Identification of motifs and mechanisms for lipid droplet targeting of the lipolytic inhibitors G0S2 and HIG2.

G0S2 and HIG2 are two selective inhibitors of ATGL (also known as PNPLA2), the key enzyme for intracellular lipolysis. Whereas G0S2 regulates triglyceride (TG) mobilization in adipocytes and hepatocytes, HIG2 functions to enhance intracellular TG accumulation under hypoxic conditions. A homologous hydrophobic domain (HD) is shared by G0S2 and HIG2 (also known as HILPDA) for binding to ATGL. However, the determinants of their lipid droplet (LD) localization are unknown. Here, we study how G0S2 and HIG2 are targeted to LDs, and identify both ATGL-independent and -dependent mechanisms. Structural prediction and studies in cells reveal that ATGL-independent localization of G0S2 to both the endoplasmic reticulum (ER) and LDs is mediated by a hairpin structure consisting of two hydrophobic sequences. Positively charged residues in the hinge region play a crucial role in sorting G0S2, which initially localizes to ER, to LDs. Interestingly, the role of these positive charges becomes dispensable when ATGL is co-expressed. In comparison, HIG2, which lacks a similar hairpin structure, is dependent on ATGL for its full LD targeting. Thus, our studies identify specific structural features and mechanisms for mediating accumulation of these two ATGL inhibitors on LDs.

Temporal Trends in Public Stroke Knowledge, 1995-2021.

BACKGROUND: Outreach campaigns have sought to reduce the burden of stroke by improving knowledge of stroke risk factors (RF) and warning signs (WS). We describe trends in stroke knowledge from 1995 to 2021. METHODS: From 1995 to 2021, 6 separate surveys were conducted in the Greater Cincinnati Northern Kentucky Region. Temporal trends in RF/WS knowledge were analyzed using logistic regression adjusting for Race, sex, age, and education. RESULTS: In 1995, 28.6% of participants (537/1880) could name ≥2 WS, compared with 50.6% (983/1944) in 2021 (trend P<0.0001 after adjustment). In 1995, 44.5% of participants (836/1880) knew ≥2 RF, compared with 56.7% (1103/1944) in 2021 (trend P<0.0001 after adjustment). Although still improved compared with 1995, fewer participants could identify ≥2 RF in 2021 (1103/1944, 56.7%) when compared with 2011 (1287/2036, 63.2%, pairwise P<0.05). This decline in RF knowledge was disproportionately larger in women (odds ratio of 0.67 for knowledge in 2021 compared with 2011 in females, P=0.047 for the interaction between sex and study year). CONCLUSIONS: Although stroke knowledge has overall improved since 1995, there is evidence for lost gains since 2011, particularly in women. Stroke outreach campaigns need ongoing evaluation.

Cervical Carotid Pseudo-Occlusions and False Dissections: Intracranial Occlusions Masquerading as Extracranial Occlusions.

BACKGROUND AND PURPOSE: Pseudo-occlusion (PO) of the cervical internal carotid artery (ICA) refers to an isolated occlusion of the intracranial ICA that appears as an extracranial ICA occlusion on computed tomography angiography (CTA) or digital subtraction angiography because of blockage of distal contrast penetration by a stagnant column of unopacified blood. We aim to better characterize this poorly recognized entity. METHODS: Retrospective review of an endovascular database (2010-2015; n=898). Only patients with isolated intracranial ICA occlusions as confirmed by angiographic exploration were included. CTA and digital subtraction angiography images were categorized according to their apparent site of occlusion as (1) extracranial ICA PO or (2) discernible intracranial ICA occlusion. RESULTS: Cervical ICA PO occurred in 21/46 (46%) patients on CTA (17 proximal cervical; 4 midcervical). Fifteen (71%) of these patients also had PO on digital subtraction angiography. A flame-shaped PO mimicking a carotid dissection was seen in 7 (33%) patients on CTA and in 6 (29%) patients on digital subtraction angiography. Patients with and without CTA PO had similar age (64.8±17.1 versus 60.2±15.7 years; P=0.35), sex (male, 47% versus 52%; P=1.00), and intravenous tissue-type plasminogen activator use (38% versus 40%; P=1.00). The rates of modified Treatment In Cerebral Ischemia 2b-3 reperfusion were 71.4% in the PO versus 100% in the non-PO cohorts (P<0.01). The rates of parenchymal hematoma, 90-day modified Rankin Scale score 0-2, and 90-day mortality were 4.8% versus 8% (P=0.66), 40% versus 66.7% (P=0.12), and 25% versus 21% (P=0.77) in PO versus non-PO patients, respectively. Multivariate analysis indicated that PO patients had lower chances of modified Treatment In Cerebral Ischemia 3 reperfusion (odds ratio 0.14; 95% confidence interval 0.02-0.70; P=0.01). CONCLUSIONS: Cervical ICA PO is a relatively common entity and may be associated with decreased reperfusion rates.

