Search

Purpose: This study describes longitudinal trends in the use of prostate-specific antigen (PSA)-based testing in two geographically distinct healthcare systems following the 2011 US Preventive Services Task Force (USPSTF) recommendations against routine PSA screening., Methods: We analyzed population-based health claims data from 253,139 men aged 40-80 who were enrolled at two US healthcare systems. We assessed trends in the percentage of eligible men receiving ≥ 1 PSA test per year by time period (2000-2008, 2009-2011, 2012-2014), age (40-54, 55-69, 70-80), and race (white, black, other, unknown), and conducted a joinpoint regression analysis., Results: Men aged 55-69 and 70-80 years of all races had similar use of PSA testing between 2000 and 2011, ranging between 47 and 56% of eligible men by year, while only 22-26% of men aged 40-54 had a PSA test per year during this period. Overall, the percentage of men receiving at least one PSA test per year decreased by 26% between 2009-2011 and 2012-2014, with similar trends across race and age groups. PSA testing declined significantly after 2011 (annual percent change = - 11.28)., Conclusions: Following the 2011 USPSTF recommendations against routine PSA screening, declines in PSA testing were observed among men of all races and across all age groups in two large US healthcare systems.

Background: In general population studies, obesity has been associated with risk of high-grade prostate cancer, but little is known about obesity and future prostate cancer risk among men with an initial benign biopsy of the prostate; a high-risk population., Methods: Within a cohort of 6,692 men followed up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 494 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and date of procedure. Body mass index at the time of the initial procedure was abstracted from medical records, and initial biopsy specimens were reviewed for the presence of prostatic intraepithelial neoplasia (PIN)., Results: Obesity was associated with the presence of PIN in the initial benign specimen [OR = 2.15; 95% confidence interval (CI) 1.13-4.11]. After adjustment for the matching variables, family history of prostate cancer, prostate-specific antigen (PSA) levels at the initial procedure, the number of PSA tests and digital rectal examinations during follow-up, obesity (OR = 1.57; 95% CI, 1.07-2.30) at the time of the initial procedure was associated with prostate cancer incidence during follow-up. Risk associated with obesity was confined to cases with follow-up less than 1,538 days, the median duration of follow-up among cases (OR = 1.95; 95% CI, 1.09-3.48)., Conclusions: Obesity is associated with the presence of PIN in benign specimens and with future prostate cancer risk after an initial benign finding., Impact: Obesity may be a factor to consider when planning clinical follow-up after a benign biopsy.

Purpose: Higher socioeconomic status (SES) men are at higher risk of prostate cancer (PCa) diagnosis, an association commonly interpreted as a function of higher rates of prostate screening among higher SES men. However, the extent to which screening explains this association has not been well quantified., Methods: Within a Detroit area cohort of 6,692 men followed up after a benign prostate procedure, a case-control study was conducted of 494 PCa cases and controls matched on age, race, duration of follow-up, and date of initial benign finding; 2000 Census data were used in a principal component analysis to derive a single factor, labeled the neighborhood SES index (NSESI), representing zip code-level SES., Results: Among cases, higher SES was associated with a younger age at initial biopsy: -1.48 years (95 % CI, -2.32, -0.64) per unit NSESI. After adjustment for confounders and duration of follow-up, higher SES was associated with more PSA tests and DRE during follow-up; 9 % (95 % CI, 2, 16) and 8 % (95 % CI, 1, 15) more respectively, per unit NSESI. Higher SES was associated with a higher risk of PCa diagnosis during follow-up, multivariable adjusted OR = 1.26 per unit increase in NSESI (95 % CI, 1.04, 1.49). Further adjustment for screening frequency somewhat reduced the association between SES and PCa risk (OR = 1.19 per unit NSESI, 95 % CI, 0.98, 1.44)., Conclusions: Differences in screening frequency only partially explained the association between higher zip code SES and PCa risk; other health care-related factors should also be considered as explanatory factors.

Background: Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II (SRD5A2) and 3 beta-hydroxysteroid dehydrogenase type II (HSD3B2) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk., Methods: Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (> or =283) alleles., Results: The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08-3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80-7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62-3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7)., Conclusions: In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism.

