Differential Hospital Participation in Bundled Payments in Communities with Higher Shares of Marginalized Populations.

BACKGROUND: Medicare's voluntary bundled payment programs have demonstrated generally favorable results. However, it remains unknown whether uneven hospital participation in these programs in communities with greater shares of minorities and patients of low socioeconomic status results in disparate access to practice redesign innovations. OBJECTIVE: Examine whether communities with higher proportions of marginalized individuals were less likely to be served by a hospital participating in Bundled Payments for Care Improvement Advanced (BPCI-Advanced). DESIGN: Cross-sectional study using ordinary least squares regression controlling for patient and community factors. PARTICIPANTS: Medicare fee-for-service patients enrolled from 2015-2017 (pre-BPCI-Advanced) and residing in 2,058 local communities nationwide defined by Hospital Service Areas (HSAs). Each community's share of marginalized patients was calculated separately for each of the share of beneficiaries of Black race, Hispanic ethnicity, or dual eligibility for Medicare and Medicaid. MAIN MEASURES: Dichotomous variable indicating whether a given community had at least one hospital that ever participated in BPCI-Advanced from 2018-2022. KEY RESULTS: Communities with higher shares of dual-eligible individuals were less likely to be served by a hospital participating in BPCI-Advanced than communities with the lowest quartile of dual-eligible individuals (Q4: -15.1 percentage points [pp] lower than Q1, 95% CI: -21.0 to -9.1, p < 0.001). There was no consistent significant relationship between community proportion of Black beneficiaries and likelihood of having a hospital participating in BPCI-Advanced. Communities with higher shares of Hispanic beneficiaries were more likely to have a hospital participating in BPCI-Advanced than those in the lowest quartile (Q4: 19.2 pp higher than Q1, 95% CI: 13.4 to 24.9, p < 0.001). CONCLUSIONS: Communities with greater shares of dual-eligible beneficiaries, but not racial or ethnic minorities, were less likely to be served by a hospital participating in BPCI-Advanced Policymakers should consider approaches to incentivize more socioeconomically uniform participation in voluntary bundled payments.

Boarding in US Academic Emergency Departments During the COVID-19 Pandemic.

STUDY OBJECTIVE: The first 2 years of the COVID-19 pandemic brought substantial and dynamic changes to emergency department volumes and throughput. The objective of this study was to describe changes in ED boarding among US academic EDs across the duration of the COVID-19 pandemic. METHODS: We conducted a retrospective analysis of monthly data collected from a convenience sample of academic departments of emergency medicine. The study period was from January 2019 to December 2021. The primary outcome was total boarding hours, and secondary outcomes included patient volume stratified by ED disposition. We used multivariable linear panel regression models with fixed effects for individual EDs to estimate adjusted means for 3-month quarters. RESULTS: Of the 73 academic departments of emergency medicine contacted, 34 (46.6%) participated, comprising 43 individual EDs in 25 states. The adjusted mean total boarding hours per month significantly decreased during the second quarter of 2020 (4,449 hours; 95% confidence interval [CI] 3,189 to 5,710) compared to the first quarter of 2019 (8,521 hours; 95% CI 7,845 to 9,197). Beginning in the second quarter of 2021, total boarding hours significantly increased beyond pre-pandemic levels, peaking during the fourth quarter of 2021 (12,127 hours; 95% CI 10,925 to 13,328). CONCLUSIONS: A sustained and considerable increase in boarding observed in selected US academic EDs during later phases of the COVID-19 pandemic may reflect ongoing stresses to the health care system, with potential consequences for patient outcomes as well as clinician well-being.

Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs.

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients' preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.

Comparative Effectiveness of an Automated Text Messaging Service for Monitoring COVID-19 at Home.