Withdrawal of Antithrombotic Agents and the Risk of Stroke.

BACKGROUND AND PURPOSE: Antithrombotic medications are effective for ischemic stroke prevention, but stoppage of these medications is associated with an increased risk of thromboembolism. The frequency of antithrombotic withdrawal in the general population is unknown. METHODS: We conducted a random phone sample of 2036 households in the Greater Cincinnati metropolitan area, representative of the stroke population by age, sex, and race, to determine the frequency of antithrombotic medication use and stoppage by physicians for medically indicated procedures. RESULTS: Sixty-two percent of survey respondents reported that they were on an antithrombotic medication. Ten percent of participants reported that they had stopped taking their medication within the past 60 days for a medically indicated intervention. Of those who stopped taking the medication, it was more common for persons taking an anticoagulant to stop their medication (20%) than those taking an antiplatelet agent (9%). Colonoscopies and orthopedic surgeries were the most common reasons for withdrawal of antiplatelet agents, whereas orthopedic and vascular surgeries were the most common reason for withdrawal of anticoagulants. CONCLUSIONS: Recommended discontinuation of antithrombotic medication for surgical or diagnostic procedures is common practice for persons in the community representative of a stroke population. Because stoppage of these medications is associated with an increased risk of thromboembolic stroke, further clinical trials are needed to determine best management practices in this setting.

"Picture to puncture": a novel time metric to enhance outcomes in patients transferred for endovascular reperfusion in acute ischemic stroke.

BACKGROUND: Comprehensive stroke centers allow for regionalization of subspecialty stroke care. Efficacy of endovascular treatments, however, may be limited by delays in patient transfer. Our goal was to identify where these delays occurred and to assess the impact of such delays on patient outcome. METHODS AND RESULTS: This was a retrospective study evaluating patients treated with endovascular therapy from November 2010 to July 2012 at our institution. We compared patients transferred from outside hospitals with locally treated patients with respect to demographics, imaging, and treatment times. Good outcomes, as defined by 90-day modified Rankin Scale scores of 0 to 2, were analyzed by transfer status as well as time from initial computed tomography to groin puncture ("picture-to-puncture" time). A total of 193 patients were analyzed, with a mean age of 65.8 ± 14.5 years and median National Institutes of Health Stroke Scale score of 19 (interquartile range, 15-23). More than two thirds of the patients (132 [68%]) were treated from referring facilities. Outside transfers were noted to have longer picture-to-puncture times (205 minutes [interquartile range, 162-274] versus 89 minutes [interquartile range, 70-119]; P<0.001), which was attributable to the delays in transfer. This corresponded to fewer patients with favorable Alberta Stroke Program Early CT Scores on preprocedural computed tomographic imaging (Alberta Stroke Program Early CT Scores >7: 50% versus 76%; P<0.001) and significantly worse clinical outcomes (29% versus 51%; P=0.003). In a logistic regression model, picture-to-puncture times were independently associated with good outcomes (odds ratio, 0.994; 95% confidence interval, 0.990-0.999; P=0.009). CONCLUSIONS: Delays in picture-to-puncture times for interhospital transfers reduce the probability of good outcomes among treated patients. Strategies to reduce such delays herald an opportunity for hospitals to improve patient outcomes.

PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein.

