Epidural anesthesia causes outbreak of mycotic aneurysms: complications of Fusarium solani meningitis.

BACKGROUND: A health advisory was issued in response to a fungal meningitis outbreak linked to epidural anesthesia exposure in two plastic surgery clinics in Mexico, from January 1 to May 13, 2023. This descriptive analysis describes the neuroendovascular and neurosurgical observations and management of patients treated at a single stroke center located along the US-Mexico Border. METHODS: We conducted a retrospective chart review of fungal meningitis patients presenting between April and July 2023. RESULTS: Among the patients diagnosed with fungal meningitis (n=12), the majority (n=11) were afflicted with angio-invasive Fusarium solani. 83% received dual antifungal therapy, with 40% initiated on alternate-day intrathecal amphotericin B. Diagnostic cerebral angiography was performed on all patients, revealing aneurysms in 58% of cases, predominantly within the posterior circulation, notably the basilar artery, with a median size of 4.2 mm (IQR 3.3-4.8). Treatment strategies included flow diversion (70%) and primary coiling (14%) for aneurysms. Ventriculostomy placement was undertaken in 67% of patients, with 37.5% of these requiring conversion to ventriculoperitoneal shunts. Subarachnoid hemorrhage development was uniformly associated with 100% mortality. CONCLUSIONS: In patients presenting with Fusarium solani meningitis, weekly angiographic surveillance proved instrumental for monitoring aneurysm and vasospasm development. Conventional angiography outperformed CT angiography due to its enhanced ability to detect small aneurysms. A proactive approach to aneurysm treatment is advocated, given their elevated rupture risk. While our findings suggest the potential reversibility of angiographic vasospasm with effective antifungal treatment, we acknowledge the challenge of drawing definitive conclusions based on a limited sample size.

Identifying how GPs spend their time and the obstacles they face: a mixed-methods study.

BACKGROUND: Although problems that impair task completion - known as operational failures - are an important focus of concern in primary care, they have remained little studied. AIM: To quantify the time GPs spend on different activities during clinical sessions; to identify the number of operational failures they encounter; and to characterise the nature of operational failures and their impact for GPs. DESIGN AND SETTING: Mixed-method triangulation study with 61 GPs in 28 NHS general practices in England from December 2018 to December 2019. METHOD: Time-motion methods, ethnographic observations, and interviews were used. RESULTS: Time-motion data on 7679 GP tasks during 238 hours of practice in 61 clinical sessions suggested that operational failures were responsible for around 5.0% (95% confidence interval [CI] = 4.5% to 5.4%) of all tasks undertaken by GPs and accounted for 3.9% (95% CI = 3.2% to 4.5%) of clinical time. However, qualitative data showed that time-motion methods, which depend on pre-programmed categories, substantially underestimated operational failures. Qualitative data also enabled further characterisation of operational failures, extending beyond those measured directly in the time-motion data (for example, interruptions, deficits in equipment/supplies, and technology) to include problems linked to GPs' coordination role and weaknesses in work systems and processes. The impacts of operational failures were highly consequential for GPs' experiences of work. CONCLUSION: GPs experience frequent operational failures, disrupting patient care, impairing experiences of work, and imposing burden in an already pressurised system. This better understanding of the nature and impact of operational failures allows for identification of targets for improvement and indicates the need for coordinated action to support GPs.

Augmented reality enhanced tele-proctoring platform to intraoperatively support a neuro-endovascular surgery fellow.

