Legislative and regulatory barriers to pharmacies dispensing buprenorphine for OUD.

INTRODUCTION: Buprenorphine (BUP) is increasingly recognized and utilized as a valuable medication for the treatment of opioid use disorder. This article focuses on the problem of regulatory restrictions on access to buprenorphine products without naloxone (mono-product), involving patients in one geographic area, but which may represent a more general access problem in the United States. DESIGN: In response to an audit by the Tennessee Board of Pharmacy, a pharmacy in northeast Tennessee designed a questionnaire to survey patient motivation for traveling long distances to fill their prescriptions for BUP, rather than buprenorphine/naloxone (BNx, combo-product), and to document their satisfaction with treatment with the mono-product. RESULTS: Questionnaires were submitted by 194 patients, living in northeast Tennessee, southwest Virginia, and southeast Kentucky. Significant, intolerable, side effects were reported by all patients in the survey prescribed BNx, but because of legislative and regulatory restrictions in their respective states, they were unable to obtain BUP closer to home. Consequently, they were required to drive significant distances from their homes to fill their prescriptions, a median distance of 52 miles, and in some cases as far as 216 miles round trip. Intolerable reactions included severe headaches, nausea and vomiting, allergies, and severe dysphoria. All patients tolerated BUP and were clinically well maintained on the mono-product. CONCLUSION: Severe, intolerable reactions/side effects from the naloxone component of BNx are not uncommon, but legislative and regulatory restrictions on the mono-product prohibit providers and pharmacies in some states from prescribing and dispensing BUP. The participants in this qualitative study found it necessary to travel significant distances to obtain their prescribed medication, thereby potentially limiting access to this life-saving therapy.

Investigating the Sequence Specific Adsorption Behavior of Polypeptides at the Solid/Liquid Interface.

Polymer adsorption at the solid/liquid interface depends not only on the chemical composition of the polymer but also on the specific placement of the monomers along the polymer sequence. However, challenges in designing polymers with well-controlled sequences have limited explorations into the role of polymer sequence on adsorption behavior to molecular simulations. Here, we demonstrate how the sequence control offered by polypeptide synthesis can be utilized to study the effects small changes in polymer sequence have on polymer adsorption behavior at the solid/liquid interface. Through a combination of quartz crystal microbalance with dissipation monitoring and total internal reflection ellipsometry, we study the adsorption behavior of three polypeptides, consisting of 90% lysine and 10% cysteine, onto a gold surface. We find different mechanisms are responsible for the adsorption of polypeptides and the resulting conformation on the surface. The initial adsorption of the polypeptides is driven by electrostatic interactions between the polylysine and the gold surface. Once adsorbed, the cysteine undergoes a thiol-Au reaction with the surface, altering the conformation of the polymer layer. Our findings suggest the conformation of the polypeptide layer is dependent on the placement of the cysteines within the sequence; polypeptide chains with evenly spaced cysteine groups adopt a more tightly bound "train" conformation as compared to polypeptides with closely grouped cysteine groups. We envision that the methodologies presented here to study sequence specific adsorption behaviors using polypeptides could be a valuable tool to complement molecular simulations studies.

Adverse effects of regulation on buprenorphine prescribing and its impact on the treatment of opioid use disorder.

PROBLEM: Drug addiction and misuse is a medical and societal problem that has exacted a heavy toll on the United States, and, indeed, the world. In the United States, opioids are currently the main driver of drug overdose deaths. Despite the proven safety and efficacy of medically assisted therapy (MAT) using buprenorphine for the treatment of opioid use disorder (OUD), as well as the fact that its use is regulated by US Federal Law, many states have enacted separate and often burdensome regulations that restrict the prescribing of buprenorphine beyond those required by the US Drug Enforcement Agency (DEA) under the provisions of the DATA 2000 Act, and unnecessarily reduce the availability of effective treatment of OUD in those states. PURPOSE: The purpose of this article is to review the pharmacology of both buprenorphine (and naloxone as an additive) and the risks associated with the misuse of buprenorphine products and to consider if such additional state oversight and restrictions improves or is deleterious to public safety in the face of this national epidemic. CONCLUSION: We conclude that the placing of unnecessary and unscientific restraints on the treatment of patients with OUD is inconsistent with the principles of harm reduction, and such restraints should be removed unless/until they can be supported by real evidence.

Microscopic origin of shear banding as a localized driven glass transition in compressed colloidal pillars.