The I148M variant of PNPLA3 is closely associated with hepatic steatosis. Recent evidence indicates that the I148M mutant functions as an inhibitor of PNPLA2/ATGL-mediated lipolysis, leaving the role of wild-type PNPLA3 undefined. Despite showing a triglyceride hydrolase activity in vitro, PNPLA3 has yet to be established as a lipase in vivo. Here, we show that PNPLA3 preferentially hydrolyzes polyunsaturated triglycerides, mobilizing polyunsaturated fatty acids for phospholipid desaturation and enhancing hepatic secretion of triglyceride-rich lipoproteins. Under lipogenic conditions, mice with liver-specific knockout or acute knockdown of PNPLA3 exhibit aggravated liver steatosis and reduced plasma VLDL-triglyceride levels. Similarly, I148M-knockin mice show decreased hepatic triglyceride secretion during lipogenic stimulation. Our results highlight a specific context whereby the wild-type PNPLA3 facilitates the balance between hepatic triglyceride storage and secretion, and suggest the potential contribution of a loss-of-function by the I148M variant to the development of fatty liver disease in humans.

Disease Progression and Serological Assay Performance in Heritage Breed Pigs following Brucella suis Experimental Challenge as a Model for Naturally Infected Feral Swine.

Invasive feral swine (Sus scrofa) are one of the most important wildlife species for disease surveillance in the United States, serving as a reservoir for various diseases of concern for the health of humans and domestic animals. Brucella suis, the causative agent of swine brucellosis, is one such pathogen carried and transmitted by feral swine. Serology assays are the preferred field diagnostic for B. suis infection, as whole blood can be readily collected and antibodies are highly stable. However, serological assays frequently have lower sensitivity and specificity, and few studies have validated serological assays for B. suis in feral swine. We conducted an experimental infection of Ossabaw Island Hogs (a breed re-domesticated from feral animals) as a disease-free proxy for feral swine to (1) improve understanding of bacterial dissemination and antibody response following B. suis infection and (2) evaluate potential changes in the performance of serological diagnostic assays over the course of infection. Animals were inoculated with B. suis and serially euthanized across a 16-week period, with samples collected at the time of euthanasia. The 8% card agglutination test performed best, whereas the fluorescence polarization assay demonstrated no capacity to differentiate true positive from true negative animals. From a disease surveillance perspective, using the 8% card agglutination test in parallel with either the buffered acidified plate antigen test or the Brucella abortus/suis complement fixation test provided the best performance with the highest probability of a positive assay result. Application of these combinations of diagnostic assays for B. suis surveillance among feral swine would improve understanding of spillover risks at the national level.

Guidance for management of free-roaming community cats: a bioeconomic analysis.

OBJECTIVES: This study used computer simulation modeling to estimate and compare costs of different free-roaming cat (FRC) management options (lethal and non-lethal removal, trap-neuter-return, combinations of these options and no action) and their ability to reduce FRC population abundance in open demographic settings. The findings provide a resource for selecting management approaches that are well matched for specific communities, goals and timelines, and they represent use of best available science to address FRC issues. METHODS: Multiple FRC management approaches were simulated at varying intensities using a stochastic individual-based model in the software package Vortex. Itemized costs were obtained from published literature and expert feedback. Metrics generated to evaluate and compare management scenarios included final population size, total cost and a cost efficiency index, which was the ratio between total cost and population size reduction. RESULTS: Simulations suggested that cost-effective reduction of FRC numbers required sufficient management intensity, regardless of management approach, and greatly improved when cat abandonment was minimized. Removal yielded the fastest initial reduction in cat abundance, but trap-neuter-return was a viable and potentially more cost-effective approach if performed at higher intensities over a sufficient duration. Of five management scenarios that reduced the final population size by approximately 45%, the three scenarios that relied exclusively on removal were considerably more expensive than the two scenarios that relied exclusively or primarily on sterilization. CONCLUSIONS AND RELEVANCE: FRCs present a challenge in many municipalities, and stakeholders representing different perspectives may promote varying and sometimes incompatible population management policies and strategies. Although scientific research is often used to identify FRC impacts, its use to identify viable, cost-effective management solutions has been inadequate. The data provided by simulating different interventions, combined with community-specific goals, priorities and ethics, provide a framework for better-informed FRC policy and management outcomes.

Estimation of wildlife damage from federal crop insurance data.

