The utility of the general practice research database to examine selected congenital heart defects: a validation study.

OBJECTIVE: The purpose of this research was (1) to validate that ventricular septal defect (VSD), tetralogy of Fallot (TOF), and coarctation of the aorta (COA) can be studied in the UK General practice research database (GPRD) and (2) to understand which of the available GPRD components (computerized medical records, questionnaires, and maternal/infant free text) provide maximal information about these heart defects. METHODS: Using a practitioner questionnaire, the positive predictive value (PPV) of the computerized medical record for VSD, TOF, and COA were determined. Both infant and maternal free text was examined. Concordance between the infant free text information and questionnaires was calculated. The proportion of infant information captured in the maternal free text was determined. RESULTS: A 93% response rate was achieved. Based on questionnaire responses, an overall PPV of 93.5% was achieved (VSD = 95%, TOF = 90%, COA = 100%). Approximately half of the records contained infant free text information including information on the type and size of VSD, echocardiogram findings, and surgery. Concordance between the infant's free text and questionnaire information occurred in most of the cases (92-100%). The proportion of infant information in the maternal free text was low (4-19%). CONCLUSION: The GPRD computerized medical records are sufficient to assess VSD, TOF, and COA. This study confirms that maternal free text provides a low yield of limited information pertaining to the infants' defect, while the infant free text may provide an additional information usually obtainable from practitioner questionnaires. The information provided by an infant free text may limit the need for practitioner questionnaire validation.

Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To evaluate the occurrence of stroke/TIA symptoms and ischemic stroke events among those with a lifetime history of migraine or other headaches with some migraine features in a biracial cohort of older adults. METHODS: Participants were 12,750 African-American and white men and women from the Atherosclerosis Risk in Communities Study (1993 to 1995). The participants were queried about their lifetime headache history and characterized using modified International Headache Society diagnostic criteria. Stroke/TIA symptoms were classified using a computerized diagnostic algorithm, and ischemic stroke events were identified and validated using medical records. Multivariate logistic regression was used to assess the relationship between headache types and stroke/TIA symptoms and ischemic stroke events. RESULTS: Migraine with aura was strongly associated with stroke symptoms (odds ratio [OR] 5.46, 95% CI: 3.64 to 8.18), TIA symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke events (OR 2.81, 95% CI: 1.60 to 4.92). Similarly, other headaches with aura were significantly associated with stroke symptoms (OR 3.68, 95% CI: 2.26 to 5.99) and TIA symptoms (OR 4.53, 95% CI: 3.08 to 6.67). In contrast, the associations for migraine without aura and other headaches without aura were not as consistent or robust. CONCLUSIONS: Migraines and other headaches, particularly those accompanied by aura, were associated with an increased occurrence of stroke/TIA symptoms and ischemic stroke events.

Menstrual patterns and risk of adult-onset diabetes mellitus.

We examined the association between menstrual patterns and risk of developing adult-onset diabetes in a prospective study of 668 white, college-educated women who completed menstrual diaries throughout their reproductive years. We calculated summary measures of cycle length and variability and bleeding duration for ages < or = 22, 23-27, 28-32, and 33-37 years. The analysis included 35,418 person-years of follow-up and 49 self-reported cases of diabetes (median age at diagnosis, 63 years). There was no association between diabetes risk and age at menarche, mean cycle length, cycle variability, or frequency of long cycles (> 42 days). Longer bleeding periods in the mid- and late reproductive years were somewhat associated with an increased risk of diabetes (adjusted rate ratio 1.4, 95% confidence interval 1.0-1.8 per day increase in bleeding duration for menses during ages 28-32). These results do not support the association of long or irregular menstrual cycles with post-menopausal diabetes incidence, but do suggest a possible association of longer bleeding duration with subsequent onset of diabetes.

Age at menopause and childbearing patterns in relation to mortality.