Here we report on compression experiments of colloidal pillars in which the evolution of a shear band can be followed at the particle level during deformation. Quasistatic deformation results in dilation and anisotropic changes in coordination in a localized band of material. Additionally, a transition from solid- to liquidlike mechanical response accompanies the structural change in the band, as evidenced by saturation of the packing fraction at the glass transition point, a diminishing ability to host anelastic strains, and a rapid decay in the long-range strain correlations. Overall, our results suggest that shear banding quantitatively resembles a localized, driven glass transition.

Robust scaling of strength and elastic constants and universal cooperativity in disordered colloidal micropillars.

We study the uniaxial compressive behavior of disordered colloidal free-standing micropillars composed of a bidisperse mixture of 3- and 6-µm polystyrene particles. Mechanical annealing of confined pillars enables variation of the packing fraction across the phase space of colloidal glasses. The measured normalized strengths and elastic moduli of the annealed freestanding micropillars span almost three orders of magnitude despite similar plastic morphology governed by shear banding. We measure a robust correlation between ultimate strengths and elastic constants that is invariant to relative humidity, implying a critical strain of ∼0.01 that is strikingly similar to that observed in metallic glasses (MGs) [Johnson WL, Samwer K (2005) Phys Rev Lett 95:195501] and suggestive of a universal mode of cooperative plastic deformation. We estimate the characteristic strain of the underlying cooperative plastic event by considering the energy necessary to create an Eshelby-like ellipsoidal inclusion in an elastic matrix. We find that the characteristic strain is similar to that found in experiments and simulations of other disordered solids with distinct bonding and particle sizes, suggesting a universal criterion for the elastic to plastic transition in glassy materials with the capacity for finite plastic flow.

Synthesis and mechanical response of disordered colloidal micropillars.

We present a new approach for studying the uniaxial compressive behavior of colloidal micropillars as a function of the initial defect population, pillar and colloid dimension, and particle-particle interaction. Pillars composed of nanometer scale particles develop cracks during drying, while pillars composed of micron scale particles dry crack-free. We subject the free-standing pillars, with diameters of 580 µm and 900 µm, to uniaxial compression experiments using a custom-built micromechanical testing apparatus. In pillars with pre-existing cracks, compression activates the macroscopic defects, leading to fracture and stochastic mechanical response as a result of the flaw distribution. Pillars that dry crack-free fail by shear bands that initiate near the punch face. While macroscopically identical, pillar-to-pillar mechanical response varies significantly. We attribute the disparate response to varying structure and environmental conditions. To isolate the effects of environment, we performed controlled experiments over a range of relative humidity levels (<2% to >98% RH). The level of atmospheric humidity affects particle-particle cohesion and friction, resulting in dramatically different mechanical responses. We discuss the results in the context of underlying particle rearrangements leading to mesoscopic shear localization and examine comparisons with atomic disordered systems such as metallic glasses.

Which environmental factors predict seasonal variation in the coral health of Acropora digitifera and Acropora spicifera at Ningaloo Reef?

The impact of physico-chemical factors on percent coral cover and coral health was examined on a spatial basis for two dominant Acropora species, A. digitifera and A. spicifera, at Ningaloo Reef (north-western Australia) in the southeast Indian Ocean. Coral health was investigated by measuring metabolic indices (RNA/DNA ratio and protein concentration), energy levels (lipid ratio) and autotrophic indices (chlorophyll a (chl a) and zooxanthellae density) at six stations during typical seasons (austral autumn 2010 (March and April), austral winter 2010 (August)) and during an extreme La Niña event in summer 2011 (February). These indices were correlated with 15 physico-chemical factors (measured immediately following coral sampling) to identify predictors for health indices. Variations in metabolic indices (protein concentration and RNA/DNA ratio) for A. spicifera were mainly explained by nitrogen, temperature and zooplankton concentrations under typical conditions, while for A. digitifera, light as well as phytoplankton, in particular picoeukaryotes, were important, possibly due to higher energy requirement for lipid synthesis and storage in A. digitifera. Optimum metabolic values occurred for both Acropora species at 26-28°C when autotrophic indices (chl a and zooxanthellae density) were lowest. The extreme temperature during the La Niña event resulted in a shift of feeding modes, with an increased importance of water column plankton concentrations for metabolic rates of A. digitifera and light and plankton for A. spicifera. Our results suggest that impacts of high sea surface temperatures during extreme events such as La Niña may be mitigated via reduction on metabolic rates in coral host. The high water column plankton concentrations and associated low light levels resulted in a shift towards high symbiont densities, with lower metabolic rates and energy levels than the seasonal norm for the coral host.

