Clinical outcome in upper gastrointestinal bleeding complicating low-dose aspirin and antithrombotic drugs.

BACKGROUND: The current risk stratification systems in upper gastrointestinal bleeding do not correct for the intake of low-dose aspirin and other antithrombotic drugs. AIM: To test the Blatchford scores in evaluating the clinical outcome in bleeders using these drugs. METHODS: We calculated the Blatchford scores in 510 bleeders, including 123 on low-dose aspirin, 44 on other antithrombotic drugs, and 68 on non-steroidal anti-inflammatory drugs. RESULTS: The median clinical scores distributed according to aetiological risk factors were as follows: no risk factors, 5; non-steroidal anti-inflammatory drugs, 8; aspirin, 7; other antithrombotics, 6; excess alcohol, 4; multiple risk factors, 7; (P = 0.003, Kruskal-Wallis test). Scores correlated positively with the duration of admission in the entire group (r(s) = 0.285; P < 0.001) and in those taking aspirin and antithrombotics (r(s) = 0.211; P = 0.029). The median scores in patients requiring the blood transfusion were 10 in the entire group and 11 in users of aspirin or antithrombotics, compared with 3 and 4, respectively, in those not transfused (P < 0.001). CONCLUSIONS: The Blatchford scores are significantly elevated in users of non-steroidal anti-inflammatory drugs, low-dose aspirin, and other antithrombotic drugs. They correlate positively with the duration of admission and the need for blood transfusion.

Upper gastrointestinal mucosal abnormalities and blood loss complicating low-dose aspirin and antithrombotic therapy.

BACKGROUND: Little is known about the site and nature of bleeding lesions related to low-dose aspirin and other antithrombotic agents. AIM: To describe the mucosal abnormalities in patients presenting with upper gastrointestinal bleeding while being treated with these drugs. METHODS: The endoscopic findings and clinical details were analysed in all patients presenting with haematemesis and/or melaena at a single centre during three calendar years. Associations between endoscopic findings and risk factors, including the intake of non-steroidal anti-inflammatory drugs, low-dose aspirin (75 mg daily) and other antithrombotic drugs including warfarin, clopidogrel, and dipyridamole, were assessed by logistic regression analysis. RESULTS: In 674 upper gastrointestinal bleeders, we found that the odds ratio for the presence of erosive oesophagitis in aspirin users was 2 (95% CI, 1-3; P = 0.03) and 3 (2-5; P = 0.0003) in patients taking other antithrombotic agents. In 41 patients with oesophagitis and taking these drugs, 36 (88%) had cardiovascular disease and only 4 (10%) had peptic symptoms. CONCLUSIONS: Erosive oesophagitis is common in patients with upper gastrointestinal bleeding taking low-dose aspirin or antithrombotic agents, and could potentially be confused with the coexisting heart disease.

Upper gastrointestinal haemorrhage associated with low-dose aspirin and anti-thrombotic drugs - a 6-year analysis and comparison with non-steroidal anti-inflammatory drugs.

BACKGROUND: Low-dose aspirin and other anti-thrombotic therapy has been increasingly used for vascular protection. AIM: To assess the possibility that the incidence of upper gastrointestinal blood loss has changed in subjects using these agents in comparison with non-steroidal anti-inflammatory drugs. METHODS: We studied the characteristics of all patients with acute upper gastrointestinal haemorrhage and attending a single hospital at 3 points over a 6-year period: 1996 (n = 204), 1999 (n = 224) and in 2002 (n = 252). RESULTS: The incidence of haemorrhage in subjects taking low-dose aspirin rose from 15 per 100 000 of the population per annum in 1996, to 18 in 1999 and 27 in 2002 (P = 0.004). The respective incidence in subjects taking other anti-thrombotic drugs was 4, 8, and 12 (P < 0.001). No significant change was detected in non-steroidal anti-inflammatory drug users. However, acute myocardial infarction mortality was 216 per 100 000 in 1996, 221 in 1999 and fell to 169 in 2002 (P < 0.001). CONCLUSIONS: The incidence of upper gastrointestinal haemorrhage in users of low-dose aspirin and other anti-thrombotic drugs has been steadily rising. This has been paralleled by a fall in cardiac mortality.

Therapeutic drug use during pregnancy: a comparison in four European countries. OECM Working Group. Occupational Exposures and Congenital Anomalies.

