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Objective. Texas mandates a two-test newborn screening program for congenital adrenal hyperplasia (CAH): one test at birth and a second test at approximately one to two weeks after birth. The authors compared the dollar cost of detecting infants with CAH clinically and through the screening program. Methods. The authors estimated the costs of screening newborns in 1994 for CAH, including resources used by the Texas Department of Health and the broader cost to society. Results. Fifteen infants with classic CAH were diagnosed in Texas in 1994 among 325,521 infants born (1:21,701 cumulative incidence). Seven infants were detected clinically and the others were detected through screening, six on the first screen and two on the second screen. The first screen identified all previously undetected infants with severe salt-wasting CAH. The cumulative cost to diagnose the seven infants detected clinically was $79,187. The incremental costs for the screening program were $115,169 per additional infant diagnosed through the first screen and $242,865 per additional infant diagnosed through the second screen. Conclusions. If the goal is early diagnosis of infants with the severe salt-wasting form of CAH, a single screen is effective. If the goal is to detect infants with the simple virilizing form of the disorder who may benefit from early treatment, the second screen is necessary, but it is not as cost-effective as the first screen. [ABSTRACT FROM AUTHOR]

No risk factor other than cryptorchidism has been consistently associated with testicular cancer, and the influence of diet on testicular cancer risk has not been extensively explored. A few studies have found increased testicular cancer risk in men whose diets are high in fat, red meats, and milk or low in fruits and vegetables. We evaluated the relationship of dietary factors and risk of testicular cancer and also examined whether this risk varied by type of testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, TX) of 160 testicular cancer cases diagnosed between 1990 and 1996 and 136 friend-matched controls. The results of multivariable logistic regression analysis showed that after adjustment for age, education, income, ethnicity, cryptorchidism, and total daily calories, increasing total fat, saturated fat, and cholesterol consumption were associated with increasing risk of nonseminoma testicular cancer, with odds ratios (ORs) for the highest vs. the lowest quartiles of 6.3, 5.3, and 4.6, respectively. The risk for seminoma testicular cancer marginally increased with increasing intake of total fat and saturated fat, with ORs for the highest vs. lowest quartiles of 1.9 and 2.1, respectively. Higher total fat consumption was nearly significantly related to increased mixed germ cell tumor risk, with an OR for highest vs. lowest quartile of 4.2. This study supports the hypothesis that diet (particularly high fat consumption) increases testicular cancer risk in young men. However, the small sample size and the possibility that these observations may be due to bias indicate that the relationship of diet and testicular cancer risk needs to be further examined within a prospective or incident case-control study. [ABSTRACT FROM AUTHOR]

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight <3000 g (OR = 2.4: 95% CI = 0.7-8.1), and birth weight >4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.

Several investigators have reported a 40% increase in the prevalence of twinning among women who have taken folic acid or multivitamins containing folic acid at the time of conception. Given that infant morbidity and mortality are greatly increased among twins, such a large increase in twinning could have serious implications. We undertook this study to determine if US fortification of enriched cereal-grain products with folic acid was associated with an unexpected increase in the prevalence of twinning in the state of Texas. We examined 1 003 207 deliveries conceived in Texas, between 1 January 1996 and 31 December 1998. We compared the prevalence of twin deliveries conceived before, during and after fortification with folic acid, mandated to begin on 1 January 1998. Comparing pregnancies conceived in 1997 with those conceived in 1996, we observed a 2.4% yearly increase in twinning, 1.024 [0.98, 1.07]. Comparing pregnancies conceived in 1998 with those conceived in 1997, we observed a 4.6% yearly increase in twinning, 1.046 [1.00, 1.09]. These increases were adjusted for maternal age, race, education, parity and season of conception. The size and pattern of these increases are consistent with the ongoing increase in twinning of 1-4% per year which began in the US prior to fortification.

Background: We compared the incidence of prostate cancer in first-degree family members of African-Americans with that in white Americans., Methods: A historical cohort design was used to enroll 330 incident cases <80 years of age that were diagnosed at the Houston VA Medical Center between June 9, 1993 and June 8, 1996. We compared incidence rates in the probands' families with the incidence rates found in contemporaneous data from the national and regional Surveillance, Epidemiology, and End-Results (SEER) program., Results: Three-hundred five probands (41% African-American) had evaluable first-degree relatives (394 African-American, 527 non-African-American). The standardized incidence ratio was 1.61 overall (95% confidence interval (CI): 1.22-2.13) and did not differ between African-American and non-African-American families: 1.58 (1.05-2.29) and 1.65 (1.06-2.45) in African-Americans and non-African-Americans, respectively., Conclusions: The similar level of familial aggregation is evidence that the higher incidence of prostate cancer in African-Americans is not attributable to a higher prevalence of germline mutations predisposing to the disease., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To determine whether multiple sclerosis (MS) is associated with occurrence of seizure activity., Patients and Methods: The medical records of all incidence patients with MS in Olmsted County, Minnesota, from 1935 to 1991 were reviewed. The incidence of seizures was calculated by using 3 methods: including only seizures that occurred after definite diagnosis of MS, including all seizures occurring after onset of the first symptoms of MS, and including any seizures regardless of the time of onset relative to MS. These incidences were age-adjusted to the 1970 US population and then compared with the age-adjusted incidence rate of seizures in the general population of Olmsted County., Results: The age-adjusted incidence of seizures among MS patients was not significantly higher than the age-adjusted incidence of seizures in the general population of Olmsted County. The age-adjusted incidence of first unprovoked seizures in Rochester, Minn, was 61 per 100,000 person-years. In patients with the definite diagnosis of MS, the age-adjusted Incidence was calculated at 61 per 100,000 person-years (95% confidence interval [CI], 7-114). In the group with seizures after onset of symptoms, the age-adjusted incidence rate was 80 per 100,000 person-years (95% CI, 24-135). In the group with seizures at any time in their life, the age-adjusted incidence rate was 82 per 100,000 person-years (95% CI, 41-158)., Conclusion: The present study does not suggest that occurrence of seizures is more common in MS patients than in the general population.

