Endometrial cancer in Olmsted County, MN: trends in incidence, risk factors and survival.

PURPOSE: We updated an earlier study in this community from 1945-1974 in order to assess trends in the incidence of, risk factors for, and survival from endometrial cancer in 1975-1991. METHODS: Incidence rates were based on all new cases of endometrial cancer diagnosed among Olmsted County, Minnesota, women during the years 1975-1991, with the population denominator from decennial census data. Risk factors were assessed with conditional logistic regression comparing the incidence cases to age- and gender-matched controls with intact uteri seen the same year the case was diagnosed. Survival was assessed using the Kaplan-Meier method. RESULTS: The incidence of endometrial cancer (age-adjusted to 1970 United States total) in 1975-1991 was 14.3 per 100,000 person-years, which is slightly increased from 1965-74. The rate was 21.7 per 100,000 person-years after adjustment for hysterectomy prevalence. As in the previous study, conjugated estrogen use for six months or more (odds ratio [OR] 2.71; 95% confidence interval [CI] 1.14-6.46) and body mass index (OR 1.06; 95% CI 1.01-1.11) increased the risk of endometrial cancer. The five-year relative survival rate (82%) was not improved over the earlier study. CONCLUSIONS: A small increase in endometrial cancer incidence was linked to the same risk factors identified in an earlier study in this community. No improvement in survival was seen.

The epidemiology of ovarian cancer: a population-based study in Olmsted County, Minnesota, 1935-1991.

PURPOSE: To determine trends in incidence and survival between 1935 and 1991 and to evaluate risk factors for ovarian cancer among Olmsted County, Minnesota women. METHODS: All newly diagnosed cases of ovarian cancer among Olmsted County women in 1975-1991 were identified using the medical records linkage system of the Rochester Epidemiology Project. In order to assess trends, incidence rates in the subset of Rochester women were compared with Rochester rates for 1935-1974. Survival was evaluated by the Kaplan-Meier product-limit method. A case-control analysis of risk factors compared Olmsted County women with invasive epithelial ovarian cancer and an age-matched group of women from the community by logistic regression. RESULTS: Altogether, 129 Olmsted County women were newly diagnosed with ovarian cancer in 1975-1991. The age-adjusted (to 1970 United States whites) incidence rate was 22.5 per 100,000 person-years. Median survival from initial diagnosis was 3.7 years. Compared to an equal number of controls, the 103 women with invasive epithelial disease were more likely to be nulliparous (odds ratio [OR] 1.9; 95% CI 0.95-3.9) but less likely to have a history of thyroid disease (OR 0.4; 95% CI 0.2-0.8), hypertension (OR 0.4; 95% CI 0.1-0.9) or nonsteroidal estrogen use (OR 0.5; 95% CI 0.2-0.9). Prior hysterectomy (OR 0.5; 95% CI 0.2-0.9) and unilateral oophorectomy (OR 0.2; 95% CI 0.04-0.7) were also associated with reduced risk. CONCLUSION: The incidence of ovarian cancer in this community in 1975-1991 was little changed from rates 20 years earlier. There has been some improvement in survival from ovarian cancer in this population compared to 1935-1974, but still less than 50% survive for 5 years. Prior hysterectomy and unilateral oophorectomy appear protective for ovarian cancer.

Nonsteroidal anti-inflammatory drug use and Alzheimer's disease: a case-control study in Rochester, Minnesota, 1980 through 1984.

OBJECTIVE: To compare the frequency of use of nonsteroidal anti-inflammatory drugs (NSAIDs) among 302 incident cases of Alzheimer's disease (AD) and age- and sex-matched control subjects. DESIGN: We undertook a retrospective case-control study, using the resources of the Rochester Epidemiology Project. MATERIAL AND METHODS: In ongoing studies of dementia in Rochester, Minnesota, we identified all incident cases of AD with onset between 1980 and 1984. From among all Rochester residents who received care at Mayo Clinic Rochester during those years, we selected one age- (within 3 years) and sex-matched control subject. For this study, exposure to a prescription NSAID was defined as prescribed use for 7 or more days during the 2-year window of time encompassing the year of onset and the year before onset among cases and the corresponding index year and the year prior for control subjects. RESULTS: The odds ratio (OR) for exposure, as described, to a prescription NSAID versus no exposure to any NSAID was 0.79 (95% confidence interval [CI], 0.45 to 1.38); the OR was 1.00 (95% CI, 0.52 to 1.92) for women and 0.40 (95% CI, 0.13 to 1.29) for men. Similarly, the overall OR for aspirin exposure versus no NSAID exposure was 0.90 (95% CI, 0.54 to 1.50). CONCLUSION: These data are suggestive but not confirmatory of a protective effect of NSAIDs for AD.