Purpose: Body size has been hypothesized to affect the risk of prostate cancer (PCa). However, previous studies have provided conflicting results, in that some show positive associations, whereas others indicate inverse associations or null findings. To further understand this we examined the effects of weight, height, body mass index and lean body mass (LBM) on PCa risk and aggressiveness in a sibling based case-control study., Materials and Methods: A total of 439 cases were recruited at major medical institutions in Cleveland, Ohio and Detroit, Michigan, and 479 unaffected brothers were recruited as controls. Conditional logistic regression with robust variance estimation was used to evaluate the association between body size and PCa., Results: Higher LBM was inversely associated with PCa, especially in men with more aggressive disease or a later age at onset. Comparing those above and below the 25th percentile showed an OR of 0.49 (95% CI 0.28 to 0.84) and 0.28 (95% CI 0.14, 0.56), respectively. Similar inverse patterns were observed for weight. No noteworthy associations were observed between PCa and height or body mass index., Conclusions: These observations suggest that PCa may be affected by LBM.

Objective: To determine the relative contribution of various risk factors to the development of Parkinson's disease (PD)., Methods: Ten variables that were independently associated with PD in a health system population-based case-control study of epidemiological risk factors for the disease were jointly assessed. Stepwise logistic regression, adjusted for sex, race and age was used to develop a multiple variate model that best predicted the presence of PD. The population attributable risk was estimated for each variable in the final model, as well as for all factors together., Results: The 10 initial variables included >20 years occupational exposure to manganese or to copper, individually; >20 years joint occupational exposure to either lead and copper, copper and iron, or lead and iron; a positive family history of PD in first- or second-degree relatives; occupational exposure to insecticides or herbicides; occupational exposure to farming; and smoking. Logistic regression resulted in a final model that included >20 years joint occupational exposure to lead and copper (p=0.009; population attributable risk [PAR]=3.9%), occupational exposure to insecticides (p=0.002; PAR=8.1%), a positive family history of PD in first- and second-degree relatives (p=0.001; PAR=12.4%), and smoking

Sarcoidosis, in the United States, more commonly and severely affects African Americans. HLA associations with sarcoidosis have been reported, but most studies used case-control designs, which may produce biased results because of population stratification. We examined transmission of HLA-DQB1 alleles in 225 African American families with at least one offspring with sarcoidosis. Of five low-resolution HLA-DQB1 alleles, *02 and *06 showed significant deviation in transmission patterns to affected offspring. High-resolution typing of these allelic subsets revealed that HLA-DQB1*0201 was transmitted to affected offspring half as often as expected (p = 0.001), whereas DQB1*0602 was transmitted to affected offspring about 20% more often than expected (p = 0.029). Examining interactions between *0201 and *0602 alleles and environmental exposures showed that *0602 varied little with respect to exposure, but sarcoidosis risk associated with *0201 often depended on exposure status. Alternatively, the *0602 allele in affected probands was associated with radiographic disease progression, but the *0201 allele showed no significant correlation with phenotype. Major differences in the amino acid sequences encoded by *0201 and *0602 alleles exist, which may explain the differential effects these alleles have on sarcoidosis susceptibility and progression in African Americans.

While sarcoidosis is thought to aggregate in families, little is known about the risk to relatives of sarcoidosis patients. To estimate the familial risk ratio (lambda) of sarcoidosis in sibs and parents of cases, the authors studied 179 African-American families ascertained through an index sarcoidosis case diagnosed at Henry Ford Hospital in Detroit, Michigan. Among those relatives enrolled between 1997 and 1999, 12 of 327 (3.7%) sibs and 11 of 161 (6.8%) parents reported a history of sarcoidosis. The lambda in this sample of relatives, estimated by computing an age, sex, and race standardized incidence ratio, was 2.24 (95% confidence interval: 1.16, 3.92) for sibs and 2.82 (95% confidence interval: 1.41, 5.05) for parents. For sibs and parents combined, lambda was 2.49 (95% confidence interval: 1.58, 3.73). Results stratified by proband characteristics indicated that lambda was greater for relatives of younger (lambda = 2.93, 95% confidence interval: 1.52, 5.12) and male (lambda = 3.98, 95% confidence interval: 1.99, 7.12) probands. A higher lambda was also found for male family members and sibs born later in the birth order. A Monte Carlo method was also used to estimate lambda, with similar results obtained. Overall, these results indicate that, in African Americans, sibs and parents of sarcoidosis cases have about a 2.5-fold increased risk for sarcoidosis and that heterogeneity in disease risk may exist among family members.

