Mortality study of 18 000 patients treated with omeprazole.

BACKGROUND: The long term safety of potent gastric acid suppressive therapy has yet to be established. METHOD: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993-1995. Death rates were compared with general population rates. RESULTS: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34-1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58-2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13-1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12-1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87-3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60-6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84-2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19-2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20-10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62-4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett's disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17-4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37-2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25-1.80)). No relationships were detected with numbers of omeprazole scripts received. CONCLUSIONS: Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration.

Review article: over-the-counter drugs and the gastrointestinal tract.

An increasing number of drugs are becoming available over-the-counter, empowering patients to treat them- selves. Although drugs presently available over-the-counter are generally safe, there are issues of safety and possible delays in diagnosis of serious conditions. Therefore it is vital that patients are made aware of the indications and limitations of over-the-counter drugs through improved communication and education. Pharmacists and drug companies will have an increasingly important role in giving information and advice to patients. This review looks at the present and future of over-the-counter medication, highlighting the safety aspects.

Provision of ERCP services and training in the United Kingdom.

BACKGROUND AND STUDY AIMS: A rising demand for hands-on training in endoscopic retrograde cholangiopancreatography (ERCP) has coincided with a need for increased scrutiny of outcomes (clinical governance) and the development of less invasive methods of pancreaticobiliary imaging. We surveyed the current provision of ERCP facilities and training throughout the United Kingdom. METHODS: Questionnaires were sent to senior endoscopists in 252 acute hospitals and to 500 trainees in gastroenterology. RESULTS: Completed forms were returned from 180 hospitals (a 71% response rate) and from 233 trainees (a 47% response rate). A median of 210 ERCPs per year are carried out at each centre (range 40-1000), under the supervision of 345 senior endoscopists. ERCP training had been started by 163 trainees (70%), of whom 42 (26%) had been given one or fewer procedures to start per week. Trainees rated their training as excellent (25%), good (28%), adequate (24%) or inadequate (22%); 193 (83%) perceived that they needed training in ERCP to ensure that future career opportunities were not denied to them. CONCLUSIONS: Some centres have insufficient capacity for training in ERCP. Some form of preselection for both trainers and trainees may be required to ensure that quality is maintained. Gastroenterology training programmes should move away from encouraging all trainees to learn ERCP, and should promote the acquisition of alternative skills.

Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs.

AIMS: To determine risk factors for peptic ulcer bleeding other than non-steroidal anti-inflammatory drugs (NSAIDs). Methods-Data on possible antecedent risk factors obtained in a large case control study of 1121 patients admitted to hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth with bleeding peptic ulcers were compared with the same information obtained in 989 population controls. Data were analysed by logistic regression with the calculation of odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From a logistic regression model, oral anticoagulants (OR 7. 8; 95% CI 2.8-21.5), previous peptic ulcer (3.8; 2.6-4.9), treatment for heart failure (5.9; 2.3-13.1), oral corticosteroid use (2.7; 1. 3-4.5), treatment for diabetes (3.1; 1.2-4.3), and current smoking (1.6; 1.2-2.0) were all independent risk factors. No association was found with use of calcium channel antagonists. Odds ratios for concomitant NSAID usage were multiplicative with the exception of current smoking. CONCLUSIONS: Some 45% of admissions for peptic ulcer bleeding in England and Wales in those aged 60 or more are calculated to be attributable to, or associated with, these accessory risk factors, which, together with those associated with aspirin or other NSAID use will account for over 80% of predisposing factors to ulcer bleeding.

Guidelines for the management of dyspepsia.

Dyspepsia is a common problem necessitating strategies for investigation and management because of the scarcity of available resources for investigation, i.e. endoscopy, and the need to focus on those at risk of serious disease. It is agreed that those in the older age group, with the presence of alarm symptoms or non-steroidal anti-inflammatory drug use require prompt endoscopy, but there remains a significant proportion of patients in whom the underlying diagnosis is unclear, presenting a management problem. Unfortunately, no universally applicable approach to investigation and management is available. Each major community needs to modify its guidelines for the management of dyspepsia based upon such factors as the local incidence of organic disease, prevalence of Helicobacter pylori infection and lifestyle. Endoscopy off acid suppressive therapy remains the only way of making a certain diagnosis. A diagnosis of gastrooesophageal reflux disease can now be made confidently by endoscopy, with selective use of 24 h pH study of the lower oesophagus. The same cannot be said for other groups with dyspepsia where symptoms alone are a poor guide to diagnosis. Evidence is beginning to emerge, however, that further stratification of dyspeptics on the basis of symptoms and other risk factors, e.g. H. pylori status, may help in management. In addition, there is a clinical need for accurate, inexpensive tests of foregut motility. Integrating clinical data with specific investigation in dyspepsia is required in order for the practising clinician to better define the dyspeptic so that patients can be managed effectively and simply.

Postmarketing surveillance of the safety of cimetidine: 15-year mortality report.

