Chronic hyponatremia and association with osteoporosis among a large racially/ethnically diverse population.

Chronic hyponatremia may contribute to decreased bone density. We studied 341,003 men and women who underwent DXA testing and observed that individuals with chronic hyponatremia (sodium < 135 mEq/L) had an 11% greater likelihood of having osteoporosis. There was a dose-dependent effect with lower sodium and stronger association with osteoporosis. INTRODUCTION: Chronic hyponatremia has been associated with both neurologic deficits and increased risk of gait abnormalities leading to falls and resultant bone fractures. Whether chronic hyponatremia contributes to decreased bone density is uncertain. We evaluated whether chronic, mild hyponatremia based on serial sodium measurements was associated with increased risk of osteoporosis within a large, ethnically diverse population. METHODS: This is a retrospective cohort study between January 1, 1998 and December 31, 2014 within Kaiser Permanente Southern California, an integrated healthcare delivery system. Men and women were aged ≥ 55 years with ≥ 2 serum sodium measurements prior to dual-energy X-ray absorptiometry (DXA) testing. Time-weighted (TW) mean sodium values were calculated by using the proportion of time (weight) elapsed between sodium measurements and defined as < 135 mEq/L. Osteoporosis defined as any T-score value ≤ - 2.5 of lumbar spine, femoral neck, or hip. RESULTS: Among 341,003 individuals with 3,330,903 sodium measurements, 11,539 (3.4%) had chronic hyponatremia and 151,505 (44.4%) had osteoporosis. Chronic hyponatremic individuals had an osteoporosis RR (95% CI) of 1.11 (1.09, 1.13) compared to those with normonatremia. A TW mean sodium increase of 3 mEq/L was associated with a lower risk of osteoporosis [adjusted RR (95% CI) 0.95 (0.93, 0.96)]. A similar association was observed when the arithmetic mean sodium value was used for comparison. CONCLUSIONS: We observed a modest increase in risk for osteoporosis in people with chronic hyponatremia. There was also a graded association between higher TW mean sodium values and lower risk of osteoporosis. Our findings underscore the premise that chronic hyponatremia may lead to adverse physiological effects and responses which deserves better understanding.

Using winter 2009-2010 to assess the accuracy of methods which estimate influenza-related morbidity and mortality.

We used the winter of 2009-2010, which had minimal influenza circulation due to the earlier 2009 influenza A(H1N1) pandemic, to test the accuracy of ecological trend methods used to estimate influenza-related deaths and hospitalizations. We aggregated weekly counts of person-time, all-cause deaths, and hospitalizations for pneumonia/influenza and respiratory/circulatory conditions from seven healthcare systems. We predicted the incidence of the outcomes during the winter of 2009-2010 using three different methods: a cyclic (Serfling) regression model, a cyclic regression model with viral circulation data (virological regression), and an autoregressive, integrated moving average model with viral circulation data (ARIMAX). We compared predicted non-influenza incidence with actual winter incidence. All three models generally displayed high accuracy, with prediction errors for death ranging from -5% to -2%. For hospitalizations, errors ranged from -10% to -2% for pneumonia/influenza and from -3% to 0% for respiratory/circulatory. The Serfling and virological models consistently outperformed the ARIMAX model. The three methods tested could predict incidence of non-influenza deaths and hospitalizations during a winter with negligible influenza circulation. However, meaningful mis-estimation of the burden of influenza can still result with outcomes for which the contribution of influenza is low, such as all-cause mortality.

Ten-year hip fracture incidence rate trends in a large California population, 1997-2006.

UNLABELLED: Hip fractures are a large public health problem with significant negative impact on an individual's overall health and survival. But while the total numbers of persons affected by hip fractures may be anticipated to increase, incidence rates appear to be declining. INTRODUCTION: To describe annual hip fracture incidence rate trends in an integrated health-care organization over 1997-2006, during which a proactive bone health program was initiated program-wide and other secular trends occurred in the population. METHODS: For this ecologic trend study, we identified all men and women ≥45 years old as of January 1 of each year. Incident fractures for each year were identified using ICD-9 diagnosis codes 820-820.9, excluding all subjects who had fractures in prior years. Annual person-time at risk for hip fracture was determined from enrollment data. Sex- and age-specific and adjusted annual incidence rates were calculated. RESULTS: The overall annual hip fracture incidence rate for men declined from 1.52/1,000 person-years in 1997 to 1.29/1,000 person-years in 2006, a 15.3% (95% confidence interval [CI]=6.2-24.5) decrease. For women, incidence declined from 2.65/1,000 person-years in 1997 to 2.24/1,000 person-years in 2006, a 15.3% (95% CI=8.7-21.9) decrease. Among subjects aged 85 years or older, incidence rates for men declined from 27.0/1,000 to 18.9/1,000 person-years, and for women they declined from 32.7/1,000 to 27.1/1,000 person-years. CONCLUSION: Hip fracture incidence has been declining in all age groups over the past 10 years. While many factors may contribute to this decline, the results are consistent with a potential benefit of the active bone health intervention.