A drug utilization study was performed using data of the OECM study on Occupational Exposures and Congenital Malformations, which was conducted in six European Registries of Congenital Anomalies (two in France, two in Italy, one in Great Britain, and one in The Netherlands): the mothers were interviewed after delivery for exposures during pregnancy, including use of therapeutic drugs. The analysis of drug use considered only the 1134 control mothers of healthy newborns, and focused on the first trimester of pregnancy: 36.2% of the interviewed mothers used at least one drug (excluding vitamins and minerals) during the first trimester. This rate varied from 22.5% in Glasgow to 50.3% and 44.2% in the French centers. Anti-infectives were the most frequent drugs (12.3% of mothers), then antinauseants (10.6%), and treatments for threatened abortion (5.5%). Important variations between countries were observed, reflecting different medical attitudes towards drug use during pregnancy.

Observer variability in assessing the clinical features of subarachnoid hemorrhage.

Clinical assessment of patients with subarachnoid hemorrhage (SAH) is important both in determining management and in predicting outcome. A previous report showed considerable observer inconsistency when patients were graded with either the Hunt and Hess or the Nishioka system. This study evaluates observer variability in assessment of the individual clinical features from which these grading systems are derived. Assessment of the presence or absence of neck stiffness caused least inter-observer variability. Headache caused most variability, due to difficulty in grading its severity. Determination of the severity of a neurological deficit proved more reliable than deciding whether or not a deficit was present. The terms used to describe the level of consciousness in the Hunt and Hess and Nishioka systems were found to be significantly less consistent than the Glasgow Coma Scale. The authors suggest that when patients with SAH are assessed it is necessary to take into account the consistency with which observers can record a clinical feature, as well as its prognostic importance.

Observer variability in grading patients with subarachnoid hemorrhage.

The management of individual patients with subarachnoid hemorrhage depends greatly on assessment of the patient's clinical condition. Difficulty in applying current grading systems prompted the authors to conduct studies of observer variability and to attempt to identify sources of inconsistency. Observers graded 15 patients by both the Hunt and Hess and Nishioka systems. Considerable observer variability was found, with up to four different grades being selected for the same patient. Kappa statistics were used to evaluate the data. This method determines observer agreement occurring in excess of chance. Kappa values for each grading system showed observer agreement to be significantly better than chance, yet revealed marked observer variation. Most variation occurred when Grade 3 was selected, irrespective of the system used. In a further study where observers graded clinical summaries, similar variation occurred; therefore, inconsistency was due mainly to difficulty in matching patients with levels described in the grading system, rather than to fluctuation in the patient's clinical condition or difference in the observers' examination technique. Variability was high when patients with systemic disease or vasospasm on angiography were graded with the Hunt and Hess system. The studies show that a simpler and more reliable grading system is required, and emphasize and need for caution when interpreting the results from different published series.

Maternal occupational risk factors for oral clefts. Occupational Exposure and Congenital Malformation Working Group.

OBJECTIVES: This study investigated the role of maternal exposures at work during pregnancy in the occurrence of oral clefts. METHODS: The occupational exposures of 851 women (100 mothers of babies with oral clefts and 751 mothers of healthy referents) who worked during the first trimester of pregnancy were studied. All the women were part of a multicenter European case-referent study conducted using 6 congenital malformation registers between 1989 and 1992. In each center, the mother's occupational history, obtained from an interview, was reviewed by industrial hygienists who were blinded to the subject's status and who assessed the presence of chemicals and the probability of exposure. Odds ratios (OR) were estimated by a multivariate analysis including maternal occupation or occupational exposures during the first trimester of pregnancy and possible confounding factors such as center of recruitment, maternal age, urbanization, socioeconomic status, and country of origin. RESULTS: After adjustment for confounding factors, cleft palate only was significantly associated with maternal occupation in services such as hairdressing [OR 5.1, 95% confidence interval (95% CI) 1.0-26.0] and housekeeping (OR 2.8, 95% CI 1.1-7.2). The analysis suggests that the following occupational exposures are associated with orofacial clefts: aliphatic aldehydes (OR 2.1, 95% CI 0.8-5.9) and glycol ethers (OR 1.7, 95% CI 0.9-3.3) for cleft lip with or without cleft palate and lead compounds (OR 4.0, 95% CI 1.3-12.2), biocides (OR 2.5, 95% CI 1.0-6.0), antineoplastic drugs (OR 5.0, 95% CI 0.8-34.0), trichloroethylene (OR 6.7, 95% CI 0.9-49.7), and aliphatic acids (OR 6.0, 95% CI 1.5-22.8) for cleft palate only. CONCLUSIONS: Due to the limited number of subjects, these results must be interpreted with caution. However, they point out some chemicals already known or suspected as reproductive toxins.

