The STARD9/Kif16a kinesin associates with mitotic microtubules and regulates spindle pole assembly.

During cell division, cells form the microtubule-based mitotic spindle, a highly specialized and dynamic structure that mediates proper chromosome transmission to daughter cells. Cancer cells can show perturbed mitotic spindles and an approach in cancer treatment has been to trigger cell killing by targeting microtubule dynamics or spindle assembly. To identify and characterize proteins necessary for spindle assembly, and potential antimitotic targets, we performed a proteomic and genetic analysis of 592 mitotic microtubule copurifying proteins (MMCPs). Screening for regulators that affect both mitosis and apoptosis, we report the identification and characterization of STARD9, a kinesin-3 family member, which localizes to centrosomes and stabilizes the pericentriolar material (PCM). STARD9-depleted cells have fragmented PCM, form multipolar spindles, activate the spindle assembly checkpoint (SAC), arrest in mitosis, and undergo apoptosis. Interestingly, STARD9-depletion synergizes with the chemotherapeutic agent taxol to increase mitotic death, demonstrating that STARD9 is a mitotic kinesin and a potential antimitotic target.

Microbleeds in the Secondary Prevention of Small Subcortical Strokes Trial: Stroke, mortality, and treatment interactions.

OBJECTIVE: To characterize cerebral microbleeds (CMBs) in lacunar stroke patients in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to assess their relationship with recurrent stroke and death, and response to assigned treatment. METHODS: SPS3 is a randomized, clinical trial conducted between 2003 and 2011. Patients with recent magnetic resonance imaging (MRI)-documented lacunar infarcts were randomly assigned in a factorial design to target levels of systolic blood pressure (130-149mmHg vs <130mmHg; open label) and to antiplatelet treatment (aspirin/clopidogrel vs aspirin/placebo; double-blinded). The current analysis involves 1,278 trial participants who had a baseline axial T2*-weighted gradient echo MRI sequence allowing for CMB detection. RESULTS: CMBs were present in 30% of 1,278 patients (mean age = 63 years). Male gender (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.3-2.3), history of hypertension (OR = 1.6, 95% CI = 1.2-2.3), increased systolic blood pressure (1.2 per 20mmHg, 95% CI = 1.1-1.4), nondiabetic status (OR = 1.4, 95% CI = 1.1-1.9), multiple old lacunar infarcts (OR = 1.9, 95% CI = 1.5-2.5), and moderate (OR = 1.7, 95% CI = 1.2-2.3) or severe (OR = 4.2, 95% CI = 3.0-5.9) white matter hyperintensities on MRI were independently associated with CMBs. During a mean follow-up of 3.3 years, overall stroke recurrence was 2.5% per patient-year. Patients with CMBs had an adjusted 2-fold increased risk of recurrent stroke (hazard ratio = 2.1, 95% CI = 1.4-3.1). CMBs were not a risk factor for death. There were no statistically significant interactions between CMBs and treatment assignments. INTERPRETATION: Patients with lacunar stroke and CMBs likely harbor a more advanced form of cerebral small vessel disease in need of efficacious therapeutic strategies. Ann Neurol 2017;82:196-207.

Vertebrobasilar ectasia in patients with lacunar stroke: the secondary prevention of small subcortical strokes trial.

BACKGROUND: The clinical implications of vertebrobasilar ectasia (VBE) in patients with cerebral small-artery disease are not well defined. We investigated whether VBE is associated with recurrent stroke, major hemorrhage, and death in a large cohort of patients with recent lacunar stroke. METHODS: Maximum diameters of the vertebral and basilar arteries were measured by magnetic resonance angiography and computed tomographic angiography in 2621 participants in the Secondary Prevention of Small Subcortical Strokes trial. VBE was defined a priori as basilar artery greater than 4.5 mm and/or vertebral artery greater than 4.0 mm. Patient characteristics and risks of stroke recurrence and mortality during follow-up (median, 3.5 years) were compared between patients with and without VBE. RESULTS: VBE affecting 1 or more arteries was present in 200 (7.6%) patients. Patient features independently associated with VBE were increasing age, male sex, white race ethnicity, hypertension, and higher baseline diastolic blood pressure. Baseline systolic blood pressure was inversely associated with VBE. After adjustment for other risk factors, VBE was not predictive of recurrent stroke (hazard ratio [HR], 1.3; 95% confidence interval [CI], .85-1.9) or major hemorrhage (HR, 1.5; CI, .94-2.6), but was of death (HR, 1.7; CI, 1.1-2.7). CONCLUSIONS: In this large well-characterized cohort of patients with recent lacunar stroke, VBE was predictive of death but not of recurrent stroke or major hemorrhage. In these exploratory analyses, the frequency of VBE was directly related to diastolic blood pressure but inversely related to systolic blood pressure.

