Current guidelines recommend a positive strategy based on symptom criteria without alarm features vs diagnostic exclusion which includes several laboratory and diagnostics procedures to exclude other organic conditions. A novel IBS diagnostic blood panel tests for the presence of two biomarkers associated with IBS-D which can complement the positive strategy. This analysis assesses the cost impact to the Danish healthcare system by introducing this test into the diagnostic pathway. A budget impact model was based on a cost-minimization decision model developed to compare the costs associated with two possible diagnostic pathways: (1) diagnostic pathway with a novel IBS diagnostic blood panel and (2) exclusionary diagnostic pathway and applied to the Danish population 18-65yrs old. Model structure was based on current literature and guidance from IBS expert clinicians. Direct medical expenses for laboratory tests, diagnostic procedures and visit costs were included in Danish Krone and weighted by utilization rates estimated by a practicing gastroenterologist in Denmark. Indirect cost only included time off work based on a published Danish study. Sigmoidoscopy, colonoscopy and SBFT were the most common diagnostic procedures reported with estimated utilization rates of 35%, 35% and 15%, respectively. Corresponding charges were kr4819, kr4819 and kr1861, respectively. Estimated total base case charges for the IBS diagnostic blood panel pathway (assumes 75% of test positive patients receive IBS-D treatment) vs the exclusionary pathway were kr11,237 vs kr12,284, respectively. If clinicians use the test 50% of the time for the 30% of the estimated 57,490 people who might have IBS-D who seek treatment, net savings to the Danish healthcare system is kr30,095,980. Cost neutrality occurs if 37% of the “test positive” patients seek IBS treatment. This economic evaluation indicates that a positive strategy may be further enhanced with a novel IBS diagnostic blood panel leading to significant cost savings.

TO THE EDITOR: Irritable bowel syndrome (IBS) is a diagnosis based on symptoms. According to the Rome II criteria the key symptom in IBS is abdominal discomfort or pain with a specified relation to defecation or changes in stool frequency and consistency. All other symptoms, such as constipation, diarrhoea, bloating, etc., can be used to support the diagnosis or to classify the patients into subgroups. It is therefore obvious that the treatment of IBS is the treatment of abdominal pain or discomfort. A clinically significant effect is only achieved when also the patient’s overall satisfaction (e.g. subject’s global assessment of relief) improves, as well as the other symptoms (1). It is explicitly stated in international guidelines that treatment for IBS should both reduce abdominal pain/discomfort and increase overall satisfaction (2, 3). Nyhlin et al. presented in this journal a well-performed multinational trial with tegaserod in patients with IBS and constipation (4). There was no effect on abdominal pain or discomfort compared to placebo, but a statistically significant, clinically modest improvement in ‘satisfactory relief’. Furthermore, there was a significant improvement in the number of bowel movements, hard stools and straining. The authors conclude that tegaserod is an effective treatment in patients suffering from IBS without diarrhoea as their primary bowel symptom. Our interpretation of the results is that tegaserod is devoid of a specific effect on IBS, but improves overall symptoms due to relief of constipation through a laxative effect in persons with constipation-predominant IBS. Exploratory subgroup analysis of the association between satisfactory relief, relief of constipation and relief of pain might give important clues. Similar results without a significant effect on pain/discomfort have been reported from another large trial with tegaserod (5). It is unclear whether the slight relief of pain seen in other trials is relief of IBS or relief of constipation-induced pain/discomfort (6, 7). Tegaserod has shown effects interpreted as antinociceptive in animal models (8). A recent study shows similar findings in healthy volunteers where the drug significantly decreased sensitivity to rectal distension when measured as inhibition of the RIII nociceptive flexion reflex (9). However, the intensity of the visceral sensations, as recorded by the persons on a verbal questionnaire, was not changed significantly posttreatment. In all, the clinical relevance of the antinociceptive effect of tegaserod is equivocal. All available trials confirm the favourable effect of tegaserod on constipation in patients with IBS, whereas the effect on the key symptoms in IBS (pain/discomfort) still seems questionable. The drug might be merely a laxative, and it has been proposed as a new pharmacological approach for the treatment of constipation for those who do not benefit from simple bulking agents, laxatives or behavioural treatment (10). Future trials should compare tegaserod with standard care (e.g. mild laxatives and analgesics) in patients with constipation-predominant IBS, and evaluate the drug as a laxative for patients without IBS.