The pattern of mortality after 15 years of observation is reported among almost 10,000 patients who were taking cimetidine when they were first recruited between 1977 and 1980. Many took the drug for a number of years, some switching to other antisecretory agents as the study progressed. The findings are reassuring and provide no evidence of any long-term adverse effects of cimetidine which might be detected by monitoring mortality rates. The data have also been used to examine the possible positive relationships between aluminium ingestion and Alzheimer's disease and H. pylori infection and ischaemic heart disease. No significant evidence was obtained in support of the existence of these relationships.

Helicobacter pylori and non-steroidal anti-inflammatory drugs: lone agents or partners in crime?

A variety of mechanisms are responsible for the gastric and duodenal mucosal injury known to result from the consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Many of these mechanisms may be influenced by coexistent infection with Helicobacter pylori. However, evidence of increased risk from NSAIDs in patients with this bacterium is contradictory. While some authors have reported that symptoms, severity and prevalence of mucosal damage are higher in H. pylori-positive individuals taking NSAIDs than in those who are H. pylori negative, others have noted no significant difference. Reasons for this conflict may include the age of the subjects studied, duration of treatment, toxicity of the NSAID employed and pathogenicity factors related to different strains of H. pylori.

Prophylactic aspirin and risk of peptic ulcer bleeding.

OBJECTIVE: To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less. DESIGN: A case-control study with hospital and community controls. SETTING: Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth. SUBJECTS: 1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls. RESULTS: 144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently. CONCLUSION: No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.

The role and limitations of H2-receptor antagonists in the treatment of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux disease (GERD) occurs in up to 44% of adults in the USA. Most individuals do not seek medical help, self-medicating with antacids. Manifestations of GERD range from symptoms without oesophagitis, which constitute the bulk of patients who self-medicate, to active oesophagitis and then to complications such as stricture and ulceration. It is the more severe cases who tend to come to the gastroenterologist, but it must be remembered that reflux symptoms are probably around 5-10 times more common than actual oesophagitis. Since acid in the refluxate is responsible for the bulk of the symptoms and mucosal damage, antacids are often used for quick relief--which of course may not be sustained. More prolonged suppression of acid secretion, such as by a histamine H2-receptor antagonist (H2RA) or a proton pump inhibitor (PPI), is required to give long-lasting symptomatic relief and heal any inflammatory change. H2-receptor antagonists inhibit acid secretion with an effect that lasts for 4-8 h with a single dose, decreasing stimulated acid secretion by around 70%. When treating oesophagitis, the H2RAs suffer from the disadvantage of their relatively short duration of action (compared with PPIs), development of tolerance, and incomplete inhibition of acid secretion in response to a meal. Therefore, it is not easy for the H2RAs to achieve optimum conditions for healing the more severe forms of oesophagitis--even very high doses may fail. In mild GERD the H2RAs have been shown to be effective in relieving symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspepsia update.

BACKGROUND: Non-Ulcer Dyspepsia (NUD) is a very common problem which has many causes. Trying to group dyspeptic patients according to symptoms has been proposed in order to improve our understanding of the problem and to aid both clinical trials and indeed practice by studying and treating homogeneous groups. REVIEW: The literature has been reviewed to see if sub-groups of dyspepsia are standing up to scrutiny and clinically relevant. RESULTS: Reflux-like dyspepsia may now be identified accurately in a high proportion by a combination of careful history and the use of intra-oesophageal 24-h pH monitoring. Acid suppressing therapy is often useful in this group. Dysmotility-like dyspepsia is currently an area of active investigation with growing evidence that there is abnormal gastric emptying. Response to pro-kinetic drugs looks encouraging. Ulcer-like dyspepsia: Appears to be the largest dyspeptic group. Acid secretion is normal. Helicobacter pylori does not correlate with any group of dyspepsia. CONCLUSION: Separating NUD into groups is becoming useful in both investigation and treatment, but more specific simple tests are needed to take this further.

'Quick and clean': authoritative health technology assessment for local health care contracting.

Commissioners of health care require rapid, accurate and usable information on health technology effectiveness to help them to decide on the content of contracts. Despite major strides in the national initiatives in health technology assessment, such information is still in short supply at the local level. In 1991 the former Wessex region (now in the new South and West Region) established a mechanism which continues to provide carefully established recommendations on new technologies. Its features include: identification of locally important topics for evaluation by the purchasers and the providers; an evaluation team, working to a well-defined format in a service-led academic institute; an arbitration committee to deliver recommendations to purchasers on the basis of both the cost-utility of proposals and the quality of the evidence; and implicit obligations for purchasers to respond to strong recommendations.

Health technology assessment and gastroenterology.

Too much clinical practice is based on unproved opinion. Health technology assessment (HTA) encourages critical review of the literature in a particular area, from which an objective assessment can be made so that clinical practice may be more scientifically based. Only a small number of centers undertake this type of work, usually at a national level. We have been able to set up a more local HTA system (the Wessex Development and Evaluation Committee) with links to clinicians and both providers and purchasers of health care within a region of 3 million people. All aspects of medicine may be reviewed and discussed by the committee; 3 examples from within the field of gastroenterology are summarized herein. Active participation of a university-based institute to provide the reviews is essential. A local HTA facility confers a number of advantages.