D. W. Kaufman

Prevalence and characteristics of opioid use in the US adult population.

&NA; This report describes the prevalence of opioid use in the US adult population, overall and in subgroups, the characteristics of opioid use, and concomitant medication use among opioid users. Data were obtained from the Slone Survey, a population‐based random‐digit dialing survey. One household member was randomly selected to answer a series of questions regarding all medications taken during the previous week. There were 19,150 subjects aged ⩾18 interviewed from 1998 to 2006. Opioids were used ‘regularly’ (⩾5 days per week for ⩾4 weeks) by 2.0%; an additional 2.9% used opioids less frequently. Regular opioid use increased with age, decreased with education level, and was more common in females and in non‐Hispanic whites. The prevalence of regular opioid use increased over time and was highest in the South Central region. Nearly one‐fifth of regular users had been taking opioids for ⩾5 years. Concomitant use of ⩾10 non‐opioid medications was reported by 21% of regular opioid users compared to 4.5% of subjects who did not use opioids. Regular opioid users were more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally‐representative telephone survey, we estimate that over 4.3 million US adults are taking opioids regularly in any given week. Information on the prevalence and characteristics of use is important as opioids are one of the most widely prescribed classes of drugs in the US.

ORAL-CONTRACEPTIVE USE IN RELATION TO MYOCARDIAL INFARCTION

The effect of oral-contraceptive use on the risk of myocardial infarction and, in particular, the possible accentuation of that effect by cigarette smoking, was investigated in 234 premenopausal women with a first infarction and 1742 hospital controls. The overall rate ratio estimate of acute myocardial infarction for women who had used oral contraceptives in the preceding month was 4.0 (95% confidence interval, 2.5--6.3). Women who smoked heavily and used oral contraceptives had a point estimate of 39 (lower two-sided 95% confidence limit, 22) compared with those who did neither. This value was appreciably larger than could be accounted for by the separate effects of cigarettes and oral contraceptives, and this suggests a considerable accentuation by cigarette smoking of the effect of oral contraceptive use on myocardial infarction.

Cigarette smoking and age at natural menopause.

In a cohort of 656 naturally postmenopausal women who were interviewed at age 60 to 69 years, and was had reached their menopause between the ages of 35 and 59 years, the mean age at menopause declined with increasing number of cigarettes smoked, from 49.4 years of age among women who had never smoked to 47.6 years of age among women who smoked at least 15 cigarettes per day (p less than 0.02). The relationship was not attributable to the onset of menopause inducing women to take up smoking.

Evaluation of case reports of aplastic anemia among patients treated with felbamate.

Summary: Purpose: Felbamate (FBM) is a new antiepileptic drug (AED) that is often effective in seizure disorders refractory to other treatments; its use has been greatly restricted after cases of aplastic anemia were reported. To elucidate the putative association between FBM and aplastic anemia, we made a detailed evaluation of the first 31 reports.

BREAST CANCER AND ALCOHOLIC-BEVERAGE CONSUMPTION

The relation between breast cancer and alcoholic-beverage consumption was evaluated in a case-control study of 1152 women with breast cancer and two groups of control women-519 with endometrial or ovarian cancer, and 2702 with non-malignant disorders. The relative-risk estimate of breast cancer, with allowance for all potential distorting factors, for women who had ever drunk alcoholic beverages relative to those who had never drunk was 1.4 (95% confidence interval, 1.0-2.0) when the comparison group was the group with endometrial or ovarian cancer and 1.9 (1.5-2.4) when the controls who had non-malignant disorders were the comparison group. The association was evident for beer, wine, and spirits. The association was not explained by any of the major known risk factors for breast cancer, but we had no information on dietary factors. The findings support the hypothesis that alcohol consumption, or related dietary factors, increases the risk of breast cancer.

Alcoholic beverages and myocardial infarction in young women.

Moderate alcohol consumption has been associated with a reduction in the risk of myocardial infarction (MI) in men. To evaluate this relation in young women, we studied 513 patients with first infarctions and 918 hospital controls, all of whom were less than 50 years of age. The estimated relative risk of MI for current drinkers, after allowance for potential confounding factors, was 0.7 (95 per cent confidence interval. 0.5 - 1.0), and the apparent reduction in risk was strongest for women drank wine. There was no evidence of an effect among ex-drinkers.

Risk of breast cancer in relation to the use of rauwolfia alkaloids.