BACKGROUND: Wildlife damage to crops is a persistent and costly problem for many farmers in the USA. Most existing estimates of crop damage have relied on direct assessment methods such as field studies conducted by trained biologists or surveys distributed to farmers. In this paper, we describe a new method of estimating wildlife damage that exploits federal crop insurance data. We focused our study on four crops: corn, soybean, wheat, and cotton, chosen because of their economic importance and their vulnerability to wildlife damage. RESULTS: We determined crop-raiding hot spots across the USA over the 2015-2019 period and identified the eastern and southern regions of the USA as being the most susceptible to wildlife damage. We estimated lower bounds for dollar and percent losses attributable to wildlife to these four crops. The combined loss across four crops was estimated at $592.6 million. The highest total estimated losses to wildlife were incurred by soybeans ($323.9 million) and corn ($194.0 million) and the highest percentage losses were estimated for soybeans (0.87%) and cotton (0.72%). CONCLUSION: We believe the proposed method is a reliable way to evaluate geographic and temporal heterogeneity in damages for the coming years. Accurate information on damages benefits various management agencies by allowing them to allocate management resources to crops and regions where the problem is relatively severe. A better understanding of damage heterogeneity can also help guide research and development of new management techniques.

Baseline ASPECTS and hypoperfusion intensity ratio influence the impact of first pass reperfusion on functional outcomes.

BACKGROUND: First pass reperfusion (FPR) has been established as a key performance metric in mechanical thrombectomy (MT). The impact of FPR may be more relevant in fast progressors. We aim to study the impact of baseline Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast CT and hypoperfusion intensity ratio (HIR) on CT perfusion on clinical outcomes after FPR. METHODS: A prospective MT database was reviewed for patients with isolated occlusion of the intracranial internal carotid artery and/or middle cerebral artery M1 segment who underwent MT with complete reperfusion (modified Thrombolyis in Cerebral Infarction score 2c-3) from January 2012 to May 2019. The overall population was divided into ASPECTS >7 versus ≤7 and the subgroup of patients with baseline CT perfusion was divided into HIR <0.3 versus ≥0.3. Univariable and multivariable analyses were performed to establish the predictors of 90-day functional independence (modified Rankin Scale (mRS) ≤2) in each subgroup. RESULTS: A total of 436 patients were included in the analyses. FPR was achieved in 254 (58.3%) patients. ASPECTS modified the effect of FPR on clinical outcomes, with FPR predicting good outcomes in patients with ASPECTS ≤7 (46% vs 29%, adjusted OR 3.748; 95% CI 1.590 to 8.838, p=0.003) while no significant effect was detected in those with ASPECTS >7 (62.3% vs 53.1%, adjusted OR 1.372; 95% CI 0.798 to 2.358, p=0.25). Similarly, FPR predicted good outcomes in patients with HIR ≥0.3 (54.8% vs 41.9%, adjusted OR 2.204; 95% CI 1.148 to 4.233, p=0.01) but not in those with HIR <0.3 (62.9% vs 52.8%, adjusted OR 1.524; 95% CI 0.592 to 3.920, p=0.38). CONCLUSIONS: The impact of FPR on functional outcomes is highly dependent on baseline imaging characteristics, with a more prominent influence in patients presenting with lower ASPECTS and/or higher HIR.

Diagnostic criteria and yield of real-time transcranial Doppler monitoring of intra-arterial reperfusion procedures.

BACKGROUND AND PURPOSE: Intra-arterial (IA) rescue procedures are increasingly used to treat acute ischemic stroke. We implemented continuous transcranial Doppler (TCD) monitoring during these procedures to detect any potentially harmful flow changes. Here, we report diagnostic criteria and yield of TCD monitoring. METHODS: We studied consecutive acute stroke patients who underwent IA reperfusion procedures. TCD flow signatures during these procedures were analyzed and any abnormal findings were documented. RESULTS: Patients were included only if there was successful insonation through the skull; of 56 eligible patients, 51 were included. IA procedures included IA tissue plasminogen activator, use of the Merci retriever, the Penumbra system, balloon angioplasty, and stenting. On TCD monitoring, contrast injections produced high-intensity signals and increased the mean flow velocity (MFV). Deployment of the Merci device appeared as high-intensity, short-duration signals with a transient MFV decrease of 11.5%. The Penumbra system produced lower-intensity signals with a greater transient decrease in MFV during aspiration. IA tissue plasminogen activator significantly increased MFV by 7.5% over Merci and Penumbra flow velocity changes. Power motion Doppler-TCD detected reocclusion in 13 patients, artery-to-artery embolization in 2 patients, air embolism in 2 patients, and hyperperfusion in 6 patients. Overall, the yield of TCD monitoring was positive in 23 (49%) patients who received IA reperfusion procedures. CONCLUSIONS: Our velocity, intensity, and flow signatures criteria for TCD monitoring of IA reperfusion procedures detect reocclusion, hyperperfusion, or thromboembolism and air embolism in nearly half of all procedures. This hemodynamic information can be particularly helpful when neurological assessment is limited or delayed.

