Jean Muris

SYSTEMATIC REVIEW: THE ROLE OF DIFFERENT TYPES OF FIBRE IN THE TREATMENT OF IRRITABLE BOWEL SYNDROME

Background : Both high‐fibre dietary advice and the prescription of fibre as a bulking agent are very common in primary and secondary care management of irritable bowel syndrome. Irritable bowel syndrome patients with constipation may have delayed intestinal transit. Therefore, fibres that accelerate intestinal transit may be beneficial in these patients. The uncertain benefits reported in several clinical studies, however, have led us to reappraise the value of fibre in irritable bowel syndrome management.

Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial

Objective To determine the effectiveness of increasing the dietary content of soluble fibre (psyllium) or insoluble fibre (bran) in patients with irritable bowel syndrome. Design Randomised controlled trial. Setting General practice. Participants 275 patients aged 18-65 years with irritable bowel syndrome. Interventions 12 weeks of treatment with 10 g psyllium (n=85), 10 g bran (n=97), or 10 g placebo (rice flour) (n=93). Main outcome measures The primary end point was adequate symptom relief during at least two weeks in the previous month, analysed after one, two, and three months of treatment to assess both short term and sustained effectiveness. Secondary end points included irritable bowel syndrome symptom severity score, severity of abdominal pain, and irritable bowel syndrome quality of life scale. Results The proportion of responders was significantly greater in the psyllium group than in the placebo group during the first month (57% v 35%; relative risk 1.60, 95% confidence interval 1.13 to 2.26) and the second month of treatment (59% v 41%; 1.44, 1.02 to 2.06). Bran was more effective than placebo during the third month of treatment only (57% v 32%; 1.70, 1.12 to 2.57), but this was not statistically significant in the worst case analysis (1.45, 0.97 to 2.16). After three months of treatment, symptom severity in the psyllium group was reduced by 90 points, compared with 49 points in the placebo group (P=0.03) and 58 points in the bran group (P=0.61 versus placebo). No differences were found with respect to quality of life. Fifty four (64%) of the patients allocated to psyllium, 54 (56%) in the bran group, and 56 (60%) in the placebo group completed the three month treatment period. Early dropout was most common in the bran group; the main reason was that the symptoms of irritable bowel syndrome worsened. Conclusions Psyllium offers benefits in patients with irritable bowel syndrome in primary care. Trial registration Clinical trials NCT00189033.

Outcome measures in irritable bowel syndrome: Comparison of psychometric and methodological characteristics

OBJECTIVES:Although there is growing interest in irritable bowel syndrome (IBS) research, there is as yet no consensus regarding the preferred outcome measure. We aimed to evaluate and to compare the validity and appropriateness of available IBS outcome measures.METHODS:IBS symptom and IBS health-related quality of life (HRQOL) scales were identified through a literature search. In a panel evaluation, six reviewers independently rated the scales according to predetermined psychometric and methodological validation criteria.RESULTS:Five IBS symptom scales and five IBS HRQOL instruments were identified. Two of the symptom scales were rated as good. The Adequate Relief question scored best. This scale demonstrates responsiveness as well as face and construct validity, and its score was considered easy to interpret and appropriate for use. According to the reviewers, the IBS Severity Scoring System performed well with regard to psychometric capacities, but its practical utility was considered debatable. The properties of the other three symptom scales were suboptimal. The practical utility of the five IBS-specific HRQOL scales was considered poor. However, the reviewers agreed that, at present, the IBS Quality of Life measurement (Patrick et al.) is the best choice, because it has been the most extensively validated and shows appropriate psychometric quality.CONCLUSIONS:The Adequate Relief question is the measure of first choice when assessing global symptomatology as an outcome in IBS studies. For a more detailed IBS symptom assessment, the IBS Severity Scoring System is preferable. Finally, the IBS Quality of Life measurement scale can be used to establish changes in health-related quality of life.

The impact of inflammatory bowel disease on labor force participation: Results of a population sampled case-control study

IntroductionInflammatory bowel diseases are chronic conditions that might cause a severe impact on social life. The aim of the study was to assess employment, chronic work disability, and sick leave in patients with inflammatory bowel disease. MethodsA postal questionnaire was sent to 984 patients with inflammatory bowel disease and 1504 controls. Age- and gender-adjusted employment and chronic work disability ratios and rates were calculated using indirect standardization. In subjects in paid employment, proportions of those having an episode of sick leave and lost workdays were analyzed. Logistic regression was used to assess the contribution of age, gender, education, and course of disease. ResultsThe results of 680 (69%) patients and 715 (48%) controls could be analyzed. For the entire group of patients, employment was 6.5% lower, compared with controls (95% CI: 4.0–9.0). Chronic work disability was 17.1% higher than expected (95% CI: 15.1–19.1). In those in paid employment, 62% of patients compared with 53% of controls had experienced one or more episodes of sick leave during the past year (p = 0.002). This resulted in 19.2 versus 11.8 days of sick leave per subject per year for patients and controls respectively (p = 0.002). Relative to controls, the risk of chronic work disability was more increased in younger (p = 0.02) and higher educated (p = 0.02) patients. Course of disease contributed to chronic work disability and sick leave. ConclusionIBD has a significant impact on labor force participation that is higher in CD compared with UC and highest in younger and more highly educated patients.

Epidemiological aspects of irritable bowel syndrome in Europe and North America.

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.

High incidence of inflammatory bowel disease in The Netherlands: results of a prospective study. The South Limburg IBD Study Group.