Biomechanical analysis of pediatric injuries and child restraint system.

Airbag related injuries to infants in rear facing child seats are common in frontal crashes. Several vehicular modifications such as deactivated passenger airbags, manual cut-off switches, depowered airbags and smart airbags have been advanced to mitigate the effect of airbag deployment on child seats. However, there is limited research effort to address the biomechanics of airbag injuries due to modification in child restraint systems. The purpose of this research is to evaluate the biomechanical effects of a protective barrier between the rear facing child restraint and the frontal passenger airbag of the vehicle. An experimental study was conducted using an Anthropometric Test Dummy (ATD) in a vehicular partial structure (buck). The rear facing child seat was placed in the right front passenger seat of the vehicle. The child seat was restrained using the three-point restraint in the vehicle. The six-month-old instrumented ATD was restrained in the child seat. The ATD was instrumented with the head tri-axial and two uni-axial linear accelerometers. The uni-axial linear acceleration was used to calculate the angular acceleration. Two different rear facing child seats, the standard rear facing infant seat and the rear facing infant seat inside the protective barrier structure were tested. In each test, the Head Injury Criteria (HIC) and angular head acceleration were measured. Results show that the HIC was reduced by 95% and the angular head acceleration was reduced by 85% by the protective barrier. The head injury values were well below the tolerance limit for the child with the barrier. The protective barrier deflected the airbag away from the ATD’s head and also acted as a shield to minimize airbag force on the child seat. In the typical infant seat, the airbag contacted the ATD’s head and exerted significant force on the child seat which rotated the seat rearward. These kinematic responses may explain the clinical observation of severe head injuries by infants in rear facing seats due to forces transmitted through the child seat and downward force from the top of the head. The present study is a first step in better understanding the injury mitigating aspects of the safety protective structure in child restraints.

Experimental biomechanical study of head injuries in lateral falls with skateboard helmet.

Traumatic brain injuries (TBI) are common in sports accidents. Helmets are generally known to provide protection to the head. However, the effectiveness of helmets in mitigating a TBI may be compromised due to the impact location and impact speed. Although it is known that the helmet decreases the linear head accelerations and the resulting head injury potential, to the best of our knowledge, limited research effort has been devoted to the study of the biomechanics of TBI in side impact conditions. The present work is designed to delineate the biomechanics of TBI in a fall impacting the parietal/temporal regions. A standing Hybrid III male dummy with pedestrian pelvis was used. The dummy was placed on a swinging platform for the fall simulation. The drop was achieved by stopping the platform with a block. The platform was swung from a predetermined height and stopped to allow the free fall of the dummy. The test was conducted with and without a skate board helmet. The impact on the dummy’s head was in the parietal and temporal regions. The head impact speed with the floor was approximately 24 kph (6.7 m/sec) The dummy was instrumented with tri-axial linear and tri-axial angular head accelerometers to measure the biomechanical injury responses. Results from three tests were compared. The linear head CG acceleration, Head Injury Criteria (HIC) and angular head accelerations were compared. Results suggest that the helmet reduced the linear head acceleration, HIC and angular head acceleration compared to the impact without a helmet. Although the linear head accelerations and HIC were reduced, the angular head accelerations even with the helmet were above nearly all proposed rotational head injury threshold in the literature. The higher angular head accelerations indicate a higher probability of concussion, acute subdural hematoma and diffuse axonal injuries. The present study is an additional step to better understand the biomechanics of TBI and the role of protective headgear systems in sports and recreational accidents.

Health plan administrative records versus birth certificate records: quality of race and ethnicity information in children.