Objective: Previous studies have shown an increased breast cancer risk associated with modest or high alcohol intake, however, few of these studies have included Hispanic women. The alcohol/breast cancer association was investigated in a New Mexico (NM) statewide bi-ethnic study., Design: A population-based, case-control study., Methods: Incident breast cancer cases (N = 712), aged 30-74 years, were ascertained by the New Mexico Tumor Registry (NMTR). Controls (N = 844) were identified by random digit dialing and were frequency-matched for ethnicity, age-group, and health planning district. Data were collected via in-person interview, which included questions regarding recent and past alcohol intake and breast cancer risk factors., Results: The highest level of recent alcohol intake, compared to no intake, was associated with breast cancer risk for postmenopausal Hispanic women (odds ratio [OR] = 2.0 95%, confidence interval [CI] 0.8-5.1, 42+ grams/ week) and postmenopausal non-Hispanic White women (OR = 2.2, 95% Cl 1.0-5.0, 148+ grams/week), although estimates were unstable and statistically non-significant. Lower recent alcohol intake (< 148 grams/week) was associated with reduced risk for non-Hispanic Whites (OR = 0.49, 95% Cl 0.35-0.69). This pattern was independent of hormone-receptor status and was present for both premenopausal (OR = 0.29, 95% Cl 0.15-0.56) and postmenopausal women (OR = 0.56, 95% Cl 0.35-0.90). Results for past alcohol intake and breast cancer association did not demonstrate any trends and were non-significant., Conclusions: Alcohol intake does not appear to have a consistent or significant association with breast cancer in Hispanic women.

Objective: To evaluate long-term mortality among people with status epilepticus (SE)., Methods: The authors performed a population-based retrospective cohort study to determine long-term mortality after SE. Between January 1, 1965, and December 31, 1984, all first episodes of SE receiving medical attention were ascertained through the Rochester Epidemiology Project Records-Linkage System. Cases surviving the first 30 days (n = 145) were followed until death or study termination (February 1996)., Results: At 10 years, cumulative mortality among 30-day survivors was 43%. The standardized mortality ratio (SMR) at 10 years was 2.8 (95% CI, 2.1-3.5). The mortality rate of those with idiopathic/cryptogenic SE was not increased (SMR = 1.1; 95% CI, 0.5-2.3). The following characteristics of SE increased long-term risk for mortality: SE > or = 24 hours in duration vs. SE < 2 hours (relative risk [RR] = 2.3; 95% CI, 1.1-5.1); acute symptomatic etiology vs idiopathic/cryptogenic etiology (RR = 2.2; 95% CI, 1.0-5.1) SE; myoclonic SE vs generalized convulsive SE (RR = 4.0; 95% CI, 1.3-13)., Conclusion: Forty percent of subjects who survived the first 30 days after an incident episode of SE die within the next 10 years. The long-term mortality rate was threefold that of the general population over the same time period. The long-term mortality rate at 10 years was worse for those with myoclonic SE, for those who presented with SE lasting more than 24 hours, and for those with acute symptomatic SE. The long-term mortality rate was not altered in those with idiopathic/cryptogenic SE. We conclude that SE alone does not modify long-term mortality.

The risk of major malformations in the offspring of mothers with epilepsy receiving antiepileptic drugs is 4--8% compared to 2--4% in the general population. Risk factors include daily dose and polytherapy. Selected drugs have been found to be associated with a higher risk of specific malformations (congenital heart defects and cleft palate with phenytoin and barbiturates; neural tube defects with valproate and carbamazepine). Although some of these findings are unquestionable, several questions are still unsolved, depending the characteristics of the target populations, the small samples of patients, and the design and limiting factors of the published reports. In the last decade, pregnancy registries have been activated by collaborative groups of physicians in Europe (EURAP), North America (NAREP), Australia and India (the latter two recently merged into EURAP), to enroll a large number of exposed women to be monitored prospectively with standardized methods, and by three pharmaceutical companies marketing lamotrigine, gabapentin and vigabatrin, as part of their post-marketing surveillance. Even though the structure of these registries and the target populations should theoretically result in the identification of a sufficient number of women exposed to different drugs and examined for the occurrence of malformations of any type and severity, the implementation of a common database with information from the existing registries may provide valuable information in a shorter time period. Although differences between some of the registries limit the possibility to pool data, a gradual development of a collaboration is highly desirable to discuss a list of design issues and assess to what extent and how data could be compared and organized.

A history of diuretic use has been shown to be protective for first unprovoked seizure in adult patients. Recent animal studies suggest that certain diuretics have anticonvulsant activity. We evaluated the potential for the anticonvulsant activity of current diuretic use in a population-based, case-control study in older adults. We also tested chlorthiazide and furosemide for seizure protection in animal models of epilepsy. Concurrent medical prescription of any diuretic was protective for the development of epilepsy [odds ratio (OR) = 0.62, 95% confidence interval (CI) = 0.39-0.99]. A protective effect for current thiazide use was observed (OR = 0.53, CI = 0.31-0.90), and a protective effect for furosemide was suggested (OR = 0.44, CI = 0.1-1.9). In mice, both chlorthiazide and furosemide suppressed the occurrence of maximal electroshock-induced seizures in a dose-dependent manner. Chlorthiazide's toxic dose for 50% of animals tested (TD50) could not be achieved even with dosing as high as 1,500 mg/kg for furosemide; TD50 was 549 mg/kg. Results were similar in rats. Furosemide and chlorthiazide are protective for unprovoked seizures in an epidemiological study and in animal models. Given the potential therapeutic value for seizure control, low toxicity, and low cost, therapeutic efficacy should be explored in clinical studies.

