Fine Particulate Matter and Parkinson Disease Risk Among Medicare Beneficiaries.

BACKGROUND AND OBJECTIVES: Numerous studies suggest that environmental exposures play a critical role in Parkinson disease (PD) pathogenesis, and large, population-based studies have the potential to advance substantially the identification of novel PD risk factors. We sought to study the nationwide geographic relationship between PD and air pollution, specifically PM2.5 (particulate matter with a diameter <2.5 micrometers), using population-based US Medicare data. METHODS: We conducted a population-based geographic study of Medicare beneficiaries aged 66-90 years geocoded to US counties and zip+4. We used integrated nested Laplace approximation to create age, sex, race, smoking, and health care utilization-adjusted relative risk (RR) at the county level for geographic analyses with PM2.5 as the primary exposure of interest. We also performed an individual-level analysis using logistic regression with cases and controls with zip+4 centroid PM2.5. We adjusted a priori for the same covariates and verified no confounding by indicators of socioeconomic status or neurologist density. RESULTS: Among 21,639,190 Medicare beneficiaries, 89,390 had incident PD in 2009. There was a nationwide association between average annual PM2.5 and PD risk whereby the RR of PD was 56% (95% CI 47%-66%) greater for those exposed to the median level of PM2.5 compared with those with the lowest level of PM2.5. This association was linear up to 13 µg/m3 corresponding to a 4.2% (95% CI 3.7%-4.8%) greater risk of PD for each additional µg/m3 of PM2.5 (p trend < 0.0001). We identified a region with high PD risk in the Mississippi-Ohio River Valley, where the risk of PD was 19% greater compared with the rest of the nation. The strongest association between PM2.5 and PD was found in a region with low PD risk in the Rocky Mountains. PM2.5 was also associated with PD in the Mississippi-Ohio River Valley where the association was relatively weaker, due to a possible ceiling effect at average annual PM2.5 levels of ∼13 µg/m3. DISCUSSION: State-of-the-art geographic analytic techniques revealed an association between PM2.5 and PD that varied in strength by region. A deeper investigation into the specific subfractions of PM2.5 may provide additional insight into regional variability in the PM2.5-PD association.

Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging.

OBJECTIVE: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure. METHODS: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the basal ganglia. We used voxelwise general linear modeling and linear regression to evaluate the association between cumulative Mn exposure, WM or basal ganglia DBSI metrics, and UPDRS3 scores, while adjusting for age. RESULTS: Mn-exposed welders had higher DBSI-derived restricted fraction (DBSI-RF), higher DBSI-derived nonrestricted fraction (DBSI-NRF), and lower DBSI-derived fiber fraction (DBSI-FF) in multiple WM tracts (all p < 0.05) in comparison to less-exposed workers and non-exposed participants. Basal ganglia ROI analyses revealed higher average caudate DBSI-NRF and DBSI-derived radial diffusion (DBSI-RD) values in Mn-exposed welders relative to non-exposed participants (p < 0.05). Caudate DBSI-NRF was also associated with greater cumulative Mn exposure and higher UPRDS3 scores. CONCLUSIONS: Mn-exposed welders demonstrate greater DBSI-derived indicators of neuroinflammation-related cellularity (DBSI-RF), greater extracellular edema (DBSI-NRF), and lower apparent axonal density (DBSI-FF) in multiple WM tracts suggesting a neuroinflammatory component in the pathophysiology of Mn neurotoxicity. Caudate DBSI-NRF was positively associated with both cumulative Mn exposure and clinical parkinsonism, indicating a possible dose-dependent effect on extracellular edema with associated motor effects.

A predictive algorithm to identify ever smoking in medical claims-based epidemiologic studies.

PURPOSE: To develop and validate an algorithm to estimate probability of ever smoking using administrative claims. METHODS: Using population-based samples of Medicare-aged individuals (121,278 Behavioral Risk Factor Surveillance System survey respondents and 207,885 Medicare beneficiaries), we developed a logistic regression model to predict probability of ever smoking from demographic and claims data. We applied the model in 1,657,266 additional Medicare beneficiaries and calculated area under the receiver operating characteristic curve (AUC) using presence or absence of a tobacco-specific diagnosis or procedure code as our "gold standard." We used these "gold standard" and lung/laryngeal cancer codes to over-ride predicted probability as 100%. We calculated Spearman's rho between probability from this full algorithm and smoking assessed in prior Parkinson disease studies, by substituting our observed and prior ("true") smoking-Parkinson disease odds ratios into the attenuation equation. RESULTS: The predictive model contained 23 variables, including basic demographics, high alcohol consumption, asthma, cardiovascular disease and associated risk factors, selected cancers, and indicators of routine medical usage. The AUC was 67.6% (95% confidence interval 67.5%-67.7%) comparing smoking probability to tobacco-specific diagnosis or procedure codes. Spearman's rho for the full algorithm was 0.82. CONCLUSIONS: Ever smoking might be approximated in administrative data for use as a continuous, probabilistic variable in epidemiologic analyses.

Biologic targets of prescription medications and risk of neurodegenerative disease in United States Medicare beneficiaries.

OBJECTIVE: To identify prescription medications associated with a lower risk of three neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. METHODS: We conducted a population-based, case-control study of U.S. Medicare beneficiaries in 2009 (42,885 incident neurodegenerative disease cases, 334,387 randomly selected controls). Using medication data from 2006-2007, we categorized all filled medications according to their biological targets and mechanisms of action on those targets. We used multinomial logistic regression models, while accounting for demographics, indicators of smoking, and health care utilization, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with all three diseases, we attempted replication in a cohort study that included an active comparator group. We constructed the cohort by following controls forward for incident neurodegenerative disease from the beginning of 2010 until death or end of 2014, i.e., up to five years after the two-year exposure lag. We used Cox proportional hazards regression while accounting for the same covariates. RESULTS: The most consistent inverse association across both studies and all three neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, represented by the gout medication, allopurinol. Allopurinol was associated with a 13-34% lower risk for each neurodegenerative disease group in multinomial regression, and a mean reduction of 23% overall, as compared to individuals who did not use allopurinol. In the replication cohort we observed a significant 23% reduction for neurodegenerative disease in the fifth year of follow-up, when comparing allopurinol users to non-users, and more marked associations with an active comparator group. We observed parallel associations for a related target-action pair unique to carvedilol. DISCUSSION/CONCLUSION: Xanthine dehydrogenase/oxidase blockade might reduce risk of neurodegenerative disease. However, further research will be necessary to confirm that the associations related to this pathway are causal or to examine whether this mechanism slows progression.

Environmental manganese exposure and cognitive control in a South African population.

OBJECTIVE: To characterize the association between environmental (residential air) manganese (Mn) exposure and cognitive performance, focusing on cognitive control, in a Black African population. METHODS: We administered the Go-No-Go, Digit Span, and Matrix Reasoning tests to population-based samples age ≥40 from a high Mn (smelter) exposed community, Meyerton (N = 629), and a demographically comparable low (background levels) non-exposed community, Ethembalethu, (N = 96) in Gauteng province, South Africa. We investigated the associations between community and performance on the cognitive tests, using linear regression. We adjusted a priori for age and sex, and examined the effect of adjustment for education, nonverbal IQ, smoking, and alcohol consumption. We measured airborne PM2.5-Mn to confirm community exposure differences. RESULTS: Compared to Ethembalethu residents, Meyerton residents' test scores were lower (poorer) for all tests: 0.55 (95 % confidence interval [CI] 0.08, 1.03) lower scores for Matrix Reasoning, 0.34 (95 % CI -0.07, 0.75) lower for Digit Span, and 0.15 (95 % CI 0.09, 0.21) lower for Go-No-Go (high frequency discriminability index [probability]). The latter represented the most marked difference in terms of z-scores (0.50, 95 % CI 0.30, 0.71 standard deviations lower). The mean of the z-score of each of the three tests was also lower (0.34, 95 % CI 0.18, 0.50 standard deviations lower). These associations were similar in men and women, but attenuated with adjustment for education. Differences for Matrix Reasoning and Digit Span between the two communities were observed only among those who had lived in Meyerton ≥10 years, whereas for Go-No-Go, differences were also apparent among those who had lived in Meyerton <10 years. Mean PM2.5-Mn at a long-term fixed site in Meyerton was 203 ng/m3 and 10 ng/m3 in Ethembalethu. CONCLUSION: Residence in a community near a high Mn emission source is associated with cognitive dysfunction, including aspects of cognitive control as assessed by the Go-No-Go test.

