Cross-Check QA: A Quality Assurance Workflow to Prevent Missed Diagnoses by Alerting Inadvertent Discordance Between the Radiologist and Artificial Intelligence in the Interpretation of High-Acuity CT Scans.

PURPOSE: The aim of this study was to implement and evaluate a quality assurance (QA) workflow that leverages natural language processing to rapidly resolve inadvertent discordance between radiologists and an artificial intelligence (AI) decision support system (DSS) in the interpretation of high-acuity CT studies when the radiologist does not engage with AI DSS output. METHODS: All consecutive high-acuity adult CT examinations performed in a health system between March 1, 2020, and September 20, 2022, were interpreted alongside an AI DSS (Aidoc) for intracranial hemorrhage, cervical spine fracture, and pulmonary embolus. CT studies were flagged for this QA workflow if they met three criteria: (1) negative results by radiologist report, (2) a high probability of positive results by the AI DSS, and (3) unviewed AI DSS output. In these cases, an automated e-mail notification was sent to our quality team. If discordance was confirmed on secondary review-an initially missed diagnosis-addendum and communication documentation was performed. RESULTS: Of 111,674 high-acuity CT examinations interpreted alongside the AI DSS over this 2.5-year time period, the frequency of missed diagnoses (intracranial hemorrhage, pulmonary embolus, and cervical spine fracture) uncovered by this workflow was 0.02% (n = 26). Of 12,412 CT studies prioritized as depicting positive findings by the AI DSS, 0.4% (n = 46) were discordant, unengaged, and flagged for QA. Among these discordant cases, 57% (26 of 46) were determined to be true positives. Addendum and communication documentation was performed within 24 hours of the initial report signing in 85% of these cases. CONCLUSIONS: Inadvertent discordance between radiologists and the AI DSS occurred in a small number of cases. This QA workflow leveraged natural language processing to rapidly detect, notify, and resolve these discrepancies and prevent potential missed diagnoses.

Noninterpretive Uses of Artificial Intelligence in Radiology.

We deem a computer to exhibit artificial intelligence (AI) when it performs a task that would normally require intelligent action by a human. Much of the recent excitement about AI in the medical literature has revolved around the ability of AI models to recognize anatomy and detect pathology on medical images, sometimes at the level of expert physicians. However, AI can also be used to solve a wide range of noninterpretive problems that are relevant to radiologists and their patients. This review summarizes some of the newer noninterpretive uses of AI in radiology.

The Use of Artificial Intelligence in the Evaluation of Knee Pathology.

Artificial intelligence (AI) holds the potential to revolutionize the field of radiology by increasing the efficiency and accuracy of both interpretive and noninterpretive tasks. We have only just begun to explore AI applications in the diagnostic evaluation of knee pathology. Experimental algorithms have already been developed that can assess the severity of knee osteoarthritis from radiographs, detect and classify cartilage lesions, meniscal tears, and ligament tears on magnetic resonance imaging, provide automatic quantitative assessment of tendon healing, detect fractures on radiographs, and predict those at highest risk for recurrent bone tumors. This article reviews and summarizes the most current literature.

Use of Shoulder Imaging in the Outpatient Setting: A Pilot Study.

