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IMPORTANCE: Optimal management of patients with asymptomatic severe carotid stenosis is uncertain, due to advances in medical care and a lack of contemporary data comparing medical and surgical treatment. OBJECTIVE: To estimate stroke outcomes among patients with medically treated asymptomatic severe carotid stenosis who did not undergo surgical intervention. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study that included 3737 adult participants with asymptomatic severe (70%-99%) carotid stenosis diagnosed between 2008 and 2012 and no prior intervention or ipsilateral neurologic event in the prior 6 months. Participants received follow-up through 2019, and all were members of an integrated US regional health system serving 4.5 million members. EXPOSURES: Imaging diagnosis of asymptomatic carotid stenosis of 70% to 99%. MAIN OUTCOMES AND MEASURES: Occurrence of ipsilateral carotid-related acute ischemic stroke. Censoring occurred with death, disenrollment, or ipsilateral intervention. RESULTS: Among 94 822 patients with qualifying imaging studies, 4230 arteries in 3737 (mean age, 73.8 [SD 9.5 years]; 57.4% male) patients met selection criteria including 2539 arteries in 2314 patients who never received intervention. The mean follow-up in this cohort was 4.1 years (SD 3.6 years). Prior to any intervention, there were 133 ipsilateral strokes with a mean annual stroke rate of 0.9% (95% confidence interval [CI], 0.7%-1.2%). The Kaplan-Meier estimate of ipsilateral stroke by 5 years was 4.7% (95% CI, 3.9%-5.7%). CONCLUSIONS AND RELEVANCE: In a community-based cohort of patients with asymptomatic severe carotid stenosis who did not undergo surgical intervention, the estimated rate of ipsilateral carotid-related acute ischemic stroke was 4.7% over 5 years. These findings may inform decision-making regarding surgical and medical treatment for patients with asymptomatic severe carotid artery stenosis.

Supplemental Digital Content is available in the text., Background and Purpose: Shelter-in-place (SIP) orders implemented to mitigate severe acute respiratory syndrome coronavirus 2 spread may inadvertently discourage patient care-seeking behavior for critical conditions like acute ischemic stroke. We aimed to compare temporal trends in volume of acute stroke alerts, patient characteristics, telestroke care, and short-term outcomes pre- and post-SIP orders. Methods: We conducted a cohort study in 21 stroke centers of an integrated healthcare system serving 4.4+ million members across Northern California. We included adult patients who presented with suspected acute stroke and were evaluated by telestroke between January 1, 2019, and May 9, 2020. SIP orders announced the week of March 15, 2020, created pre (January 1, 2019, to March 14, 2020) and post (March 15, 2020, to May 9, 2020) cohort for comparison. Main outcomes were stroke alert volumes and inpatient mortality for stroke. Results: Stroke alert weekly volume post-SIP (mean, 98 [95% CI, 92–104]) decreased significantly compared with pre-SIP (mean, 132 [95% CI, 130–136]; P

Background and Purpose: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. Methods: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. Results: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P P Conclusions: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

Background The relationship between outpatient systolic and diastolic blood pressure and cardiovascular outcomes remains unclear and has been complicated by recently revised guidelines wit...

Background: Published data suggest that treating qualified acute strokes within the extended window (EW) or 6-24 hours of last seen normal with endovascular therapy (EST) is associated with better 90-day outcome. In a real-world multi-ethnic practice setting, we assessed our experience in triaging and treating patients in the EW. Methods: In 2016, our system of care launched a telestroke program for 19 primary and 2 comprehensive stroke centers to include immediate video evaluation by a stroke neurologist. In 2018, screening in the EW began. If the patient met clinical criteria (baseline independence and initial NIHSS ≥ 6), neuroimaging was performed to assess for a large vessel occlusion (LVO). Referral for EST was made for patients with an LVO and appropriate CT perfusion criteria. Our study included all health plan members presenting within the EW in 2019. Assessment included demographics, NIHSS, neuroimaging data, LVO, discharge outcomes, 90-day mRS and mortality with 95% confidence interval. Results: In 2019, there were 5349 suspected strokes (1255 EW) evaluated by teleneurologists; 2130 (39.8%) patients were appropriate for acute stroke imaging workup. Of 2130, final study cohort included 388 (18.2%) EW patients who met clinical criteria and underwent neuroimaging workup, and 117 of these patients (30.2%) had an LVO. There were 57 (14.7%) meeting CT perfusion criteria and referred for EST. Compared to 331 who were not referred for EST, the 57 patients were older and more likely to have atrial fibrillation, higher NIHSS, and to be discharged to a short-term facility than home. The 51 patients who went for EST within our system had 90-day good (mRS 0-2), bad (mRS 5-6), and mortality rates comparable to those from DAWN and DEFUSE-3 trials [Table]. Conclusions: In our system, only a small proportion of suspected strokes met criteria for EST during the EW. It was possible in a community setting to achieve 90-day outcomes that were comparable to those from clinical trials.

Systolic and diastolic hypertension independently predict the risk of adverse cardiovascular events. It remains unclear how systolic pressure, diastolic pressure, and other patient characteristics influence the initial diagnosis of hypertension. Here, we use a cohort of 146,816 adults in a large healthcare system to examine how elevated systolic and/or diastolic blood pressure measurements influence initial diagnosis of hypertension and how other patient characteristics influence the diagnosis. Thirty-four percent of the cohort were diagnosed with hypertension within 1 year. In multivariable logistic regression of the diagnosis of hypertension, controlling for covariates, isolated systolic hypertensive measures (odds ratio [OR] 0.42 [95% confidence interval {CI} 0.41 to 0.43]) and isolated diastolic hypertensive measures (OR 0.32 [95% CI 0.31 to 0.33]) were less likely to lead to hypertension diagnosis when compared with combined hypertensive measures. Higher levels of systolic blood pressure had a greater impact on hypertension diagnosis (OR 1.77 [95% CI 1.75 to 1.79] per Z-score) than did higher levels of diastolic blood pressure (OR 1.34 [95% CI 1.32 to 1.36] per Z-score). Older age, non-white race/ethnicity, and medical comorbidities all predicted the establishment of a diagnosis of hypertension. Isolated systolic and isolated diastolic hypertension are underdiagnosed in clinical practice, and several patient-centered factors also strongly influence whether a diagnosis is made. In conclusion, our findings uncover a care gap that can be closed with increased attention to the independent influence of systolic and diastolic hypertension and the various patient-centered factors that may impact hypertension diagnosis.