Risk of Alzheimer's disease among elderly patients with anemia: population-based investigations in Olmsted County, Minnesota.

PURPOSE: To evaluate the association, if any, between Alzheimer's disease (AD) and anemia among the elderly. METHODS: Both case-control and cohort methodologies were used to evaluate this association. The case-control study included all incident cases of AD whose onset occurred during 1980-1984 in Rochester, MN (n = 302). An age- and gender-matched control was selected from among Rochester residents seen for care at Mayo Clinic during the year of onset of the case. All community medical records for cases and controls were reviewed to identify women with hemoglobin levels of < 12 g/dL and men with hemoglobin levels of < 13 g/dL during the year of onset and the prior year for cases and during the index year and year prior for controls. Logistic regression was used to estimate odds ratios (OR). The retrospective cohort study used the 618 residents of Olmsted County, MN, who were > or = 65 years of age and whose anemia, as defined above, was newly recognized in 1986. Standardized incidence ratios (SIR) for AD were estimated by use of the person-years of follow-up in the cohort and the incidence rates of AD for this community. RESULTS: In the case-control study, an almost twofold increase in occurrence of AD was associated with anemia (OR, 1.88; 95% CI, 1.17-3.03). For men and women, respectively, the ORs were 1.81 (95% CI, 0.75-4.39) and 1.96 (95% CI, 1.11-3.47). The cohort study showed no overall increase in risk of AD (SIR, 0.98; 95% CI, 0.67-1.37). For men, the SIR was a comparable 1.49 (95% CI, 0.79-2.56), whereas for women the SIR was only 0.79 (95% CI, 0.49-1.23). CONCLUSIONS: Although anemia may be a risk factor for AD in the elderly, the mechanism by which anemia contributes to the pathogenesis of AD or to the unmasking of AD symptoms is unknown.

Complications leading to surgery after breast implantation.

BACKGROUND: Local complications that require additional surgical procedures are an important problem for women with breast implants. METHODS: We studied 749 women who lived in Olmsted County, Minnesota, and received a first breast implant at the Mayo Clinic between 1964 and 1991. We identified complications that occurred after the initial procedure and after any subsequent implantation. A complication was defined as a surgical procedure performed for any of the following reasons: capsular contracture; rupture of the implant; hematoma or bleeding; infection or seroma of the wound; chronic pain; extrusion, leakage, or sweating of the implant; necrosis of the nipple, areola, or flap; malfunction of the filler port of a tissue expander; and wound dehiscence. RESULTS: During follow-up (mean, 7.8 years; range, 0 to 25.8), 208 (27.8 percent) of the women underwent 450 additional implant-related surgical procedures. Ninety-one (20.2 percent) were anticipated, staged procedures or were done because the patient requested a size change or aesthetic improvement, and 359 procedures (79.8 percent) had at least one clinical indication (thus constituting a complication). Complications occurred in 178 (23.8 percent) of the 749 women and involved 274 (18.8 percent) of the 1454 breasts with implants and 321 (18.8 percent) of the 1703 implants. The most frequent problem was capsular contraction (272 cases), followed by rupture of the implant (60), hematoma (55), and wound infection (23). The rate of complications was significantly lower (P<0.001) among women with cosmetic implants (6.5 percent at one year, 12 percent at five years) than among women who underwent implantation after mastectomy for breast cancer (21.8 percent at one year, 34 percent at five years) or prophylactic mastectomy (17.3 percent at one year, 30.4 percent at five years). CONCLUSIONS: Women who have had breast implantation frequently experience local complications during the subsequent five years. Complications were significantly less frequent among patients who received implants for cosmetic reasons than among those who received implants after mastectomy for cancer or for cancer prophylaxis.

Cause of death in Alzheimer's disease.

