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Biomedical subjects

F E Murray

Publications and source records attributed to F E Murray.

At least 19 recordsLinked to original sources

Diagnostic accuracy of magnetic resonance cholangiopancreatography and ultrasound compared with direct cholangiography in the detection of choledocholithiasis.

AIM: To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) and trans-abdominal ultrasound in the detection of choledocholithiasis, and to compare bile duct stone characteristics using endoscopic retrograde cholangiopancreatography (ERCP), MRCP and ultrasound. MATERIALS AND METHODS: Of 191 consecutive patients referred for diagnostic ERCP, choledocholithiasis was diagnosed in 34 patients using direct cholangiography. The latter took the form of ERCP (n = 29), intraoperative cholangiography (n = 3) or percutaneous transhepatic cholangiography (n = 2). All patients underwent MRCP and ultrasound examinations and their findings for choledocholitiasis were compared with those at direct cholangiography. Finally, in the 29 patients with choledocholithiasis diagnosed under ERCP, stone characteristics were compared across the three investigations of ERCP, MRCP and ultrasound. RESULTS: Compared with direct cholangiography, MRCP showed a sensitivity, specificity and diagnostic accuracy of 91%, 98% and 97%, respectively, in the diagnosis of choledocholithiasis. MRCP resulted in three false-negative and three false-positive findings, four of which occurred due to confusion with lesions at the ampulla. Ultrasound showed a sensitivity, specificity and diagnostic accuracy of 38%, 100% and 89%, respectively, in the diagnosis of choledocholithiasis. ERCP revealed a greater number of stones and these were more proximally distributed within the bile ducts when compared to MRCP. CONCLUSIONS: MRCP is highly accurate in the diagnosis of choloedocholithiasis and has the potential to replace diagnostic ERCP. MRCP underestimates the number of bile duct stones present.

Adult↗

The relationship between cyclooxygenase-2 expression and colorectal cancer.

CONTEXT: Epidemiological studies have implicated the inducible form of cyclooxygenase (COX-2) in the pathogenesis of colorectal cancer; however, its role is not fully understood. OBJECTIVE: To examine the relationship between the expression of COX-2 in human colorectal cancer and patient survival. DESIGN: Patients diagnosed as having colorectal cancer were evaluated and followed up for up to 9.4 years (median follow-up, 2.7 years). Tumor sections were stained for COX-2 using a rabbit polyclonal antibody raised against human COX-2. The extent of COX-2 staining was graded by 2 observers blinded to outcome. Preabsorption of the anti-COX-2 antibody with a COX-2 peptide abolished the staining, demonstrating the specificity of the assay. SETTING: Gastrointestinal unit of a large general teaching hospital in Dublin, Ireland. PARTICIPANTS: Seventy-six patients (median age, 66.5 years) with colorectal cancer (Dukes tumor stage A, n = 9; Dukes B, n = 30; Dukes C, n = 25; Dukes D, n = 12) whose diagnosis was made between 1988 and 1991. Fourteen normal colon biopsies were stained for COX-2 as controls. MAIN OUTCOME MEASURES: Survival in years following diagnosis compared by extent of COX-2 epithelial staining (grade 1, <1%; grade 2, 1%-19%; grade 3, 20%-49%; grade 4, > or = 50%), Dukes stage, tumor size, and lymph mode metastasis. RESULTS: COX-2 was found in tumor epithelial cells, inflammatory cells, vascular endothelium, and/or fibroblasts. The extent of epithelial staining was heterogeneous, varying markedly among different tumors. Normal tissue adjacent to the tumors also stained weakly for COX-2. No COX-2 was detected in control tissue samples. The Kaplan-Meier survival estimate was 68% in patients who had grade 1 tumor epithelial staining compared with 35% in those with higher grades combined (log-rank chi2 = 5.7; P = .02). Greater expression of COX-2 correlated with more advanced Dukes stage (Kendall tau-b, 0.22; P = .03) and larger tumor size (Kendall tau-b, 0.21; P = .02) and was particularly evident in tumors with lymph node involvement (Kendall tau-b, 0.26; P = .02). CONCLUSIONS: Our data indicate that COX-2 expression in colorectal cancer may be related to survival. These data add to the growing epidemiological and experimental evidence that COX-2 may play a role in colorectal tumorigenesis.

