International trends in sales of inhaled fenoterol, all inhaled beta-agonists, and asthma mortality, 1970-1992.

To evaluate the hypothesis that fenoterol or all inhaled beta-agonists caused an epidemic of asthma mortality in New Zealand from the late 1970s to the mid-1980s, we examined trends from 1970 to 1992 in per capita sales of inhaled fenoterol, inhaled beta-agonists, and asthma mortality in New Zealand and nine other countries that marketed fenoterol. During the last two decades, there has been a large and widespread increase in sales of inhaled beta-agonists, including fenoterol. Asthma mortality in most countries, however, has been relatively stable. Only New Zealand experienced an epidemic of asthma mortality. In addition, sales rates of fenoterol similar in magnitude to those in New Zealand near the peak of the epidemic also occurred in Belgium, Austria, and Germany, while asthma mortality in these countries remained low. Also, sales rates of all beta-agonists in Australia were similar to those in New Zealand, but no epidemic of asthma mortality occurred in Australia. Therefore, the difference between asthma mortality rates in New Zealand and other countries is not explained by differences in per capita sales of fenoterol or all beta-agonists. Within New Zealand, the beginning and end of the epidemic correlated with a rise and fall in sales of all beta-agonists, including fenoterol. From 1980 to 1989, however, sales of fenoterol and all beta-agonists doubled in New Zealand while asthma mortality declined by 40%. International data on medication sales and asthma mortality, therefore, do not point to a relation between asthma mortality and beta-agonists in general nor fenoterol in particular.

The association between asthma drugs and severe life-threatening attacks.

OBJECTIVES: To measure the association between asthma drugs and death or ICU admission due to asthma (severe life-threatening attack of asthma [SLTA]), and to assess the possibility that these associations may not be causal but due to the prescription of these drugs to patients with more severe disease (confounding). DESIGN: Retrospective cohort study of 655 asthmatics who attended an emergency department in 1986 to 1987 followed till death or May 1989. METHODS: Outcome events were death or ICU admission due to asthma (SLTA). All hospital attendances were identified and patients classified at each according to drug exposure and a wide variety of measures of asthma severity. Incidence rates were computed as total outcome events divided by person-time contributed for each subject classified according to drug use and asthma severity. Rate ratio (RR) estimates for severe asthma outcomes associated with use as compared to nonuse of asthma drugs were calculated. Severity markers were identified and used to adjust the crude RR estimates. RESULTS: One hundred five SLTAs (15 deaths, 90 ICU admissions) occurred in 66 patients. Like inhaled fenoterol, oral beta-agonists, theophylline, cromolyn, inhaled steroids, and oral steroids were all associated with an increased risk of SLTA. When adjusted progressively for measures of severity, these increased risks became insignificant except for cromolyn. CONCLUSION: Unadjusted RR estimates for severe asthma events comparing exposure to a particular drug with nonuse are overestimates due to confounding. Control with two severity markers (hospital admission in the last year, use of oral corticosteroid at the time of previous admission) removes some confounding but control for additional severity markers not available in previous studies reduces the effect estimates further. These results suggest that the problem of confounding is substantial in nonrandomized epidemiologic studies of asthma drugs. Previous studies reporting RR estimates are likely to be confounded.

Characterisation of asthma management in the Fallon Community Health Plan from 1988 to 1991.

In order to characterise asthma management in a managed care setting, we identified 10,301 patients who were diagnosed with asthma between 1 January 1988 and 31 December 1991 at a group model health maintenance organisation in central Massachusetts, US. We obtained for these patients automated utilisation files containing data on medications, hospitalisations, emergency room visits, office visits, and estimated costs of these services. The medication dispensed to the greatest proportion of patients was beta 2 agonists either by inhalation (56%) or orally (21%). Theophylline was dispensed to 23% of the patients. Maintenance therapy was inhaled anti-inflammatory medication was uncommon, as inhaled corticosteroids (17%) and sodium cromoglycate (cromolyn sodium) [8%] were dispensed to fewer patients than other asthma medications. Among patients who had been hospitalised in the previous year, 36% were presently receiving inhaled corticosteroids, and among patients who used at least one beta 2 agonist metered-dose inhaler per month, 49% were presently receiving inhaled corticosteroids. Economic analyses showed that only 8% of the patients had either a hospital admission or an emergency room visit, but hospital costs among these patients accounted for 25% of the total costs of asthma care. In addition, the top 10% most expensive patients accounted for 42% of the total cost of asthma care. We conclude that a substantial proportion of patients at increased risk of a severe attack, by virtue of having a recent hospitalisation, do not receive maintenance anti-inflammatory therapy, and that hospitalisations among a relatively small proportion of asthma patients contribute significantly to the cost of asthma care.

Oral contraceptive type and functional ovarian cysts.

OBJECTIVE: We tested the hypothesis that multiphasic, low-dose monophasic, and high-dose monophasic oral contraceptives share a common protective effect against functional ovarian cysts. STUDY DESIGN: We conducted a cohort study using the automatic files of Maine Medicaid to assemble a population of 7462 women between the ages of 15 and 44 who were prescribed an oral contraceptive between Jan. 1, 1987, and Dec. 31, 1988. We included as cases 32 women with a principal diagnosis of a functional ovarian cyst confirmed by medical records as being greater than 20 mm in diameter. RESULTS: At comparison with the absence of an oral contraceptive prescription, we observed decreasing rates of functional ovarian cysts among women prescribed multiphasic pills (rate ratio 0.91, 95% confidence interval 0.3000 to 2.31), low-dose monophasic pills with less than or equal to 35 micrograms estrogen (rate ratio 0.52, 95% confidence interval 0.17 to 1.33), and high-dose monophasic pills with greater than 35 micrograms estrogen (rate ratio 0.24, 95% confidence interval 0.01 to 1.34). CONCLUSIONS: The protective effect of oral contraceptives against functional ovarian cysts reported previously for high-dose monophasic pills may be attenuated with newer pills of lower hormonal potency.

PIP: It was hypothesized that multiphasic, low-dose monophasic, and high-dose monophasic oral contraceptives (OCs) share a common protective effect against functional ovarian cysts. A cohort study using the automatic files of Maine Medicaid examined a population of 7462 women between ages 15-44 who were given an OC between January 1, 1987-December 31, 1988. Included as cases were 32 women with a principal diagnosis of functional ovarian cyst confirmed by medical records as being 20 mm in diameter. Among women prescribed multiphasic pills, there was a decreasing rate of functional ovarian cyst (rate ratio .91, 95% confidence interval .3000-2.31), low-dose monophasic pills with or=35 mcg estrogen (rate ratio .52, 95% confidence interval .17-1.33), and high-dose monophasic pills with 35 mcg estrogen (rate ratio .24, 95% confidence interval .01-1.34). The protective effects of OCs against functional ovarian cysts reported previously for high-dose monophasic pills may be attenuated with the newer pills with lower hormonal potency.