Formulations of hormone therapy and risk of Parkinson's disease.

Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson's disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations. Neurologist-confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington State. Final analysis included 137 female cases and 227 controls. Hormone therapy use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin. Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.0-9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6-1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1-22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6-5.0). The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice.

Environmental tobacco smoke and Parkinson's disease.

BACKGROUND: Parkinson's disease is inversely associated with cigarette smoking, but its relation with passive smoking or environmental tobacco smoke exposure is rarely examined. METHODS: Within a case-control study, we assessed the association between Parkinson's disease and living or working with active smokers. Cases were newly diagnosed with idiopathic Parkinson's disease (n = 154) from western Washington State in 2002-2008. Age- and sex-matched controls (n = 173) were neurologically normal and unrelated to cases. RESULTS: Compared with never active or passive tobacco smokers, we observed reduced Parkinson's disease risks for ever passive only smokers (OR, 0.34; 95% CI, 0.16-0.73), similar to those for ever active smokers (OR, 0.35; 95% CI, 0.17-0.73). Among persons whose only tobacco smoke exposure was passive smoking at home, risk was inversely associated with years exposed. CONCLUSIONS: These observations parallel those well established for active smoking. However, it remains unresolved whether a true protective effect of tobacco smoke, generally detrimental to health, underlies these associations.

Improving quality, preventing disability and reducing costs in workers' compensation healthcare: a population-based intervention study.

BACKGROUND: Problems of poor quality and high costs are worse in the workers' compensation system than in the general medical care system, yet relatively little work has been done to improve performance in workers' compensation healthcare. OBJECTIVE: To evaluate the effect of a quality improvement intervention that provided financial incentives to providers to encourage adoption of best practices, coupled with organizational support and care management activities, aimed at reducing work disability for patients treated within the Washington State workers' compensation system. RESEARCH DESIGN: Prospective nonrandomized intervention study with nonequivalent comparison group using difference-in-difference models to estimate the effect of the intervention. PARTICIPANTS: Two cross-sections of data representing 33,910 workers' compensation claims filed in the baseline (preintervention) period from July 2001 to June 2003 and 71,696 claims filed in the postintervention period from July 2004 to June 2007 were analyzed. 46,928 (44%) of these 105,606 claims represent patients treated by over 275 providers recruited through Centers of Occupational Health and Education (COHEs) at 2 pilot regional sites. MEASURES: Outcomes, measured at 1-year follow-up, included work disability status, number of disability days, disability cost, and medical cost. RESULTS: COHE patients were less likely to be off work and on disability at 1 year postclaim receipt (OR=0.79, P=0.003). The average COHE patients experienced a reduction in disability days of 19.7% (P=0.005) and a reduction in total disability and medical costs of $510 per claim (P<0.01). For patients with back sprain, the reduction in disability days was 29.5% (P=0.003). Patients treated by providers who more often adopted occupational health best practices had, on average, 57% fewer disability days (P=0.001) compared with patients treated by providers who infrequently adopted best practices. CONCLUSIONS: Financial incentives, coupled with care management support, can improve outcomes, prevent disability, and reduce costs for patients receiving occupational healthcare. Owing to important disability prevention capacity, workers' compensation healthcare may be especially fertile ground for continued quality improvement innovation.

Occupational factors and risk of Parkinson's disease: A population-based case-control study.

BACKGROUND: Parkinson's disease (PD) has been associated with various workplace factors, but the evidence is inconsistent. OBJECTIVE: To estimate the risk of PD associated with various jobs and workplace exposures. METHODS: We conducted a population-based, case-control study of 404 incident PD cases and 526 age and sex-matched controls, collecting self-reported work histories including job titles and exposures to various industrial toxicants. Relative risks of PD from these exposures were estimated with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. RESULTS: Risk was not significantly affected by farming work, by metal work, or by exposure to pesticides, metals, or solvents. CONCLUSIONS: These findings do not provide support for the hypothesis that workplace factors affect the risk of PD.

Dietary fats, cholesterol and iron as risk factors for Parkinson's disease.

BACKGROUND: Epidemiologic findings suggest that dietary components may contribute to the etiology of Parkinson's disease (PD). This population-based case-control study evaluated PD risk and dietary intake of fats, cholesterol and iron. METHODS: Newly diagnosed case (n=420) and age/gender/ethnicity-matched unrelated controls (n=560) were identified between 1992 and 2006 from the Group Health Cooperative health maintenance organization in western Washington State, and the University of Washington Neurology Clinic. In-person interviews elicited data on food frequency habits during most of adult life. Nutritional intakes were calculated and analyzed, with adjustments made for total energy intake (the 'nutrition density' technique). RESULTS: Cholesterol intake in the highest quartile compared with the lowest quartile was associated with a decreased risk of PD in men (odds ratio (OR)=0.53, 95%CI: 0.33, 0.86). The highest versus the lowest quartile of dietary iron increased PD risk in men (OR=1.82, 95%CI: 1.11, 2.99). When the lowest quartile of cholesterol and the highest quartile for iron were compared to the highest quartile of cholesterol and the lowest quartile of iron, no association was seen in women, but for men PD risk was increased (OR=2.70, 95%CI: 1.26, 5.76). Saturated fat intake below the median in combination with iron intake above the median also increased the PD risk (OR=1.50, 95%CI: 1.07, 2.11) in both genders combined. CONCLUSIONS: A low intake of cholesterol, particularly in the presence of high iron, may be associated with an increased risk for PD.