Aged↗

The diagnostic accuracy of magnetic resonance cholangiopancreatography and ultrasound compared with direct cholangiography in the detection of choledocholithiasis.

AIM: To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) and ultrasound (US) in the diagnosis of choledocholithiasis in a large group of patients with bile duct stones confirmed at direct cholangiography. Also, to compare bile duct stones confirmed at direct cholangiography. Also, to compare bile duct stone characteristics using the three different investigations, endoscopic retrograde cholangiopancreatography (ERCP), MRCP and US. MATERIALS AND METHODS: 191 patients (M:F, 76:115; mean age, 66 years; range, 24-92 years) were investigated by direct cholangiography, MRCP and US. Their final diagnosis as determined at direct cholangiography were choledocholithiasis (n = 34), strictures (n = 47) and normal ducts (n = 110). The direct cholangiographic methods used for diagnosis of choledocholithiasis were ERCP (n = 29), intraoperative cholangiography (n = 3) and percutaneous transhepatic cholangiography (n = 2). The bile duct stone characteristics were compared using ERCP, MRCP and US in the 29 patients in whom stones were exclusively diagnosed by ERCP. RESULTS: Compared with the final diagnosis, MRCP had a sensitivity, specificity and diagnostic accuracy of 91%, 98% and 97%, respectively, in the diagnosis of choledocholithiasis. MRCP resulted in three false-negative and three false-positive findings, four of which occurred due to confusion with lesions at the ampulla. US had a sensitivity, specificity and diagnostic accuracy of 38%, 100% and 89%, respectively, in the diagnosis of choledocholithiasis. ERCP diagnosed more stones and the stones were more proximally distributed within the bile duct at ERCP when compared with MRCP. CONCLUSION: MRCP has a high diagnostic accuracy (97%), similar to that at direct cholangiography, in the diagnosis of choloedocholithiasis. It has the potential to replace diagnostic ERCP and select patients with choledocholithiasis for therapeutic ERCP.

Adult↗

A prospective comparison of magnetic resonance cholangiopancreatography with endoscopic retrograde cholangiopancreatography in the evaluation of patients with suspected biliary tract disease.

AIM: To determine the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) compared with direct cholangiography in the detection of biliary tract disease. PATIENTS AND METHODS: MRCP was performed in 100 patients in whom direct cholangiographic correlation (ERCP, n = 98; PTC, n = 9; intraoperative cholangiography, n = 3) was available for comparison. The MRCP examinations were performed using a two-dimensional multi-slice, fast spin echo (FSE) technique and a local surface coil. The diagnoses at direct cholangiography were choledocholithiasis in 30 patients, benign and malignant strictures in 28 patients and normal bile ducts in 42 patients. The nature of the strictures (benign, n = 2; tumour, n = 18; lymphnode recurrence, n = 3; unknown histology, n = 5) was determined by one or more of the following procedures: surgery (n = 8), biopsy (n = 15), cytology (n = 6) and cross-sectional imaging/follow-up findings (n = 3). RESULTS: MRCP diagnosed choledocholithiasis with a sensitivity of 93%, specificity of 99% and accuracy of 97 %. It resulted in two false-negative and one false-positive findings when compared with direct cholangiography. MRCP accurately diagnosed the presence and level of strictures in all patients. The overall sensitivity, specificity and accuracy of MRCP in the detection of bile duct lesions were 97%, 98% and 97%, respectively. CONCLUSION: MRCP has a high diagnostic accuracy when compared with direct cholangiography in the detection of bile duct disease.