Informed debate regarding the optimal use of carotid endarterectomy (CEA) for stroke risk reduction requires contemporary assessment of both long-term risk and periprocedural risk. In this study, we report long-term stroke and death risk after CEA in a large integrated health care system.All patients with documented severe (70%-99%) stenosis from 2008 to 2012 who underwent CEA were identified and stratified by asymptomatic or symptomatic indication. Those with prior ipsilateral interventions were excluded. Patients were followed up through 2017 for the primary outcomes of any stroke/death within 30 days of intervention and long-term ipsilateral ischemic stroke; secondary outcomes were any stroke and overall survival.Overall, 1949 patients (63.2% male; mean age, 71.3 ± 8.9 years) underwent 2078 primary CEAs, 1196 (58%) for asymptomatic stenosis and 882 (42%) for symptomatic stenosis. Mean follow-up was 5.5 ± 2.7 years. Median time to surgery was 72.0 (interquartile range, 38.5-198.0) days for asymptomatic patients and 21.0 (interquartile range, 5.0-55.0) days for symptomatic patients (P .001). Most of the patients' demographics and characteristics were similar in both groups. Controlled blood pressure rates were similar at the time of CEA. Baseline statin use was seen in 60.5% of the asymptomatic group compared with 39.9% in the symptomatic group (P .001), and statin adherence by 80% medication possession ratio was 19.3% asymptomatic vs 12.4% symptomatic (P .001). The crude overall 30-day any stroke/death rates were 0.9% and 1.5% for the asymptomatic group and the symptomatic group, respectively. The 5-year risk of ipsilateral stroke and a combined end point of any stroke/death by Kaplan-Meier survival analysis were 2.5% and 28.7% for the asymptomatic group and 4.0% and 31.4% for the symptomatic group, respectively. Unadjusted cumulative all-cause survival was 74.2% for the asymptomatic group and 71.8% for the symptomatic group at 5 years.In a contemporary review of CEA, outcomes for either operative indication show low adverse events perioperatively and low long-term stroke risk up to 5 years. These results are well within consensus guidelines and published trial outcomes and should help inform the discussion around optimal CEA use for severe carotid stenosis.

Background: Published data suggest that the faster acute stroke patients are treated with IV alteplase the better they do post discharge. It is not clear that reducing door-to-needle (DTN) time by 15 minutes (from 60 to 45 to 30) is associated with better functional outcome and/or less mortality. In a real-world practice setting, we assessed the effect of different DTN times on clinical outcomes. Methods: In 2016, a new standardized telestroke program for 21 stroke centers in an integrated healthcare system was launched. It included immediate evaluation by a stroke neurologist via video, expedited IV alteplase treatment, rapid CT angiographic study, and expedited transfer and treatment for patients with large vessel occlusion. From 2/15/18 to 2/25/19, we collected 90-day modified Rankin Score (mRS) for adult members who received IV alteplase. We also collected data on demographics, NIHSS, DTN times, thrombectomy, length of stay, discharge outcomes, 90-day mRS and mortality in those treated with IV alteplase stratified by the DTN time (60 vs. 45 vs. 30 minutes). Multivariate logistic regression was used to examine whether DTN category was predictive of good functional outcome (mRS=0-2) adjusted for age, gender, race, and NIHSS. Results: During the study period, the full cohort had 784 patients treated with IV alteplase. Average age was 71.5 ± 14.9 years with 51.8% female. Median NIHSS was 6. Median DTN time was 34 minutes. Those with faster DTN arrived more by EMS, had higher NIHSS, higher rate of thrombectomy, and shorter length of stay. A smaller cohort of 340 patients had a 90-day mRS. Multivariate models revealed a trend for faster DTN time being associated with less 90-day mortality (OR=0.81, p=0.24) and good functional outcome (OR=1.73, p=0.07) among EMS arrival (Table). Conclusions: In our study cohort, every 15-minute reduction in DTN had stronger association with better outcomes. Further efforts are underway to capture more complete mRS data for the full cohort.

Background: Risks and benefits of thrombectomy in elderly stroke patients remained unclear. We evaluated outcomes in the elderly who underwent endovascular therapy (EST) in a large integrated healthcare system. Methods: In 2016, our integrated healthcare system launched a new standardized acute telestroke care workflow for all 21 stroke centers. It included immediate evaluation by a stroke neurologist via video, expedited IV alteplase treatment, rapid CT angiographic investigation, and expedited transfer and EST for patients with large vessel occlusion (LVO). From January 2016 through December 2018, our study cohort included adult members who had EST within our care system. We compared patient characteristics, door-to-needle (DTN) times, door-to-groin (DTG) times, inpatient and 90-day mortality between those treated with EST aged Results: There were 291 acute stroke patients who underwent EST [Table]. The older subgroup had a higher percentage of female and higher rates of atrial fibrillation. They were more likely to arrive by EMS, to have a higher initial NIHSS and to have a faster DTN time. Average DTG times and inpatient mortality rates were not different between groups. The elderly had a higher rate of 90-day mortality. In multivariate model, being elderly was associated with higher 90-day mortality (OR=2.56, 95% CI 1.29-5.09, p=0.007). Conclusions: For those who underwent EST in a large community setting with a standardized approach to acute stroke treatment, being elderly was associated with a higher risk of 90-day mortality. Further data analyses are being carried out with additional co-morbidities, inpatient complications, and 90-day functional outcome to better understand outcomes in older patients undergoing EST.

Background: Risk of community-acquired Clostridium difficile infection (CA-CDI) following antibiotic treatment specifically for urinary tract infection (UTI) has not been evaluated. Methods: We conducted a nested case-control study at Kaiser Permanente Northern California, 2007–2010, to assess antibiotic prescribing and other factors in relation to risk of CA-CDI in outpatients with uncomplicated UTI. Cases were diagnosed with CA-CDI within 90 days of antibiotic use. We used matched controls and confirmed case-control eligibility through chart review. Antibiotics were classified as ciprofloxacin (most common), or low risk (nitrofurantoin, sulfamethoxazole/trimethoprim), moderate risk, or high risk (e.g. cefpodoxime, ceftriaxone, clindamycin) for CDI. We computed the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship of antibiotic treatment for uncomplicated UTI and history of relevant gastrointestinal comorbidity (including gastrointestinal diagnoses, procedures, and gastric acid suppression treatment) with risk of CA-CDI using logistic regression analysis. Results: Despite the large population, only 68 cases were confirmed with CA-CDI for comparison with 112 controls. Female sex [81% of controls, adjusted odds ratio (OR) 6.3, CI 1.7–24), past gastrointestinal comorbidity (prevalence 39%, OR 2.3, CI 1.1–4.8), and nongastrointestinal comorbidity (prevalence 6%, OR 2.8, CI 1.4–5.6) were associated with increased CA-CDI risk. Compared with low-risk antibiotic, the adjusted ORs for antibiotic groups were as follows: ciprofloxacin, 2.7 (CI 1.0–7.2); moderate-risk antibiotics, 3.6 (CI 1.2–11); and high-risk antibiotics, 11.2 (CI 2.4–52). Conclusions: Lower-risk antibiotics should be used for UTI whenever possible, particularly in patients with a gastrointestinal comorbidity. However, UTI can be managed through alternative approaches. Research into the primary prevention of UTI is urgently needed.

Supplemental Digital Content is available in the text., Background and Purpose— Faster treatment with intravenous alteplase in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California redesigned its acute stroke workflow across all 21 Kaiser Permanente Northern California stroke centers to (1) follow a single standardized version of a modified Helsinki model and (2) have all emergency stroke cases managed by a dedicated telestroke neurologist. We examined the effect of Kaiser Permanente Northern California’s Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke program on door-to-needle (DTN) time, alteplase use, and symptomatic intracranial hemorrhage rates. Methods— The program was introduced in a staggered fashion from September 2015 to January 2016. We compared DTN times for a seasonally adjusted 9-month period at each center before implementation to the corresponding 9-month calendar period from the start of implementation. The primary outcome was the DTN time for alteplase administration. Secondary outcomes included rate of alteplase administrations per month, symptomatic intracranial hemorrhage, and disposition at time of discharge. Results— This study included 310 patients treated with alteplase in the pre–EXpediting the PRrocess of Evaluating and Stopping Stroke period and 557 patients treated with alteplase in the EXpediting the PRrocess of Evaluating and Stopping Stroke period. After implementation, alteplase administrations increased to 62/mo from 34/mo at baseline (P