Several studies have reported increased mortality risk with early natural menopause. More recently, mortality risk was reported to be reduced among women who gave birth at age > or =40 years. The association between reproductive history and mortality was explored among 826 women in a prospective study involving 18,959 person-years of follow-up (from age 50 to 1990-1991) and 108 deaths. After adjustment for age and other covariates, the risk ratio among parous women was 1.53 (95% confidence interval: 0.58, 4.07) for natural menopause at age < or =45 years compared with > or =51 years. In contrast to a previous report, however, the highest estimated mortality risk was seen among women who gave birth in their forties (adjusted risk ratio = 2.14, 95% confidence interval: 1.05, 4.38) compared with having a last birth at ages 30-34 years.

PIP: This paper studied the association between menopausal and reproductive history and mortality risk in a cohort of 826 women in a prospective study involving 18,959 person-years of follow-up (from age 50 to 1990-91) and 108 deaths. According to studies, the risk of mortality was reduced among women who gave birth at age 40 or older. After an adjustment for age and other covariates, the risk ratio among parous women was 1.53 (95% confidence interval: 0.58, 4.07) for natural menopause at age 45 or younger compared with age 51 or older. Contrary to a previous report, the highest estimated mortality risk was seen among women who gave birth in their 40s (adjusted risk ratio = 2.14; 95% confidence interval: 1.05, 4.38) compared with having a last birth at ages 30-34.

Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: a pharmaceutical company commitment.

OBJECTIVE: Glaxo Wellcome becomes aware of prenatal exposures to its medications as early as the clinical trial phase of development. An international process for monitoring prenatal exposure to all Glaxo Wellcome medicines has been developed. For specific products there are prospective pregnancy registries. STUDY DESIGN: The registries are observational, case-registration, and follow-up studies designed to detect evidence of teratogenicity associated with specific medications. After prenatal exposure to the registry medication, pregnancies are registered prospectively, through voluntary reports by health care providers. An advisory committee of independent scientists for each registry reviews data and advises in dissemination of information. Risk of birth defects, as defined by the Centers for Disease Control and Prevention, is compared with published risks both in women in the general population and in women with the underlying condition being treated, if available. RESULTS: The following data show results from the prospective first-trimester exposures registered since establishment of each registry. The published risk of birth defects in the general population range is 3% to 5%, and the risk in women with epilepsy is 6% to 9%. The proportions of outcomes with birth defects are as follows: in the Acyclovir (antiviral medication) Pregnancy Registry (1984-1998) (19/581), 3.3% (95% confidence interval, 2.0%-5.2%); in the Lamotrigine (monotherapy and polytherapy antiepileptic medication) Pregnancy Registry (1992-September 1998) (8/123), 6.5% (95% confidence interval, 3.1%-12.8%); in the Sumatriptan (migraine medication) Pregnancy Registry (1996-October 1998) (7/183), 3.8% (95% confidence interval, 1.7%-8.0%). The Valacyclovir, Bupropion, and Naratriptan registries have insufficient data for analysis. CONCLUSION: None of the registries has provided a risk estimate exceeding that expected in the disorder treated, and no pattern of defects has been observed. Whereas information from the larger registries is reassuring regarding risk, these studies cannot rule out possible small excess risks from use of these drugs in pregnancy. Data obtained through these registries are shared with the medical community as a supplement to animal toxicology studies to assist in weighing potential risks and benefits of treatment for individual patients. The success of the registries depends on the continued willingness of the obstetrics and gynecology community to notify the registries of prenatal exposures.

Menstrual and reproductive risk factors for ischemic heart disease.

The role of hormones in ischemic heart disease is of considerable interest, but limited data are available pertaining to risk factors associated with endogenous hormones. We examined the association between menstrual and reproductive factors and ischemic heart disease in a cohort of 867 white, college-educated women who prospectively recorded menstrual cycle data for at least 5 years from their early 20s through their menopause. Ischemic heart disease history was obtained from a self-administered (N = 714) or proxy-administered (N = 153) questionnaire completed at a mean age of 73 years. The analysis included 44,899 person-years of follow-up and 45 cases of myocardial infarction, angioplasty, heart bypass surgery, or ischemic heart disease-related mortality. Ischemic heart disease risk decreased with increasing age at menarche (age-adjusted RR 0.76 per year, 95% CI = 0.60-0.95). Considering menstrual cycle characteristics ages 28-32, there was little overall association with length, variability, or bleeding duration. Ischemic heart disease risk increased with later age at first birth (age-adjusted RR 2.90 for ages 33-43 compared with 25-29) and later age at last birth (age-adjusted RR 3.79 for ages > or =40 compared with 35-39), but there was little association with high parity.