Adult↗

Prescription of acid-suppressing drugs in relation to endoscopic diagnosis: a record-linkage study.

BACKGROUND: Although widely used, few data are available on the appropriateness of prescribing of acid-suppressing drugs (ASDs), despite guidelines on the investigation and treatment of dyspeptic patients. METHODS: We created a database of 62 000 endoscopy examinations and record-linked these to a prescribing database. Endoscopic diagnoses were classified into peptic, nonpeptic and others. The H2-antagonists, omeprazole and misoprostol, were studied. RESULTS: 35 000 patients had one or more endoscopies during 1978-93; two-thirds were over 45 years of age at first endoscopy. A quarter of all patients who had been endoscoped had consistently normal examinations. Peptic oesophageal pathology was the commonest positive finding. A quarter of those prescribed ASDs between 1989 and 1993 had been endoscoped between 1978 and 1993. In those with a peptic diagnosis prescribed any ASD, the pathologies found were: oesophageal (42.9%), duodenal (36.3%) and gastro-pyloric (21.3%). Patients prescribed omeprazole were more likely to have undergone endoscopy than those prescribed other ASDs, and they were also more likely to have peptic oesophageal pathology. Long-term prescribing (>56 days per year) occurred in two-thirds of patients prescribed ASDs and 40% had at least one endoscopy. In those prescribed short-term ASDs, 20% had undergone at least one endoscopy. Peptic and nonpeptic endoscopic pathology was associated with increased ASD prescribing, but a normal endoscopy did not reduce prescribing. CONCLUSION: ASD prescribing appeared to be mainly symptom-driven. Positive endoscopic findings increased the prescribing of ASDs, but normal findings did not reduce it.

Aged↗

Protection of human gastric mucosa against aspirin-enteric coating or dose reduction?

BACKGROUND: Aspirin is widely used for cardiovascular prophylaxis. AIM: To compare the effectiveness of two widely-used strategies-dose reduction and enteric coating-for the minimization of gastric mucosal injury or toxicity. METHODS: Twelve healthy volunteers were studied. On four separate occasions each received, under blinded conditions, five daily doses of plain aspirin 300 mg, plain aspirin 75 mg, enteric-coated aspirin 300 mg or placebo. Ex vivo prostaglandin E2 synthesis was stimulated by the vortex mixing of gastric mucosal biopsies in Tris saline and measured by radioimmunoassay. Mucosal injury was quantified both by counting erosions and with a visual analogue scale. RESULTS: All three preparations reduced prostaglandin E2 synthesis by day five, by (median) 84% for plain aspirin 300 mg, by 80% for enteric coated aspirin 300 mg and by 63% for plain aspirin 75 mg. There was little mucosal injury prior to the start of each dose and period and no significant change with placebo. Plain aspirin caused a dose-dependent mucosal injury, with two (median, IQR 0-7) gastric erosions after five days of plain aspirin 75 mg, and 18 (2-26) after five days of plain aspirin 300 mg. With enteric-coated aspirin 300 mg there were 0 (0-1) gastric erosions (P = 0.003 compared to plain aspirin 300 mg P = 0.11, compared to plain aspirin 75 mg). CONCLUSION: Enteric coated aspirin reduces acute gastric mucosal injury to placebo levels, despite its inhibition of prostaglandin synthesis. Enteric coating is an appropriate strategy for the prevention of gastric mucosal damage induced by low-dose aspirin, which warrants systematic clinical evaluation.

Adult↗

The in vivo assessment of nimesulide cyclooxygenase-2 selectivity.