Cause of death among 917 of the 959 subjects in a population-based incidence cohort with Alzheimer's disease (AD) during the years 1960 to 1984 was compared to that of an age- and gender-matched control group (n = 703). In general, a summary of the diagnostic codes entered anywhere on a death certificate suggests that control subjects had more cardiovascular disease and neoplasms than did patients, while patients more often had a diagnostic code of bronchitis/pneumonia (P < 0.01). By logistic regression, this difference remained statistically significant after adjusting for age and gender.

Epidemiology of dementia in Rochester, Minnesota.

OBJECTIVE: To present the results of several retrospective epidemiologic studies of dementia in Rochester, Minnesota. MATERIAL AND METHODS: These studies were done by using the medical records-linkage resources of the Rochester Epidemiology Project. RESULTS: The incidence and prevalence of dementia increase sharply with advancing age. No difference is noted in overall age-adjusted incidence rates by gender. Rochester studies provide the only 25-year time trend analyses of the incidence of dementia in the United States. Time trends over three prevalence dates indicate an increase in prevalence in this community. Survival is decreased among patients with dementing illness. Case-control studies of Alzheimer's disease (AD) show that general medical conditions, previous head injury, thyroid disease, exposure to therapeutic radiation, anesthesia, and blood transfusion are generally not risk factors for AD. Patients with depression may have an increased risk for the development of AD. Sociodemographic factors such as education, occupation, marital status, and type of dwelling were not significantly different among patients with AD and their age-and gender-matched control subjects. CONCLUSION: The Rochester Epidemiology Project has proved to be an excellent resource for the study of the incidence, prevalence, and risk factors for dementia.

Effects of diet and exercise on qualitative and quantitative measures of LDL and its susceptibility to oxidation.

The purpose of this study was to investigate the effects of an intensive diet and exercise program on the quantity and quality of LDL as well as its susceptibility to in vitro oxidation. The diet was low in fat (< 10% kcal) and cholesterol (< 100 mg/d), while high in complex, unrefined carbohydrates (> 70% kcal) and fiber (35 g/1000 kcal). The study was composed of 80 participants in a 3-week residential program where food was provided ad libitum and there was daily aerobic exercise, primarily walking. In each subject, preparticipation and postparticipation fasting blood samples were drawn and LDL was isolated via density gradient ultracentrifugation. LDL particle diameter was determined by gradient gel electrophoresis of serum (n = 23). Isolated LDL was either separated into 6 subfractions by saline gradient equilibrium ultracentrifugation (n = 26) or subjected to in vitro copper oxidation (n = 32). Significant reductions (P < .01) in serum levels of cholesterol (20%). LDL-cholesterol (20%), HDL-cholesterol (17%), triglycerides (26%), and glucose (16%) as well as in body weight (4%) were noted for the total population. The mean particle diameter of the LDL increased (24.2 +/- 0.2 to 25.1 +/- 0.14 nm, P < .01) and was correlated with the reduction in serum triglycerides (r = .58, P < .01). Six of 22 subjects changed in LDL phenotype from B (< or = 25.5 nm) to A (> 25.5 nm). The percentage of LDL-cholesterol carried in the more dense subfractions fell significantly, while that carried by the less dense fractions increased. Initial oxidation levels fell (21%), while the lag time before copper-induced oxidation increased (13%). Reductions were observed in both the rate of oxidation (16%) and peak oxidation (20%). All of these changes should result in a dramatic reduction in the risk for atherosclerosis and its clinical sequelae.

Mental retardation in a birth cohort, 1976-1980, Rochester, Minnesota.

The cumulative incidence of mental retardation in a birth cohort of children born from 1976 through 1980 in Rochester, Minnesota (n = 5,919) was estimated. Rochester is the site of the Rochester Epidemiology Project, which captures virtually all medical care delivered locally. Passive follow-up through school and community medical records for criteria diagnostic of mild or severe mental retardation was undertaken. Thirty children were classified with mental retardation. The cumulative incidence of mental retardation by age 8 years was 9.1 per 1,000 (95% confidence interval = 6.2, 13.0) and was similar for boys and girls (8.3 vs. 10.0 per 1,000, respectively). The cumulative incidence for severe mental retardation in girls was more than twice that in boys; for mild retardation it was the opposite. The cumulative incidence among boys was 1.7 times greater than the cumulative incidence for girls. Results suggest that although the overall incidence of mental retardation by gender was similar, the severity may differ somewhat.