OBJECTIVEThe aims of this study were to evaluate a multiyear experience with subdural evacuating port system (SEPS) placement for chronic subdural hematoma (cSDH) in the intensive care unit at a tertiary neurosurgical center and to compare SEPS placement with bur hole evacuation in the operating room.METHODSAll cases of cSDH evacuation were captured over a 7-year period at a tertiary neurosurgical center within an integrated health care delivery system. The authors compared the performance characteristics of SEPS and bur hole placement with respect to recurrence rates, change in recurrence rates over time, complications, length of stay, discharge disposition, and mortality rates.RESULTSA total of 371 SEPS cases and 659 bur hole cases were performed (n = 1030). The use of bedside SEPS placement for cSDH treatment increased over the 7-year period, from 14% to 80% of cases. Reoperation within 6 months was higher for the SEPS (15.6%) than for bur hole drainage (9.1%) across the full 7-year period (p = 0.002). This observed overall difference was due to a higher rate of reoperation during the same hospitalization (7.0% for SEPS vs 3.2% for bur hole; p = 0.008). Over time, as the SEPS procedure became more common and modifications of the SEPS technique were introduced, the rate of in-hospital reoperation after SEPS decreased to 3.3% (p = 0.02 for trend), and the difference between SEPS and bur hole recurrence was no longer significant (p = 0.70). Complications were uncommon and were similar between the groups.CONCLUSIONSOverall performance characteristics of bedside SEPS and bur hole drainage in the operating room were similar. Modifications to the SEPS technique over time were associated with a reduced reoperation rate.

Background and Purpose— Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib). Methods— We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system. Results— Among 6116 patients with ischemic stroke discharged on a statin over a 5-year period, 1446 (23.6%) had a diagnosis of AFib at discharge. The mean statin adherence rate (percentage of days covered) was 85, and higher levels of percentage of days covered correlated with greater degrees of low-density lipoprotein suppression. In multivariable survival models of recurrent ischemic stroke over 3 years, after controlling for age, sex, race/ethnicity, medical comorbidities, and hospital center, higher statin adherence predicted reduced stroke risk both in patients without AFib (hazard ratio, 0.78; 95% confidence interval, 0.63–0.97) and in patients with AFib (hazard ratio, 0.59; 95% confidence interval, 0.43–0.81). This association was robust to adjustment for the time in the therapeutic range for international normalized ratio among AFib subjects taking warfarin (hazard ratio, 0.61; 95% confidence interval, 0.41–0.89). Conclusions— The relationship between statin adherence and reduced recurrent stroke risk is as strong among patients with AFib as it is among patients without AFib, suggesting that AFib status should not be a reason to exclude patients from secondary stroke prevention with a statin.

External ventricular drains (EVDs) historically have a high rate of infection, and EVD infections are a cause of significant morbidity and mortality. We have shown previously that a simple infection control protocol reduced the rate of EVD infections during a 3-year period, and the present study examines whether infection rates were durably reduced over an additional 4 years.Retrospective analysis of EVDs placed in the intensive care unit of a tertiary neurosurgical center over an additional 4 year follow-up period.In the 4-year follow-up period, 189 EVDs were placed in 173 patients. The previously observed decrease in cerebrospinal fluid culture positivity from 9.8% in the baseline period to 0.8% in the first 3 years of the protocol period continued in the 4-year follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P0.001 compared with baseline). The previously observed decrease in the rate of ventriculitis from 6.3% to 0.8% also continued in the follow-up period (0%, 0 of 189 EVD placements, 0 per 1000 catheter-days; P0.001 compared with baseline). Over the total 7 years of protocol use, the rate of culture positivity was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days) and the rate of ventriculitis was 0.3% (1 of 308 EVD placements, 0.29 per 1000 catheter-days). The only observed infection over 7 years occurred in a patient who removed their own EVD.A straightforward EVD infection control protocol substantially and durably reduces EVD infections to a near-zero rate.

Background and Purpose— Large artery occlusion (LAO) in ischemic stroke requires recognition and triage to an endovascular stroke treatment center. Noninvasive LAO detection is needed to improve triage. Methods— Prospective study to test whether noninvasive cerebral oximetry can detect anterior circulation LAO in acute stroke. Interhemispheric ΔBrSO 2 in LAO was compared with controls. Results— In LAO stroke, mean interhemispheric ΔBrSO 2 was −8.3±5.8% (n=19), compared with 0.4±5.8% in small artery stroke (n=17), 0.4±6.0% in hemorrhagic stroke (n=14), and 0.2±7.5% in subjects without stroke (n=19) ( P 2 in most LAO subjects (16/19). Discrimination of LAO at a −3% ΔBrSO 2 cut had 84% sensitivity and 70% specificity. Addition of the G-FAST clinical score (gaze–face–arm–speech– time) to the BrSO 2 measure had 84% sensitivity and 90% specificity. Conclusions— Noninvasive cerebral oximetry may help detect LAO in ischemic stroke, particularly when combined with a simple clinical scoring system.

Introduction: Accurately balancing risks of interventional treatment and intracranial hemorrhage (ICH) in the untreated course of unruptured brain arteriovenous malformation (uBAVM) patients is critical for optimal management. Observational studies of uBAVM afford an opportunity to address important gaps and previous criticisms of randomized data to help guide treatment decisions and assess long-term risk/benefit ratio. We previously published an individual patient data meta-analysis (IPDMA) in 4 MARS cohorts and identified ICH presentation and increasing age as significant predictors of ICH during follow-up, but was not powered to detect predictors in those with uBAVM. Thus, the goals of this project are to identify risk factors for ICH in uBAVMs, to estimate the risk with precision, and to create personalized, risk-prediction models. Methods: MARS is an international, multi-center study of 11 cohorts with target enrollment of 4,500 uBAVM patients ascertained through population-based or referral-based studies. We are harmonizing both retrospective and prospective data, including clinical, lifestyle, imaging, and angiographic factors. Treatments, complications, and functional outcomes (physician and patient-reported) will be updated annually between 2018-2022. We propose to: 1) identify predictors of outcome in uBAVMs using IPDMA; 2) test whether long-term outcomes differ by treatment using statistical approaches for causal inference and unbiased estimates; 3) compare treatment outcomes in randomized and non-randomized data to address generalizability; and 4) validate models and provide a novel tool for calculating individualized risks. Eligible sites have: a) prior BAVM publications; b) data from a minimum of 100 uBAVM patients; c) agree to random outcome adjudication; and d) agree to MARS data sharing policy. Discussion: The NIH-funded MARS consortium will provide important and comprehensive characterization of the untreated and treated course of uBAVMs, using large observational datasets and sophisticated epidemiological approaches. The data and models generated will be a useful resource for decision-making. We welcome participation from eligible sites with longitudinal data on uBAVM patients

OBJECTIVE: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) versus surface cooling methods (SCM) for induced hypothermia (IH).METHODS: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods.ELIGIBILITY: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM versus SCM were eligible for inclusion.RESULTS: In total, 12 studies met inclusion criteria. These enrolled 1,573 patients who received IVTM; and 4,008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI -1%, 5%)]. Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM versus SCM. There was no significant difference in other evaluated adverse events between groups.CONCLUSIONS: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest.