In man, nimesulide selectively inhibits cyclooxygenase-2 (COX-2) with little effect on haemostatic function or gastric prostaglandin formation. It causes significantly less gastrointestinal injury than naproxen, but has anti-inflammatory efficacy similar to that of naproxen and other currently available non-steroidal anti-inflammatory drugs. Naproxen suppressed arachidonic-acid-mediated platelet aggregation, reduced serum thromboxane B2 levels by 98% throughout the treatment period and reduced gastric mucosal prostaglandins (PGE2 and 6-keto-PGF1alpha) production by an average of 80%. This contrasts with nimesulide: platelet aggregation was not significantly affected, thromboxane B2 levels were only 29% lower and the gastric mucosal prostaglandins were inhibited in the order of approximately 20%. During the treatment period, both nimesulide and naproxen significantly inhibited COX-2-dependent PGE2 synthesis in the whole blood; however, naproxen had a lesser effect than nimesulide.

Anti-Inflammatory Agents, Non-Steroidal↗

Formulary management of proton pump inhibitors.

The management of dyspepsia has been radically altered by the discovery of the role of Helicobacter pylori and the advent of proton pump inhibitors (PPIs). The use of PPIs alone as antisecretory agents and as part of triple therapy regimens for H. pylori eradication accounts for a significant percentage of any healthcare system's drug budget. Thus, it is important to take into account a variety of factors when devising a formulary and considering which PPIs to include. Consideration of 3 factors are particularly crucial in this process, namely therapeutic efficacy, tolerability and cost but several other clinical and economic parameters should also be considered. The mechanisms of action of all 4 PPIs currently available (omeprazole, lansoprazole, pantoprazole and rabeprazole) are very similar, with any small differences in pharmacological properties unlikely to be of clinical significance. Therapeutic efficacy in patients with acute reflux oesophagitis is again very similar for all 4 PPIs at their standard dosages; all agents are superior to H2-antagonists. Data on maintenance therapy for reflux oesophagitis also suggest similar efficacy for omeprazole and lansoprazole; data on pantoprazole and rabeprazole are awaited. For the treatment of H. pylori-related ulcers, the consensus at present is for PPI-based triple therapy. Again, all PPIs seem equally efficacious for this indication but pantoprazole and rabeprazole have yet to receive licences for H. pylori eradication therapy (HPET) in most countries. Drug tolerability is another critical issue to consider in formulary inclusion decisions. As a class, the PPIs are well tolerated. Minor drug interactions are reported for omeprazole, lansoprazole and rabeprazole but not for pantoprazole. However, whether or not this is significant in clinical practice is open to debate. Most of the pharmacoeconomic data in these indicators, to date, relate to omeprazole and, to a lesser extent, lansoprazole. Certainly, the studies on these 2 drugs confirm the superior cost effectiveness of PPIs over H2-antagonists in the treatment of reflux oesophagitis and peptic ulceration in both the short and long-terms. Although data are awaited, there is no reason to suggest that this will be any different for pantoprazole and rabeprazole. PPI-based triple therapy for H. pylori eradication appears to be the most cost-effective treatment option for H. pylori-related peptic ulcer disease. It is clear that PPIs are superior in several regards to previously used medications in the treatment of dyspepsia. Which PPI(s) to include in a particular formulary is a more difficult decision. On review of many criteria involved in formulary decisions, differences between the individual PPIs appear minimal. The relative acquisition costs of the PPIs vary nationally and internationally and this may be a critical factor in formulary inclusion decisions. However, one should not ignore non-economic factors, as these should form the basis of any sound drug policies.

Anti-Ulcer Agents↗

Decision analysis of histamine H2-receptor antagonist maintenance therapy versus Helicobacter pylori eradication therapy: a randomised controlled trial in patients with continuing pain after duodenal ulcer.