Variation in restorative treatment decisions: application of Receiver Operating Characteristic curve (ROC) analysis.

It has been evident for many years that dentists, when planning treatment for patients, do not act in a standard manner, and previous research has shown there to be wide variations in treatment planning amongst groups of dentists. Signal detection theory and Receiver Operating Characteristic (ROC) analysis allows measurement of an observer's ability to detect a lesion, while at the same time allowing examination of how a lesion, once perceived, is judged to be in need of treatment. An ROC curve is constructed by plotting the sensitivity (or true positive rate) of decisions made, against the false positive rate (equivalent to 1-specificity) when various decision attitudes, from interventionist to non-interventionist, are held. Fifteen pairs of simulated bitewing radiographs were shown to 20 dentists, who were asked to specify, for each approximal lesion, whether or not they would place a conventional restoration. The 7200 decisions made by the dentists were validated by sectioning and microscopically examining the teeth. The mean sensitivity of the dentists' decisions, when the strictest operating thresholds were held and caries into dentine was the validating criterion, was 0.26 and the mean specificity was 0.96. ROC analysis shows that when operating at the strictest threshold, the dentists were implying that specificity was weighted as being 2.7 times more important than sensitivity. ROC analysis leads to insight into how dentists differentially weight the true and false, positive and negative, outcomes of their decisions and thus allows explanation of why two dentists would rarely make exactly the same treatment plan for one patient, and also why different treatments might be offered to two patients exhibiting the same levels of disease.

Restorative treatment thresholds and agreement in treatment decision-making.

It has been recognised for many years that treatment decision-making among dentists often shows wide variation. This study sought to examine the effect of dentists' stated treatment thresholds as a source of variation between them. Twenty dentists made 360 treatment decisions about the approximal surface of extracted teeth seen in simulated bitewing radiographs. They also stated their personal treatment thresholds, i.e. the depth of lesion which they intended to restore. One hundred and ninety pairwise comparisons of treatment decisions showed that only 16% of the dentist pairs showed substantial agreement. Dentist pairs who reported that they held the same interventive threshold achieved exactly the same mean level of agreement in treatment decision-making as dentist pairs who disagreed about the appropriate threshold for restorative intervention. The study suggests that restorative thresholds which are reported to be used by dentists may be poorly correlated with the number of positive treatment decisions actually made.

A comparison of symptoms between non-ulcer dyspepsia patients positive and negative for Helicobacter pylori.

The role of Helicobacter pylori infection in the symptom complex associated with non-ulcer dyspepsia is uncertain, despite the presence of the organism in a high proportion of these patients. In order to exclude physician bias in history taking, 18 patients (9 female) diagnosed as non-ulcer dyspepsia, after endoscopy and gallbladder ultrasonography, underwent computer interrogation using the Glasgow Diagnostic System for Dyspepsia (GLADYS). Five antral and 3 fundal endoscopic biopsies from these patients were also histologically examined for the presence of Helicobacter pylori and quantitatively analysed for polymorph and chronic inflammatory cell densities per mm2 of lamina propria using computer-linked image analysis. In the group of 9/18 patients who were positive for Helicobacter pylori, there were significantly higher antral and fundal inflammatory cell counts than in negative patients. However, analysis of the GLADYS interrogation data showed no significant positive relationships between Helicobacter pylori positivity and any gastrointestinal symptoms. These results confirm a significant association between Helicobacter pylori and superficial gastritis but suggest that non-ulcer dyspepsia in patients with Helicobacter pylori colonisation is probably not a clinically identifiable and distinct syndrome.

Geographical differences in the prevalence of dyspepsia.