Solvent exposed occupations and risk of Parkinson disease in Finland.

INTRODUCTION: Epidemiologic and toxicology studies suggest that exposure to various solvents, especially chlorinated hydrocarbon solvents, might increase Parkinson disease (PD) risk. METHODS: In a population-based case-control study in Finland, we examined whether occupations with potential for solvent exposures were associated with PD. We identified newly diagnosed cases age 45-84 from a nationwide medication reimbursement register in 1995-2014. From the population register, we randomly selected non-PD controls matched on sex, along with birth and diagnosis years (age). We included 11,757 cases and 23,236 controls with an occupation in the 1990 census, corresponding to age 40-60. We focused on 28 occupations with ≥ 5% probability of solvent exposure according to the Finnish Job Exposure Matrix. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) by logistic regression modeling, adjusting for age, sex, socioeconomic status, and smoking probability. RESULTS: Similar proportions of cases (5.5%) and controls (5.6%) had an occupation with potential exposure to any solvents. However, all occupations with a point estimate above one, and all significantly or marginally significantly associated with PD (electronic/telecommunications worker [OR = 1.63, 95% CI 1.05-2.50], laboratory assistant [OR = 1.40, 95% CI 0.98-1.99], and machine/engine mechanic [OR = 1.23, 95% CI 0.99-1.52]) entailed potential for exposure to chlorinated hydrocarbon solvents, specifically. Secondary analyses indicated exposure to polycyclic aromatic hydrocarbons and some metals might contribute to the association for mechanics. CONCLUSION: PD risk might be slightly increased in occupations with potential exposure to chlorinated hydrocarbon solvents. Confirmation is required in additional studies that adjust for other occupational exposures and smoking.

Fractures in the prodromal period of Parkinson disease.

OBJECTIVE: To examine the association between fractures and Parkinson disease (PD) during the 5-year prodromal phase as compared to controls. METHODS: We performed a population-based case-control study of Medicare beneficiaries in the United States from 2004 to 2009. We identified 89,632 incident PD cases and 117,760 comparable controls 66-90 years of age in 2009. PD case status was the outcome, and noncranial fracture the independent variable. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for association between fracture and PD in yearly time intervals prior to PD diagnosis/control reference date, after adjusting for covariates. RESULTS: There were 39,606 total fractures (25.4% cases, 14.3% controls) over the 5 years prior to the PD diagnosis/control reference date. PD was positively associated with fractures even after adjusting for age, sex, race/ethnicity, Charlson comorbidity index, alcohol use, tobacco use, and osteoporosis. The association between PD and fracture was evident at yearly time windows prior to PD diagnosis/control reference date. The association between PD and each type of fracture strengthened as the PD diagnosis/control reference date approached (all time interaction p values ≤0.02). Among beneficiaries with a mechanism of injury, the majority were attributed to falls (74.6% cases, 72.8% controls). CONCLUSION: Fractures occur more commonly during the prodromal period of PD compared to controls, especially as diagnosis date approached, suggesting that patients with PD may experience unrecognized motor and nonmotor symptoms.

Well Water and Parkinson's Disease in Medicare Beneficiaries: A Nationwide Case-Control Study.

BACKGROUND: Well water frequently is considered a risk factor for Parkinson's disease (PD), but few studies were designed appropriately to test whether geographic factors affect PD risk. OBJECTIVE: To determine the risk of PD in relation to residential use of private well water. METHODS: In a nationwide, population-based case-control study, we identified all incident PD cases (N = 89,790) and all comparable controls (N = 21,549,400) age 66-90 who solely relied on Medicare coverage in the U.S. in 2009. We estimated the probability of use of private well water using zip code of residence at diagnosis/reference and U.S. Census data on household water source. We modeled this exposure linearly in logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI) of PD risk in relation to well water use. We adjusted for age, sex and race/ethnicity, and verified that smoking and use of medical care did not confound results. We repeated analyses with a 2-year exposure lag and separately within each U.S. state. RESULTS: Use of well water was inversely associated with PD risk (OR = 0.87, 95% CI 0.85-0.89). We confirmed this association in a Cox survival analysis in which we followed controls for 5 years, death or PD diagnosis. There was little evidence that well water use increased risk of PD in any individual state. CONCLUSIONS: Although it remains possible that exposures in well water in more narrow geographic regions increase PD risk, in general these results suggest that exposures more common in urban/suburban areas might also be relevant.

Herpesvirus Infections and Risk of Parkinson's Disease.

INTRODUCTION: Herpesviruses might play a role in the pathogenesis of neurodegenerative disorders. We sought to examine a possible association between alpha herpesvirus infections and Parkinson's disease. METHODS: We conducted a population-based case-control study of incident Parkinson's disease in 2009 Medicare beneficiaries age 66-90 years (89,790 cases, 118,095 randomly selected comparable controls). We classified beneficiaries with any diagnosis code for "herpes simplex" and/or "herpes zoster" in the previous 5 years as having had the respective alpha herpesviruses. In beneficiaries with Part D prescription coverage, we also identified those prescribed anti-herpetic medications. We calculated odds ratios (OR) and 95% CI between alpha herpesvirus diagnosis/treatment and Parkinson's disease with logistic regression, with adjustment for age, sex, race/ethnicity, smoking, and use of medical care. RESULTS: Parkinson's disease risk was inversely associated with herpes simplex (OR 0.79, 95% CI 0.74-0.84), herpes zoster (OR 0.88, 95% CI 0.85-0.91), and anti-herpetic medications (OR 0.87, 95% CI 0.80-0.96). CONCLUSION: Herpesvirus infection or treatment might reduce risk of Parkinson's disease, but future studies will be required to explore whether this inverse association is causal.

Transplant and risk of Parkinson disease.

INTRODUCTION: The pathophysiology of Parkinson's disease (PD) remains unclear, but growing evidence supports a role of neuroinflammation. The purpose of this study was to investigate the association between tissue transplantation and PD risk, given the importance of immunosuppressants in post-transplant management. METHODS: We performed a case-control study among Medicare beneficiaries age 66-90 using claims from 2004 to 2009. We used International Classification of Diseases, Ninth Edition (ICD-9) and Current Procedural Terminology (CPT) codes to identify PD (89,790 incident cases, 118,095 population-based controls) and history of tissue transplant (kidney, heart, liver, lung, and bone marrow). We investigated risk of PD in relation to tissue transplant in logistic regression models, adjusting for age, sex, race, smoking, and overall use of medical care. RESULTS: Beneficiaries who had received a tissue transplant at least five years prior to PD diagnosis or reference had a lower risk of PD (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.53, 0.75) than those without tissue transplant. This inverse association was observed for kidney (OR 0.63, 95% CI 0.47, 0.84), heart (OR 0.58, 95% CI 0.40, 0.83), lung (OR 0.41, 95% CI 0.21, 0.77), and bone marrow (OR 0.57, 95% 0.38, 0.85) transplants. Associations were attenuated, but remained, following adjustment for indications for the respective type of transplant. Liver transplant was not associated with PD risk. CONCLUSIONS: Patients undergoing tissue transplant may have a lower risk of developing PD than the general population. Further studies are needed to determine if this association is causal and if immunosuppressants mediate this association.

ß2-adrenoreceptor medications and risk of Parkinson disease.