BACKGROUND: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. OBJECTIVE: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home ("COVID Watch") was associated with improved mortality. DESIGN: Retrospective cohort analysis. SETTING: Mid-Atlantic academic health system in the United States. PARTICIPANTS: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. INTERVENTION: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. MEASUREMENTS: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score-weighted risk adjustment models. RESULTS: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). LIMITATION: Observational study with the potential for unobserved confounding. CONCLUSION: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.

Naloxone prescriptions following emergency department encounters for opioid use disorder, overdose, or withdrawal.

OBJECTIVE: To determine the rate at which commercially-insured patients fill prescriptions for naloxone after an opioid-related ED encounter as well as patient characteristics associated with obtaining naloxone. METHODS: This is a retrospective cohort study of adult patients discharged from the ED following treatment for an opioid-related condition from 2016 to 2018 using a commercial insurance claims database (Optum Clinformatics® Data Mart). The primary outcome was a pharmacy claim for naloxone in the 30 days following the ED encounter. A multivariable logistic regression model examined the association of patient characteristics with filled naloxone prescriptions, and predictive margins were used to report adjusted probabilities with 95% confidence intervals. RESULTS: 21,700 patients had opioid-related ED encounters during the study period, of which 1743 (8.0%) had encounters for heroin overdose, 8825 (40.7%) for overdose due to other opioids, 5400 (24.9%) for withdrawal, and 5732 (26.4%) for other opioid use disorder conditions. 230 patients (1.1%) filled a prescription for naloxone within 30 days. Patients with heroin overdose (2.6%; 95%CI 1.7 to 3.4), recent prescriptions for opioid analgesics (1.4%; 95%CI 1.1 to 1.7), recent prescriptions for buprenorphine (1.9%; 95%CI 1.0 to 2.9), and naloxone prescriptions in the prior year (3.3%; 95%CI 1.8 to 4.8) were more likely to obtain naloxone. The rate was significantly higher in 2018 [1.9% (95%CI 1.5 to 2.2)] as compared to 0.4% (95%CI 0.3 to 0.6) in 2016. CONCLUSIONS: Few patients use insurance to obtain naloxone by prescription following opioid-related ED encounters. Clinical and policy interventions should expand distribution of this life-saving medication in the ED.

Quality Through Coopetition: An Empiric Approach to Measure Population Outcomes for Emergency Care-Sensitive Conditions.

STUDY OBJECTIVE: We develop a novel approach for measuring regional outcomes for emergency care-sensitive conditions. METHODS: We used statewide inpatient hospital discharge data from the Pennsylvania Healthcare Cost Containment Council. This cross-sectional, retrospective, population-based analysis used International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes to identify admissions for emergency care-sensitive conditions (ischemic stroke, ST-segment elevation myocardial infarction, out-of-hospital cardiac arrest, severe sepsis, and trauma). We analyzed the origin and destination patterns of patients, grouped hospitals with a hierarchical cluster analysis, and defined boundary shapefiles for emergency care service regions. RESULTS: Optimal clustering configurations determined 10 emergency care service regions for Pennsylvania. CONCLUSION: We used cluster analysis to empirically identify regional use patterns for emergency conditions requiring a communitywide system response. This method of attribution allows regional performance to be benchmarked and could be used to develop population-based outcome measures after life-threatening illness and injury.

Employment and residential characteristics in relation to automated external defibrillator locations.

BACKGROUND: Survival from out-of-hospital cardiac arrest (OHCA) is generally poor and varies by geography. Variability in automated external defibrillator (AED) locations may be a contributing factor. To inform optimal placement of AEDs, we investigated AED access in a major US city relative to demographic and employment characteristics. METHODS AND RESULTS: This was a retrospective analysis of a Philadelphia AED registry (2,559 total AEDs). The 2010 US Census and the Local Employment Dynamics database by ZIP code was used. Automated external defibrillator access was calculated as the weighted areal percentage of each ZIP code covered by a 400-m radius around each AED. Of 47 ZIP codes, only 9% (4) were high-AED-service areas. In 26% (12) of ZIP codes, less than 35% of the area was covered by AED service areas. Higher-AED-access ZIP codes were more likely to have a moderately populated residential area (P = .032), higher median household income (P = .006), and higher paying jobs (P =. 008). CONCLUSIONS: The locations of AEDs vary across specific ZIP codes; select residential and employment characteristics explain some variation. Further work on evaluating OHCA locations, AED use and availability, and OHCA outcomes could inform AED placement policies. Optimizing the placement of AEDs through this work may help to increase survival.