Purpose: Status epilepticus (SE) is a medical emergency associated with a high mortality. Clinical series have suggested that mortality after SE has decreased. No studies have systematically examined trends in incidence, mortality, and case fatality after SE in a well-defined population., Methods: All first episodes of SE receiving medical attention between January 1, 1935, and December 31, 1984, were ascertained through the Rochester Epidemiology Project Records-Linkage System and followed up until death or study termination (February 1, 1996). We calculated incidence rates in the 50-year period (1935-1984), while we considered mortality and case-fatality in the last 30-year period (1955-1984)., Results: Incidence of SE increased over time to 18.1/100,000 (1975 through 1984). The increase was related to an increased incidence in the elderly and to the advent of myoclonic SE after cardiac arrest, a condition not seen in the early decades. In the last decade, approximately 16% of the incidence was due to myoclonic SE. The mortality rates increased from 3.6 per year in the decade 1955-1965 to 4.0/100,000 per year between 1975 and 1984. The 30-day case-fatality (CF) was unchanged, although a trend toward improvement was shown after excluding myoclonic SE., Conclusions: Incidence and mortality rates of SE have increased in the last 30 years. Case fatality remained the same. The increased incidence and mortality are due to the occurrence in the last decade of myoclonic SE after cardiac arrest. The mortality in the elderly was twice that of the youngest age group, across all study periods. Changes in the age and cause distribution of SE over time are responsible for the stable survivorship. There is improvement in survivorship in the last decade when myoclonic SE is excluded.

Objective: To determine incidence of and risk factors for sudden unexpected death in epilepsy (SUDEP)., Methods: Three epilepsy centers enrolled 4,578 patients and prospectively followed these patients for 16,463 patient-years. The cohort was screened for death annually. Deaths were investigated to determine whether SUDEP occurred. Potential risk factors were compared in SUDEP cases and in controls enrolled contemporaneously at the same center., Results: Incidence of SUDEP was 1.21/1,000 patient-years and was higher among women (1.45/1,000) than men (0.98/1,000). SUDEP accounted for 18% of all deaths. Occurrence of tonic-clonic seizures, treatment with more than two anticonvulsant medications, and full-scale IQ less than 70 were independent risk factors for SUDEP. The number of tonic-clonic seizures was a risk factor only in women. The presence of cerebral structural lesions and use of psychotropic drugs at the last visit were not risk factors for SUDEP in this cohort. Subtherapeutic anticonvulsant levels at the last visit were equally common in the two groups. No particular anticonvulsant appeared to be associated with SUDEP., Conclusions: These results support the idea that tonic-clonic seizures are an important proximate cause of SUDEP. This information creates a risk profile for SUDEP that may help direct preventative efforts.

Objective: To develop a cost model that estimates the total and per case lifetime cost of bipolar disorder for 1998 incident cases in the US., Study Design: Lifetime cost simulation model., Perspective: Societal., Methods: Age- and gender-specific incidence of bipolar disorder in 1998 was estimated by simulation based on existing prevalence data. The course of illness and mental health service cost of 6 clinically defined prognostic groups was estimated based on the research literature and the judgement of panels of experts. Excess cost of general medical care was estimated based on claims data from a large insurer. Indirect cost was projected including excess unemployment and reduced earnings reported in the National Comorbidity Survey. Comorbidity treatment and indirect cost related to alcohol (ethanol) and drug abuse was added based on a National Institute on Drug Abuse study., Results: The present value of the lifetime cost of persons with onset of bipolar disorder in 1998 was estimated at 24 billion US dollars ($US). Average cost per case ranged from $US11,720 for persons with a single manic episode to $US624,785 for persons with nonresponsive/chronic episodes., Conclusion: The model indicates the potential cost savings of preventing a case of bipolar disorder and underscores the importance of achieving a stable outcome in new cases to limit the economic consequences of the disorder.

The aim of this study is to present the incidence of traumatic brain injury (TBI) and identify those characteristics of brain injuries that are associated with the development of seizures. We identified 5984 episodes of TBI (loss of consciousness, post-traumatic amnesia, or skull fracture) in Olmsted County, Minnesota, from 1935 to 1984. Of these, 4541 were followed for seizure. Injuries were classified as mild (loss of consciousness or amnesia less than 30 minutes), moderate (loss of consciousness 30 minutes to 1 day or a skull fracture), or severe (loss of consciousness of more than 1 day, subdural hematoma, or brain contusion). The incidence of TBI in the period from 1975 to 84 peaked at 800 per 100 000 in males aged 15-24. The relative risk of seizures was 1.5 (95 percent confidence interval 1.0-2.2) after mild injuries, but with no increase after 5 years; 2.9 (95 percent confidence interval 1.9-4.1) after moderate injuries; and 17.2 (95 percent confidence interval 12.3-23.6) after severe injuries. Significant risk factors were brain contusion with subdural hematoma, skull fracture, loss of consciousness or amnesia of 1 day or more, and age over 65 years. We conclude that TBI is a major public health problem and contributes to the occurrence of seizures and epilepsy., (Copyright 2000 BEA Trading Ltd.)