OBJECTIVE: A recent study observed a 2-fold greater risk of Parkinson disease (PD) in relation to the ß2-adrenoreceptor antagonist propranolol and a markedly lower risk of PD for the ß2-adrenoreceptor agonist salbutamol. We examined whether confounding by clinical indication for these medications, that is, tremor and smoking-related pulmonary conditions, explained these associations. METHODS: In a large, population-based case-control study of United States Medicare beneficiaries in 2009 with diagnosis codes, procedure codes, and prescription data (48,295 incident PD cases, 52,324 controls), we examined the risk of PD in relation to use of selected ß antagonists (propranolol, carvedilol, metoprolol), the ß2 agonist salbutamol, and other medications used for the same clinical indications (primidone, inhaled corticosteroids). We adjusted for demographics, smoking, and overall use of medical care. We then examined the effect of also adjusting for clinical indication and applying medication exposure lagging. RESULTS: Propranolol appeared to increase PD risk (odds ratio [OR] = 3.62, 95% confidence interval [CI] = 3.31-3.96). When we adjusted for tremor or abnormal involuntary movement prior to the PD diagnosis/reference date and lagged propranolol exposure, the association was 0.97 (95% CI = 0.80-1.18). Primidone, also used for tremor, was similarly sensitive to this adjustment and lagging. ß Antagonists not indicated for tremor appeared to reduce PD risk (carvedilol: OR = 0.77, 95% CI = 0.73-0.81; metoprolol: OR = 0.94, 95% CI = 0.91-0.97) and were insensitive to adjustment for indications and lagging. Neither salbutamol nor inhaled corticosteroids were consistently associated with PD risk. INTERPRETATION: ß2-adrenoreceptor agonists and antagonists do not appear to alter PD risk. Ann Neurol 2018;84:691-701.

Use of medical care biases associations between Parkinson disease and other medical conditions.

OBJECTIVE: To examine how use of medical care biases the well-established associations between Parkinson disease (PD) and smoking, smoking-related cancers, and selected positively associated comorbidities. METHODS: We conducted a population-based, case-control study of 89,790 incident PD cases and 118,095 randomly selected controls, all Medicare beneficiaries aged 66 to 90 years. We ascertained PD and other medical conditions using ICD-9-CM codes from comprehensive claims data for the 5 years before PD diagnosis/reference. We used logistic regression to estimate age-, sex-, and race-adjusted odds ratios (ORs) between PD and each other medical condition of interest. We then examined the effect of also adjusting for selected geographic- or individual-level indicators of use of care. RESULTS: Models without adjustment for use of care and those that adjusted for geographic-level indicators produced similar ORs. However, adjustment for individual-level indicators consistently decreased ORs: Relative to ORs without adjustment for use of care, all ORs were between 8% and 58% lower, depending on the medical condition and the individual-level indicator of use of care added to the model. ORs decreased regardless of whether the established association is known to be positive or inverse. Most notably, smoking and smoking-related cancers were positively associated with PD without adjustment for use of care, but appropriately became inversely associated with PD with adjustment for use of care. CONCLUSION: Use of care should be considered when evaluating associations between PD and other medical conditions to ensure that positive associations are not attributable to bias and that inverse associations are not masked.

Inflammatory bowel disease and risk of Parkinson's disease in Medicare beneficiaries.

INTRODUCTION: Gastrointestinal (GI) dysfunction precedes the motor symptoms of Parkinson's disease (PD) by several years. PD patients have abnormal aggregation of intestinal α-synuclein, the accumulation of which may be promoted by inflammation. The relationship between intestinal α-synuclein aggregates and central nervous system neuropathology is unknown. Recently, we observed a possible inverse association between inflammatory bowel disease (IBD) and PD as part of a predictive model of PD. Therefore, the objective of this study was to examine the relationship between PD risk and IBD and IBD-associated conditions and treatment. METHODS: Using a case-control design, we identified 89,790 newly diagnosed PD cases and 118,095 population-based controls >65 years of age using comprehensive Medicare data from 2004-2009 including detailed claims data. We classified IBD using International Classification of Diseases version 9 (ICD-9) diagnosis codes. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between PD and IBD. Covariates included age, sex, race/ethnicity, smoking, Elixhauser comorbidities, and health care use. RESULTS: PD was inversely associated with IBD overall (OR = 0.85, 95% CI 0.80-0.91) and with both Crohn's disease (OR = 0.83, 95% CI 0.74-0.93) and ulcerative colitis (OR = 0.88, 95% CI 0.82-0.96). Among beneficiaries with ≥2 ICD-9 codes for IBD, there was an inverse dose-response association between number of IBD ICD-9 codes, as a potential proxy for IBD severity, and PD (p-for-trend = 0.006). CONCLUSION: IBD is associated with a lower risk of developing PD.