PURPOSE: Characterize the clinical utility of diagnostic shoulder imaging modalities commonly used in the outpatient workup of shoulder pain. MATERIALS/METHODS: Retrospective review of adults imaged for outpatient shoulder pain from 1/1/2013 to 9/1/2015. To be categorized as "useful", a study had to meet one of the following criteria: change the clinical diagnosis or treatment plan, provide a final diagnosis, or guide definitive treatment. A utility score was assigned to each study based on the number of utility criteria met (range 0-4). A score of 1 was considered low utility; a score of greater than or equal to 2 was considered high utility. Statistical analysis included binary logistic regression and generalized estimating equations. RESULTS: 210 subjects (65% male); mean age 47 (range 18-84), underwent 302 imaging studies (159 X-ray, 137 MRI, 2 CT, 4 ultrasound) during the study period. 92.1% of all studies met minimum criteria for utility (score >1). Most commonly, diagnostic studies obtained during the outpatient workup of shoulder pain were found to guide definitive treatment (70.5%) or provide a final diagnosis (53%). Most X-rays were categorized as no or low utility (85.5%). 97.8% of the MRI studies were categorized as useful with most being high utility (73%). Overall, MRI was the most useful modality in all clinical scenarios (P = 0.002) and more likely to be high utility (P < 0.001) compared to X-rays. None of the investigated patient or injury characteristics were significant predictors of useful imaging. CONCLUSION: Our study suggests that both radiographs and MRI are useful in the evaluation of adult unilateral shoulder pain in the outpatient setting. MRI appears to be the most useful imaging modality in terms of helping guide diagnosis and treatment selection. This serves as a potential first step towards the development of evidence based imaging algorithms that can be used and tested in future studies.

MR Imaging of Entrapment Neuropathies of the Lower Extremity.

Entrapment neuropathies of the lower extremity are commonly encountered and present a diagnostic challenge. Historical diagnostic workhorses-the physical examination combined with electrodiagnostic studies-are now frequently supplemented by MR neurography. MR neurography is a high-resolution, noninvasive, and operator-independent imaging modality that has proven useful in diagnosis, disease severity assessment, and informing treatment decisions in the management of lower extremity entrapment neuropathies. Currently, the assessment of the peripheral nerves relies heavily on reader identification of morphologic nerve changes; however, emerging innovative MR sequences and PET/MR imaging hold the potential to provide noninvasive means of functional assessment.

Percutaneous Ultrasound-Guided Musculoskeletal Applications of Autologous Bone Marrow Aspirate Concentrate: Preliminary Experience From a Single Institution.

Emerging musculoskeletal applications for local administration of autologous bone marrow aspirate concentrate (BMAC) include treatment of fractures, osteonecrosis, osteochondral injuries, osteoarthritis, ligament injury, tendon injury, and tendonopathies. Ultrasound-guided technique for various BMAC injection sites is detailed in this technical report and our preliminary clinical experience outlined.Five patients, 1 woman and 4 men, were treated with 6 peri/intratendinous (n = 4) or intraarticular (n = 2) BMAC injections between July 5, 2015 and December 31, 2016 for the clinical indications of common hamstrings origin tendinosis (n = 4), hip labral tear (n = 1), and osteochondral lesion of the talus (n = 1).All procedures were technically successful, with BMAC locally administered to the therapeutic target and no procedural complications observed. Clinical follow-up was available for 5 of 6 procedures. Four of 5 injections resulted in self-reported symptomatic improvement (clinical follow-up range, 2-12 months). One 72-year-old man with right common hamstrings origin tendinosis reported no improvement after BMAC injection.The technology is now available to support ultrasound-guided, autologous BMAC administration by the musculoskeletal interventionalist for common indications. Our initial clinical experience is consistent with early reports in the literature. This technique is well tolerated by symptomatic patients on an outpatient basis, and rates of self-reported symptomatic relief are high. Mechanism of action, long-term safety, and long-term clinical efficacy remain largely undefined.

JOURNAL CLUB: MRI Evaluation of Midtarsal (Chopart) Sprain in the Setting of Acute Ankle Injury.