Risk of community-acquiredWe conducted a nested case-control study at Kaiser Permanente Northern California, 2007-2010, to assess antibiotic prescribing and other factors in relation to risk of CA-CDI in outpatients with uncomplicated UTI. Cases were diagnosed with CA-CDI within 90 days of antibiotic use. We used matched controls and confirmed case-control eligibility through chart review. Antibiotics were classified as ciprofloxacin (most common), or low risk (nitrofurantoin, sulfamethoxazole/trimethoprim), moderate risk, or high risk (e.g. cefpodoxime, ceftriaxone, clindamycin) for CDI. We computed the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship of antibiotic treatment for uncomplicated UTI and history of relevant gastrointestinal comorbidity (including gastrointestinal diagnoses, procedures, and gastric acid suppression treatment) with risk of CA-CDI using logistic regression analysis.Despite the large population, only 68 cases were confirmed with CA-CDI for comparison with 112 controls. Female sex [81% of controls, adjusted odds ratio (OR) 6.3, CI 1.7-24), past gastrointestinal comorbidity (prevalence 39%, OR 2.3, CI 1.1-4.8), and nongastrointestinal comorbidity (prevalence 6%, OR 2.8, CI 1.4-5.6) were associated with increased CA-CDI risk. Compared with low-risk antibiotic, the adjusted ORs for antibiotic groups were as follows: ciprofloxacin, 2.7 (CI 1.0-7.2); moderate-risk antibiotics, 3.6 (CI 1.2-11); and high-risk antibiotics, 11.2 (CI 2.4-52).Lower-risk antibiotics should be used for UTI whenever possible, particularly in patients with a gastrointestinal comorbidity. However, UTI can be managed through alternative approaches. Research into the primary prevention of UTI is urgently needed.

Background and purpose The Totaled Health Risks in Vascular Events (THRIVE) score is a previously validated ischemic stroke outcome prediction tool. Although simplified scoring systems like the THRIVE score facilitate ease-of-use, when computers or devices are available at the point of care, a more accurate and patient-specific estimation of outcome probability should be possible by computing the logistic equation with patient-specific continuous variables. Methods We used data from 12 207 subjects from the Virtual International Stroke Trials Archive and the Safe Implementation of Thrombolysis in Stroke – Monitoring Study to develop and validate the performance of a model-derived estimation of outcome probability, the THRIVE-c calculation. Models were built with logistic regression using the underlying predictors from the THRIVE score: age, National Institutes of Health Stroke Scale score, and the Chronic Disease Scale (presence of hypertension, diabetes mellitus, or atrial fibrillation). Receiver operator characteristics analysis was used to assess model performance and compare the THRIVE-c model to the traditional THRIVE score, using a two-tailed Chi-squared test. Results The THRIVE-c model performed similarly in the randomly chosen development cohort ( n = 6194, area under the curve = 0·786, 95% confidence interval 0·774–0·798) and validation cohort ( n = 6013, area under the curve = 0·784, 95% confidence interval 0·772–0·796) ( P = 0·79). Similar performance was also seen in two separate external validation cohorts. The THRIVE-c model (area under the curve = 0·785, 95% confidence interval 0·777–0·793) had superior performance when compared with the traditional THRIVE score (area under the curve = 0·746, 95% confidence interval 0·737–0·755) ( P < 0·001). Conclusion By computing the logistic equation with patientspecific continuous variables in the THRIVE-c calculation, outcomes at the individual patient level are more accurately estimated. Given the widespread availability of computers and devices at the point of care, such calculations can be easily performed with a simple user interface.

Systolic hypertension is believed to have a greater influence than diastolic hypertension on adverse cardiovascular events. We tested this hypothesis using data from an integrated healthcare system, with 36.8 million measures from 1.3 million adults. Increasing SBP was associated with risk of a composite outcome of MI, ischemic stroke, or hemorrhagic stroke (Fig A). DBP showed a very different relationship with outcomes, with higher risk at the lowest and highest levels of DBP (Fig B). We examined the impact of systolic and diastolic pressures in multivariable survival analysis controlling for age, sex, race, and comorbidities using two different approaches. We first used the burden of systolic (SBP>=140) and diastolic (DBP>=90) hypertension as predictors. Both systolic burden (hazard ratio [HR] 1.17 for z-score, 95% CI 1.16 to 1.18, P133) or DBP (>78). Again, both SBP (HR 1.39 for z-score, 95% CI 1.37 to 1.41, P

Background: Faster treatment with tPA in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California (KPNC) redesigned its acute stroke workflow across all 21 KPNC stroke centers to have all stroke alerts actively managed by a core group of vascular neurologists via telemedicine. We examined the effect of KPNC’s Stroke EXPRESS (EXpediting the PRrocess of Evaluating and Stopping Stroke) program on door-to-needle (DTN) time and symptomatic intracranial hemorrhage (sICH) rates. Methods: The Stroke EXPRESS program was rolled out across KPNC in a staggered fashion from 9/2015 to 1/2016 with the goals of expediting the evaluation and determination for tPA and speeding up the assessment for large vessel occlusion to allow for timely transfer for thrombectomy. We compared DTN times for 6 months before implementation to the same 6-month calendar period after implementation. Results: After implementation, tPA administrations increased from 38/month at baseline to 80/month (P Conclusions: Implementation of the Stroke EXPRESS regional telemedicine program in KPNC was associated with an increase in tPA administrations, markedly shorter DTN times, and no change in the rate of sICH.

Outpatient statin use is known to reduce the risk of recurrent ischemic stroke of atherothrombotic etiology, but it is not known whether statins have similar effects in ischemic stroke associated with atrial fibrillation (AF). We examined the relationship between outpatient statin adherence and the risk of recurrent ischemic stroke in patients with or without AF in a large integrated healthcare delivery system. Among 6,283 patients with ischemic stroke discharged on a statin over a 5 year period, 1,486 (23.7%) had a diagnosis of AF at discharge. Statin adherence rates, measured as percentage of days covered (PDC), averaged 85% (88% for AF patients and 84% for non-AF patients). We observed up to three years after the initial stroke, with an average of two years follow up. In multivariable survival models, after controlling for age, gender, race/ethnicity, and key medical comorbidities, higher statin adherence was found to strongly predict a reduced risk of recurrent ischemic stroke (Figure). In the second year post-stroke, the hazard ratio (HR) associated with a 10% increase in PDC was 0.93 (95% C.I. 0.89-097). The relationship between statin adherence and reduced stroke rates was similar in AF patients (HR 0.94, 95% C.I. 0.84-0.98) and non-AF patients (HR 0.93, 95% C.I. 0.88-0.98). These findings support the use of outpatient statins in all ischemic stroke patients, irrespective of stroke etiology (atherothrombotic vs. atrial fibrillation).