A screening tool to detect clinical manganese neurotoxicity.

Manganese (Mn) over-exposure in occupational settings is associated with basal ganglia toxicity and a movement disorder characterized by parkinsonism (i.e., the signs and symptoms of Parkinson disease). A simple test to help non-neurologists identify workers with clinical Mn neurotoxicity represents an unmet need. In a cohort of Mn-exposed workers from welding worksites, with extensive clinical data, we developed a linear regression model to predict the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3) score. We primarily considered factors easily obtained in a primary care or occupational medicine clinic, specifically easily assessed signs of parkinsonism and factors likely to be associated with UPDRS3 such as age, timed motor task results, and selected symptoms/conditions. Secondarily we considered other demographic variables and welding exposure. We based the model on 596 examined workers age≤65years and with timed motor task data. We selected the model based on simplicity for clinical application, biologic plausibility, and statistical significance and magnitude of regression coefficients. The model contained age, timed motor task scores for each hand, and indicators of action tremor, speech difficulty, anxiety, depression, loneliness, pain and current cigarette smoking. When we examined how well the model identified workers with clinically significant parkinsonism (UPDRS3≥15) the receiver operating characteristic area under the curve (AUC) was 0.72 (95% confidence interval [CI] 0.67, 0.77). With a cut point that provided 80% sensitivity, specificity was 52%, the positive predictive value in our cohort was 29%, and the negative predictive value was 92%. Using the same cut point for predicted UPDRS3, the AUC was nearly identical for UPDRS3≥10, and was 0.83 (95% CI 0.76, 0.90) for UPDRS3≥20. Since welding exposure data was not required after including its putative effects, this model may help identify workers with clinically significant Mn neurotoxicity in a variety of settings, as a first step in a tiered occupational screening program.

Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data.

OBJECTIVE: Studies suggest a greater risk of Parkinson's disease (PD) after traumatic brain injury (TBI), but it is possible that the risk of TBI is greater in the prodromal period of PD. We aimed to examine the time-to-TBI in PD patients in their prodromal period compared to population-based controls. METHODS: We identified 89,790 incident PD cases and 118,095 comparable controls aged > 65 years in 2009 using Medicare claims data. Using data from the preceding 5 years, we compared time-to-TBI in PD patients in their prodromal period to controls. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for TBI in a Cox regression, while adjusting for age, sex, race/ethnicity, modified Charlson comorbidity index, smoking, and alcohol use. RESULTS: Risk of TBI was greater in PD patients in their prodromal period across all age and sex groups, with HRs consistently increasing with proximity to PD diagnosis. HRs ranged from 1.64 (95% CI, 1.52, 1.77) 5 years preceding diagnosis to 3.93 (95% CI, 3.74, 4.13) in the year before. The interaction between PD, TBI, and time was primarily observed for TBI attributed to falls. Motor dysfunction and cognitive impairment, suggested by corresponding International Classification of Diseases, Ninth Revision codes, partially mediated the PD-TBI association. INTERPRETATION: There is a strong association between PD and a recent TBI in the prodromal period of PD. This association strengthens as PD diagnosis approaches and may be a result of undetected nonmotor and motor symptoms, but confirmation will be required. Ann Neurol 2017;82:744-754.

A predictive model to identify Parkinson disease from administrative claims data.