Purpose: This report concerns the 2-year extension of the study of mortality and sudden, unexpected, unexplained death in epilepsy (SUDEP) in the cohort of patients receiving vagal nerve stimulation by the NCP System for the treatment of epilepsy., Methods: A cohort of 1,819 individuals was followed 3,176.3 person-years from implantation. The 25 deaths that occurred during NCP System activation were reviewed for SUDEP by a panel., Results: The mortality rates were lower [standardized mortality ratio (SMR = 3.6)] with the extended follow-up compared to the previous finding (SMR = 5.3). The SUDEP rates (4.1 vs. 4.5 per 1,000 person-years) were similar to those in the previous study of this cohort. When the vagal nerve stimulation experience is stratified by duration of use, the rate of SUDEP was 5.5 per 1,000 over the first 2 years, but only 1.7 per 1,000 thereafter., Conclusions: The mortality and SUDEP rates are similar to those reported from clinical trials of new drugs and cohorts of severe epilepsy. The lower SUDEP rates after 2 years of follow-up are intriguing, but require further investigation.

Purpose: To provide 1995 estimates of the lifetime and annual cost of epilepsy in the United States using data from patients with epilepsy, and adjusting for the effects of comorbidities and socioeconomic conditions., Methods: Direct treatment-related costs of epilepsy from onset through 6 years were derived from billing and medical chart data for 608 population-based incident cases at two sites in different regions of the country. Indirect productivity-related costs were derived from a survey of 1,168 adult patients visiting regional treatment centers. Direct costs separate the effects of epilepsy and comorbidity conditions. Indirect costs account for the effects of other disabilities and socioeconomic conditions on foregone earnings and household activity. The estimates were applied to 1995 population figures to derive national projections of the lifetime and annual costs of the disorder., Results: The lifetime cost of epilepsy for an estimated 181,000 people with onset in 1995 is projected at $11.1 billion, and the annual cost for the estimated 2.3 million prevalent cases is estimated at $12.5 billion. Indirect costs account for 85% of the total and, with direct costs, are concentrated in people with intractable epilepsy., Conclusions: Direct costs attributable to epilepsy are below previous estimates. Indirect costs adjusted for the socioeconomic conditions of patients are above previous estimates. Findings indicate that epilepsy is unique in the large proportion of costs that are productivity-related, justifying further investment in the development of effective interventions.

We tested the hypothesis that major depression meeting DSM-III-R criteria or medical therapies for depression increase the risk for unprovoked seizures. Major depression was associated with a sixfold increased risk for unprovoked seizures (95% CI, 1.56-22). The risk remained increased even when controlling for age, sex, length of medical follow-up, and medical therapies for depression. In the absence of known prior neurological insult, major depression is associated with an increased risk for unprovoked seizures.

This study estimated the incidence of clinical neonatal seizures among infants born between 1992 and 1994 in Harris County, Texas, a county with a large and ethnically diverse population. Infants with neonatal seizures were ascertained from four sources: hospital discharge diagnoses, birth certificates, death certificates, and a study of neonatal seizures conducted concurrently with this study at a large tertiary care center in Houston, Texas. There were 207 cases of clinical neonatal seizures among 116,048 live births (an incidence of 1.8 per 1,000 live births). The incidence was highest among infants weighing less than 1,500 g (19/1,000) and decreased as birth weight increased. There was no significant difference in incidence by ethnicity. Twenty-six percent of the seizures (54/207) occurred after the infants had been discharged from the hospital where they were born. The incidence of neonatal seizures in Harris County was lower than the incidence reported recently for Fayette County, Kentucky, for 1985-1989 (3.5/1,000) and for Newfoundland, Canada, for 1990-1995 (2.5/1,000), but was higher than the incidence estimated for Rochester, Minnesota, for 1935-1984 (1/1,000).

The classification, occurrence, and predictors of sudden unexpected and unexplained death in individuals with epilepsy (SUDEP) have received considerable attention over the last few years. Specific criteria for the classification of definite, probable, possible, and not SUDEP implemented in United States epidemiologic studies are presented. The incidence of SUDEP in different epilepsy populations is presented. SUDEP is a real phenomenon, because the occurrence of such deaths, especially at relatively young ages, among individuals with epilepsy is far greater (perhaps 40-fold) than among those without epilepsy. SUDEP incidence rates are lower in population-based studies, higher in referral populations and clinical trials of adjunct drugs for complex partial epilepsy, and highest for surgical series. Seizure severity appears to be the strongest risk factor for SUDEP because higher rates are reported from studies of individuals with intractable epilepsy. Other potential risk factors, including sex, seizure etiology, younger age at onset, and partial-onset seizures, are unresolved., (Copyright 1999 BEA Trading Ltd.)

Purpose: Studies of the incidence of epilepsy are limited to a few populations in which new cases can be ascertained. Health maintenance organization (HmO) populations were studied to determine the incidence in a multiethnic, urban United States population., Methods: Cases of initial unprovoked seizure disorder or epilepsy while enrolled in an HMO between 1988 and 1994 were ascertained. Ethnicity was obtained from the medical records and was part of a nested case-control study., Results: There were 197 incidence cases of epilepsy and 275 of initial unprovoked seizure diagnosis. The incidence rate in the age range 0-64 years was 35.5 per 100,000 for epilepsy and 50.9 for initial unprovoked seizure. When compared with population-based studies, rates were slightly higher in children younger than 15, similar for the 15- to 24-year age group, but lower for ages 25-64 years. The ethnicity-specific odds ratios for initial unprovoked seizure, by using non-Hispanic white as the referent, were 1.04 (0.73-1.49) for African-American, 0.97 (0.64-1.48) for Hispanic, and 0.25 (0.08-0.84) for Asian-American., Conclusions: The lower rate in the HMO population is presumably due to a healthy-worker effect. The ethnicity-specific incidence rates do not differ in this population.