Mapping the facioscapulohumeral muscular dystrophy gene is complicated by chromsome 4q35 recombination events.

A gene responsible for facioscapulohumeral muscular dystrophy (FSHD) has been linked to polymorphisms on chromosome 4q35. Multipoint linkage analyses have placed this gene distal to all reported genetic markers on the chromosome. By using as a probe a clone isolated from a cosmid containing sequences related to a homeobox domain, de novo DNA rearrangements were reported in sporadic and familial cases of FSHD. Linkage analysis of an EcoRI polymorphism detected by this clone in twenty-four multigenerational FSHD families revealed recombinants between this marker and the disease with a recombination fraction of 0.05. Two families with apparent germline mosaicism were also identified.

Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study.

OBJECTIVES: The aim of this study was to examine a large cohort of adults who received the zoster vaccine for evidence of an increased risk of prespecified adverse events requiring medical attention. DESIGN: Two self-comparison approaches, including a case-centred approach and a self-controlled case series (SCCS) analysis were used. SETTING: Eight managed-care organizations participating in the Vaccine Safety Datalink project in the United States. SUBJECTS: A total of 193 083 adults aged 50 and older receiving a zoster vaccine from 1 January 2007 to 31 December 2008 were included. MAIN OUTCOME MEASURES: Prespecified adverse events were identified by aggregated International Classification of Diseases, Ninth Revision (ICD-9) codes in automated health plan datasets. RESULTS: The risk of allergic reaction was significantly increased within 1-7 days of vaccination [relative risk = 2.13, 95% confidence interval (CI): 1.87-2.40 by case-centred method and relative rate = 2.32, 95% CI: 1.85-2.91 by SCCS]. No increased risk was found for the following adverse event groupings: cerebrovascular events; cardiovascular events; meningitis; encephalitis; and encephalopathy; and Ramsay-Hunt syndrome and Bell's palsy. CONCLUSIONS: The results of this study support the findings from the prelicensure clinical trials, providing reassurance that the zoster vaccine is generally safe and well-tolerated with a small increased risk of allergic reactions in 1-7 days after vaccination.

Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.

OBJECTIVE: An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance. Design. Subjects were followed for 180days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions. SETTING: Two managed care organizations in California. Subjects. Number of 189,629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008. OUTCOME: Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC). RESULTS: Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31-40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR=1.29, 95% confidence interval: 1.08-1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study. CONCLUSIONS: No autoimmune safety signal was found in women vaccinated with HPV4.

Racial and ethnic disparities in diabetes risk after gestational diabetes mellitus.

AIMS/HYPOTHESIS: To investigate racial/ethnic disparities in diabetes risk after gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort study of women enrolled in the Kaiser Permanente Southern California health plan from 1995 to 2009. GDM status was identified on the basis of plasma glucose levels during pregnancy. The incidence of diabetes after the first delivery complicated by GDM before 31 December 2009 (n = 12,998) was compared with the experience for women without GDM (n = 64,668) matched on maternal age at delivery, race/ethnicity and year of delivery (1:5 ratio). Matched Cox regression was used to compare the RRs of diabetes associated with GDM within and across racial/ethnic groups. RESULTS: Compared with the women without GDM, the HRs (95% CI) of diabetes for women after GDM were 6.5 (5.2, 8.0) in non-Hispanic white, 7.7 (6.8, 8.7) in Hispanic, 9.9 (7.5, 13.1) in black and 6.3 (5.0, 7.9) in Asian/Pacific Islanders after adjustment for parity, maternal education, comorbidity and number of outpatient visits before the index pregnancy. The HR of diabetes for black women was significantly higher than that for non-Hispanic white women (p = 0.032). Further adjustment for prepregnancy BMI reduced the diabetes risk association with GDM for each racial/ethnic group, but did not explain the risk differences across groups. CONCLUSIONS/INTERPRETATIONS: Racial/ethnic disparities exist in risk of diabetes after GDM. Black women with GDM had the highest risk of developing diabetes. This highlights the importance of developing an effective diabetes screening and prevention programme in women with GDM, particularly black women with GDM.