BACKGROUND: To understand racial and ethnic disparities in health care utilization and their potential underlying causes, valid information on race and ethnicity is necessary. However, the validity of pediatric race and ethnicity information in administrative records from large integrated health care systems using electronic medical records is largely unknown. METHODS: Information on race and ethnicity of 325,810 children born between 1998-2008 was extracted from health plan administrative records and compared to birth certificate records. Positive predictive values (PPV) were calculated for correct classification of race and ethnicity in administrative records compared to birth certificate records. RESULTS: Misclassification of ethnicity and race in administrative records occurred in 23.1% and 33.6% children, respectively; the majority due to missing ethnicity (48.3%) and race (40.9%) information. Misclassification was most common in children of minority groups. PPV for White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, multiple and other was 89.3%, 86.6%, 73.8%, 18.2%, 51.8% and 1.2%, respectively. PPV for Hispanic ethnicity was 95.6%. Racial and ethnic information improved with increasing number of medical visits. Subgroup analyses comparing racial classification between non-Hispanics and Hispanics showed White, Black and Asian race was more accurate among non-Hispanics than Hispanics. CONCLUSIONS: In children, race and ethnicity information from administrative records has significant limitations in accurately identifying small minority groups. These results suggest that the quality of racial information obtained from administrative records may benefit from additional supplementation by birth certificate data.

Nontuberculous mycobacterial lung disease prevalence at four integrated health care delivery systems.

RATIONALE: Single-site clinic-based studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease, but systematic data are lacking. OBJECTIVES: To describe prevalence and trends for NTM lung disease at four geographically diverse integrated heath care delivery systems in the United States. METHODS: We abstracted mycobacterial culture results from electronic laboratory databases and linked to other datasets containing clinical and demographic information. Possible cases were defined as a single positive NTM pulmonary isolate, and definite cases were defined as two positive sputum cultures, or one positive culture from a bronchoalveolar lavage or lung biopsy. Annual prevalence was calculated using United States census data; average annual prevalence is presented for 2004-2006. Poisson regression models were used to estimate the annual percent change in prevalence. MEASUREMENTS AND MAIN RESULTS: A total of 28,697 samples from 7,940 patients were included in the analysis. Of these, 3,988 (50%) were defined as possible cases, and 1,865 (47%) of these were defined as definite cases. Average annual (2004-2006) site-specific prevalence ranged from 1.4 to 6.6 per 100,000. Prevalence was 1.l- to 1.6-fold higher among women relative to men across sites. The prevalence of NTM lung disease was increasing significantly at the two sites where trends were studied, by 2.6% per year among women and 2.9% per year among men. Among persons aged greater than or equal to 60 years, annual prevalence increased from 19.6 per 100,000 during 1994-1996 to 26.7 per 100,000 during 2004-2006. CONCLUSIONS: The epidemiology of nontuberculous mycobacterial lung disease is changing, with a predominance of women and increasing prevalence at the sites studied.

Biomechanical analysis and injury prevention in off-highway vehicular crashes - biomed 2010.

Traffic safety has significantly improved over the past several decades reducing injury and fatality rates. However, there is a paucity of research effort directed to address the safety issues in off-highway vehicular crashes, specifically the all terrain/utility vehicular crashes. Rollover crashes are severe accidents leading to the increase in fatalities and injuries. The appropriate safety measures to contain occupants in vehicular compartments are crucial in mitigating injuries in rollover crashes. The purpose of this study is to delineate the occupant kinematics in simulated rollover conditions and to evaluate the injury prevention aspects. Two utility/all terrain vehicles were used. Each vehicle was placed on the motorized test equipment in the laboratory. The motorized dynamic rollover test equipment simulated the rollover environment in a controlled manner. Human surrogate models representing 1th percentile female, 50th percentile male and 96th percentile male were utilized in the testing. The multi-phase dynamic testing was conducted to quantify the occupant kinematic responses in foreseeable real world conditions. A total of 39 tests were conducted. The vehicle with belted surrogates was rolled 90 degrees at a roll rate up to 45 degrees/second. The excursion of the head, upper extremity and lower extremities beyond the plane of the vehicular structure was measured and compared between the two vehicles using two onboard cameras and three off-board cameras. Results show that the advanced restraint system with the occupant containment feature significantly reduced the occupant excursion. Such a significant reduction of occupant movement will better protect occupants in rollover off-highway accidents.

Recurrence of preterm premature rupture of membranes in relation to interval between pregnancies.