Dementia after ischemic stroke: a population-based study in Rochester, Minnesota (1960-1984)

We used the medical records linkage system for the population of Rochester, Minnesota, to identify persons in the community who had their first cerebral infarct without previous dementia. In this cohort (n = 971), the incidence of dementia in the first year was nine times greater than expected, but if we did not observe dementia in the first year, the risk of dementia in the cohort each year thereafter was about twice the risk in the population. After the first year, a 50% increase was observed in Alzheimer's disease in the cohort compared with that in the community. Although the incidence of dementia increased with increasing age, the standardized morbidity ratios decreased with increasing age. Age, sex (male), and second stroke were significant independent predictors of dementia in a multivariate Cox proportional hazards model. There was no effect of location or clinical severity of infarct on the rate of occurrence of dementia.

Impact of referral bias on clinical and epidemiological studies of Alzheimer's disease.

We used the resources of the Rochester Epidemiology Project to compare sociodemographic and clinical characteristics in three groups of Alzheimer's disease patients. The first group included incidence cases occurring among residents of Rochester, Minnesota (population-based series; n = 241). The second group was a sample of patients referred to the Mayo Clinic form the remainder of Minnesota and the four surrounding states (n = 58); the third was a sample referred from the remainder of the United States (n = 94). Patients from Rochester were more frequently women, less highly educated, less commonly white collar workers, more frequently institutionalized, less frequently married, and more often lived along than those in the two referral groups. Patients from Rochester also had a more advanced age of onset of dementia. For occupation, education, and living arrangement, the differences across groups increased with increasing distance of referral. Clinical and epidemiological studies based on patients referred form primary to secondary or tertiary care centers may suffer from severe selection bias.

Incidence of sudden infant death syndrome in Olmsted County, Minnesota: 1945 through 1992.

OBJECTIVE: To apply uniform diagnostic criteria for sudden infant death syndrome (SIDS) for an extended period for comparison of incidence rates from 1945 to 1992 in Olmsted County, Minnesota, to investigate the influence of a person-time or live birth denominator on the estimate of incidence, to calculate the proportionate mortality rate for SIDS over time, and to evaluate the accuracy of death certificates for case ascertainment and the role of interobserver variation in case classification. DESIGN: We retrospectively reviewed the autopsy results and complete medical records for all infant death from 1945 through 1992 for residents of Olmsted County, Minnesota. MATERIAL AND METHODS: Cases were identified from a computerized list of all Olmsted County deaths of infants occurring at ages 48 hours to 365 days. All resident cases were categorized as non-SIDS, possible SIDS, SIDS, or incomplete, on the basis of findings from autopsy and clinical history. Incidence rates were calculated for two different SIDS groups and with use of denominators of person-time and live births. RESULTS: For the study period, 82 cases of SIDS were identified (97% white and 3% Asian). The mean age at death was 12.5 weeks; male infants constituted 59% of cases. No significant trend in seasonal distribution was noted; 73% of deaths occurred between midnight and noon. The incidence rate, defined as SIDS definite and possible deaths per 1,000 resident live births, increased from 0.55 in 1950 through 1953 to 1.28 in 1990 through 1992. The secular trend was best described by a linear model with constant positive slope. Similar trends were observed with other definitions of incidence. During the study period, SIDS as a percentage of total infant deaths dramatically increased, ranging from 2.5 in 1950 through 1953 to 17.9 in 1990 through 1992. The death certificate diagnosis correctly predicted 72% of SIDS cases before 1970 and 100% of cases after 1970. CONCLUSION: Since 1945, the incidence of SIDS apparently has increased, although diagnostic transfer from other causes of death probably contributes to the observed trend. The comparison of live births versus person-time as denominators showed no significant difference in incidence rates. Interobserver reliability is modest for SIDS cases diagnosed before 1970 and may contribute to the variability in reported SIDS incidence rates.

Trends in colorectal cancer over a half century in Rochester, Minnesota, 1940 to 1989.