Do cardiovascular risk factors confer the same risk for cardiovascular outcomes in rheumatoid arthritis patients as in non-rheumatoid arthritis patients?

OBJECTIVE: To compare the frequency of traditional cardiovascular (CV) risk factors in rheumatoid arthritis (RA) compared to non-RA subjects, and examine their impact on the risk of developing selected CV events (myocardial infarction (MI), heart failure (HF) and CV death) in these two groups. METHODS: We examined a population-based incidence cohort of subjects with RA (defined according to the 1987 American College of Rheumatology criteria), and an age- and sex-matched non-RA cohort. All subjects were followed longitudinally through their complete community medical records, until death, migration, or 1 January 2001. Clinical CV risk factors and outcomes were defined using validated criteria. The chi2 test was used to compare the frequency of each CV risk factor at baseline. Person-years methods were used to estimate the rate of occurrence of each CV risk factor during follow-up. Cox models were used to examine the influence of CV risk factors on the development of CV outcomes. RESULTS: A total of 603 RA and 603 non-RA subjects (73% female; mean age 58 years) were followed for a mean of 15 and 17 years (total: 8842 and 10,101 person-years), respectively. At baseline, RA subjects were significantly more likely to be former or current smokers when compared to non-RA subjects (p<0.001). Male gender, smoking, and personal cardiac history had weaker associations with CV events among RA subjects, compared to non-RA subjects. There was no significant difference between RA and non-RA subjects in the risk imparted with respect to the other CV risk factors (ie, family cardiac history, hypertension, dyslipidaemia, body mass index, or diabetes mellitus). CONCLUSION: While some traditional CV risk factors imparted similar risk among RA compared with non-RA subjects, others (ie, male gender, smoking and personal cardiac history) imparted significantly less risk for the development of CV disease. These differences in the overall impact of traditional CV risk factors suggest that strategies to prevent CV disease and mortality focused solely on controlling traditional CV risk factors may be relatively less beneficial in RA subjects than in the general population. Further research is needed to determine optimal approaches to reducing CV morbidity and mortality in persons with RA.

Regulation of methionine adenosyltransferase in normal diploid and simian virus 40-transformed human fibroblasts.

Methionine adenosyltransferase activity in normal diploid and simian virus 40 (SV40)-transformed human fibroblasts increased severalfold when cell monolayers were cultured in medium deficient in L-methionine. This increase in methionine adenosyltransferase activity required RNA and protein syntheses and probably represented a derepression of the enzyme's biosynthesis. Furthermore, studies with RNA synthesis inhibitors suggested that the regulation of this enzyme activity in human fibroblasts involved posttranscriptional mechanisms. The inclusion of homocysteine thiolactone, a metabolic precursor of methionine, in the methionine-deficient medium inhibited the derepression in normal human fibroblasts but augmented the derepression in fully transformed fibroblasts. These differences in derepression patterns thus appeared related to altered metabolism of homocysteine and/or methionine in SV40-transformed human fibroblasts and as such may serve as a transformation marker in SV40-transformed cells.

Role of HPC2/ELAC2 in hereditary prostate cancer.