BACKGROUND: Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease. However, most studies have analysed and emphasised H. pylori eradication rates rather than management/control of symptoms and the associated cost savings. Although H. pylori eradication therapy is very successful in clearing the infection, dyspeptic symptoms may persist and management of these can be expensive. OBJECTIVE: The aim of this study was to assess the cost implications in controlling symptoms using either H2-receptor antagonist maintenance therapy or H. pylori eradication therapy in patients with duodenal ulcer disease. DESIGN: This was a non-blind, prospective, randomised, parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H. pylori eradication therapy, with a 1-year follow-up. SETTING: This was a study of outpatients from general practices in Dundee, Scotland, or the Ninewells Hospital, Dundee, gastroenterology clinic. PATIENTS AND PARTICIPANTS: 119 patients with confirmed duodenal ulcer, free from active ulceration at study entry but positive for H. pylori infection, who were receiving maintenance H2-receptor antagonist therapy. INTERVENTIONS: Patients were randomised to receive either continuing maintenance therapy with ranitidine (initially 150 mg daily; 58 patients) or H. pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen (or omeprazole/clarithromycin if allergic to penicillin). MAIN OUTCOME MEASURES AND RESULTS: Overall, H. pylori eradication rates were 100% per protocol and 95.1% intention-to-treat. At completion of 1 year of follow-up, 12 of the 61 (19.7%) patients successfully eradicated of H. pylori were still dependent on acid suppression for symptom relief. H. pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year (168 Pounds vs 210 Pounds per patient; 1996 values). However, over time, post-eradication treatment costs were greater than H2-receptor antagonist therapy costs. Any potential savings were directly related to the proportion of patients needing further treatment post-eradication, the cost of endoscopy and the urea breath test. CONCLUSIONS: If dyspepsia persists long term, H. pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer.

Decision Support Systems, Clinical↗

Role of MR cholangiopancreatography in patients with failed or inadequate ERCP.

OBJECTIVE: The purpose of our study was to evaluate the usefulness of MR cholangiopancreatography in the diagnosis and further treatment of patients with failed or inadequate ERCP. SUBJECTS AND METHODS: Fifty-eight patients with failed or inadequate ERCP underwent MR cholangiopancreatography using a two-dimensional heavily T2-weighted multislice fast spin-echo technique. The final diagnosis was made on the basis of a second ERCP (n = 4), percutaneous transhepatic cholangiopancreatography (n = 19), intraoperative cholangiography (n = 6), percutaneous biopsy (n = 3), surgical findings (n = 5), or clinical follow-up (n = 21) for a mean period of 22 months (range, 7-31 months). RESULTS: MR cholangiopancreatography was technically successful in 57 patients and resulted in a sensitivity, specificity, and diagnostic accuracy of 97.1%, 100%, and 98.2%, respectively. Overall, MR cholangiopancreatography gave clinically useful information that contributed to patient management in 56 (96.6%) of the 58 patients. On the basis of the MR cholangiopancreatography findings, patients were managed using a second ERCP (n = 4), combined percutaneous and endoscopic procedure (n = 2), percutaneous biliary stent insertion (n = 13), surgery (n = 12), chemotherapy (n = 1), or conservative treatment (n = 24). CONCLUSION: MR cholangiopancreatography was found to have a unique and valuable role in the investigation of patients in whom ERCP failed or was inadequate. MR cholangiopancreatography helped us avoid using invasive procedures such as percutaneous transhepatic cholangiography in the diagnosis of bile duct disease after failed ERCP.

Adolescent↗

H2-antagonist maintenance therapy versus Helicobacter pylori eradication in patients with chronic duodenal ulcer disease: a prospective study.

BACKGROUND: Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H2-antagonist therapy in duodenal ulcer disease. AIM: To examine prospectively the efficacy of H. pylori eradication therapy with ranitidine maintenance therapy over 1 year in patients with confirmed chronic duodenal ulcer. METHODS: One hundred and nineteen patients with active H. pylori infection were randomized to receive ranitidine, 150 mg/day initially (58 patients), or omeprazole, 40 mg/day, amoxycillin 2 g/day and metronidazole 1.2 g/day for 14 days, or omeprazole 40 mg/day and clarithromycin 1.5 g/day, for 14 days (if penicillin-allergic). Symptoms were assessed using the Gastrointestinal System Rating Scale (GSRS) and SF36 quality of life index. RESULTS: 13C urea breath testing confirmed overall treatment success in 100% of patients (58/58) per protocol and 95.1% (58/61) on an intention-to-treat basis. At 4 and 12 months there were no differences in any GSRS symptoms between treatment groups. SF36 analysis showed a perceived health improvement at 4 and 12 months in patients who received H. pylori eradication. However, despite successful H. pylori eradication, one-fifth of patients still required antisecretory therapy. CONCLUSION: Following successful H. pylori eradication, chronic duodenal ulcer patients were at least as well symptomatically as when taking maintenance ranitidine. They perceived that their health had improved, but a subgroup was still acid-suppression dependent.