Trends in 10-year survival of patients with stroke hospitalized between 1980 and 2000: the Minnesota stroke survey.

BACKGROUND AND PURPOSE: We report on trends in poststroke survival, both in the early period after stroke and over the long term. We examine these trends by stroke subtype. METHODS: The Minnesota Stroke Survey is a study of all hospitalized patients with acute stroke aged 30 to 74 years in the Minneapolis-St Paul metropolis. Validated stroke events were sampled for survey years 1980, 1985, 1990, 1995, and 2000 and subtyped as ischemic or hemorrhagic by neuroimaging for survey years 1990, 1995, and 2000. Survival was obtained by linkage to vital statistics data through the year 2010. RESULTS: There were 3773 acute stroke events. Age-adjusted 10-year survival improved from 1980 to 2000 (men 29.5% and 46.5%; P<0.0001; women 32.6% and 50.5%; P<0.0001). Ten-year ischemic stroke survival (n=1667) improved from 1990 to 2000 (men 35.3% and 50%; P=0.0001; women 38% and 55.3%; P<0.0001). Ten-year hemorrhagic stroke survival showed a trend toward improvement, but this (n=489) did not reach statistical significance, perhaps because of their smaller number (men 29.7% and 45.8%; P=0.06; women 39.2% and 49.6%; P=0.2). Markers of stroke severity including unconsciousness or major neurological deficits at admission declined from 1980 to 2000 while neuroimaging use increased. CONCLUSIONS: These poststroke survival trends are likely because of multiple factors, including more sensitive case ascertainment shifting the case mix toward less severe strokes, improved stroke care and risk factor management, and overall improvements in population health and longevity.

Predictors of mortality in patients with lacunar stroke in the secondary prevention of small subcortical strokes trial.

BACKGROUND AND PURPOSE: The Secondary Prevention of Small Subcortical Stroke trial (SPS3) recruited participants meeting clinical and radiological criteria for symptomatic lacunes. Individuals randomized to dual antiplatelet therapy with clopidogrel and aspirin had an unanticipated increase in all-cause mortality compared with those assigned to aspirin. We investigated the factors associated with mortality in this well-characterized population. METHODS: We identified independent predictors of mortality among baseline demographic and clinical factors by Cox regression analysis in participants of the SPS3 trial. Separately, we examined the effect on mortality of nonfatal bleeding during the trial. RESULTS: During a mean follow-up of 3.6 years, the mortality rate was 1.78% per year for the 3020 participants (mean age, 63 years). Significant independent predictors of mortality at study entry were age, diabetes mellitus, history of hypertension, systolic blood pressure (hazard ratio [HR], 1.3 per 20 mm Hg increase), serum hemoglobin<13 g/dL (HR, 1.6), renal function (HR, 1.3 per estimated glomerular filtration rate decrease of 20 mL/min), and body mass index (HR, 1.8 per 10 kg/m2 decrease). Participants with ischemic heart disease (P=0.01 for interaction) and normotensive/prehypertensive participants (P=0.03 for interaction) were at increased risk if assigned to dual antiplatelet therapy. Nonfatal major hemorrhage increased mortality in both treatment arms (HR, 4.5; 95% confidence interval, 3.1-6.6; P<0.001). CONCLUSIONS: Unexpected interactions between assigned antiplatelet therapy and each of ischemic heart disease and normal/prehypertensive status accounted for increased mortality among patients with recent lacunar stroke given dual antiplatelet therapy. Despite extensive exploratory analyses, the mechanisms underlying these interactions are uncertain. CLINICAL TRIAL REGISTRATION URL: http://www.SPS3ClinicalTrials.gov. Unique identifier: NCT00059306.

Clinical correlates of infarct shape and volume in lacunar strokes: the Secondary Prevention of Small Subcortical Strokes trial.