OBJECTIVE: This study determined the frequency and MRI appearance of osseous and ligamentous injuries in midtarsal (Chopart) sprains and their association with ankle sprains after acute ankle injuries. Prospective diagnosis of and interobserver agreement regarding midtarsal injury among musculoskeletal radiologists were also assessed. SUBJECTS AND METHODS: Two cohorts with ankle MRI were identified via a digital PACS search: patients who had undergone MRI within 8 weeks after ankle injury and control subjects who had not sustained ankle trauma. Studies were retrospectively reviewed in consensus as well as independently, assessing ligamentous and osseous injury to the Chopart joint (calcaneocuboid and talonavicular joints) and associated lateral collateral and deltoid ligamentous injury. Interobserver agreement was calculated, and prospective radiology reports were reviewed to determine the musculoskeletal radiologist's familiarity with Chopart joint injury. RESULTS: MR images of control subjects (n = 16) and patients with ankle injury (n = 47) were reviewed. The normal dorsal calcaneocuboid and calcaneocuboid component of bifurcate ligaments were variably visualized; the remaining normal ligaments were always seen. Eleven patients (23%) had midtarsal ligamentous and osseous injury consistent with midtarsal sprain (eight acute or subacute, one probable, and two old). Six (75%) of eight acute or subacute cases had coexisting lateral collateral ligament injury. Eighty-nine percent of osseous injuries were reported prospectively, but 83% of ligamentous injuries were missed. Substantial interobserver agreement was achieved regarding diagnosis of midtarsal sprain. CONCLUSION: Midtarsal sprains are commonly associated with acute ankle injury and with ankle sprains. Presently, midtarsal sprains may be underrecognized by radiologists; thus, greater familiarity with the MRI spectrum of ligamentous and osseous injuries at the Chopart joint is important for accurate diagnosis and clinical management.

Advanced Imaging Techniques in the Knee: Benefits and Limitations of New Rapid Acquisition Strategies for Routine Knee MRI.

OBJECTIVE: The purpose of this article is to review current and emerging techniques and strategies that can be used to accelerate acquisition times in routine knee MRI. CONCLUSION: Specific techniques reviewed include 3D fast spin-echo imaging as well as new approaches to rapid image acquisition techniques (parallel imaging, compressed sensing, simultaneous multislice, and neural network reconstruction techniques) and their potential application to knee MRI.

Axial traction magnetic resonance imaging (MRI) of the glenohumeral joint in healthy volunteers: initial experience.

OBJECTIVE: Evaluate technical feasibility and potential applications of glenohumeral (GH) joint axial traction magnetic resonance imaging (MRI) in healthy volunteers. MATERIALS AND METHODS: Eleven shoulders were imaged in neutral and with 4kg axial traction at 3T. Quantitative measurements were assessed. RESULTS: Axial traction was well tolerated. There was statistically significant widening of the superior GH joint space (p=0.002) and acromial angle (p=0.017) with traction. Inter-rater agreement was high. CONCLUSION: GH joint axial traction MRI is technically feasible and well tolerated in volunteers. Traction of the capsule, widening of the superior GH joint space and acromial angle were observed.

Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction.

The purpose of this study was to determine the rate and risk factors for the development of irreversible hepatotoxicity after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and synthetic hepatic dysfunction. Two hundred fifty-one consecutive patients with HCC and hepatic dysfunction who underwent 443 TACE procedures from 2005 to 2010 were retrospectively reviewed. The included patients met one of the following criteria: a pre-TACE bilirubin level ≥ 2 mg/dL, an international normalized ratio (INR) > 1.5, a creatinine level > 1.2 mg/dL, a platelet count ≤ 60,000/mL, a Model for End-Stage Liver Disease (MELD) score > 15, Child-Turcotte-Pugh class B or C, ascites, or portal vein thrombosis. Hepatotoxicity was defined as new or worsening ascites, encephalopathy, or grade 3 or 4 toxicity (bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, or INR) according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The rate and risk factors for death or urgent liver transplantation within 6 weeks of TACE and irreversible hepatotoxicity were determined with a generalized estimating equation analysis. Reversible hepatotoxicity developed after 90 procedures (20%) in 78 patients (31%). Irreversible hepatotoxicity developed after 41 procedures (9%) in 37 patients (15%). Six patients (2%) underwent urgent liver transplantation, and 11 (4%) died within 6 weeks of TACE. Patients at increased risk for procedure-related mortality or urgent liver transplantation within 6 weeks of TACE had a baseline serum bilirubin level ≥ 4.0 mg/dL (P = 0.01), an elevated INR (P < 0.001), hypoalbuminemia with an albumin level < 2.0 g/L (P = 0.01), a serum creatinine level > 2.0 mg/dL (P = 0.02), large ascites (P = 0.002), encephalopathy (P = 0.005), or a MELD score ≥ 20 (P < 0.001). In conclusion, TACE can be performed safely in patients with baseline hepatic dysfunction. However, a poor hepatic reserve increases the risk of irreversible hepatotoxicity, which may lead to death or the need for urgent liver transplantation.