OBJECTIVE: To use administrative medical claims data to identify patients with incident Parkinson disease (PD) prior to diagnosis. METHODS: Using a population-based case-control study of incident PD in 2009 among Medicare beneficiaries aged 66-90 years (89,790 cases, 118,095 controls) and the elastic net algorithm, we developed a cross-validated model for predicting PD using only demographic data and 2004-2009 Medicare claims data. We then compared this model to more basic models containing only demographic data and diagnosis codes for constipation, taste/smell disturbance, and REM sleep behavior disorder, using each model's receiver operator characteristic area under the curve (AUC). RESULTS: We observed all established associations between PD and age, sex, race/ethnicity, tobacco smoking, and the above medical conditions. A model with those predictors had an AUC of only 0.670 (95% confidence interval [CI] 0.668-0.673). In contrast, the AUC for a predictive model with 536 diagnosis and procedure codes was 0.857 (95% CI 0.855-0.859). At the optimal cut point, sensitivity was 73.5% and specificity was 83.2%. CONCLUSIONS: Using only demographic data and selected diagnosis and procedure codes readily available in administrative claims data, it is possible to identify individuals with a high probability of eventually being diagnosed with PD.

Relative mortality in U.S. Medicare beneficiaries with Parkinson disease and hip and pelvic fractures.

BACKGROUND: Parkinson disease is a neurodegenerative disease that affects gait and postural stability, resulting in an increased risk of falling. The purpose of this study was to estimate mortality associated with demographic factors after hip or pelvic (hip/pelvic) fracture in people with Parkinson disease. A secondary goal was to compare the mortality associated with Parkinson disease to that associated with other common medical conditions in patients with hip/pelvic fracture. METHODS: This was a retrospective observational cohort study of 1,980,401 elderly Medicare beneficiaries diagnosed with hip/pelvic fracture from 2000 to 2005 who were identified with use of the Beneficiary Annual Summary File. The race/ethnicity distribution of the sample was white (93.2%), black (3.8%), Hispanic (1.2%), and Asian (0.6%). Individuals with Parkinson disease (131,215) were identified with use of outpatient and carrier claims. Cox proportional hazards models were used to estimate the risk of death associated with demographic and clinical variables and to compare mortality after hip/pelvic fracture between patients with Parkinson disease and those with other medical conditions associated with high mortality after hip/pelvic fracture, after adjustment for race/ethnicity, sex, age, and modified Charlson comorbidity score. RESULTS: Among those with Parkinson disease, women had lower mortality after hip/pelvic fracture than men (adjusted hazard ratio [HR] = 0.63, 95% confidence interval [CI]) = 0.62 to 0.64), after adjustment for covariates. Compared with whites, blacks had a higher (HR = 1.12, 95% CI = 1.09 to 1.16) and Hispanics had a lower (HR = 0.87, 95% CI = 0.81 to 0.95) mortality, after adjustment for covariates. Overall, the adjusted mortality rate after hip/pelvic fracture in individuals with Parkinson disease (HR = 2.41, 95% CI = 2.37 to 2.46) was substantially elevated compared with those without the disease, a finding similar to the increased mortality associated with a diagnosis of dementia (HR = 2.73, 95% CI = 2.68 to 2.79), kidney disease (HR = 2.66, 95% CI = 2.60 to 2.72), and chronic obstructive pulmonary disease (HR = 2.48, 95% CI = 2.43 to 2.53). CONCLUSIONS: Mortality after hip/pelvic fracture in Parkinson disease varies according to demographic factors. Mortality after hip/pelvic fracture is substantially increased among those with Parkinson disease.

Disparities in deep brain stimulation surgery among insured elders with Parkinson disease.