Recent reports of increasing incidence, especially in men, led us to update through 1989 an earlier study of colorectal cancer incidence in Rochester that covered the period 1940 through 1979. The combined data reflected cancer trends in the community over half a century. Data resources of the Rochester Epidemiology Project were used to identify new cases of colon and rectal cancer among Rochester residents. Incidence rates were estimated using decennial census data, and 95% confidence intervals were based on the Poisson distribution. The GLIM statistical package was used to evaluate trends over time. Age-adjusted (US white 1970) incidence rates of colorectal cancer for men were 53.7, 61.3, 53.7, 54.2, and 52.5 per 100,000 person-years, respectively, for the decades 1940 to 1949, 1950 to 1959, 1960 to 1969, 1970 to 1979, and 1980 to 1989. Comparable rates for women were 42.7, 49.3, 42.9, 40.7, and 40.9 per 100,000 person-years. No statistically significant changes were seen in the incidence of colon and rectum cancer for men or women. There was no consistent trend in tumor stage at diagnosis and the mean size of the initial lesion did not change with time. The incidence of colorectal cancer has not changed over the past 50 years in this community where case ascertainment has been consistent and complete.

Trends in the utilization of silicone breast implants, 1964-1991, and methodology for a population-based study of outcomes.

Using the unique data resources of the Rochester Epidemiology Project, we have designed a population-based retrospective cohort study to examine the risks and complications of silicone breast implants among 749 Olmsted County, Minnesota, women who received these devices between 1964 and 1991, and 1498 control women who did not receive such devices. In this paper, we present data describing the population-based trends in the utilization of these devices from 1964 to 1991. In addition, we discuss the case ascertainment, outcome assessment, and reliability of the data collection for the outcomes study. The utilization of breast implants increased markedly over the past 30 yr with the rate of new implants per 100,000 women (> or = 15 years of age) rising from 3.5 in 1964 to 95 in 1979, remaining stable thereafter. The prevalence of breast implants among Olmsted County women > or = 15 years of age on 1 January 1992 was approx. 1%. An examination of the characteristics of these women reveals that recent utilization of breast implants has increased more rapidly among rural than among urban women, that the proportion of women receiving implants for breast cancer mastectomy reconstruction has increased in recent years, and that the great majority of women receiving implants are married at the time of implant. These trends also revealed that the average age of women who receive implants is rising and that in more recent years both much younger and much older women are receiving implants.

The prevalence of dementia is changing over time in Rochester, Minnesota.

Resources of the Rochester Epidemiology Project were used to estimate prevalence rates for dementia on January 1, 1975, 1980, and 1985, and to evaluate trends over time. Prevalence rates increased with age for both men and women. There was no difference in the prevalence rates for January 1, 1975, and January 1, 1980, but there was a significant increase between January 1, 1980, and January 1, 1985. Similar results were found for Alzheimer's disease. Age was an important factor in the trend data. The apparent increase in prevalence over time is probably multifactorial.

Are patients with Alzheimer's disease surviving longer in recent years?

We report the survival experience of the incidence cohort of Alzheimer's disease (AD) patients in Rochester, Minnesota, whose onset occurred during the years 1960 to 1984. Survival was evaluated relative to year of onset, age at onset, and gender. Survival was better among women than men and improved for those with AD with more recent onset. The relative hazard decreased by a factor of 0.82 for each decade. The effect of age at onset was nonlinear, indicating that the hazard of death does not change at a constant rate with age.

Comparison of respondents and nonrespondents in an osteoporosis study.

We attempted to enroll an age-stratified random sample of Rochester, Minnesota women > or = 30 years of age in a population-based prospective study of the determinants of bone loss. Using the resources of the Rochester Epidemiology Project, 541 women were contacted and 305 agreed to participate. Of 236 nonrespondents, 38 were ineligible and 198 refused to participate resulting in a 61% response rate for eligible subjects. We reviewed community medical records for respondents and nonrespondents (including ineligibles) to determine whether the two groups differed with regard to variables that might be important in osteoporosis research. There was little difference between respondents and nonrespondents for a history of cigarette smoking, hyperthyroidism, thyroidectomy, or age-related fractures. Respondents survived better, were less likely to be obese or have renal failure, and more likely to have had an oophorectomy and consume alcohol (P < 0.01). These data suggest that nonrespondents were less healthy than respondents.

Incidence of multiple myeloma in Olmsted County, Minnesota: 1978 through 1990, with a review of the trend since 1945.

