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.

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.

Tobacco and alcohol use during pregnancy and risk of oral clefts. Occupational Exposure and Congenital Malformation Working Group.

OBJECTIVES: This study examined the relationship between maternal tobacco and alcohol consumption during the first trimester of pregnancy and oral clefts. METHODS: Data were derived from a European multicenter case-control study including 161 infants with oral clefts and 1134 control infants. RESULTS: Multivariate analyses showed an increased risk of cleft lip with or without cleft palate associated with smoking (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.07, 3.04) and an increased risk of cleft palate associated with alcohol consumption (OR = 2.28, 95% CI = 1.02, 5.09). The former risk increased with the number of cigarettes smoked. CONCLUSIONS: This study provides further evidence of the possible role of prevalent environmental exposures such as tobacco and alcohol in the etiology of oral clefts.

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.

Symptomatic benefit from eradicating Helicobacter pylori infection in patients with nonulcer dyspepsia.

BACKGROUND: The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers. The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known. METHODS: We performed a randomized, placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily, 500 mg of amoxicillin three times daily (with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin), and 400 mg of metronidazole three times daily (160 patients) with that of omeprazole alone (158 patients) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy. Symptoms were assessed with the Glasgow Dyspepsia Severity Score, with resolution of symptoms defined as a score of 0 or 1 in the preceding six months (maximal score, 20). One year later the patients were assessed to determine the frequency of the resolution of symptoms. RESULTS: One month after the completion of treatment, 132 of 150 patients (88 percent) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori, as compared with 7 of 152 (5 percent) in the group assigned to receive omeprazole alone. One year later, dyspepsia had resolved in 33 of 154 patients (21 percent) in the group given omeprazole and antibiotics, as compared with 11 of 154 (7 percent) in the group given omeprazole alone (95 percent confidence interval for the difference, 7 to 22 percent; P<0.001). Among the patients in the group given omeprazole and antibiotics, the symptoms resolved in 26 of the 98 patients (27 percent) who had had symptoms for five years or less, as compared with 7 of the 56 patients (12 percent) who had had symptoms for more than five years (P=0.03). CONCLUSIONS: In patients with H. pylori infection and nonulcer, or functional, dyspepsia, treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone.

Congenital malformation and maternal occupational exposure to glycol ethers. Occupational Exposure and Congenital Malformations Working Group.

Glycol ethers are found in a wide range of domestic and industrial products, many of which are used in women's work environments. Motivated by concern about their potential reproductive toxicity, we have evaluated the risk of congenital malformations related to glycol ether exposure during pregnancy as part of a multicenter case-control study, conducted in six regions in Europe. The study comprised 984 cases of major congenital malformations and 1,134 controls matched for place and date of birth. Interviews of the mothers provided information about occupation during pregnancy, sociodemographic variables, and other potential risk factors (medical history, tobacco, alcohol, drugs). A chemist specializing in glycol ethers evaluated exposure during pregnancy, using the job description given by the mother, without knowledge of case or control status. We classified malformations into 22 subgroups. The overall odds ratio (OR) of congenital malformation associated with glycol ether exposure was 1.44 [95% confidence interval (CI) = 1.10-1.90], after adjustment for several potential confounders. The association with exposure to glycol ethers appeared particularly strong in three subgroups: neural tube defects (OR = 1.94; 95% CI = 1.16-3.24), multiple anomalies (OR = 2.00; 95% CI = 1.24-3.23), and cleft lip (OR = 2.03; 95% CI = 1.11-3.73). In this last subgroup, risk, especially of an isolated defect, tended to increase with level of exposure.

The role of nurses in management with the National Health Service in Scotland.

The introduction of an internal market in health care in 1991 was the most radical change to the National Health Service (NHS) since its inception. The consequent NHS changes and reforms have had a profound impact on nursing management and inevitably on nurses in management at a personal level. This paper reports on the initial findings of a study of 158 nurses in management within the NHS in Scotland and addresses their demographic features and their management training/education pattern. It was found that the majority of respondents (77.8%) were working in their current position less than 4 years. There was a significant relationship between marital status and gender and current position (P < 0.05). A total of 58.8% of women in senior positions were single, on the other hand there was no single male respondent at a senior manager position. In total, 37 nurses in management (23.4%) had a degree qualification and there was a relationship between having a degree, age and current position. Overall, approximately half of the respondents had a formal management training qualification and only 10.1% (16 subjects) had a degree level management education. However, a large proportion (65.8%) of nurses in management believe that degree level education in management is required to be able to perform their work satisfactorily.