The effects of acellular dermal matrix in expander-implant breast reconstruction after total skin-sparing mastectomy: results of a prospective practice improvement study.

BACKGROUND: Neither outcome after total skin-sparing mastectomy and expander-implant reconstruction using acellular dermal matrix nor a strategy for optimal acellular dermal matrix selection criteria has been well described. METHODS: Prospective review of three patient cohorts undergoing total skin-sparing mastectomy with preservation of the nipple-areola complex and immediate expander-implant reconstruction from 2006 to 2010 was performed. Cohort 1 (no acellular dermal matrix) comprised 90 cases in which acellular dermal matrix was not used. Cohort 2 (consecutive acellular dermal matrix) included the next 100 consecutive cases, which all received acellular dermal matrix. Cohort 3 (selective acellular dermal matrix) consisted of the next 260 cases, in which acellular dermal matrix was selectively used based on mastectomy skin flap thickness. Complication rates were compared using chi-square analysis. RESULTS: The study included 450 cases in 288 patients. Mean follow-up was 25.5 months. Infection occurred in 27.8 percent of the no-acellular dermal matrix cases, 20 percent of the consecutive cases, and 15.8 percent of the selective cases (p = 0.04). Unplanned return to the operating room was required in 23.3, 11, and 10 percent of cases, respectively (p = 0.004). Expander-implant loss occurred in 17.8, 7, and 5 percent of cases, respectively (p = 0.001). Additional analysis of the odds ratios of developing complications after postmastectomy radiation therapy demonstrated a specific protective benefit of acellular dermal matrix in irradiated patients. CONCLUSIONS: Acellular dermal matrix use in expander-implant reconstruction after total skin-sparing mastectomy reduced major postoperative complications in this study. Maximal benefit is achieved with selected use in patients with thin mastectomy skin flaps and those receiving radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome.

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages-proliferating macrophages (promacs)-with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P = 0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.

Parkinsonism in patients with a history of amphetamine exposure.

We recently found a higher rate of prolonged amphetamine exposure in patients diagnosed with Parkinson's disease (PD) than in spouse/caregiver controls. Since distinguishing features have been described in some patients with parkinsonism due to environment exposures (e.g., manganese), we sought to compare the clinical features of patients with PD with prolonged amphetamine exposure with unexposed patients with PD. Prolonged exposure was defined as a minimum of twice a week for >or=3 months, or weekly use >or=1 year. We reviewed the clinical records of patients with PD who had participated in a telephone survey of drug and environmental exposures and compared the clinical features of patients with a history of prolonged amphetamine exposure to patients who had no such exposure. Records were available for 16 of 17 (94%) patients with prior amphetamine exposure and 127 of 137 (92%) of those unexposed. Age at diagnosis was younger in the amphetamine-exposed group (49.8 +/- 8.2 years vs. 53.1 +/- 7.4 years; P < 0.05), but other features, including presenting symptoms, initial and later treatments, development of motor fluctuations, and MRI findings were similar between these groups. Because we did not detect clinical features that differentiate parkinsonism in patients with prolonged amphetamine exposure, research to determine whether amphetamine exposure is a risk factor for parkinsonism will require detailed histories of medication and recreational drug use.

Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer.