Parkinson's disease (PD) is likely a result of both inherited and exogenous factors. In a study of 144 PD cases and 464 controls, we used PD family history as a surrogate for inherited PD susceptibility. Cases were more likely to report a first- or second-degree relative with PD: 16.0 vs. 4.3%; odds ratio (OR) = 4. 2; 95% confidence interval (CI) = 2.3-7.6. A PD family history was a greater risk factor for PD in subjects under age 70 (OR = 8.8; 95% CI = 3.4-22.8) compared with those over 70 (OR = 2.8; 95% CI = 1.3-6. 1) and in men (OR = 8.1; 95% CI = 3.4-19.2) compared with women (OR = 2.6; 95% CI = 1.1-6.0). We also tested whether a PD family history modified the effects of other PD risk factors. In subjects with a PD family history, occupational exposure to copper, lead or iron increased the risk for PD (OR = 3.0; 95% CI = 0.7-13.3), but this was not the case for those without a family history (OR = 1.1; 95% CI = 0.7-1.6). Ever smoking cigarettes was inversely associated with PD in those without a PD family history (OR = 0.6; 95% CI = 0.4-0.9), but was positively associated with PD in those with a PD family history (OR = 1.7; 95% CI = 0.5-5.9). In summary, our results suggest that a PD family history, and perhaps, therefore, an inherited susceptibility, confers a greater risk for PD in men and individuals under 70 years of age and may modify the effects of environmental risk factors for PD.

Objective: To determine whether an inverse dose-response relationship exists between cigarette smoking and PD among ever-smokers and ex-smokers., Methods: Smoking and alcohol consumption were analyzed in 144 PD patients and 464 control subjects, who were frequency matched for sex, race, and age (+/-5 years), in a population-based case-control study of men and women > or =50 years old in the Henry Ford Health System., Results: With never-smokers as the reference category, there was an inverse association between current light smokers (>0 to 30 pack-years) and PD patients (odds ratio [OR], 0.59; 95% CI, 0.23 to 1.53), and a stronger inverse association of PD with current heavy smokers (>30 pack-years; OR, 0.08; 95% CI, 0.01 to 0.62). When former >30-pack-year smokers were stratified by the interval since quitting, there was an inverse association between those who stopped >20 years ago and PD (OR, 0.86; 95% CI, 0.42 to 1.75), and a greater inverse relationship with those who stopped 1 to 20 years ago (OR, 0.37; 95% CI, 0.19 to 0.72). Alcohol consumption had no independent, significant association with PD, but heavy drinking (>10 drink-years) had a greater effect than light-moderate drinking in reducing but not eliminating the inverse association between smoking and PD., Conclusions: The inverse dose-response relationship between PD and smoking and its cessation is unlikely to be due to bias or confounding, as discussed, providing indirect evidence that smoking is biologically protective.

Background: Among the methods of retrospective occupational exposure assessment, expert review is considered the most accurate. Although expert review provides a more objective measure of exposure, depending on the exposure of interest it may still result in a significant degree of misclassification., Methods: To evaluate the reliability in occupational metal exposure assessment by expert review, we analysed job history data from a case-control study of a neurological disease. First, one industrial hygienist (IH) did an initial exposure assessment of the metals copper, iron and lead, blinded to case-control status, for 608 subjects who had 3033 total jobs. We then compared exposure assessments from the original review with a second blinded review of 60 job histories (306 jobs) by the same IH (intra-rater) and of 64 job histories (361 jobs) by a different IH (inter-rater)., Results: The per cent agreements for the intra-IH comparisons were 89.6 for copper, 87.9 for iron and 94.6 for lead, whereas the inter-IH per cent agreements were 86.4 for copper, 81.1 for iron and 76.2 for lead. Based on the assumption that reliability is related to validity, we calculated an estimate of misclassification of metal exposure by one IH. Our exposure misclassification estimates show a sizable attenuation of the odds ratio, with the expected bias similar for copper and iron when using either intra- or inter-reliability results to estimate misclassification., Conclusion: Our results suggest that variation in the expert assessment of metal exposure is due mainly to the difficulties involved in transforming an occupational history into an estimate of exposure.

Reports of racial differences in the incidence of sarcoidosis, a granulomatous disorder of unknown etiology, are primarily based on studies of military and veteran populations. To determine racial differences in sarcoidosis incidence in a metropolitan population the authors conducted a study of newly diagnosed cases that occurred between 1990 and 1994 among members of the Health Alliance Plan health maintenance organization in Detroit, Michigan. The study population was racially heterogeneous, was limited to individuals aged 20-69 years, and comprised about 5% of the Detroit metropolitan area population in that age group. Annual age-adjusted incidence, in number of new cases per 100,000, was highest in African-American females (39.1 cases). The next highest incidence was found in African-American males (29.8 cases), followed by Caucasian females (12.1) and Caucasian males (9.6). African-American females aged 30-39 years were at the greatest risk, with an annual incidence of 107/100,000. Overall, African Americans had about a threefold higher age-adjusted annual incidence (35.5/100,000) compared with Caucasians (10.9/100,000). Additional adjustment for sex, area of residence, and year of study resulted in 3.8-fold greater risk for African Americans compared with Caucasians. This study further confirmed the higher incidence of sarcoidosis in African Americans compared with Caucasians, but the racial difference was lower than previously reported. The results should be more generalizable than previous studies done with select populations and should serve as a useful frame of reference for future epidemiologic research of sarcoidosis.

