Symptomatic patients referred to an open-access upper gastrointestinal endoscopy completed a detailed, self-administered questionnaire aimed at assessing the predictive value of history in dyspepsia. Nine hundred and thirty patients were suitable for analysis. Of these, 29% were found to have organic dyspepsia. A substantial overlap of symptoms and demographic data was found among the various endoscopic diagnoses. Discriminating variables were identified by stepwise logistic regression analysis and included in predictive score models. Pain relieved by antacids, age above 40 years, previous peptic ulcer disease, male sex, symptoms provoked by berries, and night pain relieved by antacids and food were found to predict organic dyspepsia with a sensitivity and specificity of approximately 70%, when applied on the observed material. Similar probabilities were found for score models of peptic ulcer and esophagitis. In general, the low prevalence of organic diseases resulted in low positive and high negative predictive values. Accordingly, the main impact of the predictive models may be to reduce the number of negative endoscopies rather than to predict a precise diagnosis. Independent of disease category and age, 41% of the subjects expressed a fear of malignancy, emphasizing the value of reassurance from a negative endoscopy.

Little is known about the relationship between hiatus hernia (HH) and gastroesophageal reflux symptoms (GERS). Nine hundred and thirty patients submitted to gastroscopy because of symptoms completed a self-administered questionnaire. Fourteen per cent showed esophagitis (ES) and 17% HH. Forty-nine per cent of the patients with HH had endoscopic ES, and 60% of those with ES had HH. The severity of ES was dependent (p less than 0.05) on both the presence and the size of HH. After exclusion of patients with peptic ulcer and malignancy, patients with and without HH and ES were compared with regard to the presence of single symptoms and a weighted GERS score based on symptoms proven to be typical for ES. Only borderline differences were found between patients with ES and HH and those with ES and no HH. The former group, however, presented with significantly (p less than 0.001) more GERS than the patients with HH only. Nevertheless, the patients with HH as the only pathologic finding had significantly (p less than 0.01) more GERS than the patients with no major endoscopic abnormality. This study indicates a close association between HH and gastroesophageal reflux disease and supports the clinical significance of an endoscopically detected HH.

Double-blind randomized controlled trials in single subjects (N of 1 RCTs) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer-like non-ulcer dyspepsia (NUD). However, spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages. This study was carried out to identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities. We evaluated N of 1 multi-crossover trial designs, which compare the effects of single doses of cimetidine and placebo taken on-demand for symptomatic relief. Each trial consisted of six cimetidine (400 mg or 800 mg) and six placebo tablets randomized in successive pairs. The symptomatic effect of each tablet was measured 1/2-6 h after the intake. Outcomes were assessed by individual p values and confidence intervals. A minimal clinically important difference was defined, to assess the clinical significance as demonstrated by the confidence intervals. Thirteen of 25 patients (52%) with reflux- and ulcer-like NUD obtained individual p values below 0.20. Similarly, 7 of 9 patients (78%) with oesophagitis and 6 of 12 patients (50%) with peptic ulcer obtained such p values. On the basis of the 80% confidence intervals the corresponding numbers of subjects with clinically significant effect were six (NUD), three, and three. The combined data showed a significantly better effect of cimetidine than of placebo (p less than 0.0001) in each of the three diagnostic groups studied. Cimetidine taken on-demand may have a rapid symptom-relieving effect in dyspepsia.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of cimetidine and placebo was examined in 123 patients with non-ulcer dyspepsia (NUD) by means of a 12-day multi-crossover model with 5 regular interchanges between cimetidine and placebo. The evaluation of effect in individual patients was based on the number of times cimetidine was associated with less symptoms than the preceding or following placebo period. If cimetidine had no effect, the probability of being defined as a cimetidine responder was 25%. In general, cimetidine was associated with less symptoms than placebo (p less than 0.0001). Forty patients were identified as cimetidine responders (R) and the remaining patients were termed non-responders (NR). Symptoms compatible with gastroesophageal reflux were significantly more frequent in R than in NR, whereas the opposite was true for symptoms of the irritable colon syndrome. The ability of symptoms selected by stepwise logistic regression to predict response to cimetidine showed at best a sensitivity of 75% and a specificity of about 65%. No differences were found between R and NR with regard to acid secretion, endoscopic and histologic findings, or the result of an acid perfusion test. The present study supports the existence of a subgroup of cimetidine responders among patients with NUD characterized by symptoms suggestive of gastroesophageal reflux disease in the absence of confirmatory objective evidence.

Randomised controlled group trials are the gold standard in clinical research and provide information about the average effect of a treatment in a target population. Such information, however, cannot necessarily be transferred to a single patient because finding a significant effect of treatment does not mean that all the study subjects responded. Besides, in real life clinicians are often confronted with vague symptoms and poorly defined diseases; this is a different case from the strict criteria used in scientific studies. In an attempt to adapt the general knowledge about a new treatment to a particular patient the clinician tries out drugs. Such an uncontrolled trial and error approach is, however, often biased towards a false positive effect as most disorders are self limiting, the placebo effect may be appreciable, and the patient is eager to please the doctor. All these aspects tend to contribute to the myth that treatment with drugs is a prerequisite for regaining health.Controlled trials in individual patients (n of 1 trials) have a long tradition in behavioural medicine' and have recently attracted attention in clinical medicine. Such trials may improve the certainty of a treatment decision in an individual patient, and a series of such trials may permit more general inferences to be drawn about a treatment. Method of studyThe main principle in the n of 1 trial is that the patient serves as his or her own control in a study of the efficacy of a new drug compared with placebo or another drug. The treatments are administered to the patient in a double blind, randomised, multiple crossover sequence (fig 1). Each treatment period is randomly assigned and the trial design is tailored to the clinical condition, the properties of the drug(s), and the statistical requirements. Separate measures of response are obtained for each treatment period, forming the basis for the evaluation of effect.If similar prerequisites are applied for series of n of 1 trials as for a conventional group trial-strict entry criteria, uniform treatment procedures, consensus scales for outcome measures, and acceptable statistical tests-individual responders may be identified, common characteristics detected, and conclusions generalised to the target population.4 Experiences in clinical medicineNon-ulcer dyspepsia is a heterogeneous disorder in which patients are unlikely to benefit uniformly from one type of treatment. H2 receptor antagonists are often prescribed for this condition, although conventional clinical trials show conflicting results." In an attempt to indentify individual responders to H2 receptor antagonists in non-ulcer dyspepsia I and my colleagues devised a multicrossover model in which the effect of cimetidine was compared with that of placebo. We used treatment periods of one, two, and four days. The crossover model was later revised to improve its validity,1 and the current version requires that six tablets of cimetidine (400 mg or 800 mg) and six tablets of placebo are given in a double blind, randomised order. To ...