Collecting data on potentially harmful events: a method for monitoring incidents in general practice.

OBJECTIVE: The prediction and subsequent prevention of errors, which are an integral element of human behaviour, require an understanding of their cause. The incident monitoring technique was developed in the study of aviation errors in the Second World War and has been applied more recently in the field of anaesthetics. This pilot study represents one of the first attempts to apply the incident monitoring technique in the general practice environment. METHOD: A total of 297 GPs across Australia anonymously reported details of unintended events which harmed or could have harmed the patient. Reports were contemporaneously recorded on prepared forms which allowed a free text description of the incident, and structured responses for contributing and mitigating factors, immediate and long-term out-comes, additional costs etc. RESULTS AND DISCUSSION: The first 500 reports were analysed using both of qualitative and quantitative methods and a brief overview of results is presented. The methodological issues arising in the application of this technique to such a large, widely spread profession, in which episodes of care are not necessarily confined to a single consultation, are discussed. This study demonstrated that the incident monitoring technique can be successfully applied in general practice and that the resulting information can facilitate the identification of common factors contributing to such events and allow the development of preventive interventions.

Effects of misoprostol on the pharmacokinetics of indomethacin in human volunteers.

The effects of misoprostol (200 micrograms as a single dose or q.i.d. as a multiple dose) on the pharmacokinetics of indomethacin (100 mg single-dose administration or 50 mg t.i.d. multiple-dose administration) were studied in 16 healthy human volunteers under single-dose and steady-state conditions in a randomized, double-blind, placebo-controlled, balanced three-period study design. The overall absorption as shown by the values for area under the concentration curve of indomethacin was unaffected by concurrent administration of misoprostol. However, misoprostol did significantly enhance the steady-state maximum concentration of indomethacin by 32%. Thus misoprostol does not interfere with the absorption of indomethacin despite the known inhibitory effects of this protaglandin analog on acid secretion.

Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in patients with rheumatoid arthritis or osteoarthritis, and interim report on prevention by misoprostol of diclofenac associated lesions.

We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study.

Pharmacokinetics of misoprostol in the elderly, in patients with renal failure and when coadministered with NSAID or antipyrine, propranolol or diazepam.

The pharmacokinetics of misoprostol were examined in the following contexts: in coadministration with the nonsteroidal antiinflammatory agents (NSAID) aspirin, diclofenac, ibuprofen, indomethacin and piroxicam; in coadministration with agents extensively metabolized by the liver--i.e., antipyrine, propranolol and diazepam; in healthy elderly subjects; and in patients with various degrees of renal failure. No clinically important interactions between misoprostol and NSAID were observed. Similarly, no metabolic interactions between misoprostol and antipyrine, propranolol or diazepam were noted. Pharmacokinetic variable values in elderly subjects did not differ in a clinically significant manner from those in younger subjects. Finally, although values for some pharmacokinetic variables--maximum concentration of misoprostol acid, area under the concentration-time curve and elimination half-life--were increased in patients with renal failure compared with controls, these alterations do not warrant changes in misoprostol dosage. These factors are particularly relevant to safety of misoprostol administration in elderly individuals, who not only consume more NSAID than young adults, but are also more likely to have intercurrent nonarthritic illness requiring additional medication and potentially modifying drug kinetics.

Recent advances in defining the role of misoprostol in rheumatology.

Recent findings suggest that the prostaglandin E1 analog misoprostol may be associated with significant antiinflammatory and immunomodulatory effects. The addition of misoprostol to diclofenac significantly reduced the effective dose of the latter in the carrageenan acute inflammation rat model. A number of in vitro and animal studies have shown that misoprostol substantially increases the immunomodulatory effect of cyclosporine or steroids, and a study in renal transplant recipients revealed that the addition of this agent to cyclosporine and steroid treatment produced a significant improvement in renal function and a marked decrease in the incidence of graft rejection. Further, other recent data suggest that misoprostol may exert a protective effect against the damage to cartilage that appears to be induced by some nonsteroidal antiinflammatory drugs by decreasing the synthesis of cytokines. Further studies of misoprostol in these various contexts are warranted.

A multicenter international controlled comparison of two dosage regimens of misoprostol with cimetidine in treatment of gastric ulcer in outpatients.

In this double-blind, parallel-group multicenter study, patients with endoscopically proven gastric ulcers were randomly allocated to treatment with either 50 micrograms or 200 micrograms of misoprostol or 300 mg of cimetidine, each given four times daily for four weeks. Endoscopic, clinical and laboratory assessments were made before treatment and after four weeks; clinical and laboratory assessments were repeated at two weeks. In the Korean center, assessments were also made after six weeks and at eight weeks of treatment. Six hundred and thirty patients were studied. The three treatment groups were similar in age and occupation. However, the proportion of men in the misoprostol 50-micrograms, 200-micrograms and cimetidine 300-mg groups was 67%, 63%, and 59%, respectively. Therapeutic success was defined as complete healing of all ulcers, judged endoscopically. On an intent-to-treat basis, which includes all losses to follow-up and withdrawals as treatment failures, ulcer healing rates in the misoprostol 50-micrograms, 200-micrograms and cimetidine 300-mg groups were 39%, 51%, and 58%, respectively. In the Korean center, the healing rates were 38%, 64%, and 70%, respectively, after eight weeks of treatment. There was no statistically significant difference in the healing rates at four weeks between the misoprostol 200-micrograms and cimetidine 300-mg groups (P = 0.16). The healing rate with the misoprostol 200-micrograms dose was significantly better than with the 50-micrograms dose (P = 0.008). Cimetidine 300 mg relieved global pain significantly better than misoprostol 200 micrograms at two weeks (P = 0.047) but not at four weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter international controlled comparison of two dosage regimes of misoprostol and cimetidine in the treatment of duodenal ulcer in out-patients.

In this double-blind parallel group multicenter international study, patients with endoscopically proven acute duodenal ulcers were allocated randomly to treatment for four weeks with either misoprostol 50 micrograms, misoprostol 200 micrograms or cimetidine 300 mg, each given q.i.d.. Endoscopic, clinical and laboratory assessments were made prior to and after four weeks' treatment. A clinical assessment was also made at two weeks. 703 patients were recruited. The three treatment groups were similar with regard to age, sex and occupation. Therapeutic success was defined as complete healing of all ulcers on the basis of an endoscopic examination. On an intent to treat basis, which includes all losses to follow-up and withdrawals as treatment failures, the cure rates in the misoprostol 50 micrograms, misoprostol 200 micrograms and cimetidine groups were 41%, 60% and 67% respectively. There was no statistically significant difference between the misoprostol 200 micrograms and the cimetidine 300 mg groups (P = 0.11). Both were significantly better than the low dose misoprostol group (P less than 0.001). All three treatments were well tolerated and severe adverse events were rare.