Are preventive drugs preventive enough? A study of patients' expectation of benefit from preventive drugs.

OBJECTIVES: The study aimed to find the threshold of benefit for a hypothetical cholesterol-lowering drug below which the subject would not be prepared to take the drug. We also looked at whether proximity to the target event (myocardial infarction) and the subjects' views on drug taking affected this threshold. DESIGN: We studied 307 subjects using a written questionnaire and interview. Group 1 (102 subjects) had just been discharged from the coronary care unit. Group 2 (105 subjects) were taking cardio-protective drugs but had no recent history of myocardial infarction. Group 3 (100 subjects) had no history of myocardial infarction and were taking no cardio-protective drugs. RESULTS: Median values for the threshold of benefit below which the subject would not take the preventive drug were 20%, 20%, and 30% absolute risk reduction for Groups 1, 2 and 3 respectively. Median values for expectation of average prolongation of life were 12, 12 and 18 months respectively. Only 27% of subjects would take a drug offering 5% or less absolute risk reduction over five years. Subjects' views on medicinal drug taking in general and proximity to the target event were predictors of the acceptance of preventive drugs. Eighty percent of subjects wished to be told the numerical benefit of a preventive drug before starting on it. CONCLUSION: For the majority, the expectation of benefit from a preventive drug is higher than the actual benefit provided by current drug strategies. There is a tension between the patient's right to know about the chance of benefiting from a preventive drug and the likely reduction in uptake if they are so informed.

Lansoprazole is superior to ranitidine as maintenance treatment for the prevention of duodenal ulcer relapse.

AIM: To compare lansoprazole 30 mg once daily, lansoprazole 15 mg once daily and ranitidine 150 mg once nightly in the prevention of duodenal ulcer relapse in patients whose duodenal ulcers had been previously healed with lansoprazole 30 mg once daily or ranitidine 300 mg nightly. METHODS: A double-blind, parallel group, randomized multicentre study conducted in 33 centres in the UK, Eire, Sweden and Australia. Two hundred and nineteen patients with a duodenal ulcer were randomized to receive lansoprazole 30 mg and 217 to receive ranitidine 300 mg for 8 weeks. Patients were then re-randomized to receive lansoprazole 30 mg (122 patients), lansoprazole 15 mg (121 patients) or ranitidine 150 mg (116 patients) for 12 months. All patients had an endoscopically-proven duodenal ulcer at baseline and were considered suitable for long-term maintenance therapy to prevent relapse. RESULTS: Significantly more patients were healed on lansoprazole (98%) compared to ranitidine (89%) (P < 0.001, Fisher's exact test). Lansoprazole provided more rapid symptom relief than ranitidine. Lansoprazole 30 mg and lansoprazole 15 mg increased the probability of not relapsing in comparison to ranitidine (P = 0.001 and 0.06, respectively, life-table analysis). Relapse rates over the 12 months were lower in the lansoprazole treatment groups (lansoprazole 30 mg, 5%; lansoprazole 15 mg, 12%; and ranitidine, 21%; lansoprazole 30 mg vs. ranitidine 150 mg, P = 0.002). Symptoms were well controlled in both groups during the maintenance phase. All treatments were well tolerated with no major differences seen in adverse event profiles between treatment groups. CONCLUSIONS: Both doses of lansoprazole (30 mg and 15 mg) were superior to ranitidine 150 mg in the prevention of duodenal ulcer relapse. Lansoprazole was superior to ranitidine in terms of symptom control and duodenal ulcer healing. Both treatments were well tolerated.

Successful medical treatment of peptic pyloric stenosis: Dr Sippy revisited.

BACKGROUND: Surgery and balloon dilatation are perceived by many as the principal treatments for peptic pyloric stenosis. We questioned whether, with the availability of modern acid suppressant treatment, this was still appropriate or whether patients could be managed with medical treatment alone. METHODS: Seventeen consecutive patients with peptic pyloric stenosis were treated with endoscopic gastric drainage, followed by oral omeprazole in 15 or cimetidine in two. Gastric emptying half times for solids and liquids were assessed in 11 of the 17 patients when they had become asymptomatic. RESULTS: Endoscopic drainage and medical treatment successfully relieved symptoms in all 17 patients, although the gastric emptying studies in 11 patients still showed prolongation in eight. Symptoms resolved completely after a mean of 28 days. Five patients relapsed when changed from omeprazole to cimetidine treatment, but all responded to re-starting omeprazole. Four patients remain well on cimetidine alone. CONCLUSIONS: Medical treatment preceded by endoscopic gastric drainage was effective in all patients in this series and may be the preferred choice of treatment in patients with pyloric stenosis.

The one-stop dyspepsia clinic--an alternative to open-access endoscopy for patients with dyspepsia.