PURPOSE: To gain recent epidemiologic information about inflammatory bowel disease in The Netherlands, a prospective study over four years (1991–1995) was performed. METHODS: The incidence of inflammatory bowel disease and its subgroups was examined using standardized reports of newly diagnosed patients. A separate study compared the Inflammatory Bowel Disease Registration and computerized diagnostic files of a subgroup of general practitioners with the aim of estimating completeness of case ascertainment. RESULTS: The following mean incidence rates (per 100,000 inhabitants and year) were found: 6.9 (95 percent confidence interval, 5.9–7.9) for Crohns disease, 10 (95 percent confidence interval, 8.7–11.2) for ulcerative colitis (23 percent of these with ulcerative proctitis), and 1.1 (95 percent confidence interval, 0.7–1.5) for indeterminate colitis. In the age category 20 to 29 years, the incidence rate of Crohns disease with small-bowel involvement was higher in females than in males. In extended ulcerative colitis, a male preponderance was observed in the older age groups. Estimated case ascertainment was 78 percent. CONCLUSIONS: Compared with recent studies in neighboring countries, the observed age and gender standardized incidence rates are high in the south of The Netherlands. Completeness of case ascertainment might have contributed to this observation; however, case ascertainment was low in ulcerative proctitis. In the study area, differences in age and gender standardized incidence rates and in disease localizations could be compatible with an influence of environmental risk factors.

Integrated disease management improves one-year quality of life in primary care COPD patients: a controlled clinical trial

UNLABELLED AIMD: To assess the long-term effectiveness of an integrated disease management (IDM) program (consisting of optimal medication, reactivation, education, and exacerbation management) in primary care patients with chronic obstructive pulmonary disease (COPD). METHOD Controlled trial comparing the effects of IDM on quality of life--assessed by the St. Georges Respiratory Questionnaire (SGRQ)--in primary care COPD patients. The minimal clinically important change on the SGRQ was accepted as being -4 points. Baseline and one year differences were compared using paired sample T-tests. The differential effects of an FEV1/FVC ratio <0.7 and dyspnoea as assessed by the Medical Research Council (MRC) Dyspnoea scale were investigated. RESULTS The average age of subjects was 63 years, with an average post-bronchodilator FEV1 of 67% predicted, average FEV1/FVC ratio of 0.65, a mean of 35 pack-years smoking, and 63% were male. No significant differences existed between groups at baseline. After one year of IDM, SGRQ had improved by -4.6 points (95% CI, -7.2 to -2.0; p=0.001) in the intervention group, versus -0.7 points (95% CI, - 3.0 to 1.6; p=0.6) in the usual care group. In patients with an FEV1/FVC ratio <0.7, SGRQ improved by -5.9 points (95% CI, -9.6 to -2.2; p=0.002) in the IDM group, while in the usual care group SGRQ improved by -0.8 points (95% CI, -4.1 to 2.4; p=0.6). In patients with an MRC Dyspnoea score >2 and FEV1/FVC <0.7, SGRQ improved by -13.4 points (95% CI, -20.8 to -6.1; p=0.002) in the IDM group, versus -0.3 points (95% CI, -5.5 to 4.9; p=0.9) in the usual care group. CONCLUSION In this study, IDM improved one-year quality of life in primary care COPD patients, compared to usual care. The improvement in SGRQ was both clinically relevant and statistically significant, and was greatest in patients with FEV1/FVC <0.7 and MRC Dyspnoea score >2.

Effect and cost-effectiveness of step-up versus step-down treatment with antacids, H2-receptor antagonists, and proton pump inhibitors in patients with new onset dyspepsia (DIAMOND study): a primary-care-based randomised controlled trial.

BACKGROUND Substantial physician workload and high costs are associated with the treatment of dyspepsia in primary health care. Despite the availability of consensus statements and guidelines, the most cost-effective empirical strategy for initial management of the condition remains to be determined. We compared step-up and step-down treatment strategies for initial management of patients with new onset dyspepsia in primary care. METHODS Patients aged 18 years and older who consulted with their family doctor for new onset dyspepsia in the Netherlands were eligible for enrolment in this double-blind, randomised controlled trial. Between October, 2003, and January, 2006, 664 patients were randomly assigned to receive stepwise treatment with antacid, H(2)-receptor antagonist, and proton pump inhibitor (step-up; n=341), or these drugs in the reverse order (step-down; n=323), by use of a computer-generated sequence with blocks of six. Each step lasted 4 weeks and treatment only continued with the next step if symptoms persisted or relapsed within 4 weeks. Primary outcomes were symptom relief and cost-effectiveness of initial management at 6 months. Analysis was by intention to treat (ITT); the ITT population consisted of all patients with data for the primary outcome at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00247715. FINDINGS 332 patients in the step-up, and 313 in the step-down group reached an endpoint with sufficient data for evaluation; the main reason for dropout was loss to follow-up. Treatment success after 6 months was achieved in 238 (72%) patients in the step-up group and 219 (70%) patients in the step-down group (odds ratio 0.92, 95% CI 0.7-1.3). The average medical costs were lower for patients in the step-up group than for those in the step-down group (euro228 vs euro245; p=0.0008), which was mainly because of costs of medication. One or more adverse drug events were reported by 94 (28%) patients in the step-up and 93 (29%) patients in the step-down group. All were minor events, including (other) dyspeptic symptoms, diarrhoea, constipation, and bad/dry taste. INTERPRETATION Although treatment success with either step-up or step-down treatment is similar, the step-up strategy is more cost effective at 6 months for initial treatment of patients with new onset dyspeptic symptoms in primary care.

Meta-analysis: the diagnostic value of alarm symptoms for upper gastrointestinal malignancy.

Background : With the advent of empirical treatment strategies for patients with dyspeptic symptoms, it becomes increasingly important to select patients with a high risk of having cancer for immediate endoscopy. Usually alarming symptoms are used for this matter, but their diagnostic value is by no means clear.

Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study

BackgroundPragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit.DiscussionThe first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participants reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity.SummaryIt is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic – explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial.