Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

BACKGROUND: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. METHODS: Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. RESULTS: Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. CONCLUSIONS: Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.

[Admission pattern at a department of internal medicine. Factors of significance for readmission within three months after discharge]. / Indlaeggelsesmønstret på en almen intern medicinsk afdeling. Faktorer af betydning for fornyet indlaeggelse inden for tre måneder efter udskrivelse.

The aim of the study was to investigate factors of significance for readmission of patients in a department of internal medicine. The study was based on hospital computerized data files. All admissions from the 1st of January to the 31st of December 1995 were included. During that period the department had 6061 admissions of 4152 patients. The readmission rate was 1.46. All patients were followed three months after discharge. Within that period 1119 (27%) of the patients were readmitted. A high frequency of readmission was especially found within the first ten days after discharge. Length of stay in hospital did not influence readmission rate. Women, patients in the age group 71-90 years and patients with chronic diseases were more likely to be readmitted. The demonstrated factors relating to a high readmission rate are difficult to influence. A prospective study including the primary health care system and a clinical evaluation of the patients is needed to examine causes of the high number of readmission within the first ten days after discharge.

Reliability of diagnostic tests.

The reliability of a diagnostic test depends on the accuracy and reproducibility of the test results. The accuracy is defined by comparing the test results with a final true diagnosis. The predictive values are here the most important clinical measures. Since it may be impossible to establish a final true diagnosis the reliability must in some cases be measured by a determination of reproducibility. The reproducibility is measured by comparing results of repeated examinations of the same patient. The reproducibility is measured by the use of the kappa coefficient which adjusts the observed agreement for expected chance agreement. A study of reliability of a diagnostic test should fulfill the same methodological requirements as other clinical studies. Both the predictive values and the kappa coefficient are supposed to depend on the prevalence and this should be noticed when results of different studies are compared. Reliability of diagnostic tests is often poor and scientific development of how to improve clinicians' diagnostic practice is much needed.

Acute admissions to medical departments. A comparison between an urban and a rural district.

To compare hospitalization into medical departments, acute admissions into a city hospital and into a district hospital were compared prospectively over a two-week period. Patients referred to the city hospital were on average older, were more frequently living alone and they had a greater amount of social care attendance in their homes. On the other hand, distribution of referral diagnoses, overall patient activity, occupational status and contact with relatives were similar in the two areas. Sub-acute or acute illness was considered the main cause of admission in both areas; the amount of admissions for social reasons was 13 percent to the city hospital versus 3 percent to the district hospital. Relevant alternatives to hospitalization seemed to exist in 50 percent of the admissions to the city hospital versus only 3 percent to the district hospital. Since patients admitted for social reasons block hospital beds for a longer time period than those admitted for other reasons, these differences may to some extent explain why length of hospital stay is longer in city hospitals than in rural ones.

The Helicobacter pylori theory and duodenal ulcer disease. A case study of the research process.

OBJECTIVES: To describe the medical research process from the time of the generation of a new theory to its implementation in clinical practice. The Helicobacter pylori (H. pylori) theory, i.e. the theory that H. pylori plays a significant causal role in duodenal ulcer disease was chosen as a case. MATERIAL: Abstracts from 1984 to 1993, identified in the CD-Rom, Medline system, ("Silverplatter"), using the search terms Campylobacter pylori and Helicobacter pylori, and reviews and editorials about H. pylori in some of the most widespread clinical journals. RESULTS: 2204 papers on H. pylori were published, of which 64% (1,403) were original articles. Of these, 30% (415/1,403) were descriptive clinical studies, 5% (64) were epidemiological studies, 33% (459) were laboratory studies of disease mechanisms, 8% (112) were therapeutic intervention studies, and 24% (336) concerned diagnostic and therapeutic techniques. A total of 204 of the clinical studies addressed duodenal ulcer disease. Of these, 72% (147) were cross-sectional studies, 3% (7) were observational cohort studies and 25% (50) were therapeutic intervention studies. Thirty-one editorials and reviews concerning the etiological role of H. pylori in duodenal ulcer disease had been published in some of the most widespread clinical journals. In half of the papers the authors were convinced of the causal role of H. pylori in duodenal ulcer disease, while in the remainder they were sceptical. In seven cases the authors stated which patients should be selected for H. pylori eradication treatment. CONCLUSION: Descriptive clinical studies and laboratory studies of disease mechanisms were the prevailing types of research about H. pylori. Comparatively few therapeutic intervention studies were done; this fact may have hampered the acceptance of the H. pylori theory and the introduction of eradication therapy in clinical practice.

[The clinical consequence of blood culture results]. / Den kliniske konsekvens af bloddyrkningssvar.

The effect of blood culture results on patient management in a department of internal medicine was analyzed retrospectively. In a series of 300 patients 538 blood cultures were taken. Fifty-four (10%) of blood cultures from 44 of the 300 patients were positive, but in 16 patients cultures yielded organisms considered to be contaminants. Only 28 (9.3%) patients' cultures showed growth of clinically significant pathogenic bacteria. Antimicrobial chemotherapy was instituted in 234 (78%) patients before culture results were available. For only 21 (7%) patients did the result of the blood culture have any therapeutic consequences. The high frequency and lack of impact of negative blood cultures demands a more appropriate protocol for blood culturing, and guidelines are suggested.

Do clinicians accept the role of Helicobacter pylori in duodenal ulcer disease: a survey of European gastroenterologists and general practitioners.

OBJECTIVES: To examine to what extent clinicians in Europe accepted the theory of the casual role of Helicobacter pylori (H.pylori) in duodenal ulcer disease in the year 1992, and to what extent the theory had influenced their diagnostic and therapeutic habits in the management of duodenal ulcer patients at that time. DESIGN: Postal questionnaire. SETTING: Three European countries: the UK, the Netherlands, and Denmark. SUBJECTS: Three hundred and three gastroenterologists, 250 general practitioners, 83 junior hospital doctors. MAIN OUTCOME MEASURES: Number of doctors believing H. pylori to be a significant cause of duodenal ulcer disease, use of diagnostic tests for detection of H. pylori and therapeutic regimens for eradicating H. pylori. RESULTS: Four hundred and forty-two doctors replied. Eighty-four per cent of the British doctors, 73% of the Dutch doctors, and 47% of the Danish doctors accepted the role of H. pylori in duodenal ulcer disease. The rates were higher among gastroenterologists than among general practitioners. Eighty-four per cent of the British doctors, 80% of the Dutch doctors, and 48% of the Danish doctors used diagnostic tests for H. pylori, most frequently histological examination (64%). In patients with duodenal ulcer disease, H. pylori eradication was undertaken by 93% of the British doctors, 89% of the Dutch doctors, and 60% of the Danish doctors. A triple therapy (a bismuth salt, metronidazole, and either amoxicillin or tetracycline) was used by 57% (181/315) of the doctors. CONCLUSIONS: H.pylori treatment is frequently used in some countries. However, the role of H. pylori in duodenal ulcer disease has not been accepted to the same extent in different European countries.

Opinions in Denmark on the causes of peptic ulcer disease. A survey among Danish physicians and patients.

The aim of the study was to investigate opinions among Danish patients and physicians on causes of peptic ulcer disease. Fifty-nine patients with an ulcer history and 77 physicians with a special interest in gastroenterology participated. They were given a questionnaire listing 16 possible causes of peptic ulcer and indicated for each whether they believed it was a contributory cause of the disease. The patients stated 0-10 causes each (median, 4), and the physicians 3-12 causes (median, 6) (p < 0.01). Younger physicians stated more causes than did the older ones (p < 0.01), and female physicians stated more causes than did their male colleagues (p < 0.01). Seventy-five per cent of the patients indicated that psychologic factors, such as grief, anxiety, and stress, were contributory causes of peptic ulcer disease, whereas only around 40% believed that coffee/tea, alcohol, smoking, side effects of medicine, and working conditions played a causal role. Around 95% of the physicians indicated that medical drugs and smoking were contributory causes of peptic ulcer disease, and around 80% that alcohol and psychologic factors were so. Only 30-40% of the physicians believed that coffee/tea, food habits, infection, and working conditions could play a causal role in ulcer disease. It is concluded that the opinion on causal agents in peptic ulcer disease differ considerably among both patients and physicians. Opinions on causes of diseases may influence the way we treat and advise our patients, and attempts should thus be made to unify our knowledge and interpretations of causes of diseases to reach more solid ground in counselling our patients.

[Reproducibility of electrocardiographic interpretation in patients with suspected myocardial infarction. A controlled study of the effect of a training trial]. / Reproducerbarheden af bedømmelse af elektrokardiogrammer hos patienter mistaenkt for akut myokardieinfarkt. En kontrolleret undersøgelse af effekten af et undervisiningsforsøg.