OBJECTIVE: To identify sociodemographic, clinical, and physician/practice factors associated with deep brain stimulation (DBS). DBS is a proven surgical therapy for Parkinson disease (PD), but is recommended only for patients with excellent health, results in significant out-of-pocket costs, and requires substantial physician involvement. METHODS: Retrospective cohort study of more than 657,000 Medicare beneficiaries with PD. Multivariable logistic regression models examined the association between demographic, clinical, socioeconomic status (SES), and physician/practice factors, and DBS therapy. RESULTS: There were significant disparities in the use of DBS therapy among Medicare beneficiaries with PD. The greatest disparities were associated with race: black (adjusted odds ratio [AOR] 0.20, 95% confidence interval [CI] 0.16-0.25) and Asian (AOR 0.55, 95% CI 0.44-0.70) beneficiaries were considerably less likely to receive DBS than white beneficiaries. Women (AOR 0.79, 95% CI 0.75-0.83) also had lower odds of receiving DBS compared with men. Eighteen percent of procedures were performed on patients with PD who had cognitive impairment/dementia, a reported contraindication to DBS. Beneficiaries treated in minority-serving PD practices were less likely to receive DBS, regardless of individual race (AOR 0.76, 95% CI 0.66-0.87). Even after adjustment for demographic and clinical covariates, high neighborhood SES was associated with 1.4-fold higher odds of receiving DBS (AOR 1.42, 95% CI 1.33-1.53). CONCLUSIONS: Among elderly Medicare beneficiaries with PD, race, sex, and neighborhood SES are strong independent predictors of DBS receipt. Racial disparities are amplified when adjusting for physician/clinic characteristics. Future investigations of the demographic differences in clinical need/usefulness of DBS, ease of DBS attainment, and actual/opportunity DBS costs are needed to inform policies to reduce DBS disparities and improve PD quality of care.

Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study.

BACKGROUND: Manganese (Mn) is a common component of welding fume. Exposure to Mn fume has been associated with parkinsonism. A simple and reliable screening tool to evaluate Mn exposed workers for neurotoxic injury would have broad occupational health application. METHODS: This study investigated 490 occupational welders recruited from a trade union list. Subjects were examined by a movement disorders specialist using the Unified Parkinson Disease Rating Scale motor subsection 3 (UPDRS3). Parkinsonism, intermediate, and normal groups were defined as UPDRS3 score ≥ 15, 6-15, and <6, respectively. Workers completed a health status questionnaire (PDQ39) and a Parkinson disease (PD) Symptoms Questionnaire. Areas under receiver operator curve (AUC) were analyzed based on these scores, adjusted for age, smoking, race, gender, and neurologist, using normal as the reference. RESULTS: The AUC was 0.79 (95% confidence interval [CI]=0.73-0.84) for PDQ39 and 0.78 (95% CI=0.72-0.85) for PD Symptoms Questionnaire score. At 70% sensitivity, the specificity for PDQ39 score and PD Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and 80.1%, respectively. CONCLUSIONS: These results suggest the questionnaires have reasonably good sensitivity and specificity to predict parkinsonism in Mn exposed workers. These questionnaires could be a valuable first step in a tiered screening approach for Mn exposed workers.

Variables associated with return to sport following anterior cruciate ligament reconstruction: a systematic review.

BACKGROUND: As one of the purposes of anterior cruciate ligament reconstruction (ACLR) is to return athletes to their preinjury activity level, it is critical to understand variables influencing return to sport. Associations between return to sport and variables representing knee impairment, function and psychological status have not been well studied in athletes following ACLR. PURPOSE: The purpose of this review was to summarise the literature reporting on variables proposed to be associated with return to sport following ACLR. STUDY DESIGN: Systematic review. METHODS: Medline, EMBASE, CINAHL and Cochrane databases were searched for articles published before November 2012. Articles included in this review met these criteria: (1) included patients with primary ACLR, (2) reported at least one knee impairment, function or psychological measure, (3) reported a return to sport measure and (4) analysed the relationship between the measure and return to sport. RESULTS: Weak evidence existed in 16 articles suggesting variables associated with return to sport included higher quadriceps strength, less effusion, less pain, greater tibial rotation, higher Marx Activity score, higher athletic confidence, higher preoperative knee self-efficacy, lower kinesiophobia and higher preoperative self-motivation. CONCLUSIONS: Weak evidence supports an association between knee impairment, functional and psychological variables and return to sport. Current return to sport guidelines should be updated to reflect all variables associated with return to sport. Utilising evidence-based return to sport guidelines following ACLR may ensure that athletes are physically and psychologically capable of sports participation, which may reduce reinjury rates and the need for subsequent surgery.