BACKGROUND AND PURPOSE: Infarct size and location are thought to correlate with different mechanisms of lacunar infarcts. We examined the relationship between the size and shape of lacunar infarcts and vascular risk factors and outcomes. METHODS: We studied 1679 participants in the Secondary Prevention of Small Subcortical Stroke trial with a lacunar infarct visualized on diffusion-weighted imaging. Infarct volume was measured planimetrically, and shape was classified based on visual analysis after 3-dimensional reconstruction of axial MRI slices. RESULTS: Infarct shape was ovoid/spheroid in 63%, slab in 12%, stick in 7%, and multicomponent in 17%. Median infarct volume was smallest in ovoid/spheroid relative to other shapes: 0.46, 0.65, 0.54, and 0.90 mL, respectively (P<0.001). Distributions of vascular risk factors were similar across the 4 groups except that patients in the ovoid/spheroid and stick groups were more often diabetic and those with multicomponent had significantly higher blood pressure at study entry. Intracranial stenosis did not differ among groups (P=0.2). Infarct volume was not associated with vascular risk factors. Increased volume was associated with worse functional status at baseline and 3 months. Overall, 162 recurrent strokes occurred during an average of 3.4 years of follow-up with no difference in recurrent ischemic stroke rate by shape or volume. CONCLUSIONS: In patients with recent lacunar stroke, vascular risk factor profile was similar among the different infarct shapes and sizes. Infarct size correlated with worse short-term functional outcome. Neither shape nor volume was predictive of stroke recurrence. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

BACKGROUND: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. METHODS: Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. RESULTS: Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. CONCLUSIONS: In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.

Extended-release niacin therapy and risk of ischemic stroke in patients with cardiovascular disease: the Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcome (AIM-HIGH) trial.

BACKGROUND AND PURPOSE: In Atherothrombosis Intervention in Metabolic Syndrome with low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial, addition of extended-release niacin (ERN) to simvastatin in participants with established cardiovascular disease, low high-density lipoprotein cholesterol, and high triglycerides had no incremental benefit, despite increases in high-density lipoprotein cholesterol. Preliminary analysis based on incomplete end point adjudication suggested increased ischemic stroke risk among participants randomized to ERN. METHODS: This final analysis was conducted after complete AIM-HIGH event ascertainment to further explore potential relationship between niacin therapy and ischemic stroke risk. RESULTS: There was no group difference in trial primary composite end point at a mean 36-month follow-up among 3414 patients (85% men; mean age, 64±9 years) randomized to simvastatin plus ERN (1500-2000 mg/d) versus simvastatin plus matching placebo. In the intention-to-treat analysis, there were 50 fatal or nonfatal ischemic strokes: 18 (1.06%) in placebo arm versus 32 (1.86%) in ERN arm (hazard ratio [HR], 1.78 [95% confidence interval {CI}, 1.00-3.17; P=0.050). Multivariate analysis showed independent associations between ischemic stroke risk and >65 years of age (HR, 3.58; 95% CI, 1.82-7.05; P=0.0002), history of stroke/transient ischemic attack/carotid disease (HR, 2.18; 95% CI, 1.23-3.88; P=0.0079), elevated baseline Lp(a) (HR, 2.80; 95% CI, 1.25-6.27 comparing the middle with the lowest tertile; HR, 2.31; 95% CI, 1.002-5.30 comparing the highest with the lowest tertile; overall P=0.042) but a nonsignificant association with ERN (HR, 1.74; 95% CI, 0.97-3.11; P=0.063). CONCLUSIONS: Although there were numerically more ischemic strokes with addition of ERN to simvastatin that reached nominal significance, the number was small, and multivariable analysis accounting for known risk factors did not support a significant association between niacin and ischemic stroke risk. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00120289.

Aspirin and clopidogrel for prevention of ischemic stroke.

This review examines the role of platelets in ischemic stroke, platelet activation mechanisms, aspirin's rise as an antithrombotic agent, clopidogrel's appearance on the stage, a possible role for combination therapy, antiplatelet resistance, practical considerations, and future directions. Reviewed in this chapter are issues central to optimal antiplatelet therapy: efficacy, safety, resistance, and biochemical/laboratory testing. Current guidelines do not recommend combination aspirin and clopidogrel use, however recent research indicates dual antiplatelet therapy with combined aspirin and clopidogrel may have specific roles in secondary prevention of ischemic stroke. A cautious and analytical interpretation of the literature is advised before application of this knowledge to clinical practice. The best recommendation at this time is to follow the published guidelines for secondary prevention of ischemic stroke.

Utilization of intravenous thrombolysis in 3-4.5 hours: analysis of the Minnesota stroke registry.