Warfarin dosing in patients with impaired kidney function.

BACKGROUND: In patients with kidney impairment, warfarin, a drug metabolized primarily by the cytochrome P-450 system, is initiated at similar doses and managed similarly as in the general medical population. Unfortunately, few data exist to guide dose adjustment in patients with decreased kidney function. Here, we determine the degree of warfarin dose reduction associated with kidney impairment and make recommendations for warfarin dosing. STUDY DESIGN: Cross-sectional analysis. SETTING & PARTICIPANTS: Long-term warfarin users followed up at anticoagulation clinics (n = 980); 708 participants from the University of Alabama (UAB) and 272 participants from the University of Chicago (UIC). PREDICTOR: No/mild (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2)), moderate (eGFR, 30-59 mL/min/1.73 m(2)), and severe (eGFR < 30 mL/min/1.73 m(2)) kidney impairment; CYP2C9 and VKORC1 genotype; age; race; sex; body mass; sociodemographic factors; smoking status; alcohol; vitamin K intake; comorbid conditions (eg, congestive heart failure); and drug interactions (eg, amiodarone and statins). OUTCOME & MEASUREMENT: Warfarin dose (milligrams per day) was evaluated using linear regression after adjustment for clinical, demographic, and genetic factors. RESULTS: Prevalences of moderate (31.8% and 27.6%) and severe kidney impairment (8.9% and 6.6%) were similar in the UAB and UIC cohorts. Warfarin dose requirements were significantly lower in patients with moderate and severe kidney impairment compared with those with no/mild kidney impairment in the UAB (P < 0.001) and UIC (P < 0.001) cohorts. Compared with patients with no/mild kidney impairment, patients with moderate kidney impairment required 9.5% lower doses (P < 0.001) and patients with severe kidney impairment required 19% lower doses (P < 0.001). LIMITATIONS: No measurement of warfarin, serum albumin, vitamin K, and coagulation factors; no evaluation of other markers (eg, cystatin). CONCLUSION: Moderate and severe kidney impairment were associated with a reduction in warfarin dose requirements.

Body Mass Index and Clinical Outcomes in Large Vessel Occlusion Acute Ischemic Stroke after Endovascular Therapy.

BACKGROUND AND PURPOSE: Several reports have described lower mortality rates in overweight or obese patients as compared to normal weight ones. In the past decade, several studies have investigated the phenomenon, commonly known as the obesity paradox, with mixed results thus far. We sought to determine whether outcomes differ between patients with large vessel occlusion strokes (LVOS) after endovascular therapy (ET) according to their body mass index (BMI). METHODS: We reviewed our prospectively collected endovascular database at a tertiary care academic institution. All patients that underwent ET for acute LVOS were categorized according to their BMI into 4 groups: (1) underweight (BMI < 18.5), (2) normal weight (BMI = 18.5-25), (3) overweight (BMI = 25-30), and (4) obese (BMI > 30). Baseline characteristics, procedural radiological as well as outcome parameters where compared. RESULTS: A total of 926 patients qualified for the study, of which 20 (2.2%) were underweight, 253 (27.3%) had a normal weight, 315 (34%) were overweight, and 338 (36.5%) were obese. When compared with normal weight (reference), overweight patients were younger, had higher rates of dyslipidemia and diabetes and higher glucose levels, while obese patients were younger, less often smokers, and had higher rates of hypertension and diabetes and higher glucose levels. Other baseline and procedural characteristics were comparable. The rates of successful reperfusion (modified treatment in cerebral ischemia, 2b-3), parenchymal hematomas, 90-day good clinical outcomes (modified Rankin scale, 0-2), and 90-day mortality were comparable between groups. On multivariate analysis, BMI was not associated with good outcomes nor mortality. CONCLUSION: In patients treated with mechanical thrombectomy, BMI is not associated with outcomes. However, patients who are overweight or obese have more comorbidities and a higher stroke risk and, thus, should strive for a normal weight.