PURPOSE: Incidence rates of multiple myeloma appear to have increased in recent decades, but it is difficult to compare the incidence rates over time because of changes in laboratory procedures, differences in diagnostic criteria, and variations in indexing of medical records. However, Olmsted County, Minnesota, provides a rare opportunity to minimize these limitations, because the medical care has been provided mainly by the Mayo Clinic. PATIENTS AND METHODS: Records of Olmsted County residents with a diagnosis of multiple myeloma from January 1, 1978 through December 31, 1990 were reviewed. Criteria for diagnosis and residency were the same as in previous Olmsted County studies. RESULTS: The incidence rate per 100,000 age-adjusted to the 1950 United States white population was 5.4 for males and 2.8 for females; the overall rate was 4.1. The rates were age-adjusted to the 1950 United States population for comparison with earlier data from this population. The rates increased with age for both sexes. There was no significant change in incidence rates from 1945 through 1990. A comparison of the median age for Olmsted County patients with the age of those referred to the Mayo Clinic from elsewhere indicated that the local patients were appreciably older (74 v. 62 years, respectively). Thirty-two of 55 patients (58%) with multiple myeloma from 1978 through 1990 had a monoclonal plasma-cell proliferative process before the diagnosis of multiple myeloma. CONCLUSION: The incidence rate of multiple myeloma in Olmsted County, Minnesota, has not changed significantly during the past 46 years. We believe that reports of increasing rates over time are mainly due to improved case ascertainment.

Incidence and prevalence of Huntington's disease in Olmsted County, Minnesota (1950 through 1989).

OBJECTIVE: To calculate average annual incidence rates for Huntington's disease (HD) from 1950 through 1989 and to estimate prevalence rates of the disease for January 1, 1960, and January 1, 1990. DESIGN: Health care records from all sources, including hospitals, outpatient clinics, and long-term care institutions, are readily available for all inhabitants of Olmsted County, Minnesota. The diagnoses entered in these records have been coded and indexed. All health care records containing a diagnosis that might suggest HD were reviewed, and those patients for whom the symptoms of HD began between January 1, 1950, and December 31, 1989, were identified. We used specific criteria for diagnosing HD. PARTICIPANTS: Health care records were reviewed; residence in Olmsted County during the year of symptom onset was required. MAIN OUTCOME MEASURES: Average annual incidence rates and prevalence rates for January 1, 1960, and January 1, 1990. RESULTS: Overall incidence rates were 0.4 (95% confidence interval [CI], 0.1 to 0.8) for women and 0.2 (95% CI, 0.04 to 0.6) for men per 100,000 person-years. Estimated prevalence rates for January 1, 1960, per 100,000 person-years were 6 (95% CI, 0.7 to 21.5) for women and 6.6 (95% CI, 0.8 to 23.8) for men. For January 1, 1990, the prevalence rates were 1.8 (95% CI, 0.04 to 10.2) for women and 2 (95% CI, 0.05 to 10.9) for men. CONCLUSIONS: Incidence and prevalence rates of HD in this community are similar to those reported in other communities. The small numbers of affected persons do not allow an estimate of variation over time.

Fracture risk in patients with Alzheimer's disease.

OBJECTIVE: To assess the risk of fracture following onset of Alzheimer's disease. DESIGN: Retrospective (historical) cohort study. SETTING: Population-based in Rochester, Minnesota. PARTICIPANTS: All 543 Rochester residents with onset of Alzheimer's disease during the 10-year period, 1975-84, and an equal number of age- and sex-matched controls from the community. MEASUREMENTS: Fractures were assessed through review of each subject's complete (inpatient and outpatient) medical records in the community. MAIN RESULTS: Rochester residents with Alzheimer's disease were no more likely to have a history of fracture prior to onset than were matched controls from the same population. During the year of onset, there was a 2-fold excess of fractures at various sites among those with Alzheimer's disease. The risk ratio for any fracture subsequently was 1.1 (95% CI 0.9, 1.3), and this slight increase was accounted for entirely by a 2.7-fold increase in the risk of hip fracture (95% CI 1.8, 4.2). CONCLUSIONS: Fracture risk was not increased before the onset of Alzheimer's disease, although there was an excess of fractures around the time that Alzheimer's disease came to clinical attention. Fracture risk was not elevated thereafter except for a substantial increase in the risk of hip fracture. This suggests a link with certain falls rather than generalized disuse osteoporosis.