Adolescent↗

Changes in liver histopathology in women infected with hepatitis C through contaminated anti-D immunoglobulin injections in Ireland.

OBJECTIVE: To evaluate histological findings in untreated chronic hepatitis C patients at diagnosis 17 years after infection and to assess histological progression on repeat liver biopsy 2 years later. PATIENTS: Thirty patients infected with hepatitis C virus (HCV), genotype 1b, by contaminated anti-D immunoglobulin in Ireland in 1977 were studied. These patients were diagnosed in 1994 for the first time. All patients were positive for HCV-RNA by polymerase chain reaction (PCR). METHODS: Each patient underwent two liver biopsies approximately 2 years apart 17 and 19 years after initial infection. The liver biopsies were scored by two pathologists by the modified histological activity index using a numerical score. At first liver biopsy at time of presentation, eight patients had normal alanine aminotransferase (ALT), four had an ALT of more than 100 IU/I and 18 had an ALT level between 40 and 100 IU/I. RESULTS: In the initial (1994) biopsies, the median grade (inflammation) was 5/18, range 1-9 and the median stage (fibrosis) was 2/6, range 0-6. One patient showed cirrhosis (stage 6/6) and six patients (20%) had developed moderate fibrosis (stage 3-4/6). On the repeat biopsy, 2 years later, median grade (inflammation) was 5/18, range 2-9 and stage (fibrosis) was 1/6, range 0-6. CONCLUSION: This group of patients, infected with HCV genotype 1b and untreated for 19 years, allows evaluation of the natural history of this virus. The majority of patients showed mild chronic hepatitis. Only one patient had developed cirrhosis. There was no significant histological disease progression between the two biopsy specimens over a 2 year period. The results suggest that the prognosis in such cases could at least be guardedly optimistic and that sequential liver biopsy may be performed less frequently.

Adult↗

Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies.

We report a patient with clinical, biochemical and immunological indices suggestive of autoimmune hepatitis with marked transaminasaemia, raised immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A coagulation screen revealed a transient, markedly increased, activated, partial thromboplastin time and a normal prothrombin time, with elevated levels of anticardiolipin antibodies and the presence of lupus anticoagulant, indicating the presence of antiphospholipid antibodies. Subsequent histology confirmed moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune therapy was commenced. This presentation illustrates the rare association of anti-phospholipid antibodies with autoimmune chronic active hepatitis presenting with a temporarily abnormal coagulation screen.

Actins↗

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.

Age Factors↗

A cohort study (with re-sampled comparator groups) to measure the association between new NSAID prescribing and upper gastrointestinal hemorrhage and perforation.

This cohort study examined the relationship between newly prescribed NSAIDs (none in the previous six months) and upper gastrointestinal hemorrhage and perforation in Tayside, Scotland. Exposure was classified by prescription duration. The study population consisted of the population of Tayside. A Comparator Group was chosen at random (within age and sex strata). Two hundred re-sampled comparator groups were created. Statistical analyses were carried out by Poisson regression (repeated for each of the re-samples). The analyses controlled for age, sex, prior hospitalization for upper gastrointestinal events, prior endoscopy, and the use of ulcer healing drugs. There were 78,191 subjects in the NSAID group, and 78,207 in each of the comparator groups. The increased risk with NSAIDs was only apparent for subjects without a history of upper gastrointestinal events; univariate rate ratio = 2.76 (1.90, 4.01). The final, re-sampled estimate of NSAID risk was rate ratio = 2.48 (1.87, 3.29).