The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery. Tissue (diagnostic core biopsy/final surgical specimen), blood, and magnetic resonance images were obtained before/after treatment. The primary endpoint was Ki-67 (proliferation) reduction. Secondary endpoints were change in cleaved caspase-3 (CC3, apoptosis), MRI tumor volume, and serum C-reactive protein (CRP, inflammation). Planned subgroup analyses compared disease grade, statin dose, and estrogen receptor status. Forty of 45 patients who enrolled completed the protocol; 29 had paired Ki-67 primary endpoint data. Proliferation of high grade tumors decreased by a median of 7.2% (P = 0.008), which was statistically greater than the 0.3% decrease for low grade tumors. Paired data for CC3 showed tumor apoptosis increased in 38%, remained stable in 41%, and decreased in 21% of subjects. More high grade tumors had an increase in apoptosis (60 vs. 13%; P = 0.015). Serum CRP did not change, but cholesterol levels were significantly lower post statin exposure (P < 0.001). Fluvastatin showed measurable biologic changes by reducing tumor proliferation and increasing apoptotic activity in high-grade, stage 0/1 breast cancer. Effects were only evident in high grade tumors. These results support further evaluation of statins as chemoprevention for ER-negative high grade breast cancers.

Spontaneous hemoperitoneum from a ruptured mesenteric branch arterial aneurysm: report of a case.

We report a case of spontaneous intraperitoneal hemorrhage from a ruptured mesenteric branch artery aneurysm in a patient presenting with syncope. A 54-year-old woman was brought to our emergency department as a medical code, following two syncopal episodes. Computed tomography, carried out to rule out aortic aneurysmal disease, revealed hemoperitoneum without evidence of solid organ injury. Emergency exploratory laparotomy revealed a large jejunal mesenteric hematoma accompanying a ruptured mesenteric branch artery aneurysm with active extravasation. We ligated and excised the lesion and diagnosis was confirmed on final pathologic examination. We report this case because general surgeons should be aware of these vascular lesions and the basic guidelines for treatment.

Total skin-sparing mastectomy: complications and local recurrence rates in 2 cohorts of patients.

PURPOSE: Dissemination of the total skin-sparing mastectomy (TSSM) technique is limited by concerns of nipple viability, flap necrosis, local recurrence risk, and the technical challenge of this procedure. We sought to define the impact of surgical and reconstructive variables on complication rates and assess how changes in technique affect outcomes. PATIENTS AND METHODS: We compared the outcomes of TSSM in 2 cohorts of patients. Cohort 1: the first 64 TSSM procedures performed at our institution, between 2001 and 2005. Cohort 2: 106 TSSM performed between 2005 and 2007. Outcomes of cohort 1 were analyzed in 2005. At that time, potential risk factors for complications were identified, and efforts to minimize these risks by altering operative and reconstructive technique were then applied to patients in cohort 2. The impact of these changes on outcomes was assessed. Logistic regression was used to determine the association between predictor variables and adverse outcomes (Stata 10). RESULTS: The predominant incision type in cohort 2 involved less than a third of the nipple areola complex (NAC), and the most frequent reconstruction technique was tissue expander placement. Between cohort 1 and cohort 2, nipple survival rates rose from 80% to 95% (P = 0.003) and complication rates declined: necrotic complications (30% --> 13%; P = 0.01), implant loss (31% --> 10%; P = 0.005), skin flap necrosis (16%-11%; not significant), and significant infections (17%-9%, not significant). Incisions involving >30% of the NAC (P < 0.001) and reconstruction with autologous tissue (P < 0.001) were independent risk factors for necrotic complications. The local recurrence rate was 0.6% at a median follow-up of 13 months (range, 1-65), with no recurrences in the NAC. CONCLUSION: Focused improvement in technique has resulted in the development of TSSM as a successful intervention at our institution that is oncologically safe with high nipple viability and early low rates of recurrence. Identifying factors that contribute to complications and changing surgical and reconstructive techniques to eliminate risk factors has greatly improved outcomes.

Menopausal hormone therapy and breast cancer phenotype: does dose matter?