The HPC2/ELAC2 gene on chromosome 17p was recently identified as a candidate gene for hereditary prostate cancer (HPC). To confirm these findings, we screened 300 prostate cancer patients (2 affected members/family) from 150 families with HPC for potential germ-line mutations using conformation-sensitive gel electrophoresis, followed by direct sequence analysis. The minimum criteria for our families with HPC was the presence of 3 affected men with prostate cancer. A total of 23 variants were identified, including 13 intronic and 10 exonic changes. Of the 10 exonic changes, 1 truncating mutation was identified, a Glu216Stop nonsense mutation. This nonsense variant was found in 2 of 3 affected men in a single family. The remaining nine alterations included five missense, three silent, and one variant in the 3' untranslated region. To additionally test for potential associations of polymorphic variants and increased risk for disease, we genotyped two common polymorphisms, Ser217Leu and Ala541Thr, in 446 prostate cancer patients from 164 families with HPC and 502 population-based controls. The frequency of the Leu217 variant was similar for patients (32.3%) and controls (31.8%), as was the frequency of the Thr541 variant (5.4% among patients versus 5.2% among controls). In contrast to previous reports, we found no association of the joint effects of Leu271 and Thr541 (odds ratio, 1.04; 95% confidence interval, 0.57-1.89). Overall, our results did not reveal any association between these two common polymorphisms and the risk for HPC. The finding of a nonsense mutation in the HPC2/ELAC2 gene confirms its potential role in genetic susceptibility to prostate cancer. However, our data also suggest that germ-line mutations of the HPC2/ELAC2 are rare in HPC and that the variants Leu217 and Thr541 do not appear to influence the risk for HPC. Cumulatively, these results suggest that alterations within the HPC2/ELAC2 gene play a limited role in genetic susceptibility to HPC.

Constitutive behavior of methionyl-tRNA synthetase compared to repressible behavior of methionine adenosyltransferase in mammalian cells.

Methionine adenosyltransferase, one of the two major enzymes utilizing methionine, is regulated by the levels of methionine in the growth medium (Jacobsen, S.J., Hoffman, R.M. and Erbe, R.W. (1980) J. Natl. Cancer Inst. 65, 1237--1244, and Caboche, M. and Mulsant, P. (1978) Somatic Cell Genet. 4, 407--421). We report here that methionyl-tRNA synthetase, unlike methionine adenosyltransferase, behaves in a constitutive manner with respect to the concentration of methionine in the culture medium. This behavior is seen in Chinese hamster ovary cells and in normal diploid and SV40-transformed human fibroblasts. Although the kinetics of regulation of methionine adenosyltransferase and methionyl-tRNA synthetase by exogenous methionine are clearly different, the levels of the two enzymes in the human cell lines are similar.

Syncope in children and adolescents.

OBJECTIVES: The objectives of this study were to 1) define the incidence of syncope coming to medical attention among children and adolescents, 2) determine the outcome of syncope in these patients, and 3) determine changes over time in the evaluation and charges for evaluating this problem. BACKGROUND: Syncope occurs commonly in children and adolescents. However, the mid- and long-term outcome of children and adolescents who experience syncope is unknown. METHODS: Utilizing the Rochester Epidemiology Project, we determined the incidence, outcome and charges for medical evaluation for patients seeking medical attention for syncope during an early 5-year period (1950 to 1954) and a more recent 5-year period (1987 to 1991). RESULTS: The incidence of syncope coming to medical attention was 71.9 and 125.8/100,000 population for the early and more recent cohort, respectively. The incidence was higher for female than for male patients. The incidence peaked in 15- to 19-year old patients. Acute illness and noxious stimuli were associated with 24% and 23% of the episodes, respectively. Although long-term survival was not different from that of the general population, one child died suddenly, and another had hereditary prolonged QT interval syndrome. These were two of only six patients who had exertional syncope. Total charges for evaluation of syncope were similar in the two time periods. However, charges for testing procedures were greater for the more recent cohort. CONCLUSIONS: In general, syncope in children and adolescents is a benign event. Syncope occurring during exercise may identify patients with a potentially fatal condition. Detailed evaluation should be considered for patients who have syncope during exercise or who have a family history of syncope, sudden death, myocardial disease or arrhythmias. It may be prudent to obtain an electrocardiogram for all patients who seek medical attention for syncope.

Use of echocardiography in the management of congestive heart failure in the community.