The epidemiology of dyspepsia is reviewed with reference to the factors that affect prevalence, including definitions of the term, case mix, and selection. Period prevalence of dyspepsia in several different populations gives an average of 32%, of which 24% is accounted for by recognized ulcer disease. Dyspepsia appears to comprise about 70% of patients' gastrointestinal problems in a large prospective survey carried out in general practice in England, higher than some other estimates. The proportion of gastrointestinal disease in general practice consultations is examined, and while it accounts for about 5% of all consultations, it accounts for about 14% of patients consulting with a problem. There seems to have been a decline of 15% over 30 years. The difficulty of establishing the population prevalence of functional dyspepsia is emphasized, and several studies in which the proportion in general gastrointestinal outpatients has been measured are reviewed. Some data from a Glasgow study in which clinical histories have been recorded directly from patients by a computer system (GLADYS) show the prevalence of several common gastrointestinal symptoms in a clinic population and also of dysmotility-like dyspepsia. Such descriptive data should also be used for predicting diagnosis and for selecting patients to investigate.

Computer aided diagnosis of jaundice. A comparison of two data bases.

A computer system for probabilistic diagnosis of jaundice was tested on a patient sample from a geographical area different from that for which it was first constructed. 144 consecutive patients with jaundice seen in two Stockholm hospitals were interviewed and examined to record a total of 82 indicants from history, demographic details, physical findings and laboratory tests. Data were compared with those of 319 jaundiced patients previously interviewed and examined at different London hospitals. It was found that disease incidences were different in the two patient samples. There were more patients with acute viral hepatitis, chronic active hepatitis and primary biliary cirrhosis in the London data base whereas the Stockholm data base included significantly more patients with Gilbert's syndrome and alcoholic cirrhosis. Indicant frequencies, standardised for disease incidence, differed with respect to age (Stockholm patients were on average six years older), time from onset of first symptom to hospital admission (Stockholm patients had on average a two-week shorter history of disease) and a number of symptoms such as nausea, vomiting, anorexia, weight loss, itching, pale stools and dark urine which were more frequent among the London patients. Differences in hospital admission policy was regarded as an important reason for the differences in indicant frequency. The results of probabilistic diagnosis were poor. Only 49% of the cases were correctly classified into twelve diagnostic groups. In particular the computer model was poor at separating different causes of malignant bile duct obstruction and at differentiating between malignant and benign bile duct obstruction. However, all cases of acute viral hepatitis were correctly classified and the computer model was 87% accurate in differentiating between medical and surgical jaundice. Reclassification of the 144 patients on their own data showed the computer system to be well calibrated and 97% of the cases were correctly classified according to this procedure. In conclusion, the computer system could not be directly transferred for use in a Swedish hospital but the results of reclassification were sufficiently encouraging to warrant prospective studies.

Taking a calculated risk: predictive scoring systems in dyspepsia.

The derivation of a predictive index is illustrated using 14 simple questions to assess the chance of the presence of an ulcer. The evaluation and use of such a 'calculated-risk' is briefly described.

Transferability of a computer system for medical history taking and decision support in dyspepsia. A comparison of indicants for peptic ulcer disease.

The transferability of a British data base for differential diagnosis of dyspepsia using data obtained by computer interrogation was tested in 467 Swedish patients. The diagnostic value for peptic ulcer disease of symptoms such as frequent night pain relieved by food or antacids, smoking, family history of ulcer, food relief pain, male sex, and episodic pain was shown to be reproducible. However, for a number of symptoms their value for the diagnosis of peptic ulcer disease could not be reproduced in Swedish patients. The combined value of indicants was tested using a computer based algorithm for calculating diagnostic probabilities. The performance of this algorithm was poor when British data were applied to Swedish patients but reclassification of the Swedish patients on their own data base showed promising results. Crean and colleagues in Glasgow have developed a computer system for automated interrogation of patients with dyspepsia. The system utilises a large number of questions to obtain information regarding a maximum of 160 diagnostic indicants. The symptoms elicited from a patient can be compared with those of a large number of previously examined patients and the probabilities of ten different diagnoses can be calculated. The calculation of diagnostic probabilities is based on scores reflecting the diagnostic value of different symptoms in different diseases. After careful translation of questions the system has been transferred for use in Sweden. The present report is based on data from patients seen during the first two years with the system at a Swedish hospital.(ABSTRACT TRUNCATED AT 250 WORDS)