Background The Totaled Health Risks in Vascular Events (THRIVE) score is a clinical prediction score that predicts ischemic stroke outcomes in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute therapy. We have previously found an association between THRIVE and risk of post-tissue plasminogen activator symptomatic intracranial hemorrhage in the National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator trial and risk of radiographic hemorrhage in Virtual International Stroke Trials Archive. Aims The study aims to validate the relationship between THRIVE and symptomatic intracranial hemorrhage among tissue plasminogen activator-treated patients in the large Safe Implementation of Thrombolysis in Stroke – Monitoring Study (SITS-MOST). Methods This is a retrospective analysis of the prospective SITS-MOST to examine the relationship between THRIVE and symptomatic intracranial hemorrhage after tissue plasminogen activator treatment. Symptomatic intracranial hemorrhage after tissue plasminogen activator was defined according to each of three standard definitions: the NINDS, European Cooperative Acute Stroke Study (ECASS), and Safe Implementation of Thrombolysis in Stroke (SITS) criteria. Multivariable logistic regression was used to confirm the relationship of THRIVE and individual THRIVE components with the risk of symptomatic intracranial hemorrhage and to examine the relationship of THRIVE, symptomatic intracranial hemorrhage, and functional outcome. Results The odds ratio for symptomatic intracranial hemorrhage at each increased level of THRIVE score is 1·34 (95% CI 1·27 to 1·41, P < 0·001) for symptomatic intracranial hemorrhage by NINDS criteria, 1·36 (95% CI 1·27 to 1·46, P < 0·001) for symptomatic intracranial hemorrhage by ECASS criteria, and 1·21 (95% CI 1·09 to 1·36, P < 0·001) for symptomatic intracranial hemorrhage by SITS criteria. In receiver-operator characteristics analysis, the C-statistic for THRIVE prediction of symptomatic intracranial hemorrhage was 0·65 (95% CI 0·62 to 0·67) for symptomatic intracranial hemorrhage by NINDS criteria, 0·66 (95% CI 0·63 to 0·69) for symptomatic intracranial hemorrhage by ECASS criteria, and 0·61 (95% CI 0·56 to 0·66) for symptomatic intracranial hemorrhage by SITS criteria. Each component of the THRIVE score predicts the risk of symptomatic intracranial hemorrhage, with independent impact of each component in multivariable analysis. Conclusions The THRIVE score predicts the risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator administration. This external validation of the relationship between THRIVE and symptomatic intracranial hemorrhage in a prospective study further strengthens the role of the THRIVE score in the prediction of poststroke outcomes.

Background Collaterals may affect revascularization, ischemic severity, and clinical outcomes in acute stroke owing to internal carotid artery (ICA) occlusion. Objective To examine the hypothesis that morphology of occlusive thrombus and collateral flow patterns may influence the outcome of ICA occlusions after mechanical thrombectomy. Methods Pooled analyses of ICA occlusions in the MERCI and Multi-MERCI trials employed central angiography review readings to categorize lesions as I, L, or T clots and functional lesions based on collateral flow patterns. Demographic variables, procedural details, and clinical outcomes were compared across ICA lesion types. Results A total of 72 subjects (mean age 67 years (SD 16), 51% female, median National Institutes of Health Stroke Scale 20 (range 8–35)) were included, with 90-day modified Rankin score ≤2 in 28% and 51% mortality. Clots were categorized as an I lesion in 9/72 (12.5%), L lesion in 12/72 (16.7%), and T lesion in 51/72 (70.8%). Based on collateral flow patterns, cases were categorized as having a functional I lesion in 7/72 (9.7%), functional L in 38/72 (52.8%), and functional T in only 27/72 (37.5%). Multivariate analyses showed that a functional T lesion, with insufficient collateral flow to ipsilateral anterior cerebral arteries via the contralateral ICA, was a strong predictor of both revascularization success and subsequent clinical outcomes. Conclusions Collateral flow patterns distinguish the nature and impact of ICA occlusions on expected revascularization and subsequent clinical outcomes in acute ischemic stroke. The nomenclature of terminal ICA occlusions introduced here (carotid I9s, L9s, and T9s) may enhance future endovascular trials targeting such proximal occlusions. Trial registration number NCT00318071 (http://clinicaltrials.gov). MERCI was not registered because enrollment began before July 1, 2005.

To compare the safety and effectiveness of three methods of reversing coagulopathic effects of warfarin in patients with potentially life-threatening intracranial hemorrhage.A retrospective electronic medical record review of 63 patients with warfarin-related intracranial hemorrhage between 2007 and 2010 in an integrated health care delivery system was conducted. The three methods of rapid warfarin reversal were fresh-frozen plasma (FFP), activated factor VII (FVIIa; NovoSevenRT [Novo Nordisk, Bagsværd, Denmark]), and prothrombin complex concentrate (PCC; BebulinVH [Baxter, Westlake Village, California, USA], ProfilnineSD [Grifols, North Carolina, USA]), each used adjunctively with vitamin K (Vit K, phytonadione). We determined times from reversal agent order to laboratory evidence of warfarin reversal (international normalized ratio [INR]) in the first 48 hours and compared INR rebound rates and complications in the first 48 hours.Reversal with FFP took more than twice as long compared with FVIIa or PCC. To reach an INR of 1.3, mean (±SD) reversal times were 1933 ± 905 minutes for FFP, 784 ± 926 minutes for FVIIa, and 980 ± 1021 minutes for PCC (P0.001; P0.01 between FFP and FVIIa, P0.05 between FFP and PCC). INR rebound occurred in 0 of 31 patients for FFP, 4 of 8 for FVIIa, and 0 of 7 for PCC (P = 0.001). Complications were uncommon. FVIIa was 15 and 3.5 times as expensive as FFP and PCC, respectively.As an adjunct to Vit K for rapid warfarin reversal, FVIIa and PCC appear more effective than FFP. Either FVIIa or PCC are reasonable options for reversal, but FVIIa is considerably more expensive and may have greater risk of INR rebound.

Background and Purpose— Several outcome prediction scores have been tested in patients receiving acute stroke treatment with previous generations of endovascular stroke treatment devices. The TREVO-2 trial was a randomized controlled trial comparing a novel endovascular stroke treatment device (the Trevo device) to a previous-generation endovascular stroke treatment device (the Merci device). Methods— We used data from the TREVO-2 trial to validate the Totaled Health Risks in Vascular Events (THRIVE) score in patients receiving treatment with a third-generation endovascular stroke treatment device and to compare THRIVE to other predictive scores. We used logistic regression to model outcomes and compared score performance with receiver operating characteristic curve analysis. Results— In the TREVO-2 trial, the THRIVE score strongly predicts clinical outcome and mortality. The relationship between THRIVE score and outcome is not influenced by either success of recanalization or the type of device used (Trevo versus Merci). The superiority of the Trevo device to the Merci device is evident particularly among patients with a low-to-moderate THRIVE score (0–5; 53.8% good outcome with Trevo versus 27.5% good outcome with Merci). In receiver operating characteristic curve analysis, the THRIVE score was comparable or superior to several other outcome prediction scores (HIAT, HIAT-2, SPAN-100, and iScore). Conclusions— The THRIVE score strongly predicts clinical outcome and mortality in the TREVO-2 trial. Taken together with THRIVE validation data from patients receiving intravenous tissue-type plasminogen activator or no acute treatment, the THRIVE score has broad predictive power in patients with acute ischemic stroke, which is likely because THRIVE reflects a set of strong nonmodifiable predictors of stroke outcome. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org .

BACKGROUND External ventricular drains (EVDs) are associated with high rates of infection, and EVD infections cause substantial morbidity and mortality. OBJECTIVE To determine whether the introduction of an evidence-based EVD infection control protocol could reduce the rate of EVD infections. METHODS This was a retrospective analysis of an EVD infection control protocol introduced in a tertiary care neurointensive care unit. We compared rates of cerebrospinal fluid culture positivity and ventriculitis for the 3 years before and 3 years after the introduction of an evidence-based EVD infection control protocol. A total of 262 EVD placements were analyzed, with a total of 2499 catheter-days. RESULTS The rate of cerebrospinal fluid culture positivity decreased from 9.8% (14 of 143; 11.43 per 1000 catheter-days) at baseline to 0.8% (1 of 119; 0.79 per 1000 catheter-days) in the EVD infection control protocol period (P = .001). The rate of ventriculitis decreased from 6.3% (9 of 143; 7.35 per 1000 catheter-days) to 0.8% (1 of 119; 0.79 per 1000 catheter-days; P = .02). CONCLUSION The introduction of a simple, evidence-based infection control protocol was associated with a dramatic reduction in the risk of EVD infection.