OBJECTIVE: The purpose of this study was to examine whether the recurrence risk of preterm premature rupture of membranes (PPROM) is modified by the interpregnancy interval (IPI). STUDY DESIGN: We used the Missouri 1989-1997 longitudinally linked data to examine the recurrence risk of PPROM in women with first 2 (n = 150,929) and first 3 (n = 30,011) successive pregnancies. Race-specific recurrence risks were examined. Adjusted odds ratios (ORs) were used to estimate risks. RESULTS: Risks of PPROM in the second pregnancy among women with and without previous PPROM were 5.7% and 2.3%, respectively, among white women (OR, 8.7; 95% confidence interval, 6.7-11.4) and 10.3% and 4.3%, respectively, among African American women (OR, 7.2; 95% confidence interval, 5.1-10.1). Short IPI was associated with increased risk for PPROM recurrence, with substantially higher risk for African American women than white women. However, long IPI was associated with increased recurrence among African American women. CONCLUSION: Women with previous PPROM are at increased risk for recurrence, and a short IPI is associated with increased risk.

Effect of chorioamnionitis on early childhood asthma.

OBJECTIVE: To examine the association between chorioamnionitis and childhood asthma based on gestational age at birth and race/ethnicity. DESIGN: A retrospective cohort study using the Kaiser Permanente Southern California (KPSC) Matched Perinatal records. SETTING: Kaiser Permanente Southern California, Pasadena, California. PARTICIPANTS: All singleton children born in KPSC hospitals between 1991 and 2007 (N = 510 216). MAIN EXPOSURE: Clinically diagnosed chorioamnionitis. MAIN OUTCOME MEASURES: Physician-diagnosed asthma in children aged 8 years or younger. RESULTS: The incidence rates of asthma among preterm- and full term-born children of pregnancies complicated by chorioamnionitis were 100.7 and 39.6 per 1000 person-years, respectively (incidence rate ratio, 2.9; 95% confidence interval [CI], 2.6-3.3). Children aged 8 years or younger with asthma were more likely to be born to women who were aged 35 years or older, African American, had 13 or more years of education, had maternal asthma, used antibiotics, had chorioamnionitis during the pregnancy, and had a male child. Multivariable Cox regression analysis revealed that children born at 23 to 28, 29 to 33, and 34 to 36 weeks' gestation after pregnancies complicated by chorioamnionitis had a 1.23-fold (95% CI, 1.02-1.49), 1.51-fold (95% CI, 1.26-1.80), and 1.20-fold (95% CI, 1.03-1.47), respectively, increased risk of asthma compared with children of similar gestational age born after pregnancies not complicated by chorioamnionitis. A preterm pregnancy complicated by chorioamnionitis was associated with increased risk of asthma among white (hazard ratio [HR], 1.66; 95% CI, 1.32-2.07), African American (HR, 1.98; 95% CI, 1.60-2.44), and Hispanic (HR, 1.70; 95% CI, 1.45-2.00), but not Asian/Pacific Islander (HR, 1.15; 95% CI, 0.83-1.58) women. CONCLUSION: Findings suggest that chorioamnionitis at preterm gestation is independently associated with increased risk of childhood asthma.

Racial and ethnic disparities in the trends in primary cesarean delivery based on indications.

OBJECTIVE: To examine trends in primary cesarean deliveries by indications and race/ethnicity. STUDY DESIGN: We examined temporal trends in primary cesarean deliveries from 1991 through 2008 among singleton births (n = 540,953) in Kaiser Permanente Southern California hospitals using information from maternal hospitalizations and infant birth certificates. In addition, relative increases and 95% confidence intervals (CIs) were used to estimate differences in primary cesarean section rates by indication for the earliest (1991-1992) and most recent (2007-2008) periods. Racial/ethnic disparities in primary cesarean deliveries were examined by comparing the relative risks from multiple logistic regression models. RESULTS: The rate of primary cesarean section among white, African American, Hispanic, and Asian/Pacific Islander women increased by 61.6%, 64.1%, 62.4%, and 70.2%, respectively, between 1991 and 2008. In comparison to the primary cesarean section rate for white women, the rate was 25% (95% confidence interval [CI], 22-29%) higher for African American women, 19% (95% CI, 16-23%) higher for Asian/Pacific Islander women, but 14% (95% CI, 13-16%) lower for Hispanic women. After adjustment for confounding factors, primary cesarean section rates remained significantly higher for African American women but lower for Hispanic women compared with white women. Indication subtypes-specific rates of primary cesarean section varied markedly across race/ethnicity. CONCLUSION: We found that the overall primary cesarean section rate has increased over time. In addition, there is a wide variability in rate of indications for primary cesarean section by race/ethnicity.

The association between stillbirth in the first pregnancy and subsequent adverse perinatal outcomes.