OBJECTIVES: Attempts to establish a clinical diagnosis in dyspeptic patients have generally been unrewarding. However, studies in unselected dyspeptic patients are lacking. The aim of this study was to determine the value of the unaided clinical diagnosis by general practitioners (GP) and by experienced gastroenterologists (GA) in unselected dyspeptic patients in primary care. METHODS: Three hundred forty-seven patients with epigastric pain/discomfort for more than 2 wk who were consulting general practitioners (n = 73), but without alarm symptoms. GPs and GAs gave a provisional diagnosis based on an unstructured interview. All patients underwent endoscopy within 5 days of referral. Validity of the provisional diagnoses was measured using the endoscopic diagnoses as the gold standards. RESULTS: For GPs, the sensitivity of a provisional diagnosis of peptic ulcer was 61% [95% confidence intervals (CI): 46–74%]; for specificity 73%, the 95% CI was 68–78%; and for positive predictive values, it was 28%, the 95% CI was 20–37%. GAs were more reluctant to predict ulcer, leading to a higher specificity: 84% (95% CI: 79–88%), but a similar sensitivity: 55% (95% CI: 40–69%). The GPs were unable to distinguish between functional and organic dyspepsia (chance-corrected overall validity: 9%; 95% CI: 0–18%). GPs and GAs agreed in their provisional diagnosis in only 45% of the patients, in whom the diagnosis was confirmed by endoscopy in 2/3. CONCLUSION: The unaided clinical diagnosis given by the GP and by the GA in dyspeptic patients in primary care is unreliable. Nearly half of patients with ulcer or esophagitis were misclassified, despite a high susceptibility to organic disease. Different patients were problematic for GPs and GAs, which may indicate that most dyspeptic patients do not present with symptoms characteristic of a specific disease.

Methods: Consecutive patients presenting in primary care with dyspepsia (>__ two weeks of epigastric pain or discomfort, no alarm symptoms) were randomized to H. pylori testing (13C Urea breath test) or endoscopy before deciding on treatment.In the H. pylori testing group all infected patients had eradication therapy.H. pylori negative patients who had taken NSAID's were endoscoped.H. pylori negative patients with reflux symptoms were treated

Background: Most dyspeptic patients in primary care are managed without confirmatory investigations. In this study the reliability of the unaided clinical diagnosis and the diagnostic value of dyspepsia subgrouping are evaluated in unselected dyspeptic patients in primary care. Methods: Six hundred and twelve unselected dyspeptic patients were referred for interview and endoscopy. General practitioners stated a provisional diagnosis and a proposed management strategy. Before endoscopy, patients were classified on the basis of predominant symptoms as reflux-, ulcer-, or dysmotility-like or as unclassifiable Results: The sensitivity and the positive predictive value of the diagnosis of ulcer were 0.58 and 0.29, respectively, and those for esophagitis 0.30 and 0.43. The predictive value of a clinical diagnosis of functional dyspepsia was high, but, considering the high prevalence of the condition, the chance-corrected validity was at the same level as for the other diagnoses (0.18-0.22). Classification of patients by predominant symptoms increased the a priori probability of ulcer and esophagitis in the respective subgroups. However, more than one-third of the patients with ulcer or esophagitis were classified in inappropriate subgroups. Conclusions: It is difficult to select an appropriate management strategy for dyspeptic patients on the basis of symptoms and history alone. Dyspepsia subgroups are of limited help in the decision process because of the low predictive value of the endoscopic diagnosis.

This study compared two strategies for the management of dyspepsia: therapy based on prompt endoscopy (group 1) vs an empirical treatment strategy with diagnostic endoscopy only in case of therapeutic failure or symptomatic relapse within one year (group 2). Patients without jaundice, bleeding, anaemia, or a previously diagnosed ulcer and with symptoms severe enough to justify empirical H2-blocker therapy were included. Symptoms, drug consumption, and sick-leave days were evaluated through monthly diaries. Patients with non-organic dyspepsia did not receive ulcer drugs. Of 414 patients randomized, 373 completed one year follow-up. In 68 (33%) of the 208 group 1 patients organic disease was found at endoscopy (ulcer in 45 patients). Endoscopy was eventually performed in 136 (66%) of 206 group 2 patients. Case selection for endoscopy was not improved by the empirical treatment strategy since the diagnostic profile was not altered and 40% of the presumed ulcer cases remained undiagnosed. After one year no differences in symptoms or quality of life measures were found. The empirical treatment strategy in dyspepsia was associated with higher costs, mainly due to increases in number of sick-leave days and in ulcer drug use. Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify H2-blocker treatment.