The functional polymorphism of the hemoglobin-binding protein haptoglobin influences susceptibility to idiopathic Parkinson's disease.

Oxidative stress and iron have been widely implicated in the etiology of Parkinson's disease (PD). Hemoglobin is the richest source of iron in the body. The human Haptoglobin (Hp) protein is a plasma alpha-2 glycoprotein that removes free Hemoglobin from the circulation and tissues and is important in protection from oxidative stress, in immune system regulation, and angiogenesis. A common genetic polymorphism of Hp exists in the population, where the Hp 1-1, Hp 2-1, and Hp 2-2 forms exhibit profound functional differences. In this study, the Hp genotype corresponding to phenotypes Hp 1-1, 2-1 and 2-2 was determined in 312 idiopathic PD patients and 420 normal control subjects. A significant increase in the number of subjects carrying the Hp 2-1 genotype was present among PD patients. The distribution of Hp genotypes among PD patients (16.0% Hp 1-1, 56.4% Hp 2-1, 27.6% Hp 2-2) was significantly different from the distribution in controls (15.2% Hp 1-1, 48.1% Hp 2-1, 36.7% Hp 2-2) (chi(2) = 6.99, P = 0.030). The odds ratios for PD risk for Hp 2-1 and Hp 1-1 versus Hp 2-2 genotype were 1.51 (1.07-2.12) and 1.36 (0.86-2.15), respectively. Overall, the association of Hp-1 allele with PD resulted stronger among subjects who were never-smokers as compared to ever-smokers. Also, among ever-smokers, Hp genotypes were significantly associated with PD only among women, but not men, indicating the presence of a gene x gender x smoking interaction. To our knowledge, this is the first study that investigates the association of Hp genotypes with the risk of PD.

Calcium channel blockers and beta-blockers in relation to Parkinson's disease.

We investigated the risk of Parkinson's disease (PD) associated with calcium channel blockers (CCBs) and beta-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for beta-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation.

Nonsteroidal anti-inflammatory drugs and risk of Parkinson's disease.

Inflammation and oxidative stress have been implicated as pathogenic mechanisms in Parkinson's disease (PD). Evidence from in vitro and animal studies suggests a possible protective role of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin. We investigated the risk of PD associated with use of aspirin and nonaspirin NSAIDs in a population-based case-control study among enrollees of Group Health Cooperative, a health maintenance organization in the Seattle area. Subjects included 206 cases between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 randomly selected controls frequency-matched by age, sex, duration of enrollment, and clinic. We obtained information on participants' age, smoking, and medical history from interview. Exposure to NSAIDs was ascertained from an automated pharmacy database. Medications filled within 5 years of the interview were excluded. After adjusting for age, sex, smoking, duration of enrollment, and clinic, the risk of PD among individuals who received nonaspirin NSAIDs between 1977 and 1992 was 0.90 (95% CI: 0.59-1.35) and 1.67 (95% CI: 0.60-4.60) between 1993 and 2002. Use of ibuprofen was not associated with PD (OR: 0.89; 95% CI: 0.60-1.32). The risk of PD associated with aspirin or aspirin-containing medications was 0.74 (95% CI: 0.49-1.12). We observed no trend in risk according to number of fills for these drugs. Our results provide only limited support for the hypothesis that use of aspirin may reduce the risk of this disease, and no indication of protection from other NSAIDs.

Diabetes, smoking, and other medical conditions in relation to Parkinson's disease risk.

Associations of Parkinson's disease (PD) with diabetes mellitus (DM) and other medical conditions were investigated in a case-control study of 352 newly diagnosed PD case and 484 control subjects. Men with DM had a significantly lower risk of PD, than men without DM (odds ratio (OR) = 0.52, 95% confidence interval (CI) = 0.28, 0.97), whereas the association in women was weaker (OR = 0.80, 95% CI = 0.35, 1.83). PD risk was reduced among male and female smokers, with and without diabetes. However, among diabetics, the PD risk was especially reduced in non-smoking men (OR = 0.09, 95% CI = 0.02, 0.44). Other medical conditions showed no strong relations with PD.