OBJECTIVE: We sought to examine the association between first-pregnancy stillbirth and subsequent adverse perinatal outcomes. STUDY DESIGN: This cohort study examined the first 2 singleton deliveries at 20-44 weeks' gestation from 1991-2008 (n = 71,315) using birth certificate, hospitalization, and outpatient encounter files. Multivariable logistic regression models were used to assess the association. RESULTS: Stillbirth was observed in 5.3 of 1000 first deliveries. There was an increased risk of ischemic placental disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.2-2.1), fetal distress (OR, 2.8; 95% CI, 1.7-4.5), chorioamnionitis (OR, 2.3; 95% CI 1.5-4.3), extreme preterm birth (OR, 4.2; 95% CI, 1.8-9.9), and early neonatal mortality (OR, 8.3; 95% CI, 3.7-18.6) in pregnancies after stillbirth vs pregnancies after live birth. Interpregnancy intervals <2 and > or =4 years after stillbirth increased the risk of ischemic placental disease and spontaneous preterm birth. Risks varied by stillbirth subtype. CONCLUSION: A first-pregnancy stillbirth may increase adverse perinatal outcomes in subsequent pregnancy.

Pooled analysis of tobacco use and risk of Parkinson disease.

CONTEXT: Epidemiologic studies have reported that cigarette smoking is inversely associated with Parkinson disease (PD). However, questions remain regarding the effect of age at smoking onset, time since quitting, and race/ethnicity that have not been addressed due to sample size constraints. This comprehensive assessment of the apparent reduced risk of PD associated with smoking may provide important leads for treatment and prevention. OBJECTIVE: To determine whether race/ethnicity, sex, education, age at diagnosis, and type of tobacco modify the observed effects of smoking on PD. DESIGN, SETTING, AND PARTICIPANTS: We conducted the first ever pooled analysis of PD combining individual-level data from 8 US case-control and 3 cohort studies (Nurses' Health Study, Health Professionals Follow-Up Study, and Honolulu-Asia Aging Study) conducted between 1960 and 2004. Case-control studies provided data for 2328 PD cases and 4113 controls matched by age, sex, and ethnicity; cohort studies contributed 488 cases and 4880 controls selected from age- and sex-matched risk sets. MAIN OUTCOME MEASURE: Incident PD. RESULTS: We confirmed inverse associations between PD and smoking and found these to be generally stronger in current compared with former smokers; the associations were stronger in cohort than in case-control studies. We observed inverse trends with pack-years smoked at every age at onset except the very elderly (>75 years of age), and the reduction of risk lessened with years since quitting smoking. The risk reductions we observed for white and Asian patients were not seen in Hispanic and African American patients. We also found an inverse association both for smoking cigars and/or pipes and for chewing tobacco in male subjects. CONCLUSIONS: Our data support a dose-dependent reduction of PD risk associated with cigarette smoking and potentially with other types of tobacco use. Importantly, effects seemed not to be influenced by sex or education. Differences observed by race and age at diagnosis warrant further study.

Evaluation of Parkinson's disease in entrants on the Nebraska State Parkinson's Disease Registry.

We examined a sample of individuals in the Nebraska State Parkinson's Disease Registry (NSPDR) to determine what proportion meets standard criteria for Parkinson's disease (PD). The NSPDR was established in 1996 in an effort to understand the high prevalence of PD in Nebraska. Only minimal demographic data are included for each entrant. Subjects enter the NSPDR by means of diagnosing physicians, pharmacists dispensing anti-PD medications and the patients themselves. A series of 356 registrants diagnosed between 1997 and 2001 were contacted and invited to participate in a case-control study. Medical records were reviewed by a single abstractor in a standard manner. When patients consented, history was filled in by interview. A subset of patients were examined by a movement disorders specialist, who assigned all patients a probability of PD. Where sufficient information was available, 78% of registrants were confirmed to have PD (i.e., percent probability > 50%), including 83% of the patients previously diagnosed by a neurologist. Tremor was an initial symptom in 72% of confirmed versus 39% of excluded cases, and resting tremor was present in 86% of those that were confirmed. The most frequent reasons for exclusion were drug-induced Parkinsonism, multiple systems atrophy, vascular disease, and essential tremor. Use of the NSPDR for epidemiologic study requires careful review of the data set before assignment of cases. When histories are compiled in a standardized, comprehensive manner, the necessity for actual patient examinations can be minimized.