BACKGROUND: The American Heart Association and the American Stroke Association recommend intravenous (IV) thrombolysis up to 4.5 h from acute ischemic stroke symptom onset based on its proven benefit in improving patient outcomes. We analyzed data from the Minnesota Stroke Registry to assess the rates of IV thrombolytic utilization and the process of care in this expanded window. METHODS: We identified patients who had received IV recombinant tissue plasminogen activator (rt-PA) at any of the 19 participating hospitals from January 1, 2008 till December 31, 2010. Treatment groups were those actually treated by IV rt-PA in 0-3 h and those treated by IV rt-PA in 3-4.5 h. Duration from symptom onset to arrival in the emergency department (ED) was dichotomized to cohorts of 0-2 and 2-3.5 h. We determined the overall utilization of IV rt-PA in the expanded window and calculated door-to-needle times for the two treatment windows. We also ascertained the rates of symptomatic intracerebral hemorrhage between the two treatment groups. RESULTS: Out of the total 519 patients who received IV rt-PA for acute ischemic stroke, 433 (83%) were treated within 0-3 h and 86 (17%) within 3-4.5 h. Of all the patients who received IV rt-PA within 3-4.5 h, 45% arrived at the ED within 2 h of symptom onset. Median door-to-needle time for the 0- to 3-hour window was 74.5 min [interquartile range (IQR) 57-90] and 54 min (IQR 43.5-70.5) for the 3- to 4.5-hour window. Based on arrival time to the ED, door-to-needle time of ≤60 min was achieved by only 31% (142/458) of patients who arrived within 0-2 h of their symptom onset compared to 61% (37/61) of those who arrived at the ED within 2-3.5 h of their symptom onset. Fifty-nine (14%) patients in the 0- to 3-hour group and 17 (20%) patients in the 3- to 4.5-hour group received a combination of IV rt-PA and endovascular treatments. Among patients with documented admission National Institutes of Health Stroke Scale scores, the values (median with IQR) were different between the 0- to 3- and the 3- to 4.5-hour group, i.e. 10 (IQR 5-18) and 7 (IQR 4-14), respectively. CONCLUSION: Patients who received IV rt-PA within the 3- to 4.5-hour window comprised 17% of all IV rt-PA cases treated in the Minnesota Stroke Registry hospitals after the new guidelines recommended a time window expansion. Almost half of these patients would have qualified for treatment within the 0- to 3-hour window as they presented within 0-2 h of symptom onset. Patients arriving 2-3.5 h after symptom onset received thrombolysis on average 20 min faster than patients arriving within 2 h of symptom onset.

Agreement in endovascular thrombolysis patient selection based on interpretation of presenting CT and CT-P changes in ischemic stroke patients.

BACKGROUND: To evaluate the agreement in patient selection based on computed tomography (CT) and CT-perfusion (CT-P) imaging interpretation between stroke specialists in stroke patients considered for endovascular treatment. METHODS: All endovascular-treated acute ischemic stroke patients were identified through a prospective database from two comprehensive stroke centers; 25 consecutively treated patients were used for this analysis. Initial CT images and CT-P data were independently interpreted by five board eligible/certified vascular neurologists with additional endovascular training to decide whether or not to select the patient for endovascular treatment. The CT/CT-P images were evaluated separately and used as the sole imaging decision making criteria, 2 weeks apart from each other (memory wash-out period). For each set of imaging data inter-rater and intra-rater agreement scores were obtained using Cohen's kappa statistic to assess the proportion of agreement beyond chance. RESULTS: Kappa values for the treatment decisions based on CT images was 0.43 (range 0.14-0.8) (moderate agreement), and for the decisions based on CTP images was 0.29 (range 0.07-0.67) (fair agreement) among the five subjects. There was substantial variability within the group and between images interpretation. Observed agreement on decision to treat with endovascular therapy was found to be 75% with CT images and 59% with CT-P images (with no adjustment for chance). Kappa values for intra-rater agreement were -0.14 (ranged -0.27-0.27) (poor agreement). CONCLUSIONS: There is considerable lack of agreement, even among stroke specialists, in selecting acute ischemic stroke patients for endovascular treatment based on CT-P changes. This mandates a careful evaluation of CT-P for patient selection before widespread adoption.

Five-year rehospitalization outcomes in a cohort of patients with acute ischemic stroke: Medicare linkage study.