A Randomized Trial Testing the Effect of Narrative Vignettes Versus Guideline Summaries on Provider Response to a Professional Organization Clinical Policy for Safe Opioid Prescribing.

STUDY OBJECTIVE: Clinical guidelines are known to be underused by practitioners. In response to the challenges of treating pain amid a prescription opioid epidemic, the American College of Emergency Physicians (ACEP) published an evidence-based clinical policy for opioid prescribing in 2012. Evidence-based narratives, an effective method of communicating health information in a variety of settings, offer a novel strategy for disseminating guidelines to physicians and engaging providers with clinical evidence. We compare whether narrative vignettes embedded in the ACEP daily e-newsletter improved dissemination of the clinical policy to ACEP members, and engagement of members with the clinical policy, compared with traditional summary text. METHODS: A prospective randomized controlled study, titled Stories to Promote Information Using Narrative trial, was performed. Derived from qualitative interviews with 61 ACEP physicians, 4 narrative vignettes were selected and refined, using a consensus panel of clinical and implementation experts. All ACEP members were then block randomized by state of residence to receive alternative versions of a daily e-mailed newsletter for a total of 24 days during a 9-week period. Narrative newsletters contained a selection of vignettes that referenced opioid prescription dilemmas. Control newsletters contained a selection of descriptive text about the clinical policy, using length and appearance similar to that of the narrative vignettes. Embedded in the newsletters were Web links to the complete vignette or traditional summary text, as well as additional links to the full ACEP clinical policy and a Web site providing assistance with prescription drug monitoring program enrollment. The newsletters were otherwise identical. Outcomes measured were the percentage of subjects who visited any of the Web pages that contained additional guideline-related information and the odds of any unique physician visiting these Web pages during the study. RESULTS: There were 27,592 physicians randomized, and 21,226 received the newsletter during the study period. When each physician was counted once during the study period, there were 509 unique visitors in the narrative group and 173 unique visitors in the control group (4.8% versus 1.6%; difference 3.2%; 95% confidence interval [CI] 2.7% to 3.7%). There were 744 gross visits from the e-newsletter to any of the 3 Web pages in the narrative group compared with 248 in the control group (7.0% versus 2.3%; odds ratio 3.2; 95% CI 2.7 to 3.6). During the study, the odds ratio of any physician in the narrative group visiting one of the 3 informational Web sites compared with the control group was 3.1 (95% CI 2.6 to 3.6). CONCLUSION: Among a national sample of emergency physicians, narrative vignettes outperformed traditional guideline text in promoting engagement with an evidence-based clinical guideline related to opioid prescriptions.

Do hospital service areas and hospital referral regions define discrete health care populations?

BACKGROUND: Effective measurement of health care quality, access, and cost for populations requires an accountable geographic unit. Although Hospital Service Areas (HSAs) and Hospital Referral Regions (HRRs) have been extensively used in health services research, it is unknown whether these units accurately describe patterns of hospital use for patients living within them. OBJECTIVES: To evaluate the ability of HSAs, HRRs, and counties to define discrete health care populations. RESEARCH DESIGN: Cross-sectional geographic analysis of hospital admissions. SUBJECTS: All hospital admissions during the year 2011 in Washington, Arizona, and Florida. MEASURES: The main outcomes of interest were 3 metrics that describe patient movement across HSA, HRR, and county boundaries: localization index, market share index, and net patient flow. Regression models tested the association of these metrics with different HSA characteristics. RESULTS: For 45% of HSAs, fewer than half of the patients were admitted to hospitals located in their HSA of residence. For 16% of HSAs, more than half of the treated patients lived elsewhere. There was an equivalent degree of movement across county boundaries but less movement across HRR boundaries. Patients living in populous, urban HSAs with multiple, large, and teaching hospitals tended to remain for inpatient care. Patients admitted through the emergency department tended to receive care at local hospitals relative to other patients. CONCLUSIONS: HSAs and HRRs are geographic units commonly used in health services research yet vary in their ability to describe where patients receive hospital care. Geographic models may need to account for differences between emergent and nonemergent care.