Changes in treatment alternatives and the emphasis on cost containment and managed care have increased the interest in information on the cost of epilepsy. The last comprehensive cost study in the USA was in 1975. That study estimated the national cost of epilepsy at $3.6 billion for 2.1 million cases. On a per patient basis the 1975 figure represents $7440 in 1995 US dollars, $1150 (15%) for direct treatment-related costs and $6290 (85%) for indirect employment-related costs. Since then, various cost-of-illness (COI) studies in the USA and other countries have offered estimates ranging from $6000 to $15000 per patient per year, with percentages of direct and indirect cost varying greatly. To assist those interested in interpreting or producing cost information, this paper reviews the state of research on the cost of epilepsy and discusses several methodological issues. A comprehensive study begun in 1993 to update the 1975 estimates for the USA is also described. Recommendations are provided to stimulate discussion about the best methods to use in future research.

Controversy continues as to whether traumatic brain injury is a risk factor for Alzheimer's disease. The authors examined a related hypothesis that among persons with traumatic brain injury who develop Alzheimer's disease, time to onset of the disease is reduced. They used data on all documented episodes of traumatic brain injury that occurred from 1935 to 1984 among Olmsted County, Minnesota, residents. Community-based medical records were used to follow traumatic brain injury cases who were aged 40 years or older at last contact prior to June 1, 1988, for Alzheimer's disease until last contact, death, or June 1, 1988. The test of the hypothesis was restricted to those cases who developed Alzheimer's disease. The expected time to onset of Alzheimer's disease was derived from a life table constructed by using age-of-onset distributions within sex groups for a previously identified cohort of Rochester, Minnesota, Alzheimer's disease incidence cases without a history of head trauma. The authors found that of the 1,283 traumatic brain injury cases followed, 31 developed Alzheimer's disease, a number similar to that expected (standardized incidence ratio = 1.2, 95% confidence interval 0.8-1.7). However, the observed time from traumatic brain injury to Alzheimer's disease was less than the expected time to onset of Alzheimer's disease (median = 10 vs. 18 years, p = 0.015). The results suggest that traumatic brain injury reduces the time to onset of Alzheimer's disease among persons at risk of developing the disease.

We asked whether acute symptomatic status epilepticus (SE) increases the risk for subsequent unprovoked seizure compared with less prolonged acute symptomatic seizure. We also explored whether the risk of unprovoked seizure differs by cause. We ascertained all first episodes of acute symptomatic seizure among residents of Rochester, Minnesota, through the Rochester Project's records-linkage system. Information was collected on seizure duration, age, sex, cause, and subsequent unprovoked seizure. At 10 years of follow-up, the risk of unprovoked seizure was 41% for those with acute symptomatic seizure with SE and 13% for those without SE. Controlling for age, sex, and cause, SE increased the risk for subsequent unprovoked seizure 3.3-fold (95% confidence interval, 1.8-6.1) compared with brief acute symptomatic seizures. Among patients with SE, the risk of unprovoked seizure was increased 18.8-fold for patients with anoxic encephalopathy, 7.1-fold for patients with a structural cause, 3.6-fold for patients with a metabolic cause. The increased risk for unprovoked seizure after SE compared with shorter seizures may be due to SE being a marker for severity of injury, damage caused by SE, or a biological substrate associated with the tendency to experience SE.

Objective: To determine the population-based incidence of sudden unexplained death in epilepsy (SUDEP) and to determine the risk of SUDEP compared with the general population., Background: Prior studies of SUDEP have described a wide range of incidence and have suffered from selection bias and other methodologic limitations. A population-based study of the incidence of SUDEP has never been performed. Furthermore, the risk of sudden death in the epilepsy population has not been compared with that of the general population., Methods: All deaths in persons whose epilepsy was diagnosed between 1935 and 1994 in Rochester, MN, were reviewed. The rate of SUDEP was compared with the expected rate of sudden death in the general population for patients age 20 to 40 years to determine the standardized mortality ratio (SMR)., Results: We identified nine cases of SUDEP. SUDEP accounted for 8.6% (7 of 81) of the deaths in persons 15 to 44 years of age. The incidence of SUDEP was 0.35 per 1,000 person-years. SMR for SUDEP was 23.7 (95% confidence interval, 7.7 to 55.0) compared with the general population., Conclusions: The incidence of SUDEP in our study was 0.35 per 1,000 person-years. SUDEP was responsible for 1.7% of deaths in our cohort. SUDEP is a rare cause of death in the epilepsy population but exceeds the expected rate of sudden death in the general population by nearly 24 times.

We determined the incidence of status epilepticus (SE) by ascertaining all first episodes of SE in Rochester, Minnesota through the Rochester Epidemiology Project's records-linkage system between January 1, 1965 and December 31, 1984. Information was collected on age, gender, duration, seizure type, and etiology. The age-adjusted incidence of SE was 18.3 per 100,000 population. SE incidence was U-shaped, peaking under 1 year and over 60 years of age. The incidence of SE was greater for males than for females, for acute symptomatic etiology than any other etiology, and for partial SE that did not generalize than any other seizure type. Status of long duration (at least 2 hours) occurred more frequently among infants and the elderly than among persons aged 1 to 65 years. Cumulative incidence was 4 per 1,000 to age 75 and showed the greatest increase after age 60. Given the aging of the population, SE will become an increasingly important public health problem.