We examined the effect of a training programme to reduce interobserver variation in interpretation of electrocardiography in suspected myocardial infarction. Sixteen doctors with 6-24 months of clinical training in internal medicine read serial electrocardiographic recordings in 107 patients and assessed whether signs indicative of acute myocardial infarction were present. There was disagreement in approximately 70% of cases. Eight of the doctors were randomly allocated to attend an eight hour long intensive course on interpretation of electrocardiography in myocardial infarction. The remaining eight participants were allocated to a control group, received no training, and were not told about the subject of the study. All the doctors then reviewed another series of electrocardiographic recordings. No difference was found in the level of agreement within the two groups before and after the training programme, or between the two groups before and after the training. The raters' ability to discriminate between electrocardiograms with a high and low indication of infarction remained unaffected. We conclude that the training programme did not increase agreement regarding the interpretation of electrocardiographic data in suspected myocardial infarction. Our results suggest that the diagnostic approach of physicians is established at a very early stage in their clinical training. The effect of training programmes should be evaluated by the use of randomized clinical studies.

Observer variability of radionuclide left ventricular volume determination at rest and during exercise.

The reproducibility expressed as the intra- and interobserver variation in the determination of cardiac left ventricular (LV) volumes by the radionuclide multigated equilibrium technique in the upright position is presented. No systematic difference was found in the reproducibility between LV volumes determined in healthy subjects and cardiac patients or between examinations performed at rest and during exercise. The intra- and interobserver variation were of the same magnitude. SD of the difference was 8 to 9 ml for LV end-diastolic volume, 4 to 7 ml for LV end-systolic volume, and 2 to 5% for LV ejection fraction. Thus, there is a 95% probability that repeat measurements, either by the same observer or by 2 independent observers, will result in the same LV end-diastolic volume within 18 ml, LV end-systolic volume within 11 ml, and LV ejection fraction within 8%. Only 15% of the variation can be ascribed to determination of the attenuation correction factor.

Inadequacy of the WHO classification of the thyroid gland.

In order to evaluate the reproducibility of the WHO classification of goitre, the observer variation was estimated as kappa coefficients. Three observers independently inspected and palpated the thyroid gland of 53 patients twice and assessed the thyroid according to the five grades of the WHO classification. The thyroid volume was also measured by ultrasonography. We found kappa values from 0.15 to 0.70 in the interobserver study, and from 0.02 to 0.89 in the intraobserver study. Considerable overlap between the five grades was demonstrated when the assessments were related to volume estimated by ultrasonography. Description of the thyroid gland according to the WHO classification is inaccurate and not reproducible and is therefore of limited value.

Observer homogeneity in the histologic diagnosis of Helicobacter pylori. Latent class analysis, kappa coefficient, and repeat frequency.

Four pathologists independently examined 82 antral mucosal biopsy specimens for the presence of Helicobacter pylori and indicated whether their assessments were certain. The pathologists made a positive diagnosis in from 56% to 84% of the specimens (significant heterogeneity, p < 0.01). The frequency of uncertain diagnoses was from 4% to 20% (p < 0.01). Uncertain statements occurred more frequently among negative than among positive diagnoses. For the six pairs of observers the kappa coefficients were between 0.39 and 0.82. By a latent class analysis measures of diagnostic accuracy were calculated comparing the observers' assessments with an estimated consensus diagnosis. The predictive values of a positive diagnosis ranged from 0.70 to 1.00. By calculation of repeat frequencies--that is, the probability that an observer's statement was confirmed by another observer--it became evident that uncertain statements were less frequently (61%) confirmed than were certain ones (85%). It is concluded that observer homogeneity is only moderate with regard to the histologic diagnosis of H. pylori, which should be considered both in daily clinical routine and in scientific studies. Disagreement between observers was associated with negative diagnoses, presumably because the pathologists felt more uncertain in these cases.

Reliability in the interpretation of the course of serum enzyme concentration changes in suspected acute myocardial infarction.

The aim of the study was to determine interobserver variation in the interpretation of the course of serum enzyme concentration changes in suspected acute myocardial infarction. The study was performed retrospectively and had no relation to the treatment of the patients. In 107 patients, two specialists in cardiology, two specialists in internal medicine, and two trainees, independently evaluated courses of enzyme concentrations and decided whether they were suggestive of acute myocardial infarction. Frequency of positive assessments varied for the six observers from 33 to 53% (P less than 0.01). Pairwise comparison of observers showed a median agreement rate of 0.90 (range 0.78 to 0.96). After adjusting for chance agreement a median kappa value of 0.79 (range 0.56-0.92), was achieved. No difference was found in level of agreement between specialists and trainees. Interobserver variation is an important consideration in the interpretation of the course of serum enzyme concentrations and may have an extensive impact on the final diagnosis of acute myocardial infarction.