Background Statin administration early in ischemic stroke may influence outcomes. Our aim was to determine the clinical impact of increasing statin administration early in ischemic stroke hospitalization. Methods and Results This is a retrospective analysis of a multicenter electronic medical record ( EMR ) intervention to increase early statin administration in ischemic stroke across all 20 hospitals of an integrated healthcare delivery system. A stroke EMR order set was modified from an “opt‐in” to “opt‐out” mode of statin ordering. Outcomes were mortality by 90 days, discharge disposition, and increase in stroke severity. We examined the relationship between intervention and outcome using autoregressive integrated moving average (ARIMA) time‐series modeling. The EMR intervention increased both overall in‐hospital statin administration (from 87.2% to 90.7%, P P P diff ]=0.02, P =0.016) and discharge to home or rehabilitation facility ( P diff =0.04, P =0.034) associated with the intervention. The increase in statin administration P diff =0.17, P =0.033) and rate of discharge to home or rehabilitation ( P diff =0.29, P =0.011), as well as a decreased rate of neurological deterioration in‐hospital ( P diff =−0.14, P =0.026). Conclusions A simple EMR change increased early statin administration in ischemic stroke and was associated with improved clinical outcomes. This is, to our knowledge, the first EMR intervention study to show that a modification of an electronic order set resulted in improved clinical outcomes.

Background The modified Rankin Scale (mRS) is a 6-level outcome scale used to assess level of function in neurological disease. Objective We examined the interobserver reliability and intraobserver reliability of the mRS-9Q, a 9-question "yes/no" survey that measures the mRS score in neurosurgical and neurological patients. Methods The mRS-9Q was administered in person or by telephone, and a Web-based tool was used to calculate the mRS score and to perform error checking. Part 1 compared the mRS-9Q with an mRS structured interview (n = 80). Part 2 compared mRS-9Q administration by telephone and by hard copy (n = 80). Part 3 compared mRS-9Q administration by an expert interviewer with administration by a nonexpert (n = 83). Part 4 examined reproducibility of the mRS-9Q over a 2-week period (n = 84). Results Agreement was very good in all study parts. In Part 1 (mRS-9Q vs mRS with structured interview), κ = 0.80 and κw = 0.96. In Part 2 (mRS-9Q telephone vs hard copy), κ = 0.83 and κw = 0.95. In Part 3 (mRS-9Q expert vs nonexpert), κ = 0.73 and κw = 0.93. In Part 4 (mRS-9Q reproducibility), κ = 0.76 and κw = 0.93. Conclusion The mRS-9Q is a simple, easy-to-administer survey with a custom Web-based mRS calculation and error-checking tool. The mRS-9Q can reliably determine the mRS by hard copy survey or by telephone and can be administered by experts or nonmedical study personnel. The mRS-9Q can be used to measure functional outcome in a broad population of patients with neurosurgical and neurological diseases.

Background We recently developed the Totaled Health Risks In Vascular Events (THRIVE) score to predict outcomes after endovascular stroke treatment. The THRIVE score, which incorporates age, National Institutes of Health Stroke Scale score, and three medical comorbidities (hypertension, diabetes mellitus, and atrial fibrillation), was developed using data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Aims We set out to perform external validation of the THRIVE score using data from the largest registry of endovascular stroke treatment performed to date, the Merci Registry. Methods We compared the performance of the THRIVE score in two different data sets: the development cohort (the MERCI and Multi MERCI trials, n = 305) and a validation cohort (the Merci Registry, a prospective multicenter registry of patients undergoing endovascular stroke treatment, n = 1000). We examined the predictive utility of the THRIVE score across the range of clinical outcomes and used receiver–operator characteristics curve analysis to compare score performance in the two data sets. Results The THRIVE score predicted good outcome, death, and the full range of the modified Rankin Scale in a similar fashion between the MERCI trials and the Merci Registry. Receiver–operator characteristics curve comparisons showed no statistically significant difference in the performance of the THRIVE score between the two data sets: for good outcome, the receiver–operator characteristics area under the curve was 0.293 for the MERCI trials and 0.266 for the Merci Registry ( P = 0.47) and for death, the receiver–operator characteristics area under the curve was 0.692 for the MERCI trials and 0.717 for the Merci Registry ( P = 0.48). The THRIVE score and vessel recanalization were also found to be independent and unrelated predictors of clinical outcome. Conclusions The THRIVE score reliably predicts outcomes after endovascular stroke treatment and may be useful as a clinical prognostic tool and to perform severity adjustments in stroke clinical research.

Background and Purpose— Statins reduce infarct size in animal models of stroke and have been hypothesized to improve clinical outcomes after ischemic stroke. We examined the relationship between statin use before and during stroke hospitalization and poststroke survival. Methods— We analyzed records from 12 689 patients admitted with ischemic stroke to any of 17 hospitals in a large integrated healthcare delivery system between January 2000 and December 2007. We used multivariable survival analysis and grouped-treatment analysis, an instrumental variable method that uses treatment differences between facilities to avoid individual patient-level confounding. Results— Statin use before ischemic stroke hospitalization was associated with improved survival (hazard ratio, 0.85; 95% CI, 0.79–0.93; P P P 60 mg/day) statin use (hazard ratio, 0.43; 95% CI, 0.34–0.53; P P P Conclusions— Statin use early in stroke hospitalization is strongly associated with improved poststroke survival, and statin withdrawal in the hospital, even for a brief period, is associated with worsened survival.

An acute subdural hematoma (SDH) requiring surgical intervention is treated with craniotomy or craniectomy, in part because it is generally accepted that coagulated blood present in the acute phase cannot be adequately evacuated by less-invasive means such as bur hole drainage. However, a hyperacute SDH in the first few hours after trauma can have mixed-density components on CT scans that are thought to represent subdural blood that is not yet fully coagulated. The authors report a case in which a hyperacute SDH in a patient receiving antiplatelet therapy was treated with the novel technique of temporizing subdural evacuation port system (SEPS) placement. Placement of an SEPS in the intensive care unit allowed for rapid surgical treatment of the patient's elevated intracranial pressure (ICP) by drainage of 70 ml of fresh subdural blood. After initial SEPS-induced stabilization, the patient underwent operative treatment of the SDH by craniotomy. The combined approach of emergency SEPS placement followed by craniotomy resulted in a dramatic recovery, with improvement from coma and extensor posturing to a normal status on neurological evaluation 5 weeks later. In appropriately selected cases, patients with a hyperacute SDH may benefit from SEPS placement to quickly treat elevated ICP, as a bridge to definitive surgical treatment by craniotomy.

Chronic hypertension and anticoagulation are important risk factors for the development of intracerebral hemorrhage (ICH). Spontaneous ICH occurring in the Emergency Department (ED) following a normal unenhanced computed tomography (CT) scan of the brain and an acute blood pressure (BP) surge is exceedingly rare and has, to our knowledge, never been reported in the literature.Single case observation in a suburban tertiary care medical center.A neurologically intact 72-year-old man whose BP and neurologic status were monitored during an ED evaluation suddenly became unresponsive following an acute BP surge. A CT of the brain shortly before the episode was normal; following the episode, a repeat CT demonstrated a large right ganglionic ICH.We present a rare case of an elderly man on warfarin who developed a spontaneous ICH during an ED evaluation following an acute BP surge. We propose that the ICH occurred as a result of the BP surge and was contributed to by warfarin anticoagulation.