BACKGROUND: Duration and type of menopausal hormone therapy (HT) has been associated with increased breast cancer risk and the development of estrogen receptor (ER)-positive tumors. The effect of HT dose on breast cancer tumor characteristics remains undefined. We sought to determine if HT dosing regimens influence breast cancer phenotype. METHODS: We conducted a retrospective review of incident female breast cancers occurring in the year 2003 listed in the Kaiser Permanente Northern California Cancer Registry. Type of HT, dose, number of tablets dispensed, tumor phenotype, stage, grade, and histology were obtained from electronic records for women aged >/=50 years who had more than 1 year of uninterrupted pharmacy data (n = 1701). A dose index of HT exposure was created and odds ratios were used to determine if tumor phenotype varied between exposure groups. These results were compared with a previously published analysis of HT duration on tumor phenotype conducted with the same dataset. RESULTS: The cumulative effect of estrogen and progesterone hormone therapy as calculated by factoring both dose and duration of HT use prior to breast cancer diagnosis did not reveal any new associations that were not previously identified by analysis of HT duration of exposure alone. Low-dose-index combination-HT users were less likely to have tumors with an ER-positive phenotype. An overall trend developed in which low- and high-dose-index exposed women had the lowest rates of ER- and progesterone receptor (PR) -positive tumors. CONCLUSION: Duration of use is an adequate surrogate for determining overall exposure to HT when considering the effect of HT on breast cancer phenotype.

Biologic significance of false-positive magnetic resonance imaging enhancement in the setting of ductal carcinoma in situ.

BACKGROUND: Imaging patterns of benign proliferative processes often complicate the assessment of ductal carcinoma in situ (DCIS) by magnetic resonance imaging (MRI). We investigated the pathologic and biologic characteristics of false positive enhancement by breast MRI. METHODS: DCIS (n = 45), benign (n = 5), and false-positive (MRI enhancement and nonmalignant pathology) (n = 10) cases were characterized by immunohistochemistry and MRI features. RESULTS: For DCIS cases, images that overestimated pathologic size had heterogeneous enhancement on MR, were estrogen receptor positive, and were low grade by pathology. False-positives had higher rates of proliferation, angiogenesis, and inflammation compared with benign tissue but lower values than DCIS. Benign proliferative processes accounted for all false-positive and size overestimated cases. CONCLUSIONS: Lesions that enhance on MRI have higher proliferation, angiogenesis, and inflammation compared with nonproliferative breast tissue. Benign proliferative processes often enhance on MRI and are difficult to differentiate from low-grade, ER+ DCIS lesions. False-positive MRI enhancement may reflect a spectrum of change within high-risk tissue.

Amphetamine exposure is elevated in Parkinson's disease.

BACKGROUND: Since the 1930's, amphetamine drugs have been used therapeutically and recreationally. High doses are associated with acute injury to axon terminals of dopaminergic neurons. It is unknown whether low dose exposure to amphetamine over a prolonged time period is associated with the development of Parkinson's disease (PD). METHODS: A telephone survey of drug and chemical exposure was administered to patients from three faculty practice clinics at UCSF. Patients were asked to participate if they had been diagnosed with peripheral neuropathy (PN), amyotrophic lateral sclerosis (ALS), or PD between the ages of 40 and 64. Spouses or caregivers were also asked to participate. "Amphetamine exposure" was defined as a prior use of amphetamine, methamphetamine or dextroamphetamine. "Prolonged exposure" was defined as amphetamine use that occurred more than twice a week for > or =3 months or weekly usage for > or =1 year and had to occur before diagnosis of the neurological condition. RESULTS: Prolonged exposure to either prescribed or non-prescribed amphetamine was common, occurring in 15% with PN (11/76), 13% with ALS (9/72), and 11% with PD (17/158). Prolonged amphetamine exposure was more frequent in diseased patients compared to spouses when all diseases were combined (adjusted OR=3.15, 95% CI 1.42-7.00, p=0.005). When tested alone, only the Parkinson's disease group retained statistical significance (adjusted OR=8.04, 95% CI 1.56-41.4, p=0.013). For most individuals, exposure occurred long before diagnosis (averages: PN 25 years, ALS 28 years, and PD 27 years). CONCLUSIONS: The elevated rate of prolonged amphetamine exposure in PD is intriguing and bears further investigation.