BACKGROUND AND PURPOSE: The purposes of this study were to track mortality and rehospitalizations over 5 years poststroke in a stroke cohort (SC) and compare long-term risks of complications to a matched nonstroke cohort (NSC). METHODS: A cohort design with a matched NSC comparison was used. The SC constituted a validated database of acute ischemic stroke patients, ≥65 years, hospitalized across 19 Minnesota hospitals in the year 2000. The NSC was constructed from the year 2000 General Medicare Population by matching SC members on age, race, and sex. Both cohorts were tracked across 5 years of Medicare claims data to identify dates and causes of rehospitalization and death dates. Kaplan-Meier survival curves estimated cumulative incidence rates. Cox models calculated adjusted hazard ratios. RESULTS: Event rates and adjusted hazard ratios were: mortality: 1 year SC=24%, NSC=4%; 5 years SC=49%, NSC=24% (hazard ratio, 4.4; 95% CI, 3.6 to 5.5). Overall rehospitalization rates were: 1 year SC=49%, NSC=20%; 5 years SC=83%; NSC=63% (hazard ratio, 2.6; 95% CI, 2.2 to 3.0). Cause-specific 5-year rehospitalization rates were significantly higher in SC versus NSC for recurrent ischemic stroke, heart failure, cardiac events, any vascular events, pneumonia, and hip fractures. The excess risk of mortality and rehospitalizations in the SC persisted beyond the initial aftermath of the acute stroke (i.e., beyond 30 days poststroke) and persisted even after 1 year poststroke. Average acute care Medicare charges in SC were more than doubled those in NSC. CONCLUSIONS: The high rates of acute care poststroke readmissions indicate a need for trials to prevent long-term complications in stroke survivors.

TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells.

Tumor necrosis factor alpha (TNF-alpha) production is abnormally high in Fanconi anemia (FA) cells and contributes to the hematopoietic defects seen in FA complementation group C-deficient (Fancc(-/-)) mice. Applying gene expression microarray and proteomic methods to studies on FANCC-deficient cells we found that genes encoding proteins directly involved in ubiquitinylation are overrepresented in the signature of FA bone marrow cells and that ubiquitinylation profiles of FA-C and complemented cells were substantially different. Finding that Toll-like receptor 8 (TLR8) was one of the proteins ubiquitinylated only in mutant cells, we confirmed that TLR8 (or a TLR8-associated protein) is ubiquitinylated in mutant FA-C cells and that TNF-alpha production in mutant cells depended upon TLR8 and the canonical downstream signaling intermediates interleukin 1 receptor-associated kinase (IRAK) and IkappaB kinase-alpha/beta. FANCC-deficient THP-1 cells and macrophages from Fancc(-/-) mice overexpressed TNF-alpha in response to TLR8 agonists but not other TLR agonists. Ectopically expressed FANCC point mutants were capable of fully complementing the mitomycin-C hypersensitivity phenotype of FA-C cells but did not suppress TNF-alpha overproduction. In conclusion, FANCC suppresses TNF-alpha production in mononuclear phagocytes by suppressing TLR8 activity and this particular function of FANCC is independent of its function in protecting the genome from cross-linking agents.

3D-printed B4C collimation for neutron pressure cells.

A design for an incident-beam collimator for the Paris-Edinburgh pressure cell is described here. This design can be fabricated from reaction-bonded B4C but also through fast turnaround, inexpensive 3D-printing. 3D-printing thereby also offers the opportunity of composite collimators whereby the tip closest to the sample can exhibit even better neutronic characteristics. Here, we characterize four such collimators: one from reaction-bonded B4C, one 3D-printed and fully infiltrated with cyanoacrylate, a glue, one with a glue-free tip, and one with a tip made from enriched 10B4C. The collimators are evaluated on the Spallation Neutrons and Pressure Diffractometer of the Spallation Neutron Source and the Wide-Angle Neutron Diffractometer at the High Flux Isotope Reactor, both at Oak Ridge National Laboratory. This work clearly shows that 3D-printed collimators perform well and also that composite collimators improve performance even further. Beyond use in the Paris-Edinburgh cell, these findings also open new avenues for collimator designs as clearly more complex shapes are possible through 3D printing. An example of such is shown here with a collimator made for single-crystal samples measured inside a diamond anvil cell. These developments are expected to be highly advantageous for future experimentation in high pressure and other extreme environments and even for the design and deployment of new neutron scattering instruments.

Utility of dysphagia screening results in predicting poststroke pneumonia.