OBJECTIVES: We evaluated the use and the impact of echocardiography in patients receiving an initial diagnosis of congestive heart failure in Olmsted County, Minnesota, in 1991. BACKGROUND: The American College of Cardiology/American Heart Association clinical practice guidelines recommend echocardiography in all patients with suspected congestive heart failure. No data are available on use and impact of echocardiography in management of congestive heart failure in a community. METHODS: The medical records linkage system of the Rochester Epidemiology Project was used to identify all 216 patients who satisfied the Framingham criteria for congestive heart failure. Of these, 137 (63%) underwent echocardiography within 3 weeks before or after the episode of congestive heart failure (Echo group), and the other 79 patients constitute the No-Echo group. RESULTS: The No-Echo group patients were older (p=0.022), were more likely to be female (p=0.072), had milder symptoms (p=0.001) and were less often hospitalized at diagnosis (p=0.001). Fewer patients in the No-Echo group were treated with angiotensin-converting enzyme inhibitors (p=0.001). Advanced age (> or = 80 years), lower New York Heart Association functional class, absence of a fourth heart sound on examination, absence of cardiomegaly or signs of congestive heart failure on chest radiography and absence of known valve disease were independently related to the decision not to obtain an echocardiogram. Survival after adjustment for age, functional class and gender was lower in the No-Echo group than the Echo group (risk ratio=0.607, p=0.017). CONCLUSIONS: The underuse of echocardiography appears to be associated with poorer survival and underuse of angiotensin-converting enzyme inhibitor therapy.

Gender differences in use of stress testing and coronary heart disease mortality: a population-based study in Olmsted County, Minnesota.

OBJECTIVES: We sought to examine the utilization of exercise stress testing in relation to age and gender in a population-based setting. BACKGROUND: The utilization of noninvasive procedures has been shown to be associated with the subsequent use of invasive procedures. Yet, there are no population-based data on the utilization of stress testing; in particular, although gender differences in the use of invasive procedures have been reported, the use of noninvasive procedures has not been examined in relation to gender. METHODS: In Olmsted County, Minnesota, passive surveillance of the medical care of the community is provided through the Rochester Epidemiology Project. A population-based cohort of Olmsted County residents undergoing exercise tests was identified. The medical records of residents with prevalent and incident exercise tests in 1987 and 1988 were reviewed. For persons with an initial test (incidence cohort), data on clinical presentation, test indications and results were abstracted. Stress test utilization rates were calculated, and crude rates were directly adjusted to the age distribution of the 1980 U.S. population. To help interpret patterns of use at the population level, coronary heart disease mortality rates (International Classification of Diseases, 9th revision, codes 410 to 414) were calculated (crude and directly adjusted to the overall age distribution of the 1980 U.S. population) and used as an indicator of coronary disease burden. RESULTS: A total of 2,624 tests were performed. The crude utilization rate (per 100,000) was 1,888 for men and 703 for women (rate ratio for men over women 2.7, 95% confidence interval [CI] 2.5 to 2.9); it remained significantly higher in men across all age strata. The crude incidence rate (per 100,000) of initial stress tests was 1,112 for men and 517 for women (rate ratio 2.2, 95% CI 1.9 to 2.4). For both men and women, the incidence increased with age; however, incidence remained lower in women in all age strata. At the time that they underwent an initial test, women were more symptomatic and had poorer exercise performance than men. The rate ratio of men over women for coronary heart disease mortality was 1.1 (95% CI 0.9 to 1.2). The age-adjusted rate ratios for stress test utilization were 2.8 (95% CI 2.5 to 3.0), and that for coronary heart disease mortality was 1.9 (95% CI 1.7 to 2.2). CONCLUSIONS: These population-based data show that during the study period, the utilization of stress testing in Olmsted County was lower in women than in men. Women in the incidence cohort were older and more symptomatic and had poorer exercise performance than men. Such differences should be considered when examining the utilization of subsequent invasive procedures according to gender.

New diagnostic and treatment guidelines for benign prostatic hyperplasia. Potential impact in the United States.

BACKGROUND: The Agency for Health Care Policy and Research (AHCPR) recently released the clinical practice guidelines for the diagnosis and treatment of benign prostatic hyperplasia. Prevalence estimates from a population-based cross-sectional study, the baseline component of a cohort study of the natural history of prostatism, were used to assess their potential impact in the United States. METHODS: The study group comprised a population-based sample of white men aged 50 to 79 years who were randomly selected within age- and residence-specific strata from the Olmsted County, Minnesota, population (1990 census, 105,720). These 1317 men completed symptom assessments and diagnostic evaluations that paralleled the AHCPR guidelines, including the measurement of urinary flow rates and, for a subset (n = 303), ultrasonic determination of postvoiding residual urine volume. RESULTS: The application of the AHCPR benign prostatic hyperplasia diagnostic guidelines to the study cohort (American Urologic Association Symptom Index > 7 and peak urinary flow rate < 15 mL/s) suggests that 17% of men aged 50 to 59 years, 27% of men aged 60 to 69 years, and 35% of men aged 70 to 9 years are eligible to discuss treatment options. Application of these percentages to the 1990 US white population suggests that approximately 5.6 million men aged 50 to 79 years are eligible to discuss treatment options. This number will double by the year 2020 owing to the aging of the population. CONCLUSION: The projected number of men potentially meeting AHCPR guidelines to discuss treatment options for benign prostatic hyperplasia could have a substantial impact on the health care system; this will be compounded by the aging of the population.