How, why, and for whom do emergency medicine providers use prescription drug monitoring programs?

OBJECTIVE: The prescription opioid epidemic is currently responsible for the greatest number of unintentional deaths in the United States. One potential strategy for decreasing this epidemic is implementation of state-based Prescription Drug Monitoring Programs (PDMPs), which are designed for providers to identify patients who "doctor shop" for prescriptions. Emergency medicine physicians are some of the most frequent PDMP users and opioid prescribers, but little is known about how they actually use PDMPs, for which patients, and for what reasons. METHODS: We conducted and transcribed semistructured qualitative interviews with 61 physicians at a national academic conference in October 2012. Deidentified transcripts were entered into QSR NVivo 10.0, coded, and analyzed for themes using modified grounded theory. RESULTS: There is variation in pattern and frequency of PDMP access by emergency physicians. Providers rely on both structural characteristics of the PDMP, such as usability, and also their own clinical gestalt impression when deciding to use PDMPs for a given patient encounter. Providers use the information in PDMPs to alter clinical decisions and guide opioid prescribing patterns. Physicians describe alternative uses for the databases, such as improving their ability to facilitate discussions on addiction and provide patient education. CONCLUSION: PDMPs are used for multiple purposes, including identifying opioid misuse and enhancing provider-patient communication. Given variation in practice, standards may help direct indication and manner of physician use. Steps to minimize administrative barriers to PDMP access are warranted. Finally, alternative PDMP uses should be further studied to determine their appropriateness and potentially expand their role in clinical practice.

Hidden in plain sight: a crowdsourced public art contest to make automated external defibrillators more visible.

OBJECTIVES: We sought to explore the feasibility of using a crowdsourcing study to promote awareness about automated external defibrillators (AEDs) and their locations. METHODS: The Defibrillator Design Challenge was an online initiative that asked the public to create educational designs that would enhance AED visibility, which took place over 8 weeks, from February 6, 2014, to April 6, 2014. Participants were encouraged to vote for AED designs and share designs on social media for points. Using a mixed-methods study design, we measured participant demographics and motivations, design characteristics, dissemination, and Web site engagement. RESULTS: Over 8 weeks, there were 13 992 unique Web site visitors; 119 submitted designs and 2140 voted. The designs were shared 48 254 times on Facebook and Twitter. Most designers-voters reported that they participated to contribute to an important cause (44%) rather than to win money (0.8%). Design themes included: empowerment, location awareness, objects (e.g., wings, lightning, batteries, lifebuoys), and others. CONCLUSIONS: The Defibrillator Design Challenge engaged a broad audience to generate AED designs and foster awareness. This project provides a framework for using design and contest architecture to promote health messages.

How do physicians adopt and apply opioid prescription guidelines in the emergency department? A qualitative study.