BACKGROUND AND PURPOSE: Endovascular treatments are being increasingly used in acute ischemic stroke, and better tools are needed to determine which patients may benefit most from these techniques. We hypothesized that specific chronic diseases can be used, along with age and stroke severity, to predict endovascular stroke treatment outcomes. MATERIALS AND METHODS: Data from 2 single-arm trials of a thrombectomy device, MERCI and Multi MERCI, were pooled for analysis. A predictive score was developed by using the independent contribution of variables in multivariable analysis. RESULTS: HTN, DM, and AFib were found to predict outcomes. These 3 conditions contribute equally to a CDS that predicts outcomes independent of other predictor variables, including age, stroke severity, and vessel recanalization. A 10-level predictive score, the THRIVE score, which incorporates age, stroke severity, and the CDS, was developed. The THRIVE score strongly predicts outcome and mortality at 90 days. CONCLUSIONS: Specific chronic diseases influence poststroke outcomes among patients undergoing endovascular stroke treatment, independent of other predictors of outcome. The THRIVE score reflects the contributions of chronic disease, age, and stroke severity and strongly predicts endovascular stroke treatment outcomes.

Background and Purpose Hypertonic saline (3% NaCl) infusions can be used to treat acute neurologic hyponatremia (ANH) in critically ill patients with neurological and neurosurgical disorders such as subarachnoid hemorrhage. Adjustments in the rate of hypertonic saline infusions to treat ANH are needed to achieve a goal sodium range and are usually made on an empiric basis. To date, no data are available to determine how reliably such adjustments achieve stable, normal serum sodium concentrations or how often iatrogenic hypernatremia occurs during the course of treatment with hypertonic saline. Methods We have instituted a standardized sliding-scale hypertonic saline protocol to minimize patient-to-patient variability of hypertonic saline administration and to attempt to achieve safe rates of sodium correction and stable maintenance of serum sodium concentration with minimal overshoot. Here, we present a retrospective analysis of the performance characteristics of our standardized hypertonic saline protocol over a 1-year period, in 49 patients. Results The mean rate of initial sodium correction was 0.44 ± 0.36 (mEq/l)/h. During the maintenance infusion phase, 84.3 ± 17.8% of the time was spent in goal range (Na 136–145 mEq/l), 14.9 ± 18.1% of the time was spent in mild undershoot (Na 130–135 mEq/l), and 0.7 ± 3.1% of the time was spent in overshoot (Na >145 mEq/l). No adverse events attributable to infusion of hypertonic saline were encountered. Conclusion Our hypertonic saline sliding-scale protocol for treatment of ANH can be used reliably and achieves normal sodium concentrations in a safe manner with minimal overshoot.

Primary intraventricular hemorrhage (IVH), bleeding in the ventricular system without a discernable parenchymal component, is a rare neurological disorder. To better define the features of primary IVH and the yield of diagnostic angiography in this condition, we retrospectively analyzed all cases of primary IVH evaluated at a tertiary referral hospital over a 6-year period and performed a systematic review of the literature.For the retrospective case series, all patients with primary IVH admitted to the neurovascular service at a single tertiary referral center over a 6-year period were identified by screening a departmental database. For the systematic review of the literature, all case series of patients with primary IVH diagnosed by computed tomography were identified in the Medline database.From the systematic review, the majority of patients with spontaneous primary IVH presented with headache (69%), nausea/vomiting (53%), and altered mental status (66%). Most primary IVH patients had associated hydrocephalus (62%), and about one-third required ventricular drainage (34%). Diagnostic cerebral angiography was positive for a bleeding source in 56%. The two most common causes identified by angiography were arteriovenous malformations (58% of positive angiograms) and aneurysms (36% of positive angiograms). Approximately one-third of patients with primary IVH do not survive hospital discharge (39%). Patient age and amount of IVH independently predicted in-hospital mortality.Primary IVH is a rare form of intracerebral hemorrhage, with varying short-term outcomes that depend on patient age and the extent of intraventricular hemorrhage. The yield of diagnostic cerebral angiography in the setting of primary IVH is very high. The two most common causes of primary IVH identified on angiography are arteriovenous malformations and aneurysms. Routine catheter angiography in the setting of primary IVH is warranted.

Intracranial hemorrhage in patients with mechanical heart valves carries a risk of thrombosis and of rehemorrhage. Because interruption of anticoagulation with a mechanical heart valve may lead to thrombotic events, cardiologist recommendations generally lean toward minimizing the time off

Introduction: Hematoma expansion (HE) is a cause of excess mortality in intracerebral hemorrhage (ICH), and HE is potentially preventable if at-risk patients can be identified. Contrast extravasation on initial computed tomographic angiography (CTA) strongly predicts HE, yet most centers do not integrate CTA into early ICH management. We therefore asked whether other variables available at presentation might be used to predict HE. Methods: We searched the electronic medical records of a large integrated healthcare delivery system to identify patients with a hospitalization discharge diagnosis of ICH during a three year period (2008-2010). HE was defined as ICH volume increase by 1/3 or by 12.5mL, as determined by ABC/2 estimation, within 48 hours of presentation. Pre-specified patient variables including age, gender, medical comorbidities, medication use, and in-hospital vital signs were extracted. Stepwise multivariable logistic regression was performed to model HE in patients with at least two head CT scans (HE group), and HE or death by 48 hours among patients with only one head CT (HE+D group). The area under the receiver operating characteristic curve (AUROC) and pseudo r-squared (pseudo-r2) statistics were used to assess model goodness-of-fit. Results: For the 2 study cohorts, 91/257 (35%) had HE and 163/343 (48%) had HE+D. In stepwise multivariable logistic regression, antithrombotic use (OR = 1.9, P=0.04) and initial mNIHSS (OR = 1.06, P=0.001) were significant predictors in the HE model (AUROC = 0.6712, pseudo-R2 = 0.0641). In the HE+D model, age (OR = 1.02, P=0.02), initial mNIHSS (OR = 1.07, P Conclusion: Our model predicting HE+D was better fitted than the HE model. The resemblance to known predictors of ICH mortality in the HE+D model suggests that the improved fit may be driven by mortality rather than HE. CTA contrast extravasation remains the strongest predictor of HE and merits consideration as a standard in early ICH care.

The embryonic ventricular zone (VZ) of the cerebral cortex contains migrating neurons, radial glial cells, and a large population of cycling progenitor cells that generate newborn neurons. The latter two cell classes have been assumed for some time to be distinct in both function and anatomy, but the cellular anatomy of the progenitor cell type has remained poorly defined. Several recent reports have raised doubts about the distinction between radial glial and precursor cells by demonstrating that radial glial cells are themselves neuronal progenitor cells (Malatesta et al., 2000; Hartfuss et al., 2001; Miyata et al., 2001; Noctor et al., 2001). This discovery raises the possibility that radial glia and the population of VZ progenitor cells may be one anatomical and functional cell class. Such a hypothesis predicts that throughout neurogenesis almost all mitotically active VZ cells and a substantial percentage of VZ cells overall are radial glia. We have therefore used various anatomical, immunohistochemical, and electrophysiological techniques to test these predictions. Our data demonstrate that the majority of VZ cells, and nearly all mitotically active VZ cells during neurogenesis, both have radial glial morphology and express radial glial markers. In addition, intracellular dye filling of electrophysiologically characterized progenitor cells in the VZ demonstrates that these cells have the morphology of radial glia. Because the vast majority cycling cells in the cortical VZ have characteristics of radial glia, the radial glial precursor cell may be responsible for both the production of newborn neurons and the guidance of daughter neurons to their destinations in the developing cortex.