Congestive heart failure in the community: trends in incidence and survival in a 10-year period.

OBJECTIVE: To compare the incidence of congestive heart failure and the survival in patients with congestive heart failure in Rochester, Minn, in 1981 with that observed in 1991. METHODS: Population-based, descriptive epidemiological study with ecological and individual level comparisons over time. Olmsted County, Minnesota, where the Rochester Epidemiology Project provides passive surveillance of the population for health outcomes. All 248 patients fulfilled the Framingham criteria, 107 patients presenting with the new onset of congestive heart failure in 1981 and 141 patients in 1991. The community inpatient and outpatient medical records of all incident cases were reviewed to evaluate the presenting characteristics of patients at diagnosis. RESULTS: The incidence of congestive heart failure after adjustment for age and sex to the US population was not significantly different in the 1991 cohort compared with that in 1981 (3.0 per 1000 person-years; 95% confidence interval, 2.5-3.5 vs 2.8 per 1000 person-years; 95% confidence interval, 2.2-3.3; P = .55). The survival of patients with new diagnosis of congestive heart failure was similar in the 2 cohorts (P = .53). Survival adjusted for age, sex, and New York Heart Association functional class was not significantly different in patients with congestive heart failure in 1981 and 1991 (relative risk, 0.907; P = .55). CONCLUSIONS: These data suggest that recent advances in management of cardiovascular disease, as used in the community, had not yet impacted incidence or survival of patients with congestive heart failure in the community during the 10-year study period. This highlights the need to continue efforts to ensure that advances in diagnosis and therapy are incorporated into the care of patients with congestive heart failure in the community.

Predictive properties of serum-prostate-specific antigen testing in a community-based setting.

BACKGROUND: Most studies that have described the sensitivity and specificity of prostate-specific antigen (PSA) as a screening test have been conducted in urology practice settings or in media-based screening programs. The control patients from these settings may have a higher prevalence of urologic disorders that increase serum PSA levels than that of the general population in which screening efforts might take place, leading to biased estimates of sensitivity and specificity. OBJECTIVE: To determine the sensitivity and specificity of serum PSA levels for the early detection of prostate cancer in a population-based setting. PATIENTS AND METHODS: This population-based case-control study was conducted in Olmsted County, Minnesota, where the Rochester Epidemiology Project could identify all incident cases of prostate cancer through passive surveillance of medical care provided to local residents. Case patients were all 177 men (age range, 50-79 years) who were newly diagnosed as having prostate cancer from 1990 through 1992 and had a prediagnostic serum PSA determination (90% of all incident cases). Control patients were randomly selected from the Olmsted County population and had undergone a clinical examination to exclude prostate cancer. RESULTS: The median (25th and 75th percentiles) of serum PSA levels was 9.4 ng/mL (5.4 and 18.6 ng/mL, respectively) for case patients and 1.2 ng/mL (0.7 and 2.1 ng/mL, respectively) for control patients (P < .001). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve was 0.94 (SE, 0.01). The predictive power declined somewhat with age, with areas under the curve of 0.96, 0.94, and 0.90 for men in their 50s, 60s, and 70s, respectively. When cases were restricted to the 155 men with clinically localized disease, the area under the curve was essentially unchanged (0.94; SE, 0.01) and still much greater than the estimates of 0.75 that were reported from urology practice- and media-based settings. CONCLUSIONS: In a community-based setting, serum PSA levels provide better discrimination between men with and without clinically localized prostate cancer than has been observed in studies that were conducted in urologic practices. These results suggest that previous decision analyses may have underestimated the predictive value of PSA for the detection of prostate cancer in a primary care or community-wide screening program.

Risk factors and the anatomic distribution of coronary artery disease.