BACKGROUND: Remote tele-proctoring has been conducted in neuro-endovascular surgery, however, evidence to support its use in the fellowship training is limited. We demonstrate a novel augmented reality tele-proctoring platform to enable a remote attending to guide a fellow. METHODS: A consecutive series of neuro-endovascular cases were performed by a neuro-endovascular fellow with remote guidance from an attending surgeon. The fellow and attending were connected using a commercially available cloud-based platform designed to capture and stream up to four live video feeds from a clinical environment to a remote user. In this setting, two video streams were obtained directly from the anteroposterior and lateral cameras on the biplane. Additional video of the operator from a telescopic camera was streamed live to the remote attending surgeon. The attending could provide immediate vocal feedback and also deploy the platform's augmented reality tools to communicate with the fellow in the angiography suite. RESULTS: A total of 10 cases were performed on eight patients utilizing the cloud-based tele-proctoring platform to facilitate instruction. The series included diagnostic angiograms and interventions such as intracranial balloon angioplasty, carotid stenting, and intracranial stenting. All cases were a technical success. No complications or deaths occurred. When compared to similar cohort of 10 cases prior to these which utilized a traditional instruction paradigm; we saw no differences in contrast use (p = 0.38), fluoroscopy time (p = 0.85), or technical success. CONCLUSIONS: This study demonstrates successful use of an augmented reality tele-proctoring platform to guide a neuro-endovascular fellow through complex neuro-interventional procedures from a remote setting.

Measuring Burden of Illness in Phenylketonuria (PKU): Development of the PKU Symptom Severity and Impacts Scale as a Robust Patient-Reported Outcome.

INTRODUCTION: Phenylketonuria (PKU) is a rare, metabolic genetic disorder that can cause various neuropsychological symptoms that often affect patients' health-related quality of life, even for patients with good metabolic control. To date, no patient-reported outcomes (PRO) instrument combines the measurement of neuropsychological and dietary concepts to capture the broad impact of PKU on quality of life. This article presents the development of the PKU Symptom Severity and Impacts Scale (PKU-SSIS), a PRO instrument that is designed to evaluate neuropsychological symptoms and impacts in early-treated patients with PKU. METHODS: A draft instrument was developed based on a targeted literature review, PKU expert physician interviews, and an advisory board consisting of patients with PKU. Qualitative interviews combining concept elicitation/cognitive interviews were conducted with patients with classic PKU aged at least 15 years old. A separate sample of 20 patients with PKU completed the draft PKU-SSIS in a paper survey format, to enable preliminary assessment of any floor and ceiling effects. RESULTS: Patient interviews elicited four key symptom themes: neurocognitive function, emotional and behavioral, physical functioning, and physical health. Four impact themes were also identified: social function, physical health, emotions, and level of independence. No floor or ceiling effects were identified. CONCLUSION: The final instrument included 22 items, covering three symptom domains (1. emotional, mood, and psychological; 2. (neuro)cognitive, executive, and intellectual function; and 3. physical health), and four impact domains (1. social relations, 2. level of independence, 3. general well-being, and 4. self-care). The PKU-SSIS will help to address an important gap in the evaluation of existing and future treatments for PKU.

Operational failures and how they influence the work of GPs: a qualitative study in primary care.

BACKGROUND: Operational failures, defined as inadequacies or errors in the information, supplies, or equipment needed for patient care, are known to be highly consequential in hospital environments. Despite their likely relevance for GPs' experiences of work, they remain under-explored in primary care. AIM: To identify operational failures in the primary care work environment and to examine how they influence GPs' work. DESIGN AND SETTING: Qualitative interview study in the East of England. METHOD: Semi-structured interviews were conducted with GPs (n = 21). Data analysis was based on the constant comparison method. RESULTS: GPs reported a large burden of operational failures, many of them related to information transfer with external healthcare providers, practice technology, and organisation of work within practices. Faced with operational failures, GPs undertook 'compensatory labour' to fulfil their duties of coordinating and safeguarding patients' care. Dealing with operational failures imposed significant additional strain in the context of already stretched daily schedules, but this work remained largely invisible. In part, this was because GPs acted to fix problems in the here-and-now rather than referring them to source, and they characteristically did not report operational failures at system level. They also identified challenges in making process improvements at practice level, including medicolegal uncertainties about delegation. CONCLUSION: Operational failures in primary care matter for GPs and their experience of work. Compensatory labour is burdensome with an unintended consequence of rendering these failures largely invisible. Recognition of the significance of operational failures should stimulate efforts to make the primary care work environment more attractive.