A database on dyspepsia.

A prospective study of dyspepsia was carried out in a primary referral hospital between 1974-1987 including 1540 patients of whom 1433 were seen as outpatients. The study protocol was agreed in advance and a structured questionnaire was used to elicit relevant clinical information: up to three diagnoses were permitted for each patient. The commonest principal diagnoses were duodenal ulcer (26%), functional dyspepsia (22%), and irritable bowel syndrome (IBS) (15%); alcohol related dyspepsia (4%) was as common as gastric carcinoma or symptomatic gall stones. Multiple diagnoses were common (31% given two diagnoses, and 6% given three) so that in all 2111 diagnoses were given to 1540 patients; the functional disorders (IBS and functional dyspepsia) considered together accounted for 39% of all diagnoses made. Whereas organic conditions were diagnosed by clinicians with confidence (63-98% considered 'certain'), even when given as the principal or first diagnosis IBS was considered 'certain' in only 61% and functional dyspepsia 48%. The demographic symptom data, together with information on tobacco and alcohol use, and work lost are described in detail.

Collecting, communicating and using information: the educational issues. A report from the Royal College of Physicians Committee on Medical Information Technology.

Few of the major advances in information science and technology have yet been successfully introduced in health care. Their implementation could improve both quality of care and the working environment of clinicians, but this will not be achieved by investing in hardware and software alone. Investment in education is also required.

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.

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.

The economic consequences of NSAID-induced gastropathy in the United Kingdom and commentary on the article by G. de Pouvourville.

The iatrogenic cost factor of treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) is defined as the increase in cost resulting from NSAID-induced gastroduodenal ulcers. The iatrogenic cost factor of NSAIDs for the National Health Service (NHS) in the United Kingdom was calculated using the model of de Pouvourville (1992). The cost factor is defined as the ratio of the shadow price of the NSAID to the NHS price. The shadow price is calculated from the incidence of NSAID-induced gastroduodenal ulcers and the costs of treating them and the price of the drugs. The NHS iatrogenic cost factors of 10 NSAIDs were similar to those calculated by de Pouvourville for the French national health insurance system, Assurance-Maladie, and ranged from 1.08 for diclofenac/misoprostol to 2.38 for ibuprofen.

Issues in the cross-national assessment of health technology.

With the growing international literature in economic evaluation and the rapid spread of new health technologies, there is a need to undertake, or at least interpret, economic evaluations on the international level. However, the ways in which cross-national differences affect the cost-effectiveness of health technologies or their evaluations have never been studied. This paper explores these issues by taking advantage of a unique situation in which the same economic evaluation of a new indication for a health technology was conducted simultaneously in four countries using an identical methodology. The study showed that if prior agreement on methods can be reached and local data applied, economic evaluations can be undertaken in a way that facilitates the extrapolation of results from country to country.

How accurate are SMR1 (Scottish Morbidity Record 1) data?

The accuracy of recording of data on SMR1 forms was reviewed for gastrointestinal diagnoses in the Greater Glasgow Health Board area and compared to previous studies. A total of 778 cases from 1987 formed the study sample and 761 (96.9%) were available for review. Recording on the SMR1 appears to have improved since 1971 and there were relatively few errors in the basic details. The crude agreement between DG1C data (primary diagnosis) and the casenote diagnosis was 560/761 (73.6%) with a Kappa statistic of 0.67. Agreement about the presence of arthritis (as a co-diagnosis) was poor so that uncritical use of SMR1 data might lead to serious underestimation of resource measures, such as length of stay, for patients with significant arthritis in addition to a gastrointestinal problem. In these data patients with arthritis found on casenote review and not recorded on the SMR1 had mean lengths of stay between 61% and 70% greater than patients without any evidence of significant arthritis.

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.