Perinatal audit. Are experts biased by knowledge of outcome? A controlled study.

Perinatal audit is a method widely used for quality assurance in medicine. In clinical medicine, experiments have revealed that physicians' prior knowledge and expectations may bias their assessments. This study examined whether experts in perinatal audit were biased in their evaluation of perinatal and neonatal care when they had knowledge of the outcome. A panel of experts evaluated the quality of care in 48 infants who died in the neonatal period and 48 paired infants who survived it. The 48 pairs were randomly allocated to two groups. In the first group, the outcome of neonatal death or neonatal survival appeared in the case histories, whereas in the second group the outcome was blind. There were no differences in the assessment of quality of antenatal, delivery, and neonatal care comparing the result of the evaluation between the cases with knowledge of the outcome and the cases without knowledge of outcome. Our results indicate that the experts were not biased by the knowledge of outcome when they assessed the quality of peri- and neonatal care.

Interpretation of the electrocardiogram in suspected myocardial infarction: a randomized controlled study of the effect of a training programme to reduce interobserver variation.

We examined the effect of a training programme to reduce interobserver variation in interpretation of electrocardiography in suspected myocardial infarction. Sixteen doctors with 6-24 months of clinical training in internal medicine read serial electrocardiographic recordings in 107 patients and assessed whether signs indicative of acute myocardial infarction were present. There was disagreement in approximately 70% of cases. Eight of the doctors were randomly allocated to attend an 8-h intensive course on interpretation of electrocardiography in myocardial infarction. The remaining eight participants were allocated to a control group, received no training, and were not told about the subject of the study. All the doctors then reviewed another series of electrocardiographic recordings. No difference was found in the level of agreement within the two groups before and after the training programme, or between the two groups before and after the training. The raters' ability to discriminate between electrocardiograms with a high and low indication of infarction remained unaffected. We conclude that the training programme did not increase agreement regarding the interpretation of electrocardiographic data in suspected myocardial infarction. Our results suggest that the diagnostic approach of physicians is established at a very early stage in their clinical training. The effect of training programmes should be evaluated by the use of randomized clinical studies.

Reliability of first-pass radionuclide determination of cardiac output in the upright position at rest and during exercise.

The reliability of non-invasive determination of cardiac output using first-pass radionuclide cardiography at rest and during exercise in the upright position was evaluated in 20 patients with coronary artery disease. Cardiac output values ranged from 2.97 to 5.99 l/min at rest and from 5.08 to 10.82 l/min during exercise. Cardiac output results obtained by the radionuclide method were compared with those derived from the thermodilution technique performed simultaneously. The mean difference between the two techniques was 0.02 l/min at rest and -0.34 l/min during exercise; the limits of agreement (mean +/- 1.96 SD) were -1.29 to 1.33 l/min and -1.97 to 1.29 l/min, respectively, indicating an acceptable level of agreement. A high reproducibility of the radionuclide technique was found, with a mean difference between determinations by two observers of 0.03 l/min at rest and 0.21 l/min during exercise, the corresponding limits of agreement being -0.75 to 0.81 l/min and -0.79 to 1.21 l/min, respectively. With the aid of a variance component analysis of two determinations by each of four observers, 95% confidence intervals of +/- 10% at rest and +/- 12% during exercise were computed for the radionuclide cardiac output measurements. The observer variation was most pronounced for the part of the cardiac output determination related to measurement of left ventricular equilibrium activity during exercise. First-pass radionuclide cardiography is a reliable method for determination of cardiac output in cardiac patients at rest and during exercise in the upright position.

Observer variation in the clinical assessment of the thyroid gland.

In order to evaluate the reliability of clinical assessment of the thyroid gland, two specialists in endocrinology and two younger doctors independently examined 53 patients twice, and assessed whether they had a diffuse goitre, a multinodular goitre, a solitary nodule or a normal gland. In 30% of the patients all four observers were in agreement, whereas in 47% and 23% of the patients, two and three different diagnoses were given, respectively. Inter-observer variation was determined and kappa values between -0.04 and 0.54 were found. Intra-observer variation was smaller, revealing kappa values between 0.44 and 1.00. The present study suggests that clinical assessment of the thyroid gland may lead to misclassification of the type of thyroid disease, and thereby to a less than optimal choice of therapy.