risk of dying from other causes early in the disease clinical course.

A critical review of epidemiological studies in inflammatory bowel disease.

This review addresses the difficulty in interpreting the results of epidemiological studies in IBD and in making meaningful comparisons between studies. Both ulcerative colitis and Crohn disease appear to be more common in some industrialized countries such as Scandinavia, United Kingdom, North America and less common in Central and Southern Europe, Asia and Africa. Given data showing an increased incidence of ulcerative colitis in the United Kingdom, it is crucial that more studies be conducted in developing countries. While the incidence of Crohn disease has increased strikingly in many areas, the incidence of ulcerative colitis has remained fairly stable in most. This could be due to the rising number of community-based studies, as well as the improved accuracy in diagnosing Crohn disease. Although, the incidence of IBD among Blacks in Africa is low, infection rates are high, life expectancy is lower than in developed countries. Data from the USA suggest that rates are similar in Afro-American and Caucasian populations. Rates for Jewish populations may be slightly higher than in non-Jewish populations but this also varies geographically. Careful attention to genetic, environmental, and socioeconomic factors must be accounted for in these studies. There is no strong evidence to support that IBD is more common in urban than in rural settings and migration towards more accessible health care has not been adequately addressed. Recent epidemiological studies suggest that mortality rates for IBD are similar to that of the general population for the majority of patients. However, older patients with IBD and newly diagnosed cases with severe diseases are at increased risk of dying. Epidemiological studies remain important in assisting with health policy planning and in hypothesis testing of etiological factors. As better diagnostic techniques become widely available and public health registries are increasingly used, it is possible that geographic differences will diminish. International collaborative studies will be better equipped to answer research questions addressing risk factors and disease natural history. We have summarized in Table V the essential criteria to conduct a sound epidemiological study, which would permit future testing of hypotheses among different populations.

Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk.

Increased intestinal permeability to several specific molecular probes has been observed in patients with Crohn's disease and their first-degree relatives. A positive family history is also a potent risk factor for inflammatory bowel disease. Although it has been argued that increased permeability in relatives may confer an increased future risk of developing Crohn's disease, long-term follow-up of such family members has been lacking. We describe a 24-year-old woman with a positive family history of Crohn's disease who had an elevated gut permeability to (51)Cr-EDTA at age 13, as part of a cross-sectional cohort study in patients and their first-degree relatives. She was asymptomatic at the time, and extensive investigation found no evidence of microscopic or macroscopic Crohn's disease. Repeat investigation because of symptom onset at age 21 revealed ileocolonic Crohn's disease, which required treatment with systemic corticosteroids to induce a clinical remission. In this case, a permeability defect was clearly identified to precede the onset of Crohn's disease in a subject at increased risk. This observation provides support for the hypothesis that increased gut permeability to macromolecules is an early step in the pathogenesis of this disorder.

Quality of life rapidly improves with budesonide therapy for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group.

Our aims were to assess the impact on health-related quality of life (HRQOL) of a controlled ileal release (CIR) formulation of budesonide in active Crohn's disease (CD) and further define the role of HRQOL, using the Inflammatory Bowel Disease Questionnaire (IBDQ), in assessing outcome in CD. A randomized trial was conducted in 258 patients with active ileal or ileocecal CD. Budesonide CIR 1.5 mg, 4.5 mg, 7.5 mg, or placebo was given b.i.d. for 8 weeks. IBDQ score changes were compared among groups. Correlations for IBDQ and Crohn's Disease Activity Index (CDAI) scores were calculated. Mean IBDQ scores improved significantly over placebo by 2 weeks in budesonide 15 mg (155+/-38; p = 0.006) and 9 mg groups (157+/-33; p = 0.0002). Bowel, systemic, social, and emotional subscores were also significantly better (p < 0.002) at 2 and 8 weeks in the 9 mg group. Improved HRQOL scores correlated well with decreased CDAI (-0.8 < r < -0.4). Average per item change in IBDQ at remission was 1.17 to 1.48. Prior surgery (p < 0.005) or current smoker (p < 0.05) status predicted poorer initial HRQOL but not response. Budesonide CIR 9 or 15 mg/day rapidly and significantly improved HRQOL in active CD.

Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis.

Oral aminosalicylates such as sulfasalazine and mesalamine are widely prescribed for the treatment of mild or moderately active distal ulcerative colitis. However, a critical review of the literature demonstrates that rectal 5-aminosalicylic acid (5-ASA) is the optimal therapy for this disease. Meta-analyses of published trials show that rectally delivered 5-ASA is superior to placebo and to conventional rectal corticosteroids in inducing remission of distal ulcerative colitis, whereas the combination of rectal 5-ASA with a rectal corticosteroid or oral aminosalicylate is superior to rectal 5-ASA alone. For maintaining remission of distal ulcerative colitis, rectal 5-ASA is significantly better than placebo and at least as effective as oral 5-ASA. The dosage forms available for rectal delivery include suppositories, foams, and liquid enemas, and selection among these preparations should be guided by the proximal extent of disease and patient preference. The efficacy of rectal 5-ASA is complemented by its low rate of reported adverse effects, which may reflect its reduced potential for systemic absorption. This review summarizes the evidence supporting the role of rectal 5-ASA as a first-line therapy for mild or moderately active distal ulcerative colitis, and offers guidelines for its use.

Quality of life measurement in gastrointestinal and liver disorders.

Modern medicine has had a considerable impact on mortality rates for serious illness. Many chronic diseases which have previously been associated with an increased mortality now have survival rates approaching those of the background population. However, chronic diseases such as cancer, chronic pain syndromes, and chronic inflammatory conditions impose a considerable burden on families, the health care system, and society. Health related quality of life (HRQOL) is a concept that has developed from the need to estimate the impact of such chronic diseases. HRQOL measurement is a conceptual framework which attempts to predict daily function and well being based on subjective attitudes and experiences of physical, social, and emotional health. It has been evaluated predominantly from the patient's viewpoint as proxy respondents appear to underestimate the full effect of chronic illness on functional status. Measuring HRQOL in clinical research is most frequently undertaken using multi-item questionnaires to estimate daily function. Factors which affect HRQOL can be broadly classed as disease related and disease independent. The use of different assessment techniques permits comparisons between and within disorders. Generic and disease specific instruments used together enhance the ability to direct treatment for individuals and patient populations. Psychometrically sound questionnaires must be used. However, the type of instrument and research methods adopted depend on the question of interest. We have attempted to catalogue and critically assess the disease specific instruments used in the assessment of chronic gastrointestinal disease.

A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators.

BACKGROUND: Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS: We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.

A simple classification of Crohn's disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998.

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.