Familial clustering of sarcoidosis and the higher prevalence and clinical severity of sarcoidosis in African Americans suggests etiologic heterogeneity. To test for heterogeneity in familial risk of sarcoidosis, we studied 3,395 siblings and parents of 558 index cases (361 African American, 197 Caucasian) diagnosed at Henry Ford Hospital between 1951 and 1994. Using the age- and sex-specific cumulative incidence of sarcoidosis in our sample, we found a statistically significant heterogeneity in familial risk of disease (P < .001). To determine if this was due to a greater risk of sarcoidosis in African Americans, we recalculated disease probabilities using age-, sex-, and race-specific disease cumulative incidence and found the same amount of heterogeneity in familial risk (P < .001). Index cases (n = 69) from high-risk families were more likely to be African American (odds ratio [OR] = 3.24; 95% confidence interval (CI) = 1.71-6.14) and to have an offspring or second- degree relative affected (OR = 6.21; 95% CI = 2.86-13.45). We conclude that the heterogeneity of familial sarcoidosis risk found in this study is supportive of multiple etiologies. Our results also show that a quantitative assessment of familial risk based on siblings and parents may be a useful screening tool for identifying families with additional affected members. Of the high-risk families, African Americans made up a greater-than-expected percentage even after accounting for differences in disease prevalence. We suggest targeting African Americans for studies of sarcoidosis that focus on Mendelian hypotheses and genetic linkage.

Using data from death certificates, we compared underlying causes of death for two populations of Michigan decedents: (1) persons 40 years of age and older for whom Parkinson's disease (PD) was listed as a contributing cause of death and who died in the years 1970 through 1989, and (2) all persons in Michigan over 40 years of age who died in 1970, 1980, or 1990. PD decedents were approximately 1.5 times more likely to die from cerebrovascular disease and three to four times more likely to die from pneumonia/influenza, but they had just 29% of the expected number of deaths due to cancer. These associations were maintained irrespective of gender or race. PD decedents had diabetes mellitus and heart diseases as frequently as decedents in the general population, but liver diseases were less frequent among PD decedents. These trends held throughout the 21-year study period. When we stratified cancers by whether they are known to be (1) highly related, (2) moderately related, or (3) weakly related or unrelated to smoking, there were still 2.5 times fewer cancers unrelated or weakly related to smoking among PD decedents than among decedents in the general population. We believe that the greater frequency of cerebrovascular disease in PD decedents may be due to a detection bias, since PD patients are more likely to be seen by neurologists, who are more apt to diagnose and document diseases of the nervous system. Pneumonia/influenza is more common among PD patients because of their relative immobility near the end of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Parkinson's disease (PD) mortality rates in Michigan counties for 1986-1988 were calculated with respect to potential heavy metal exposure (iron, zinc, copper, mercury, magnesium, and manganese) from industry based on recent census data. Individuals were counted as a PD death if the diagnosis was listed as an "underlying" or "related" cause of death on the death certificate. Counties with an industry in the paper, chemical, iron, or copper related-industrial categories (ICs) had statistically significantly (p < 0.05) higher PD death rates than counties without these industries. Significant correlations of chemical (rs = 0.22; p = 0.05), paper (rs = 0.22; p = 0.05) and iron (rs = 0.29; p = 0.008) industry densities with PD death rates were also present. Counties were divided into high (> 15/100,000 individuals 45 years old and over) and low (< = 15/100,000) PD death rate counties by cluster analysis. Geographically, counties with high PD mortality were located mainly in the southern half of the lower peninsula and eastern half of the upper peninsula; low PD death rate counties formed two distinct clusters in the western edge of the upper peninsula and the north-central portion of the lower peninsula. Other possible risk factors that may explain the varied distribution of PD death rates in Michigan were examined. Those significantly correlated with PD mortality included population density (rs = 0.31; p = 0.005), farming density (rs = 0.25; p = 0.02), and well water use (rs = -0.24; p = 0.03). These ecologic findings suggest a geographic association between PD mortality and the industrial use of heavy metals.