STUDY OBJECTIVE: An increase in prescriptions for opioid pain medications has coincided with increasing opioid overdose deaths. Guidelines designed to optimize opioid prescriptions written in the emergency department have been implemented, with substantial controversy. Little is known about how physicians perceive and apply these guidelines. We seek to identify key themes about emergency physicians' definition, awareness, use, and opinions of opioid-prescribing guidelines. METHODS: We conducted semistructured qualitative interviews with a convenience sample of 61 emergency physicians attending the American College of Emergency Physicians Scientific Assembly (October 2012, Denver, CO). Participants varied with respect to age, sex, geographic region, practice setting, and years of practice experience. We analyzed the interview content with modified grounded theory, an iterative coding process to identify patterns of responses and derive key themes. The study team examined discrepancies in the coding process to ensure reliability and establish consensus. RESULTS: When aware of opioid-prescribing guidelines, emergency physicians often defined them as policies developed by individual hospitals that sometimes reflected guidelines at the state or national level. Guidelines were primarily used by physicians to communicate decisions to limit prescriptions to patients on discharge rather than as tools for decisionmaking. Attitudes toward guidelines varied with regard to general attitudes toward opioid medications, as well as the perceived effects of guidelines on physician autonomy, public health, liability, and patient diversion. CONCLUSION: These exploratory findings suggest that hospital-based opioid guidelines complement and occasionally supersede state and national guidelines and that emergency physicians apply guidelines primarily as communication tools. The perspectives of providers should inform future policy actions that seek to address the problem of opioid abuse and overdose through practice guidelines.

Use of social media across US hospitals: descriptive analysis of adoption and utilization.

BACKGROUND: Use of social media has become widespread across the United States. Although businesses have invested in social media to engage consumers and promote products, less is known about the extent to which hospitals are using social media to interact with patients and promote health. OBJECTIVE: The aim was to investigate the relationship between hospital social media extent of adoption and utilization relative to hospital characteristics. METHODS: We conducted a cross-sectional review of hospital-related activity on 4 social media platforms: Facebook, Twitter, Yelp, and Foursquare. All US hospitals were included that reported complete data for the Centers for Medicare and Medicaid Services Hospital Consumer Assessment of Healthcare Providers and Systems survey and the American Hospital Association Annual Survey. We reviewed hospital social media webpages to determine the extent of adoption relative to hospital characteristics, including geographic region, urban designation, bed size, ownership type, and teaching status. Social media utilization was estimated from user activity specific to each social media platform, including number of Facebook likes, Twitter followers, Foursquare check-ins, and Yelp reviews. RESULTS: Adoption of social media varied across hospitals with 94.41% (3351/3371) having a Facebook page and 50.82% (1713/3371) having a Twitter account. A majority of hospitals had a Yelp page (99.14%, 3342/3371) and almost all hospitals had check-ins on Foursquare (99.41%, 3351/3371). Large, urban, private nonprofit, and teaching hospitals were more likely to have higher utilization of these accounts. CONCLUSIONS: Although most hospitals adopted at least one social media platform, utilization of social media varied according to several hospital characteristics. This preliminary investigation of social media adoption and utilization among US hospitals provides the framework for future studies investigating the effect of social media on patient outcomes, including links between social media use and the quality of hospital care and services.

Buprenorphine-Precipitated Withdrawal Among Hospitalized Patients Using Fentanyl.