Background: Patients with a single unprovoked seizure have about a 35 percent risk of recurrence in the subsequent five years. We studied the risk of recurrence after two unprovoked seizures., Methods: We prospectively followed 204 patients with a first unprovoked seizure from the day of the initial seizure. Information was obtained from patients (and verified by a review of their medical records) about the dates and circumstances of any subsequent seizures. The risk of a second, third, and fourth seizure was estimated by the Kaplan-Meier method., Results: Of the 204 patients, 63 had a second seizure, 41 a third seizure, and 26 a fourth seizure. The mean age of the patients was 36 years, 10 percent were less than 16 years of age, 70 percent were male, 71 percent had epilepsy of unknown cause, and 66 percent had generalized seizures. The risk of a second unprovoked seizure was 33 percent. Among those with a second seizure, the risk of a third unprovoked seizure was 73 percent; among those with a third unprovoked seizure, the risk of a fourth was 76 percent. Most recurrences occurred within one year of the second or third seizure. The risk of a third seizure was higher in those with a presumed cause of epilepsy (relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.4)., Conclusions: Although only about one third of patients with a first unprovoked seizure will have further seizures within five years, about three quarters of those with two or three unprovoked seizures have further seizures within four years.

Purpose: To determine rates of all-cause mortality and of sudden, unexpected, unexplained deaths in epilepsy (SUDEP) in a cohort of individuals treated with the Neuro Cybernetic Prosthesis (NCP) System for intractable epilepsy, and; to contrast the NCP experience with other epilepsy cohorts., Methods: A cohort of 791 individuals were followed for 1,335 person-years from implantation. Of the total cohort, 120 individuals had their NCP System devices deactivated. The 15 deaths which occurred during NCP System activation were reviewed for SUDEP by a panel. There were three additional deaths and 242.5 person-years of monitoring after deactivation., Results: The standardized mortality ratios for NCP System were 5.3, 95% confidence interval (CI) 3.0-8.7; and for the time period after device deactivation, 4.4, 95% CI 0.9-12.8. Six of the deaths during stimulation were considered definite or probable SUDEP and two as possible SUDEP. Seven were not considered to be SUDEP. The incidence of definite/probable SUDEP was 4.5 per 1,000 person-years and 6.0 per 1,000 person-years for definite/probable/possible SUDEP., Conclusions: The mortality rates and standardized mortality ratios are comparable with studies of young adults with intractable epilepsy who were not treated with NCP System. These SUDEP rates are not significantly different from those reported in the recent studies of lamotrigine (LTG), gabapentin (GBP), and tiagabine (TGB). The higher rates of SUDEP in the NCP System cohort, as compared with recent drug trials, presumably is explained by the selection of relatively higher-risk patients for the NCP System device.

Background: The risk of seizures is increased after traumatic brain injury, but the extent and duration of the increase in risk are unknown. The purpose of this study was to identify the characteristics of brain injuries that are associated with the development of seizures., Methods: We identified 4541 children and adults with traumatic brain injury (characterized by loss of consciousness, post-traumatic amnesia, or skull fracture) in Olmsted County, Minnesota, during the period from 1935 through 1984. Injuries were classified as mild (loss of consciousness or amnesia lasting less than 30 minutes), moderate (loss of consciousness for 30 minutes to 24 hours or a skull fracture), or severe (loss of consciousness or amnesia for more than 24 hours, subdural hematoma, or brain contusion). We compared the incidence of new unprovoked seizures in this cohort with population rates, using standardized incidence ratios and Cox proportional-hazards analysis., Results: The overall standardized incidence ratio was 3.1 (95 percent confidence interval, 2.5 to 3.8). The standardized incidence ratio was 1.5 (95 percent confidence interval, 1.0 to 2.2) after mild injuries but with no increase over the expected number after five years, 2.9 (95 percent confidence interval, 1.9 to 4.1) after moderate injuries, and 17.0 (95 percent confidence interval, 12.3 to 23.6) after severe injuries. In the multivariate analysis, significant risk factors for later seizures were brain contusion with subdural hematoma, skull fracture, loss of consciousness or amnesia for more than one day, and an age of 65 years or older., Conclusions: The increased risk of seizures after traumatic brain injury varies greatly according to the severity of the injury and the time since the injury.

Background: Sialyl-Tn (STn) represents an aberrantly glycosylated mucin epitope that is expressed in breast carcinoma and other adenocarcinomas and is an important factor in the development of novel immunotherapeutic approaches. The primary aim of the current study was to investigate the influence of STn expression on the prognoses of patients with breast carcinoma., Methods: A cohort of 207 women diagnosed with invasive breast carcinoma who were treated with anthracycline-containing adjuvant chemotherapy and were enrolled in a randomized clinical trial were studied. Expression of STn was determined by an immunohistochemical procedure in which the B72.3 monoclonal antibody was used. Kaplan-Meier and Cox proportional regression survival analyses were used to compare low STn and high STn patients., Results: Forty-eight (23%) of the 207 specimens demonstrated high STn staining (>25% cells were immunoreactive). During a median follow-up of 5 years, high STn patients had worse disease free survival than low STn patients (55% vs. 74%, respectively; P = 0.03). High STn expression was significantly associated with age (P = 0.04) but not with other conventional prognostic markers. In multivariate analysis using the Cox regression model, high STn emerged as an independent prognostic indicator for disease free survival (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.09-3.73) and for overall survival (HR, 2.16; 95% CI, 0.95-4.92)., Conclusions: The results of this study suggest that STn may be a valuable marker for identifying women at high risk of developing recurrent breast carcinoma who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.

Purpose: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE., Methods: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied all first episodes of afebrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996)., Results: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of duration or seizure type was shown after adjusting for other risk factors., Conclusions: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.

Interest in sudden unexpected and unexplained death in individuals with epilepsy (SUDEP) was rekindled in the United States by Jay and Leestma during the early 1980s and more recently by antiepileptic drug (AED) trials and medicolegal issues. The incidence of SUDEP has been and is being evaluated in North America and the United Kingdom. Specific criteria for the classification of definite, probable, possible, and unlikely SUDEP implemented in United States epidemiologic studies are presented. Evidence for the increased relative risk for sudden death in epilepsy compared with the general population is also discussed.