No associations between Parkinson's disease and polymorphisms of the quinone oxidoreductase (NQO1, NQO2) genes.

Reactive oxygen species derived from dopamine metabolism can induce oxidative stress and thus may contribute to Parkinson's disease (PD) pathogenesis. The quinone oxidoreductases, nicotinamide adenine dinucleotide (phosphate) (NAD[P]H): quinone oxidoreductase 1 (NQO1) and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) detoxify quinones and quinonoid compounds. We investigated associations of genetic polymorphisms of NQO1 (C609T) and NQO2 (I/D, 29 base pairs) with PD in a population-based case-control study of 190 idiopathic PD cases and 305 unrelated controls matched on age and sex. No associations were detected for either gene variant or for any allele combinations.

Pesticides and risk of Parkinson disease: a population-based case-control study.

BACKGROUND: Pesticide exposures are suspected risk factors for Parkinson disease (PD), but epidemiological observations have been inconsistent. OBJECTIVE: To investigate associations between pesticide exposures and idiopathic PD. DESIGN: Population-based case-control study. SETTING: Group Health Cooperative, a health care system in western Washington State, and the University of Washington. PARTICIPANTS: Two hundred fifty incident PD case patients and 388 healthy control subjects (age- and sex-matched). We assessed self-reported pesticide exposures using a structured interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using logistic regression models, controlling for age, sex, and smoking. RESULTS: Odds ratios for occupational exposures were not significant but suggested a gradient that paralleled occupational exposures (pesticide worker: OR, 2.07; 95% CI, 0.67-6.38; crop farmer: OR, 1.65; 95% CI, 0.84-3.27; animal and crop farmer: OR, 1.10; 95% CI, 0.60-2.00; and dairy farmer: OR, 0.88; 95% CI, 0.46-1.70). Odds ratios for organophosphates paralleled the World Health Organization hazard classifications, with parathion much higher than diazinon or malathion. We also found elevated ORs from herbicides (OR, 1.41; 95% CI, 0.51-3.88) and paraquat (OR, 1.67; 95% CI, 0.22-12.76). We found no evidence of risk from home-based pesticide exposures. We found significantly increased ORs from lifelong well water consumption (OR, 1.81; 95% CI, 1.02-3.21). CONCLUSIONS: The findings for occupational pesticide exposures are consistent with a growing body of information linking pesticide exposures with PD. However, the lack of significant associations, absence of associations with home-based exposures, and weak associations with rural exposures suggest that pesticides did not play a substantial etiologic role in this population.

A communitywide intervention to improve outcomes and reduce disability among injured workers in Washington State.

One pressing challenge facing the U.S. health care system is the development of effective policies and clinical management strategies to address deficiencies in health care quality. In collaboration with researchers at the University of Washington, the Washington State Department of Labor and Industries has created a communitywide delivery system intervention to improve health outcomes and reduce disability among injured workers. This intervention is currently being tested in two sites in western and eastern Washington. So far, it appears to be possible to engage physicians and health care institutions in quality improvement initiatives and to form effective public-private partnerships for this purpose. Furthermore, collaborating with university researchers may help enhance the scientific rigor of the quality improvement initiative and create more opportunities for a successful evaluation.

Patient satisfaction, treatment experience, and disability outcomes in a population-based cohort of injured workers in Washington State: implications for quality improvement.

OBJECTIVE: To determine what aspects of patient satisfaction are most important in explaining the variance in patients' overall treatment experience and to evaluate the relationship between treatment experience and subsequent outcomes. DATA SOURCES AND SETTING: Data from a population-based survey of 804 randomly selected injured workers in Washington State filing a workers' compensation claim between November 1999 and February 2000 were combined with insurance claims data indicating whether survey respondents were receiving disability compensation payments for being out of work at 6 or 12 months after claim filing. STUDY DESIGN: We conducted a two-step analysis. In the first step, we tested a multiple linear regression model to assess the relationship of satisfaction measures to patients' overall treatment experience. In the second step, we used logistic regression to assess the relationship of treatment experience to subsequent outcomes. PRINCIPAL FINDINGS: Among injured workers who had ongoing follow-up care after their initial treatment (n = 681), satisfaction with interpersonal and technical aspects of care and with care coordination was strongly and positively associated with overall treatment experience (p < 0.001). As a group, the satisfaction measures explained 38 percent of the variance in treatment experience after controlling for demographics, satisfaction with medical care prior to injury, job satisfaction, type of injury, and provider type. Injured workers who reported less-favorable treatment experience were 3.54 times as likely (95 percent confidence interval, 1.20-10.95, p = .021) to be receiving time-loss compensation for inability to work due to injury 6 or 12 months after filing a claim, compared to patients whose treatment experience was more positive.

Use of attorneys and appeal filing in the Washington State workers' compensation program: does patient satisfaction matter?