Differences in the importance of risk factors according to the anatomic location of coronary artery disease (CAD) were assessed in 4722 men and 1069 women who underwent arteriography. Examined characteristics included total and high-density lipoprotein (HDL)-cholesterol, triglycerides, obesity, smoking, alcohol consumption, diabetes, and hypertension. Of these risk factors, the ratio of total to HDL-cholesterol showed the highest correlation with the overall severity of CAD (r = 0.24, men; r = 0.38, women); in contrast, its relation to left main (LM) disease was much lower (r = 0.10, men; r = 0.08 women) than were correlations with stenotic disease in the left anterior descending, circumflex, and right coronary arteries. Other risk factors also showed weaker associations with LM disease than with stenoses in other vessels, and none was related to increased LM disease after controlling for disease in other vessels. For example, as compared with men who had no significant CAD, those with 1-, 2-, and 3-vessel disease had mean increases in total cholesterol of 12, 18, and 19 mg/dl, respectively. In contrast, after adjusting for disease in other vessels, LM disease (present in 293 men) was associated with only a 4 mg/dl increase in mean cholesterol levels (P = 0.20). These results indicate that the relation of risk factors to CAD differs according to the location of the stenotic disease, and that LM disease is poorly predicted by the standard risk factors.

Time trends in the prevalence of atherosclerosis: a population-based autopsy study.

PURPOSE: Mortality from coronary heart disease is declining but little is known about trends in the prevalence of atherosclerosis. Autopsy rates in Olmsted County, Minnesota, are higher than the national average, offering an opportunity to address this matter. In this study, we determined the prevalence of anatomic coronary disease among autopsied Olmsted County residents and examined the generalizability of these findings. SUBJECTS AND METHODS: Reports of the 2,562 autopsies performed between 1979 and 1994 on Olmsted County residents > or =20 years of age were reviewed for the presence of coronary disease. RESULTS: Among autopsied decedents less than 60 years old at death and among coroner's cases, the prevalence of anatomic coronary disease declined with time (P for trend = 0.05); no trend was detected among older persons or noncoroner's cases. By logistic regression analysis, the crude odds ratio ([OR] per 5 years) for the association between time and anatomic coronary disease was 0.94 (95% confidence interval [CI]: 0.86 to 1.03; P = 0.18]. Age, sex, and antemortem diagnosis of heart disease were also strongly related to the presence of disease. After adjustment for sex and antemortem diagnosis of heart disease, the prevalence of anatomic coronary disease decreased more in younger people than in older people (age 40 years: OR 0.43 [95% CI: 0.24 to 0.80]; age 60 years: OR 0.62 [95% CI: 0.45 to 0.87]; age 80 years: OR 0.89 [95% CI: 0.64 to 1.23]). CONCLUSION: The prevalence of anatomic coronary disease at autopsy decreased between 1979 and 1994, particularly among younger people, supporting the notion that the burden of coronary disease has shifted toward the elderly. These results suggest that the decreased incidence of coronary artery disease has contributed to the recent decrease in coronary mortality, particularly among younger people.

The surprisingly high acceptability of low-efficacy vaccines for otitis media: a survey of parents using hypothetical scenarios.

OBJECTIVE: To determine parental thresholds for accepting vaccines for otitis media prevention given tradeoffs of efficacy, adverse effects, and administration mode. METHOD: We interviewed 601 randomly selected parents with children 0 through 6 years of age presenting to our community pediatric clinic. For each of five hypothetical vaccines, which varied administration mode from nasal spray to two injections and adverse effects from mild to severe, parents indicated the lowest number of otitis media episodes that the vaccine had to prevent in the next 6 months for them to accept the vaccine. RESULTS: About half the parents would accept any one of the vaccines if it would prevent three or more infections in the next 6 months. When the vaccine would prevent one episode of otitis media over the next 6 months, 33% of parents would accept the medial vaccine (one injection in the thigh, with some children getting a red, sore injection site and a few having a fever of < or = 102 degrees F for one day). Seventeen percent accepted a vaccine requiring two injections (influenza vaccine-like) or having increased adverse effects (pneumococcal vaccine-like) despite the vaccine only preventing one episode of otitis media over the next 6 months. No substantial differences in these proportions were found when compared among groups by reason-for-visit, recent occurrence of otitis media, or a history of recurrent otitis media in a sibling. CONCLUSION: Many parents will accept low efficacy vaccines for otitis media prevention. Parental acceptance does not vary with the child's otitis media experience but does vary with severity of adverse effects and administration mode of the vaccine.