Health Perceptions, Stroke Risk, and Readiness for Behavior Change: Gender Differences in Young Adult African Americans.

The presence of traditional cardiovascular risk factors has increased among young African American (AA) adults, making them more susceptible to stroke. We examined baseline data from the Stroke COunseling for Risk REduction (SCORRE) study to describe health perceptions, stroke risk, and readiness for behavior change along with gender differences in a cohort of young AA. Self-administered questionnaires were used to assess perceptions of general health, stroke risk, competence to live a healthy lifestyle, and readiness for behavior change. Actual stroke risk was measured using the American Heart Association (AHA) Life's Simple 7® (LS7) program. Data were collected from 116 participants (86 women, 30 men) who had a mean age of 24.6 (SD = 4.5). On average, participants had 2.6 (SD = 1.1) out of 7 risk factors for stroke, rated their overall health at the midpoint of the scale ("good"), perceived a low risk of future stroke, felt competent they could live a healthy lifestyle, but were not at a stage of readiness for behavior change. A significantly higher proportion of men than women met AHA recommendations for physical activity (77% vs. 49%; p < 0.01), but had blood pressure readings > 120/80 (70% vs. 34%; p < 0.01), and smoked cigarettes/cigars (20% vs. 2%; p < 0.01). Fewer men than women were at a stage of readiness for behavior change to reduce stroke risk (13% vs. 40%; p < 0.01). Stroke risk needs to be assessed early in AA and the LS7 can be used to assess and communicate risk. Understanding gender differences may help with tailoring stroke prevention education and treatment programs.

Endovascular Therapy and Ethnic Disparities in Stroke Outcomes.

BACKGROUND AND PURPOSE: Ethnic disparities in stroke are well described, with a higher incidence of disability and increased mortality in Blacks versus Whites. We sought to compare the clinical outcomes between those ethnic groups after stroke endovascular therapy (ET). METHODS: We performed a retrospective review of the prospectively acquired Grady Endovascular Stroke Outcomes Registry between September 1, 2010 and September 30, 2015. Patients were dichotomized into two groups - Caucasians and African-Americans - and matched for age, pretreatment glucose level, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Baseline characteristics as well as procedural and outcome parameters were compared. RESULTS: Out of the 830 patients treated with ET, 308 pairs of patients (n = 616) underwent primary analysis. African-Americans were younger (p < 0.01), had a higher prevalence of hypertension (p < 0.01) and diabetes (p = 0.04), and had higher Alberta Stroke Program Early CT Score values (p = 0.03) and shorter times to treatment (p = 0.01). Blacks more frequently had Medicaid coverage and less private insurance (29.6 vs. 11.4% and 41.5 vs. 60.3%, respectively, p < 0.01). The remaining baseline characteristics, including baseline NIHSS score and CT perfusion-derived ischemic core volumes, were well balanced. There were no differences in the overall distribution of 90-day modified Rankin scale scores (p = 0.28), rates of successful reperfusion (84.7 vs. 85.7%, p = 0.91), good outcomes (49.1 vs. 44%, p = 0.24), or parenchymal hematomas (6.5 vs. 6.8%, p = 1.00). Blacks had lower 90-day mortality rates (18 vs. 24.6%, p = 0.04) in univariate analysis, which persisted as a nonsignificant trend after adjustment for potential confounders (OR 0.52, 95% CI 0.26-1.03, p = 0.06). CONCLUSIONS: Despite unique baseline characteristics, African-Americans treated with ET for large vessel occlusion strokes have similar outcomes as Caucasians. Greater availability of ET may diminish the ethnic/racial disparities in stroke outcomes.

The Economics of a Successful Raccoon Rabies Elimination Program on Long Island, New York.