LEARNING OBJECTIVES: Specify the frequency with which injured workers in Washington State's compensation system retained an attorney or filed an appeal, and the personal and job-related correlates of these actions. Analyze the relationship between workers' legal actions and their satisfaction in two domains: how well the claim was managed administratively, and how well the worker and claim manager communicated with one another. Characterize the relationship between retaining an attorney and long-term disability. ABSTRACT: Little is known about how often injured workers retain attorneys or file appeals in the workers' compensation system. We conducted a population-based study to examine the frequency of attorney retention and appeal filing in the Washington State workers' compensation program and the factors related to this event. Data for the study were provided by a survey conducted on 804 injured workers who were interviewed an average of 159 days after claim receipt. Attorney retention and appeal filing were examined up to 28 months later. Seven percent of the workers either retained an attorney or filed an appeal. Workers who were less satisfied with claims administration procedures were more likely to retain an attorney or file an appeal (P<0.05). The average length of time from claim receipt to attorney retention (368 days) suggests that retaining an attorney is a correlate rather than a predictor of long-term disability.

DNA sequence analysis of monoamine oxidase B gene coding and promoter regions in Parkinson's disease cases and unrelated controls.

The allele G of the intron 13 G/A polymorphism of the monoamine oxidase B gene (MAO-B) has been associated with Parkinson's disease (PD) in several studies. Apart from a potential direct effect on splicing processes, the association of this intronic polymorphism with PD is due possibly to linkage disequilibrium with other mutations in the coding or promoter regions of the gene. We addressed this latter hypothesis by determining the DNA sequence of the entire MAO-B coding region comprising 15 exons and partial intronic sequences flanking each exon, in 33 cases with idiopathic PD and 38 unrelated controls. The promoter region of MAO-B gene up to base -1,369 from ATG (start point of mRNA translation) was also sequenced to identify variants with potential functional effects on gene transcription. In the promoter region, a new polymorphism consisting of a C to T single base change was detected in position -1,114 from ATG, with an allelic frequency of 3.5%, but it was not associated with PD risk. No commonly occurring (>10%) polymorphisms were found in the exons or the intronic sequences flanking the exons, although several rare variants were detected in the coding and promoter regions.

Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.

Oxidative stress is widely thought to contribute significantly to the pathogenesis Parkinson's disease (PD). Given the role of glutathione S-transferases (GSTs) in the conjugation of electrophiles and protection against reactive oxygen species, genes encoding the GSTs have been considered candidates for association studies of PD. We tested for associations between genotypes of GSTM1(homozygous deletion vs. non-deleted), GSTT1(homozygous deletion vs. non-deleted), and GSTP1 (Ile104Val and Ala113Val) and PD in a case-control study of 214 idiopathic PD cases and 330 age- and gender-matched, unrelated controls of Caucasian ethnicity. No significant associations with any of the GST genotypes were observed. However, there was a marginally significant difference in the distribution of GSTP1 104 genotypes between cases and controls (P=0.07), with an excess of Ile104Val heterozygotes found among cases (odds ratio (OR)=1.43; 95% Confidence Interval (CI): 0.98-2.08). This difference in the genotype distribution was strongest among smokers (OR for heterozygote=1.92; 95% CI: 1.12-3.29) versus non-smokers and among males (OR for heterozygote=1.99; 95% CI: 1.24-3.19) versus females. The distribution of GSTP1 Ile104Val and Ala113Val haplotypes did not differ between cases and controls. Taken together, these results suggest a potentially minor role of GSTP1 in PD, but do not give evidence for associations with either GSTM1 or GSTT1.

Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.

A reduced risk for Parkinson's disease (PD) among cigarette smokers has been observed consistently during the past 30 years. Recent evidence suggests that caffeine may also be protective. Findings are presented regarding associations of PD with smoking, caffeine intake, and alcohol consumption from a case-control study conducted in western Washington State in 1992-2000. Incident PD cases (n = 210) and controls (n = 347), frequency matched on gender and age were identified from enrollees of the Group Health Cooperative health maintenance organization. Exposure data were obtained by in-person questionnaires. Ever having smoked cigarettes was associated with a reduced risk of PD (odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.4, 0.8). A stronger relation was found among current smokers (OR = 0.3, 95% CI: 0.1, 0.7) than among ex-smokers (OR = 0.6, 95% CI: 0.4, 0.9), and there was an inverse gradient with pack-years smoked (trend p < 0.001). No associations were detected for coffee consumption or total caffeine intake or for alcohol consumption. However, reduced risks were observed for consumption of 2 cups/day or more of tea (OR = 0.4, 95% CI: 0.2, 0.9) and two or more cola drinks/day (OR = 0.6, 95% CI: 0.3, 1.4). The associations for tea and cola drinks were not confounded by smoking or coffee consumption.