A qualitative study of design stakeholders' views of developing and implementing a registry-based learning health system.

BACKGROUND: New opportunities to record, collate, and analyze routine patient data have prompted optimism about the potential of learning health systems. However, real-life examples of such systems remain rare and few have been exposed to study. We aimed to examine the views of design stakeholders on designing and implementing a US-based registry-enabled care and learning system for cystic fibrosis (RCLS-CF). METHODS: We conducted a two-phase qualitative study with stakeholders involved in designing, implementing, and using the RCLS-CF. First, we conducted semi-structured interviews with 19 program personnels involved in design and delivery of the program. We then undertook 11 follow-up interviews. Analysis of interviews was based on the constant comparative method, supported by NVivo software. RESULTS: The organizing principle for the RCLS-CF was a shift to more partnership-based relationships between patients and clinicians, founded in values of co-production, and facilitated by technology-enabled data sharing. Participants proposed that, for the system to be successful, the data it collects must be both clinically useful and meaningful to patients and clinicians. They suggested that the prerequisites included a technological infrastructure capable of supporting data entry and joint decision-making in an accessible way, and a set of social conditions, including willingness from patients and clinicians alike to work together in new ways that build on the expertise of both parties. Follow-up interviews highlighted some of the obstacles, including technical challenges and practical constraints on refiguring relationships between clinicians and patients. CONCLUSIONS: The values and vision underlying the RCLS-CF were shared and clearly and consistently articulated by design stakeholders. The challenges to realization were often not at the level of principle, but were both practical and social in character. Lessons from this study may be useful to other systems looking to harness the power of "big data" registries, including patient-reported data, for care, research, and quality improvement.

Impacts of Operational Failures on Primary Care Physicians' Work: A Critical Interpretive Synthesis of the Literature.

PURPOSE: Operational failures are system-level errors in the supply of information, equipment, and materials to health care personnel. We aimed to review and synthesize the research literature to determine how operational failures in primary care affect the work of primary care physicians. METHODS: We conducted a critical interpretive synthesis. We searched 7 databases for papers published in English from database inception until October 2017 for primary research of any design that addressed problems interfering with primary care physicians' work. All potentially eligible titles/abstracts were screened by 1 reviewer; 30% were subject to second screening. We conducted an iterative critique, analysis, and synthesis of included studies. RESULTS: Our search retrieved 8,544 unique citations. Though no paper explicitly referred to "operational failures," we identified 95 papers that conformed to our general definition. The included studies show a gap between what physicians perceived they should be doing and what they were doing, which was strongly linked to operational failures-including those relating to technology, information, and coordination-over which physicians often had limited control. Operational failures actively configured physicians' work by requiring significant compensatory labor to deliver the goals of care. This labor was typically unaccounted for in scheduling or reward systems and had adverse consequences for physician and patient experience. CONCLUSIONS: Primary care physicians' efforts to compensate for suboptimal work systems are often concealed, risking an incomplete picture of the work they do and problems they routinely face. Future research must identify which operational failures are highest impact and tractable to improvement.

Worldwide Organization of Neurocritical Care: Results from the PRINCE Study Part 1.

INTRODUCTION: Neurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study). METHODS: In this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal-Wallis test followed by the Dunn procedure to test for differences in practices among world regions. RESULTS: We analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority of respondents reported having a dedicated neuro-ICU (67% overall; highest in North America: 82%; and lowest in Oceania: 14%). CONCLUSION: The PRINCE Study results suggest that there is significant variability in the delivery of neurocritical care. The study also shows it is feasible to undertake international collaborations to gather global data about the practice of neurocritical care.

Global Survey of Outcomes of Neurocritical Care Patients: Analysis of the PRINCE Study Part 2.