The most sensitive investigative tool for the upper gastrointestinal tract is endoscopy, and many gastroenterologists offer an open-access endoscopy service to general practitioners. However, for patients with dyspepsia, endoscopy is not always the most appropriate initial investigation, and the one-stop dyspepsia clinic allows for different approaches. We have audited, over one year, the management and outcomes of patients attending a one-stop dyspepsia clinic. All patients seen in the clinic were included, and for those not endoscoped the notes were reviewed one year after the end of the study to check for reattendances and diagnoses originally missed. Patients' and general practitioners' views of the service were assessed by questionnaire. 485 patients were seen, of whom 301 (62%) were endoscoped at first attendance. In 66 patients (14%), endoscopy was deemed inappropriate and only one of these returned subsequently for endoscopy. 118 patients (24%) were symptom-free when seen in the clinic and were asked to telephone for an appointment if and when symptoms recurred; half of these returned and were endoscoped. Oesophagitis and duodenal ulcer were significantly more common in this 'telephone endoscopy' group than in those endoscoped straight from the clinic. Overall, 25% of patients referred were not endoscoped. Important additional diagnoses were made from the clinic consultation. General practitioners and patients valued the system, in particular the telephone endoscopy service. 84% of general practitioners said they would prefer the one-stop dyspepsia clinic to open-access endoscopy.

Is respiratory sinus arrhythmia present in atrial fibrillation? A study using two quantitative methods.

Two quantitative techniques have been evaluated to examine whether respiratory sinus arrhythmia can be detected in atrial fibrillation. Cyclical changes in heart rate during deep breathing indicating respiratory sinus arrhythmia were seen in 11/15 control patients, but only 1/44 patients with atrial fibrillation. Power spectrum analysis suggested that more subtle variations in heart rate with breathing may be present in some patients with atrial fibrillation where it was not detectable by simpler techniques. These results support the hypothesis that although respiratory sinus arrhythmia is not detectable in atrial fibrillation by conventional means, there may still be some mediation of heart rate either by vagal or extravagal mechanisms.

Open access endoscopy: is the lost outpatient clinic of value?

To test the value of an outpatient visit in patients with dyspepsia, 79 patients considered suitable for open access endoscopy by their general practitioners were instead seen in the medical outpatient clinic first. In 35 patients immediate endoscopy was seen as an inappropriate investigation and 23 of these were spared endoscopy. In 11 patients important extra diagnoses were made in the clinic which would have been delayed or missed had the patients been sent straight for open access endoscopy. Sixty-eight per cent of patients, when asked by questionnaire, said they preferred to be seen in the clinic first rather than come for open access endoscopy. These results lend support to the traditional medical clinic appointment followed by endoscopy if and when appropriate rather than the open access endoscopy system.

The neuroleptic malignant syndrome: a missed diagnosis?

The neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to major tranquilizer drugs characterised by hyperpyrexia, extrapyramidal disorders and altered consciousness. First described in 1968 by Delay and Deniker, early case reports suggested a mortality of between 20 and 30%. Though the syndrome is now more widely recognised, the diversity of its clinical features may not always be appreciated and may lead to diagnostic confusion with other, more common, disorders. We report on two severe cases of NMS: in the first the diagnosis was initially thought to be sepsis from a urinary tract infection, and in the second the primary clinical diagnosis was of a mid brain infarction.

A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma.

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.

Neuropathy and fatal hepatitis in a patient receiving amiodarone.

Muscle weakness, neuropathy, and transient rises in hepatic enzyme activity have been reported with the use of the antiarrhythmic agent amiodarone. A 68 year old teetotaller with normal liver function was given amiodarone for resistant supraventricular arrhythmias. He presented 19 months later with vomiting, muscle weakness and wasting, sensory neuropathy, and hepatomegaly. Liver biopsy showed fibrosis and the presence of hyaline. The amiodarone was withdrawn. Three months later he developed ascites. Oesophageal varices were found and he later died. The liver showed micronodular cirrhosis. The large volume of distribution and long half life of amiodarone may explain the persistence of toxicity, which may have been aggravated by simultaneously administered doxepin in this case. Amiodarone should be withdrawn if abnormal liver function or neuropathy develops.

Splenic atrophy in adult coeliac disease: is it reversible?

A study of splenic function in 28 patients with adult coeliac disease showed no significant correlation between the half life of heat-damaged red cells and either the duration of pre-treatment exposure to gluten or the length of time on a gluten free diet. A significant correlation was found between splenic size and duration of treatment; those patients who had been taking a gluten free diet for the longest time had the smallest spleens. Blood films from 11 of these 28 patients taken before treatment with a gluten free diet were compared with those taken between two and 15 years after the start of treatment. There was no tendency for the hyposplenic changes to regress. In the majority, the changes became more prominent despite strict adherence to the gluten free diet. These findings suggest that splenic atrophy in adult coeliac disease is not reversed by treatment with a gluten free diet and is unlikely to be related to the state of the jejunal mucosa or the duration of initial exposure to gluten.