BACKGROUND AND PURPOSE: Dysphagia screening before oral intake (DS) is a stroke care quality indicator. The value of DS is unproven. Quality adherence and outcome data from the Paul Coverdell National Acute Stroke Registry were examined to establish value of DS. METHODS: Adherence to the DS quality indicator was examined in patients with stroke discharged from Paul Coverdell National Acute Stroke Registry hospitals between March 1 and December 31, 2009. Patients were classified as unscreened (US), screened and passed (S/P), and screened and failed. Associations between screening status and pneumonia rate were assessed by logistic regression models after adjustment for selected variables. RESULTS: A total of 18 017 patients with stroke discharged from 222 hospitals in 6 states were included. A total of 4509 (25%) were US; 8406 (47%) were S/P, and 5099 (28%) were screened and failed. Compared with US patients, screened patients were significantly more impaired. Pneumonia rates were: US 4.2%, S/P 2.0%, and screened and failed 6.8%. After adjustment for demographic and clinical features, US patients were at a higher risk of pneumonia (OR, 2.2; 95% CI, 1.7 to 2.7) compared with S/P patients. CONCLUSIONS: Data suggest that patients are selectively screened based on stroke severity. Pneumonia rate was higher in US patients compared with S/P patients. Clinical judgment regarding who should be screened is imperfect. S/P patients have a lower pneumonia rate indicating that DS adds accuracy in predicting pneumonia risk. The Joint Commission recently retired DS as a performance indicator for Primary Stroke Center certification. These results suggest the need to implement a DS performance measure for patients with acute stroke.

Cost-effectiveness analysis of protected carotid artery stent placement versus endarterectomy in high-risk patients.

PURPOSE: To determine the cost-effectiveness of carotid angioplasty with stent placement (CAS) under emboli protection versus carotid endarterectomy (CEA) in patients with severe carotid stenosis considered to be at high surgical risk for CEA. METHODS: The probabilities of various outcomes were adopted from the SAPPHIRE trial results. The quality-adjusted life year (QALYs) associated with each treatment modality were estimated by using the frequencies of various quality-adjusted outcomes (QALY weights of ipsilateral stroke, myocardial infarction, and death). Total cost associated with each intervention was computed using the frequency of stroke, myocardial infarction, and death in each group. Costs are expressed in 2006 US$. Incremental cost-effectiveness ratios (ICERs) were estimated for a 1-year postprocedure period. RESULTS: The mean (range) estimated net costs at 1 year for patients treated with CAS and CEA were $12,782 ($12,205-$13,563) and $8,916 ($8,267-$9,766), respectively. Overall QALYs for the CAS and CEA groups were 0.753 and 0.701 [within a range of 0.0 (meaning death) to 0.815 (meaning no adverse events)]. The mean cost per QALY gained for CAS was $16,223 ($15,315-$17,474) and the mean cost per QALY gained for CEA was $12,745 ($11,372-$14,605). The estimated median ICER for CAS versus CEA treatment was $67,891 (-$129,372 to $379,661). CONCLUSION: The proven non-inferiority of CAS versus CEA in high-surgical-risk patients with severe carotid stenosis might provide a marginal benefit that is offset by the higher cost associated with this procedure.

Stroke rates: 1980-2000: the Minnesota Stroke Survey.

In this paper, the authors report trends in hospitalized stroke rates among Minneapolis-St. Paul, Minnesota (population 2.6 million) metropolitan area residents aged 30-74 years from 1980 to 2000. Cases were identified from lists of discharge diagnoses provided by hospitals serving the target population. Age-adjusted, sex-specific stroke attack rates were computed for each survey year by using 5 different diagnostic definitions: 2 based purely on International Classification of Diseases, Ninth Revision (ICD-9) codes and 3 including clinical and neuroimaging criteria. Stroke rates, as measured by a highly specific clinical definition, remained stable from 1980 to 2000 for women. For men, these rates declined modestly from 1980 to 1990 and leveled off during 1990-2000. In contrast, use of stroke-related ICD-9 discharge codes declined significantly from 1980 to 2000: 35% among men and 16% among women. Neuroimaging use increased significantly from 75% of cases in 1980 to 98% in 2000. Short-term (28-day) stroke survival improved significantly, by 16% for women and 12% for men, from 1980 to 2000. The decline in stroke ICD-9 code usage reflects the influence of increased neuroimaging on discharge coding. The improved short-term survival in the face of stable, clinically defined stroke rates may imply treatment advances or ascertainment of less severe strokes, possibly masking a true decline in stroke rates.