Pregnancy and perinatal outcomes in migraineurs using sumatriptan: a prospective study.

BACKGROUND: Sumatriptan is an acute treatment for migraine which is often used by women in their child-bearing years, and who become unexpectedly pregnant. Within the context of the post-marketing use of sumatriptan injection for the acute treatment of migraine, and in compliance with approved labeling, we wished to compare perinatal pregnancy outcomes in women who did and did not use the drug after conception. METHODS: Open-label, prospective study conducted in 12,339 migraineurs (including 9,861 women) whose demography and consumption pattern of sumatriptan injections were typical, and were predicted to include 150 pregnancies. Outcome of pregnancy was the end-point. RESULTS: There were 168 of 173 pregnancies that were well-documented. Sumatriptan was only used prior to conception in 92 cases. There were 76 first trimester exposures to sumatriptan. There were no differences in pregnancy outcome between the two groups. CONCLUSIONS: Perinatal and pregnancy outcome did not differ between patients who had and had not used sumatriptan after conception, at the resolution of these sample sizes. This study design complements the ongoing pregnancy registry, which is now widened to patients exposed to all formulations of sumatriptan.

Epidemiology of menstruation and its relevance to women's health.

PIP: The data on the menstrual cycle as a health endpoint and as a risk factor for chronic disease are inadequate. Specifically, the data on menstrual cycle length and blood loss do not have the detail on within-woman variability needed to allow women and clinicians to anticipate certain bleeding changes that tend to develop at different life stages, to distinguish between potentially pathologic alterations from short-term aberrations, and to recognize bleeding patterns that may be risk factors for the development of chronic disease. Lack of data on bleeding changes in premenopausal and menopausal women concerns many health professionals considering the many physician visits for abnormal bleeding and the prevalence of hysterectomy among women aged more than 35. Thus, development of objective criteria on how much bleeding is too much is needed so women can determine whether their daily blood loss is or is not a concern. Women also need more information on what constitutes menstrual dysfunction. Some basic research needs include definition of population patterns of gynecologic disease, identification of potentially modifiable risk factors, the influence of recreational activity in gynecologically mature women, influence of hard physical activity in the context of women's daily work life, interaction of low weight and physical activity in developing countries, effects of work stress, effects of family interactions, effects of violence, environmental risk factors (e.g., pesticides), and physiologic variation across the menstrual cycle. Research on menstrual cycle-related risk factors for chronic disease could explain women's long term health status and identify preventive strategies for premenopausal women. Current women's health research tends to ignore hormonal influences. The limited available research on immune parameters suggests that follicular/luteal classification may not be able to detect meaningful variation. In conclusion, a comprehensive research program would fill the many gaps in scientific knowledge about the menstrual cycle.^ieng

Greater incidence of electrocardiographic left ventricular hypertrophy in black men than in white men in Evans County, Georgia.

Population-based studies of black populations in the United States and Puerto Rico have reported higher prevalences of electrocardiographic left ventricular hypertrophy compared to white or lighter-skinned populations residing in the same areas. This study examines the incidence and correlates of electrocardiographic left ventricular hypertrophy in a population-based, biracial cohort of 435 white and 163 black men from the Evans County, Georgia, Heart Study, who were examined at entry in 1960 and reexamined in 1967. Only men over 35 years of age who were free of cardiovascular disease and had normal electrocardiograms at entry were eligible. Black men had a nearly fourfold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (13.5% vs 3.7%, respectively; incidence ratio 3.7; 95% CI 3.2-4.4). After statistically adjusting for age, systolic blood pressure, weight, and the change in weight and blood pressure, black men had a threefold greater incidence of electrocardiographic left ventricular hypertrophy compared to white men (logistic odds ratio 3.0; 95% CI 1.6-6.1). In summary, black men showed a significantly greater risk of developing electrocardiographic left ventricular hypertrophy at 7-year follow-up in Evans County compared to their white counterparts. This elevated risk could not be explained by the independent or joint effects of risks factors for electrocardiographic left ventricular hypertrophy.