BACKGROUND: Neurocritical care is devoted to the care of critically ill patients with acute neurological or neurosurgical emergencies. There is limited information regarding epidemiological data, disease characteristics, variability of clinical care, and in-hospital mortality of neurocritically ill patients worldwide. We addressed these issues in the Point PRevalence In Neurocritical CarE (PRINCE) study, a prospective, cross-sectional, observational study. METHODS: We recruited patients from various intensive care units (ICUs) admitted on a pre-specified date, and the investigators recorded specific clinical care activities they performed on the subjects during their first 7 days of admission or discharge (whichever came first) from their ICUs and at hospital discharge. In this manuscript, we analyzed the final data set of the study that included patient admission characteristics, disease type and severity, ICU resources, ICU and hospital length of stay, and in-hospital mortality. We present descriptive statistics to summarize data from the case report form. We tested differences between geographically grouped data using parametric and nonparametric testing as appropriate. We used a multivariable logistic regression model to evaluate factors associated with in-hospital mortality. RESULTS: We analyzed data from 1545 patients admitted to 147 participating sites from 31 countries of which most were from North America (69%, N = 1063). Globally, there was variability in patient characteristics, admission diagnosis, ICU treatment team and resource allocation, and in-hospital mortality. Seventy-three percent of the participating centers were academic, and the most common admitting diagnosis was subarachnoid hemorrhage (13%). The majority of patients were male (59%), a half of whom had at least two comorbidities, and median Glasgow Coma Scale (GCS) of 13. Factors associated with in-hospital mortality included age (OR 1.03; 95% CI, 1.02 to 1.04); lower GCS (OR 1.20; 95% CI, 1.14 to 1.16 for every point reduction in GCS); pupillary reactivity (OR 1.8; 95% CI, 1.09 to 3.23 for bilateral unreactive pupils); admission source (emergency room versus direct admission [OR 2.2; 95% CI, 1.3 to 3.75]; admission from a general ward versus direct admission [OR 5.85; 95% CI, 2.75 to 12.45; and admission from another ICU versus direct admission [OR 3.34; 95% CI, 1.27 to 8.8]); and the absence of a dedicated neurocritical care unit (NCCU) (OR 1.7; 95% CI, 1.04 to 2.47). CONCLUSION: PRINCE is the first study to evaluate care patterns of neurocritical patients worldwide. The data suggest that there is a wide variability in clinical care resources and patient characteristics. Neurological severity of illness and the absence of a dedicated NCCU are independent predictors of in-patient mortality.

Coproducing healthcare service improvement for people with common mental health disorders including psychotic experiences: a study protocol of a multiperspective qualitative study.

INTRODUCTION: Some people, who have common mental health disorders such as depression and anxiety, also have some psychotic experiences. These individuals may experience a treatment gap: their symptoms neither reach the increasingly high threshold for secondary care, nor do they receive full benefit from current interventions offered by the Improving Access to Psychological Therapies (IAPT) programme. The result may be poorer clinical and functional outcomes. A new talking therapy could potentially benefit this group. Informed by principles of coproduction, this study will seek the views of service users and staff to inform the design and development of such a therapy. METHODS AND ANALYSIS: Semistructured interviews will be conducted with IAPT service users, therapists and managers based in three different geographical areas in England. Our sample will include (1) approximately 15 service users who will be receiving therapy or will have completed therapy at the time of recruitment, (2) approximately 15 service users who initiated treatment but withdrew, (3) approximately 15 therapists each with at least 4-month experience in a step-3 IAPT setting and (4) three IAPT managers. Data analysis will be based on the constant comparative method. ETHICS AND DISSEMINATION: The study has been approved by the London Harrow Research Ethics Committee (reference: 18/LO/0642), and all National Health Service Trusts have granted permissions to conduct the study. Findings will be published in peer-reviewed academic journals, and presented at academic conferences. We will also produce a 'digest' summary of the findings, which will be accessible, visual and freely available.