A study of heart disease mortality and morbidity in patients with epilepsy in Rochester, Minnesota, U.S.A., is presented. In a cohort of 725 incident cases of epilepsy followed for approximately 10,000 person-years, 237 deaths and 48 incident cases of ischemic heart disease were noted. Overall, the cohort mortality rate was 2.1 times that of the general population. For those with idiopathic epilepsy, the mortality rate was 1.6 times that of the general population. For ischemic heart disease, the epilepsy cohort experienced a standardized mortality rate (SMR) of 1.6, slightly higher for remote symptomatic than idiopathic epilepsy. For sudden death as the initial manifestation of heart disease, the SMR was 2.3. The ratio was not significantly higher for those with idiopathic epilepsy but was 3.9 for remote symptomatic epilepsy. The findings show much lower incidence rates and relative incidence of sudden death than all of the more recent sudden unexpected death in epilepsy studies. Reasons for this discrepancy are discussed.

Background: Multiethnic population-based studies of dementia are lacking in the literature; therefore, we conducted a study to determine the incidence and prevalence of dementia among, black, white, and Hispanic municipal retirees age 50 and older., Methods: In 1991, city of Houston municipal workers who retired between 1980 and 1984 received in-home screening for cognitive impairment using the Mini-Mental State Examination and were referred for comprehensive neurologic evaluation if indicated. Families of deceased retirees were interviewed, medical records were reviewed, and death certificates were obtained to determine case status of the retiree. Study participation was 90%., Results: Crude prevalence of dementia, among retirees age 60 and older, was 2.65 per 100 population. Age-adjusted to the 1970 US population, age 60 to 80, the prevalence was 1.85 per 100 population. Age-adjusted prevalence of dementia was similar among Hispanic and black men, 4.75 and 4.80 respectively, and lowest among white men, 2.42 per 100 population. Forty-three percent of the prevalent cases (30% of the incidence cases) were not previously diagnosed. The cumulative incidence of dementia calculated to age 80 was 39% for Hispanic men, 28% for black men, and 14% for white men. Fifty-five percent of the incidence cases were diagnosed as having ischemic vascular dementia (IVD), 20% as having probable or possible Alzheimer's dementia (AD), and 25% as having unspecified dementia., Conclusions: Risk of dementia by age 80 was more pronounced for Hispanic and black men compared with white men. IVD was the predominant cause of dementia among both black and white men. Grouping Hispanics with whites may mask differences when studying dementia.

Randomized trials are the optimal approach for evaluations of treatment efficacy but may not always be feasible. We study the adequacy of the case-control design in evaluating efficacy in a situation where the investigated therapy, namely the administration of magnesium sulfate for the prevention of eclampsia in patients with preeclampsia, has a suspected strong protective effect. A total of 66 cases of eclampsia were ascertained from among deliveries occurring between 1977 and 1992 at two hospitals in Houston, Texas. Randomly selected preeclamptic controls were matched to cases based on hospital and month of delivery. Magnesium sulfate administration prior to seizure occurrence had a strong protective effect against eclampsia in patients with preeclampsia (OR, 0.02; 95% CI, 0.01-0.05). This protective effect remained when controls were stratified by the degree of severity of preeclampsia (mild-to-moderate OR, 0.03, 95% CI, 0.01-0.09 and severe OR, 0.005; 95% CI, 0.0005-0.04) and when cases were stratified by the timing of the first seizure (antepartum and intrapartum seizures OR, 0.01; 95% CI, 0.003-0.05 and postpartum seizures OR, 0.03; 95% CI, 0.005-0.15). The effect also remained after adjustment for other important predictors in a multivariate logistic regression model (OR, 0.11; 95% CI, 0.03-0.38). The results of this study are in support of a recent randomized trial on the efficacy of magnesium sulfate as a prophylactic agent against eclampsia. Although there are serious potential sources of bias in this study, the magnitude of the protective effect of magnesium sulfate minimizes the likelihood that this effect can be explained by bias. Observational studies could be appropriate complements or alternatives to randomized trials in situations where a strong treatment effect is expected.

Purpose: The present study was conducted to determine the rate of sudden unexplained death in epilepsy (SUDEP) in a well-defined cohort of patients included in the lamotrigine (LTG) clinical development database., Methods: A panel of scientists experienced in the area of SUDEP was assembled and provided with case summaries on all deaths (n = 45) reported during the initial clinical development of LTG. The panel developed a set of criteria for classifying cases as SUDEP (definite or highly probable), possible SUDEP, or non-SUDEP. This classification algorithm was then applied to the LTG cases, and SUDEP rates were calculated using patient-years of exposure as the denominator., Results: At the time of the study, 4,700 patients (5,747 patient-years of exposure) were included in the worldwide LTG clinical trials database. In this cohort, 45 deaths were reported. Eighteen were judged by the panel to be SUDEP, 6 were defined as possible SUDEP, 20 were judged to be due to other causes (non-SUDEP), and 1 lacked sufficient data from which to make a classification. The overall SUDEP rate (definite/ highly probable SUDEP and possible SUDEP combined) was calculated to be 3.5 in 1,000 patient-years of exposure to LTG., Conclusions: The rate of SUDEP in this cohort of patients was comparable to the rate that would be expected in young adults with severe epilepsy (the subgroup of patients believed to be at highest risk of SUDEP). The data suggest that the rate of SUDEP in the LTG clinical development program is a function of the clinical trial population and is unrelated to drug treatment.