Raccoon rabies is endemic in the eastern U.S.; however, an epizootic had not been confirmed on Long Island, New York until 2004. An oral rabies vaccination (ORV) program was initiated soon after the first rabies-positive raccoon was discovered, and continued until raccoon rabies was eliminated from the vaccination zone. The cost-effectiveness and economic impact of this rabies control program were unknown. A public health surveillance data set was evaluated following the ORV program on Long Island, and is used here as a case study in the health economics of rabies prevention and control efforts. A benefit-cost analysis was performed to determine the cost-effectiveness of the program, and a regional economic model was used to estimate the macroeconomic impacts of raccoon rabies elimination to New York State. The cost of the program, approximately $2.6 million, was recovered within eight years by reducing costs associated with post-exposure prophylaxis (PEP) and veterinary diagnostic testing of rabies suspect animals. By 2019, the State of New York is projected to benefit from the ORV program by almost $27 million. The benefit-cost ratio will reach 1.71 in 2019, meaning that for every dollar spent on the program $1.71 will be saved. Regional economic modeling estimated employment growth of over 100 jobs and a Gross Domestic Product (GDP) increase of $9.2 million through 2019. This analysis suggests that baiting to eliminate rabies in a geographically constrained area can provide positive economic returns.

Endovascular Therapy in Strokes with ASPECTS 5-7 May Result in Smaller Infarcts and Better Outcomes as Compared to Medical Treatment Alone.

INTRODUCTION: Intra-arterial therapy (IAT) for large vessel occlusion strokes (LVOS) has been increasingly utilized. The benefit of IAT in patients with midrange Alberta Stroke Program Early Computed Tomography Score (ASPECTS) remains to be established. MATERIALS AND METHODS: This was a retrospective analysis of LVOS with ASPECTS 5-7 treated with IAT (n = 86) or medical therapy alone (intravenous tissue plasminogen activator; n = 15) at two centers from 2009 to 2012. Definitions were as follows: symptomatic intracranial hemorrhage = any parenchymal hematoma; successful reperfusion = mTICI ≥2b; good and acceptable outcomes = 90-day mRS 0-2 and 0-3, respectively. Final infarct volumes (FIV) were calculated based on 24-hour CT/MRI scans. RESULTS: Mean age (67 ± 14 vs. 67 ± 19 years) and baseline NIHSS (20 ± 5 vs. 20 ± 6) were similar in the two groups. Successful reperfusion was achieved in 58 (67%) IAT patients. Symptomatic and asymptomatic intracranial hemorrhage occurred in 9 (10%) and 31 (36%) IAT patients, respectively. The proportion of 90-day good and acceptable outcomes was 20 (17/86) and 33% (28/86), respectively. Successful IAT reperfusion was associated with smaller FIV (p = 0.015) and higher rates of good (p = 0.01) and acceptable (p = 0.014) outcomes. There was a strong trend towards a higher hemicraniectomy requirement in medically as compared to endovascularly treated patients (20 vs. 6%; p = 0.06) despite similar in-hospital mortality. The median FIV was significantly lower with IAT versus medical therapy [80 ml (interquartile range, 38-122) vs. 190 ml (121-267); p = 0.015]. CONCLUSIONS: Despite a relatively low probability of achieving functional independence, IAT in LVOS patients with ASPECTS 5-7 appears to result in lower degrees of disability and may lessen the need for hemicraniectomy. Therefore, it may be a reasonable option for patients and families who favor a shift from severe to moderate disability.

Periprocedural cost-effectiveness analysis of mechanical thrombectomy for acute ischemic stroke in the stent retriever era.

BACKGROUND: Early reperfusion is critical for favorable outcomes in acute ischemic stroke (AIS). Stent retrievers lead to faster and more complete reperfusion than previous technologies. Our aim is to compare the cost-effectiveness of stent retrievers to the previous mechanical thrombectomy devices. METHODS: Retrospective review of endovascularly treated large-vessel AIS. Data from all consecutive patients who underwent thrombectomy from January 2012 through November 2012 were collected. Baseline characteristics, the total procedural cost, the rates of successful recanalization [modified thrombolysis in cerebral ischemia (mTICI) scores of 2b or 3], and the length of stay at the hospital were compared between the stent retriever (SR) and the non-stent retriever (NSR) groups. RESULTS: After excluding the patients who underwent concomitant extracranial stenting (n = 22) or received intra-arterial tissue plasminogen activator only (n = 6), the entire cohort included 150 patients. The cost of the reperfusion procedure was significantly higher in the SR compared to the NSR group (USD 13,419 vs. 9,308, p <0.001). We were unable to demonstrate a statistically significant difference in the rates of mTICI 2b/3 reperfusion (81 vs. 74%, p = 0.337) or the length of stay (11.1 ± 9.1 vs. 12.8 ± 9.6 days, p = 0.260) amongst the SR and the NSR patients. CONCLUSION: The procedural costs of thrombectomy for AIS are increasing and account for the bulk of hospitalization reimbursement. The impact of these expenditures in the long-term sustainability of stroke centers deserves greater consideration. While it is likely that the SR technology results in higher rates of optimal reperfusion, better clinical outcomes, and shorter lengths of stay, larger studies are needed to prove its cost-effectiveness.