Background: It is difficult to assess volume status in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The euvolemic state (dry weight) in ESRD patients is determined clinically but has limitations. We hypothesized that a combination of ventricular interdependence (VI)_the physiologic phenomenon whereby filling of one ventricle is affected by filling of the contralateral ventricle during different phases of the respiratory cycle_and inferior vena cava diameter (IVCd) predicts volume status in ESRD patients undergoing HD. Methods: Echocardiograms were performed in 20 patients immediately pre- and post-HD. Clinical assessment of volume status was performed by a single nephrologist blinded to echocardiographic data. VI was defined as peak expiratory to inspiratory mitral inflow E velocity ratio. Hypovolemia was defined as IVCd 20 mm and VI >15%. Results: 65% of patients were men, and 60% had a history of heart failure. A total of 40 volume clinical assessments were performed (20 pre- and 20 post-HD): 23 were categorized as hypovolemic, 5 euvolemic, and 12 hypervolemic. 21 of 23 (91%) hypovolemic assessments met echo definition for hypovolemia. None of 5 (0%) euvolemic assessments met echo definition of euvolemia. 12 of 12 (100%) hypervolemic assessments met echo definition of hypervolemia. (Figure. Columns and error bars represent mean +/- standard error of mean. P=0.007, Kruskal-Wallis equality-of-populations rank test.) Conclusions: In ESRD patients undergoing HD, echocardiographic definition of volume status using IVCd and VI accurately predicts hypo- and hypervolemia. There was poor correlation between echo and clinical volume assessment for euvolemia. This is the first study to examine volume status in HD patients with concomitant cardiac disease using IVCd, and VI. Further studies are needed to determine whether clinical or echo assessment of euvolemia is accurate.

Background Hematoma expansion confers excess mortality in intracerebral haemorrhage, and is potentially preventable if at-risk patients can be identified. Contrast extravasation on initial computed tomographic angiography strongly predicts hematoma expansion but is not very sensitive, and most centers have not yet integrated computed tomographic angiography into acute intracerebral haemorrhage management. We therefore asked whether other presentation variables can predict hematoma expansion. Methods We searched the electronic medical records of a large integrated healthcare delivery system to identify patients with a hospitalization discharge diagnosis of intracerebral haemorrhage between the years 2008 and 2010. Hematoma expansion was defined as radiographic increase by 1/3 or by 12·5 ml within 48 h of presentation. Pre-specified patient demographic and clinical presentation variables were extracted. Stepwise multivariable logistic regression was performed to model hematoma expansion. Because some patients may have died from hematoma expansion without a second head computed tomography, we constructed a separate model including patients that died without a second head computed tomography in 48 h, hematoma expansion or death. Results Ninety-one of 257 patients (35%) had hematoma expansion. Antithrombotic use (odds ratio = 1·9, P = 0·04) and initial mNIHSS (modified National Institutes of Health Stroke Scale; odds ratio = 1·06, P = 0·001) were significant predictors in the hematoma expansion model (area under the Receiver–Operator Characteristics curve, AUROC = 0·6712, pseudo- r2 = 0·0641). 163 of 343 patients (48%) had hematoma expansion or death. Age (odds ratio = 1·02, P = 0·02), initial mNIHSS (odds ratio = 1·07, P < 0·001), and initial hematoma volume (odds ratio = 1·01, P = 0·03) were significant predictors of hematoma expansion or death (AUROC = 0·7579, pseudo- r2 = 0·1722). Conclusion Clinical and noncontrast radiographic variables only weakly predict hematoma expansion. Examination of other indicators, such as computed tomographic angiography contrast extravasation (the ‘spot sign’), may prove more valuable in acute intracerebral haemorrhage care.

Background The Totaled Health Risks in Vascular Events (THRIVE) score strongly predicts clinical outcome, mortality, and risk of thrombolytic haemorrhage in ischemic stroke patients, and performs similarly well in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute treatment. It is not known if the THRIVE score predicts outcomes with the Solitaire endovascular stroke treatment device. Aims To validate the relationship between the THRIVE score and outcomes after treatment with the Solitaire endovascular stroke treatment device. Methods The study conducted a retrospective analysis of the prospective SWIFT and STAR trials to examine the relationship between THRIVE and outcomes after treatment with the Solitaire device. We examined the relationship between THRIVE and clinical outcomes (good outcome or death at 90 days) among patients in SWIFT and STAR. Receiver-operator characteristics curve analysis was used to compare THRIVE score performance with other stroke prediction scores. Multivariable modeling was used to confirm the independence of the THRIVE score from procedure-specific predictors (successful recanalization or device used) and other predictors of functional outcome. Results The THRIVE score strongly predicts good outcome and death among patients treated with the Solitaire device in SWIFT and STAR (Mantel-Haenszel chi-square test for trend P < 0·001 for good outcome, P = 0·01 for death). In receiver-operator characteristics (ROC) curve comparisons, totaled health risks in vascular events score is superior to Stroke Prognostication using Age and NIH Stroke Scale score-100 ( P < 0·001) and performed similarly to Houston Intra-Arterial Therapy score (HIAT) ( P = 0·98) and HIAT-2 ( P = 0·54). In multivariable models, THRIVE's prediction of good outcome is not altered after controlling for recanalization or after controlling for device used. The THRIVE score remains a strong independent predictor after controlling for the above predictors together with time to procedure, rate of symptomatic haemorrhage, and use of general anesthesia. Of note, use of general anesthesia was not an independent predictor of outcome in SWIFT + STAR after controlling for totaled health risks in vascular events and other factors. Conclusions The THRIVE score strongly predicts clinical outcome and mortality in patients treated with the Solitaire device in the SWIFT and STAR trials. The lack of interaction between THRIVE and procedure-specific elements such as vessel recanalization or device choice makes the THRIVE score a reasonable candidate for use as a patient selection criterion in stroke clinical trials.

NMDA receptors play important roles in learning and memory and in sculpting neural connections during development. After the period of peak cortical plasticity, NMDA receptor-mediated EPSCs (NMDAR EPSCs) decrease in duration. A likely mechanism for this change in NMDA receptor properties is the molecular alteration of NMDA receptor structure by regulation of NMDA receptor subunit gene expression. The four modulatory NMDAR2A–D (NR2A–D) NMDA receptor subunits are known to alter NMDA receptor properties, and the expression of these subunits is regulated developmentally. It is unclear, however, how the four NR2 subunits are expressed in individual neurons and which NR2 subunits are important to the regulation of NMDA receptor properties during developmentin vivo. Analysis of NR2 subunit gene expression in single characterized neurons of postnatal neocortex revealed that cells expressing NR2A subunit mRNA had faster NMDAR EPSCs than cells not expressing this subunit, regardless of postnatal age. Expression of NR2A subunit mRNA in cortical neurons at even low levels seemed sufficient to alter the NMDA receptor time course. The proportion of cells expressing NR2A and displaying fast NMDAR EPSCs increased developmentally, thus providing a molecular basis for the developmental change in mean NMDAR EPSC duration.