As a means of examining the virus-relatedness of acute lymphoblastic leukemia (ALL) in children, we investigated the association between month-of-birth and the occurrence of ALL in 1487 children aged 0-15 years at the time of diagnosis. Our hypothesis being that evidence of seasonal variation in births of ALL cases would suggest exposure to a transmissible etiologic agent during the perinatal period. The data were obtained from the Surveillance, Epidemiology, and End Results (SEER) Program and consisted of children diagnosed during the years 1973-1986. Aggregate monthly incidence rates of ALL stratified by month-of-birth, for each SEER site, all sites combined, and for broad geographic regions were calculated. No evidence for an association between month-of-birth and childhood ALL was found.

Purpose: Hypertension is an established risk factor for clinically detected stroke, which is in turn a risk factor for epilepsy. This relation suggested that hypertension, particularly severe and uncontrolled, might increase the risk of epilepsy in the absence of prior clinically detected stroke., Methods: Subjects in this population-based case-control study were the 145 incident cases of first unprovoked seizure aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow-up. Using the records-linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, all blood pressure readings before each case's first seizure came to medical attention. Subjects were classified as hypertensive if they had at least two readings of > or = 160/95 mm Hg or if there was electrocardiographic evidence for left ventricular hypertrophy., Results: Severe uncontrolled hypertension increased the risk of unprovoked seizure. Left ventricular hypertrophy without diuretic treatment was associated with an 11-fold increased risk of unprovoked seizure: left ventricular hypertrophy treated with diuretics did not increase the risk., Conclusions: In the absence of clinically detected stroke, left ventricular hypertrophy without diuretic use may increase the risk of unprovoked seizures, and diuretic treatment may protect against this increased risk.

Studies based on the Rochester Epidemiology Project medical records-linkage system have provided important insights into the epidemiology of epilepsy. The incidence of all convulsive disorders in Rochester, Minnesota, during a 50-year period exceeded 130 per 100,000 person-years. The age-adjusted incidence of epilepsy was 44 per 100,000 person-years; of a first unprovoked seizure, 61; and of acute symptomatic seizures excluding febrile convulsions, 31. In addition, 2% of the population experienced a febrile convulsion before the age of 5 years. The cumulative incidence of epilepsy through age 74 years was 3.0%, of all unprovoked seizures was 4.1%, and of any convulsive disorder approached 10%. For epilepsy, single unprovoked seizures, and acute symptomatic seizures, the incidence was significantly higher in males than in females, and it was high in the first year of life but highest in those age 75 years or older. For epilepsy alone, approximately 60% of incidence cases experienced partial seizures, and two-thirds had no clearly identified antecedent. Cerebrovascular disease was the most commonly identified antecedent of epilepsy, accounting for 11% of cases. Over time, the incidence of epilepsy and of unprovoked seizures decreased in children and increased in the elderly population. The age-adjusted prevalence of active epilepsy on Jan. 1, 1980, was 6.8 per 1,000 residents. Prevalence was low in the first decade of life, increased to a plateau in the adult years, and further increased in the elderly population. Almost 1.5% of the population older than 75 years of age had active epilepsy. About 25% of prevalence cases had an identified cause; 60% experienced partial epilepsy.

The contributions of the Rochester (Minnesota) Epidemiology Project and Mayo Clinic studies in the evaluation of the causes of epilepsy are summarized. The development of the unique population-based medical records-linkage resource is chronicled, and the measures of occurrence and association used in epidemiologic study designs to assess the causes of epilepsy are presented. The historical cohort design is optimal for the study of the relationship between common central nervous system insults and seizures, and case-control studies are best used for analysis of relatively rare seizure disorders. The major findings about the etiologic roles of traumatic brain injuries, central nervous system infections, cerebrovascular disease, brain tumors, neurodegenerative diseases, developmental disabilities, perinatal insults, and familial factors are discussed. The role of genetic factors in epilepsy has been controversial, perhaps because of the numerous causes of seizures and their episodic nature. Both potential environmental and genetic causes will continue to be assessed.

We conducted a case-control study to investigate the relation between dietary fiber, calcium, and total fat and the risk of colorectal adenomatous polyps. We used a food frequency questionnaire to assess the usual diet for 157 cases and 480 controls. In multivariate analyses, dietary fiber was inversely associated with risk of adenomatous polyps. The odds ratio (OR) for individuals in the highest vs the lowest quartile was 0.5 [95% confidence interval (CI) = 0.3-0.9]. We found an inverse association between dietary calcium and risk of adenomatous polyps, but the protective effect was present only for individuals in the fourth vs the first quartile (OR = 0.7; 95% CI = 0.3-1.3). Intake of total fat was positively associated with risk of adenomatous polyps, but we saw no consistent trend. Calcium intake appeared to modify the effect of total fat intake on the risk of adenomatous polyps.

We assessed the relations of genetic and environmental factors in the etiology of epilepsy. The study population comprised 9,705 first-degree relatives of 1,951 adults with epilepsy ascertained from voluntary organizations. We calculated standardized morbidity ratios for specific etiologies of epilepsy in the relatives of probands with the same etiologies, using population incidence rates from Rochester, MN, as the reference. Relatives of probands with idiopathic/cryptogenic epilepsy had increased risk for idiopathic/cryptogenic epilepsy and for epilepsy associated with neurological deficit presumed present at birth (cerebral palsy or mental retardation) but not for symptomatic epilepsy associated with postnatal central nervous system insults. Relatives of probands with neurodeficits had increased risks for idiopathic/cryptogenic epilepsy. Risk for epilepsy was not increased among relatives of probands with postnatal symptomatic epilepsy. The degree of increased risk of idiopathic/cryptogenic epilepsy in relatives of probands with idiopathic/cryptogenic epilepsy diminished with increasing age of the relatives; risk was not increased at age 35 or older. These findings support the possibility of shared genetic susceptibility to epilepsy and cerebral palsy, and suggest that the genetic contributions to postnatal symptomatic epilepsy are minimal.