Discharge disposition to skilled nursing facility after endovascular reperfusion therapy predicts a poor prognosis.

OBJECTIVE: We explore the impact of discharge disposition (independent rehabilitation facility (IRF) vs skilled nursing facility (SNF)) on 90 day outcomes in persons with stroke who received acute endovascular treatment. METHODS: Using a database from a single primary care stroke center, discharge disposition, National Institutes of Health Stroke Scale (NIHSS), Totaled Health Risks in Vascular Events (THRIVE), Houston Intra-Arterial Therapy 2 (HIAT-2), and Acute Physiology and Chronic Health Evaluation (APACHE II) scores, and successful reperfusion were obtained. Univariate analysis was performed to assess predictors of good clinical outcome, as defined by 90 day modified Rankin Scale (mRS) scores ≤2. A binary logistic regression model was used to determine the impact of placement to an IRF versus an SNF on clinical outcomes. RESULTS: 147 subjects were included in the analysis with a mean age of 63±14 years and median NIHSS of 18 (IQR 14-21). Final infarct volumes, and modified APACHE II, THRIVE, and HIAT-2 scores were similar between those discharged to an IRF and those discharged to an SNF.However, their 90 day outcomes were significantly different, with far fewer patients at SNFs achieving good clinical outcomes (25% vs 46%; p=0.023). Disposition to SNF was significantly associated with a lower probability of achieving an mRS score of 0-2 at 90 days (OR = 0.337 (95% CI 0.12 to 0.94); p<0.04). CONCLUSIONS: Subjects discharged to SNFs and IRFs after thrombectomy have similar medical and neurological severity at admission and similar final infarct volumes at discharge. Despite these similarities, patients discharged to an SNF had a significantly lower probability of achieving a good neurological outcome. These results have implications for future acute stroke trial design.

Delivering a "dose of hope": a faith-based program to increase older african americans' participation in clinical trials.

BACKGROUND: Underrepresentation of older-age racial and ethnic minorities in clinical research is a significant barrier to health in the United States, as it impedes medical research advancement of effective preventive and therapeutic strategies. OBJECTIVE: The objective of the study was to develop and test the feasibility of a community-developed faith-based intervention and evaluate its potential to increase the number of older African Americans in clinical research. METHODS: Using a cluster-randomized design, we worked with six matched churches to enroll at least 210 persons. We provided those in the intervention group churches with three educational sessions on the role of clinical trials in addressing health disparity topics, and those in the comparison group completed surveys at the same timepoints. All persons enrolled in the study received ongoing information via newsletters and direct outreach on an array of clinical studies seeking participants. We evaluated the short-, mid-, and longer-term effects of the interventional program on clinical trial-related outcomes (ie, screening and enrollment). RESULTS: From 2012 to 2013, we enrolled a balanced cohort of 221 persons in the program. At a 3-month follow-up, mean intention to seek information about clinical trials was higher than baseline in both treatment (mu=7.5/10; sigma=3.1) and control arms (mu=6.6/10; sigma=3.3), with the difference more pronounced in the treatment arm. The program demonstrated strong retention at 3-month (95.4%, 211/221) and 6-month timepoints (94.1%, 208/221). CONCLUSIONS: The "Dose of Hope" program addressed an unmet need to reach an often overlooked audience of older African Americans who are members of churches and stimulate their interest in clinical trial participation. The program demonstrated its appeal in the delivery of effective messages and information about health disparities, and the role of clinical research in addressing these challenges.