SummaryIn a case-control study of 1881 women with breast cancer and 1523 controls with benign conditions, 65 cases (3.5%) and 64 controls (4.2%) reported having used a drug that contained rauwolfia, giving a rate ratio estimate of 0.8 (95% confidence interval, 0.5–1.1). Use that ended more than a year previously was negatively associated with breast cancer (rate ratio, 0.5; 95% confidence interval, 0.2–0.9). The risk of breast cancer did not vary significantly according to duration of use. Nor did it vary within strata of varying base-line risk, such as age at first pregnancy. The data suggest that rauwolfia alkaloids do not increase the risk of breast cancer.

DIAZEPAM AND THE RISK OF BREAST CANCER

The relation of breast cancer to diazepam use was evaluated in a case-control study of 1236 women with breast cancer and 728 control subjects with other malignancies. Compared to women who never used diazepam, the relative risk for women who used the drug at least 4 days per week for at least 6 months was estimated to be 0.9, with 95% confidence limits of 0.5 and 1.6. There was no apparent association for recent use, or for use in the distant past, although confidence intervals were fairly wide in these categories. The results were not explained by various potential confounding factors, including the major risk factors for breast cancer. The findings suggest that regular diazepam use does not increase the risk of breast cancer relative to other cancers.

Hydralazine use in relation to cancers of the lung, colon, and rectum

SummaryIt has been suggested, based on animal experiments and limited human data, that the antihypertensive drug hydralazine might be carcinogenic, and among the sites of concern are the lung and colon.To assess the possible relationship between the use of hydralazine and lung and colorectal cancers in humans, we compared 1006 cases of lung cancer with 3531 hospital control subjects, and 972 cases of colorectal cancer with 3276 controls. Data were collected by interview in hospitals in the United States and Canada.Overall, 1.1% of the lung cancer cases, 1.6% of the colorectal cancer cases, and 1.5% of the controls had used hydralazine. Compared with those who had never used hydralazine, the relative risk estimate of lung cancer for those who first took the drug at least 18 months before hospital admission was 1.1 (95% confidence interval 0.4–2.9). The estimate for use for at least 1 year was 1.4 (0.5–3.8) and for use for at least 5 years the estimate was 0.9 (0.2–4.3). The corresponding relative risk estimates for colorectal cancer were 1.2 (0.5–2.5) for any use, 1.7 (0.8–3.7) for use for at least one year, and 2.4 (0.8–6.9) for five or more years of use. Other antihypertensive treatments and risk factors, including cigarette smoking in the analysis of lung cancer, were taken into account in these estimates.Although the effect of use after long latent intervals could not be evaluated, the results provide no support for the hypothesis that hydralazine use increases the risk of lung cancer. There is also no evidence that hydralazine increases the risk of colorectal cancer, but an effect after extended durations of use cannot be ruled out.

Meclizine in pregnancy in relation to congenital malformations.

A total of 50 282 mother-child pairs were prospectively studied in 12 hospitals in the USA.4 Meclizine was taken by 1014 women during the first four lunar months of pregnancy. A total of 3248 children (6-5 %) were malformed. Of these, 1128 had one or more of six malformations showing considerable variability among the 12 hospitals (non-uniform malformations). Rates were reasonably uniform for all other malformations, affecting 2277 children (uniform malformations). The uniform malformations, and a subset of major malformations (1393 children), were separately evaluated, as were ten further subsets, eight of which were based on anatomical location; two further subsets comprised syndromes and tumours. Many malformed children had multiple lesions, and the subsets were not mutually exclusive. Of the non-uniform malformations, only inguinal hernia (683) and clubfoot (192) are considered here. Various risk factors (such as parity, diabetes, cigarettes) were identified for each of the malformation outcomes.4 For any drug exposure group, use of multiple logistic risk function models made it possible to obtain an estimate of the expected number of malformed children, in the absence of drug exposure. The ratio of the observed to the expected number gave a standardised relative risk (SRR) that simultaneously took into account potential confounding from all identified risk factors. Malformation rates among 1014 children exposed and 49 268 non-exposed were similar for the largest outcomes (see table). Among the smaller outcomes, an association was present for defects of the eye and ear (121 children; standardised relative risk, 2-79; P <0 05). None of the specific ocular defects (see foot of the table) individually accounted for the association. Four of the defects (cataract, glaucoma/buphthalmos, corneal opacity, and coloboma) were judged on embryological grounds to be of the type that could arise at any time during pregnancy4; there were no further cases of any of these defects among 449 additional children first exposed to meclizine after the fourth lunar month. A total of 189 children had oral clefts, of whom