Peptic ulceration is a common condition and is associated with considerable expense. Introduction of H2-blockers in the latter part of the nineteen seventies offered a new and effective therapeutic alternative for the patient with chronic peptic ulceration. On the basis of a review of the literature, the present authors have attempted to assess the consequences of the introduction of H2-blockers for the expenses of peptic ulceration. Introduction of medication is found to have reduced the expenses involved in peptic ulceration on account of elective operations but on account of the increased costs of medication, the total direct costs involved in the treatment of peptic ulceration have possibly increased after the introduction of the medication. Attempts are made to compare this with the reduction in the indirect costs achieved by reduction in loss of production involved by fewer early retirals and sick leaves on account of peptic ulceration, fewer deaths connected with peptic ulceration among young persons and, in general, improved quality of life for patients with peptic ulceration although it is difficult to provide a valid estimation of the savings involved.

In a retrospective questionnaire-study, we have attempted to elucidate how open access endoscopy influences management of dyspeptic patients, with special focus on young patients (less than 40 year), since the proportion of examinations with findings not requiring medical treatment are consistently reported higher in this age group. During a one-year period, 436 patients referred for open access endoscopy and their general practitioners completed questionnaires giving details of medical treatment, consultation rate for dyspepsia and global assessment before and 6-18 months after the endoscopy. Relevant changes in medical treatment (stopped in patients with no or minor abnormalities or started in patients with major abnormalities) was found for 27% of the patients, irrespective of age group. The result of the endoscopy provided reassurance for 70% of the patients with no or minor abnormalities. Reassurance was coupled with a lower consultation rate and with fewer symptoms. Altogether, 83% of the young patients with no or minor abnormalities had a positive outcome of the endoscopy. As the endoscopy service introduced relevant and lasting prescription habits and reduced consultation rates at general practitioners, also for younger dyspeptic patients with no or minor abnormalities, the strategy generally proposed of a trial with H2-receptor antagonists before considering referral for endoscopy should be subjected to formal clinical trial evaluating all relevant levels of efficacy.

In spring 1989, H2-receptor blockers and sucralfate were released for sale over-the-counter in Denmark and, simultaneously, the automatic National Health Insurance subsidy for all ulcer medicine was discontinued. The consequences of these alterations for the pressure on the diagnostic measures for upper dyspepsia are assessed by analysis of the number of referrals for gastroscopy, outpatient history-taking or radiographic examination of the stomach and oesophagus. The consequences for the consumer pattern were assessed in questionnaire investigations both to the practitioners who prescribed ulcer medicine before the alterations were introduced and also to patients who bought ulcer medicine after these alterations. Only approximately 3% of ulcer medicine is sold directly over-the-counter without medical assessment or control. No problems in safety were observed as regards incorrect treatment or delayed diagnosis. The relative proportion of patients with demonstrated indications for necessary ulcer medicine has increased after the alterations primarily on account of decrease in employment of medicine in therapeutic trials. This does not appear, however, to have resulted in any marked increased in the diagnostic possibilities. Potent ulcer medicine has not become generally accepted as over-the-counter medicine. The health and health-economic consequences should, therefore, be followed up for a more prolonged period.

The results of placebo-controlled clinical trials of the treatment of non-ulcer dyspepsia with antacids, H2-receptor blockers, pirenzepine, sucralfate and colloidal bismuth subcitrate are reviewed. The methodological difficulties involved in connection with clinical trials of treatment of a vaguely defined condition such as non-ulcer dyspepsia are discussed with particular attention to the criteria for inclusion, assessment of effect and selection bias. None of the pharmacological agents have proved convincingly better than a placebo but sub-groups of the condition probably exist where symptomatic effects may be anticipated.

With the object of investigating whether the release of H2-blockers and sucralfate for over-the-counter sale in 1989 in Denmark and the simultaneous discontinuation of the general subsidy for potent ulcer medicine have had any influence on the frequency of hospitalisation for ulcer complications, the number of these were investigated in the County of Funen during a nine-year period prior to these alterations. The number of hospitalisations on account of ulcer complications during the first year after the alterations and thereafter were assessed on the basis of the prior tendency. In addition, the characteristics of the patients were assessed by a retrospective review of the case reports for the one-year periods before and after the alterations in the dispensing rules. The number of hospitalisations on account of ulcer complications in the County of Funen rose by 45% during the period 1.4.1980-31.3.1989. No increases in the number of hospitalisations after the alterations could be demonstrated. The number of patients admitted to Odense Hospital with ulcer complications and their characteristics are, similarly, unchanged after the alterations. Three case histories are, however, registered in which the alterations may have influenced the development of the ulcer complications. There appear to be good ground to continue registration of ulcer complications with the object of investigating the long-term consequences of these alterations particularly if potent ulcer medicine is used to a greater extent as over-the-counter medicine.

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.