Adult↗

Omeprazole is more effective than cimetidine for the relief of all grades of gastro-oesophageal reflux disease-associated heartburn, irrespective of the presence or absence of endoscopic oesophagitis.

BACKGROUND: Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis, but excluded the substantial group of gastro-oesophageal reflux disease (GERD) patients with reflux symptoms but without endoscopic abnormality. This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis. METHODS: A total of 221 patients with heartburn and oesophageal mucosa grade 0 (normal, n = 51), 1 (no macroscopic erosions, n = 52), 2 (isolated erosions, n = 97) or 3 (confluent erosions, n = 21) were randomized to receive double-blind either omeprazole 20 mg daily or cimetidine 400 mg q.d.s. for a period of 4 weeks. Those still symptomatic after 4 weeks of treatment received omeprazole 20 mg daily for a further 4 weeks. RESULTS: There was no correlation between severity of heartburn and endoscopic grade at entry (correlation coefficient = 0.196). After 4 weeks of treatment, the proportion of patients in whom heartburn was controlled (no more than mild symptoms on no more than 1 day in the previous 7) on omeprazole (66%; 74/112) was more than double that on cimetidine (31%; 34/109) (P < 0.0001). There was no significant difference between the relief of heartburn in the 47% of patients without unequivocal oesophagitis (endoscopic grade 0 or 1) and in the 53% of patients with erosive oesophagitis (grade 2 or 3) (P = 0.31). Only treatment with omeprazole (P < 0.0001) and lower severity of heartburn at entry (P < 0.01) were significant in predicting heartburn relief. Amongst those patients requiring an additional 4 weeks of treatment with omeprazole, 67% (54/81) reported that their heartburn was controlled after 8 weeks of treatment. CONCLUSION: We conclude that omeprazole is superior to cimetidine for the relief of all grades of heartburn in GERD, whether or not the patient has unequivocal endoscopic oesophagitis.

Adolescent↗

Helicobacter pylori infection status in relation to antibiotic and non-steroidal prescribing in patients on maintenance treatment for chronic duodenal ulcer.

UNLABELLED: It has been suggested that establishing Helicobacter pylori infection status is irrelevant prior to H. pylori eradication treatment in chronic duodenal ulcer, as virtually all may benefit from therapy. OBJECTIVE: The aim of the present study was (i) to determine the prevalence of active H. pylori infection in patients with proven chronic duodenal ulcer on long-term H2-antagonist prophylactic treatment and whether knowledge of this would influence the use of eradication therapy and (ii) to assess other factors which might influence the clinical diagnosis or H. pylori status, such as non-steroidal and antibiotic use. METHODS: One hundred and forty-five patients receiving long-term H2-antagonists for chronic duodenal ulcer were recruited. Their case records and a prescribing database were reviewed. Patients underwent endoscopy with biopsies for rapid urease test, histology and H. pylori culture. Serum was immunoblotted and an enzyme-linked immunosorbent assay for H. pylori was performed. RESULTS: Of the 145 patients, 128 (88%) were H. pylori biopsy positive. Twelve of the 17 H. pylori biopsy-negative patients had anti-H. pylori immunoglobulin G (IgG) antibodies and 10 of the 17 H. pylori-negative patients had previously received antibiotics for other indications. Nine patients were exposed to non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) and one had additional aspirin exposure. CONCLUSION: Only 11.7% of patients on maintenance treatment for chronic duodenal ulcer had no current infection with H. pylori, although more than 70% of these had serological evidence of previous infection. Confirmation of active infection may be indicated where there is a history of NSAID or antibiotic exposure and may result in more precise targeting of eradication therapy, thus avoiding unnecessary and potentially hazardous treatment.

Adult↗