Importance: Buprenorphine treatment of opioid use disorder (OUD) is safe and effective, but opioid withdrawal during treatment initiation is associated with poor retention in care. As fentanyl has replaced heroin in the drug supply, case reports and surveys have indicated increased concern for buprenorphine-precipitated withdrawal (PW); however, some observational studies have found a low incidence of PW. Objective: To estimate buprenorphine PW incidence and assess factors associated with PW among emergency department (ED) or hospitalized patients. Design, Setting, and Participants: This retrospective cohort study at 3 academic hospitals in Philadelphia, Pennsylvania, included adults with OUD who underwent traditional or high-dose buprenorphine initiation between January 1, 2020, and December 31, 2021. Exclusion criteria included low-dose buprenorphine initiation and missing documentation of opioid withdrawal severity within 4 hours of receiving buprenorphine. Exposure: Buprenorphine initiation with an initial dose of at least 2 mg of sublingual buprenorphine after a Clinical Opiate Withdrawal Scale (COWS) score of 8 or higher. Additional exposures included 4 predefined factors potentially associated with PW: severity of opioid withdrawal before buprenorphine (COWS score of 8-12 vs ≥13), initial buprenorphine dose (2 vs 4 or ≥8 mg), body mass index (BMI) (<25 vs 25 to <30 or ≥30; calculated as weight in kilograms divided by height in meters squared), and urine fentanyl concentration (0 to <20 vs 20 to <200 or ≥200 ng/mL). Main Outcome and Measures: The main outcome was PW incidence, defined as a 5-point or greater increase in COWS score from immediately before to within 4 hours after buprenorphine initiation. Logistic regression was used to estimate the odds of PW associated with the 4 aforementioned predefined factors. Results: The cohort included 226 patients (150 [66.4%] male; mean [SD] age, 38.6 [10.8] years). Overall, 26 patients (11.5%) met criteria for PW. Among patients with PW, median change in COWS score was 9 points (IQR, 6-13 points). Of 123 patients with confirmed fentanyl use, 20 (16.3%) had PW. In unadjusted and adjusted models, BMI of 30 or greater compared with less than 25 (adjusted odds ratio [AOR], 5.12; 95% CI, 1.31-19.92) and urine fentanyl concentration of 200 ng/mL or greater compared with less than 20 ng/mL (AOR, 8.37; 95% CI, 1.60-43.89) were associated with PW. Conclusions and Relevance: In this retrospective cohort study, 11.5% of patients developed PW after buprenorphine initiation in ED or hospital settings. Future studies should confirm the rate of PW and assess whether bioaccumulated fentanyl is a risk factor for PW.

Association between mandatory bundled payments and changes in socioeconomic disparities for joint replacement outcomes.

OBJECTIVE: To determine whether mandatory participation by hospitals in bundled payments for lower extremity joint replacement (LEJR) was associated with changes in outcome disparities for patients dually eligible for Medicare and Medicaid. DATA SOURCES AND STUDY SETTING: We used Medicare claims data for beneficiaries undergoing LEJR in the United States between 2011 and 2017. STUDY DESIGN: We conducted a retrospective observational study using a differences-in-differences method to compare changes in outcome disparities between dual-eligible and non-dual eligible beneficiaries after hospital participation in the Comprehensive Care for Joint Replacement (CJR) program. The primary outcome was LEJR complications. Secondary outcomes included 90-day readmissions and mortality. DATA EXTRACTION METHODS: We identified hospitals in the US market areas eligible for CJR. We included beneficiaries in the intervention group who received joint replacement at hospitals in markets randomized to participate in CJR. The comparison group included patients who received joint replacement at hospitals in markets who were eligible for CJR but randomized to control. PRINCIPAL FINDINGS: The study included 1,603,555 Medicare beneficiaries (mean age, 74.6 years, 64.3% women, 11.0% dual-eligible). Among participant hospitals, complications decreased between baseline and intervention periods from 11.0% to 10.1% for dual-eligible and 7.0% to 6.4% for non-dual-eligible beneficiaries. Among nonparticipant hospitals, complications decreased from 10.3% to 9.8% for dual-eligible and 6.7% to 6.0% for non-dual-eligible beneficiaries. In adjusted analysis, CJR participation was associated with a reduced difference in complications between dual-eligible and non-dual-eligible beneficiaries (-0.9 percentage points, 95% CI -1.6 to -0.1). The reduction in disparities was observed among hospitals without prior experience in a voluntary LEJR bundled payment model. There were no differential changes in 90-day readmissions or mortality. CONCLUSIONS: Mandatory participation in a bundled payment program was associated with reduced disparities in joint replacement complications for Medicare beneficiaries with low income. To our knowledge, this is the first evidence of reduced socioeconomic disparities in outcomes under value-based payments.

GTPase activity plays a key role in the pathobiology of LRRK2.

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD) and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s) underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.