Therapeutic Benefit of Cilostazol in Patients with Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized and Nonrandomized Studies.

OBJECTIVE: To assess the effectiveness of cilostazol, a selective inhibitor of phosphodiesterase type III, in preventing cerebral ischemia related to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). METHODS: A total of six clinical studies met the inclusion criteria and were included in the meta-analysis. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. The primary endpoint was cerebral ischemia related to vasospasm. Secondary endpoints were angiographic vasospasm, new cerebral infarct, mortality, and death or disability at the final follow-up. RESULTS: A total of 136 (22%) of 618 subjects (38 and 98 assigned to cilostazol and control treatments, respectively) with SAH developed cerebral ischemia related to vasospasm. The risk of cerebral ischemia related to vasospasm was significantly lower in subjects assigned to cilostazol treatment (RR 0.43; 95% CI 0.31-0.60; p< 0.001). The risks of angiographic vasospasm (RR 0.67, 95% CI 0.54-0.84, p< 0.001 ) and new cerebral infarct (RR 0.37, 95% CI 0.24-0.57, p< 0.001) were significantly lower in subjects assigned to cilostazol treatment. There was a significantly lower rate of death or disability in subjects assigned to cilostazol treatment at follow-up (PR 0.55, 95% 0.39-0.78, p = 0.001). CONCLUSION: The reduction in rates of cerebral ischemia related to vasospasm and death or disability at follow-up support further evaluation of oral cilostazol in patients with aneurysmal SAH in a large randomized clinical trial.

The Experience of Transitional Care for Non-Medically Complex Older Adults and Their Family Caregivers.

Transitional care research has mainly focused on the experiences of older adults with complex medical conditions. To date, few publications examine the experience of transitional care for non-medically complex older adults. In this article, we draw on and thematically analyze interview and audio-diary data collected at three hospitals in Eastern England, and we explore the experience of transitional care of 18 older adults and family caregivers. Participants reported mixed experiences when describing their care transitions, which indicated variations in care quality. To achieve independence and overcome the difficulties with care transitions, participants used a range of interrogative techniques, such as questioning and information seeking. We contend that the existing transitional care interventions are inappropriate to address the care needs of non-medically complex older adults and family caregivers. Implications for frontline health care staff and health services researchers are discussed.

Human Albumin Use in Adults in U.S. Academic Medical Centers.

OBJECTIVE: To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. DESIGN: Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. SETTING: One hundred twenty academic medical centers and 299 affiliated hospitals. PATIENTS: A total of 12,366,264 hospitalization records. INTERVENTIONS: Analysis of rates and predictors of albumin administration, and estimated costs. MEASUREMENTS AND MAIN RESULTS: Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30-1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26-3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459-68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889-7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825-9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001. CONCLUSIONS: The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.

Multidisciplinary protocol for rapid head computed tomography turnaround time in acute stroke patients.

BACKGROUND: The door-to-computed tomography (CT) head reporting time is an essential step to determining eligibility for thrombolysis in acute stroke patients, but the specific components of the process have not been reported in detail. METHODS: We performed a retrospective cross-sectional analysis of the prospectively collected Get-With-The-Guidelines database in our comprehensive stroke center to evaluate the effect of a structured multidisciplinary protocol on head CT times in acute stroke patients under consideration for thrombolysis. RESULTS: The median CT turnaround time in the first 6-month period was 27 (interquartile range [IQR], 27) and decreased in all subsequent periods after implementation of a formal protocol to 18 (IQR, 12; range, 17-20 minutes; P < .0001 for all pairwise comparisons). The median CT turnaround time was 18 (IQR, 12) versus 20 (IQR, 14) minutes for patients with admission diagnosis of stroke (n = 1123) versus nonstroke (n = 685; P < .0001), respectively. CONCLUSIONS: A structured multidisciplinary protocol for obtaining acute stroke protocol head CT scan was associated with reduced CT turnaround time over the study period. Prospective studies should be done to determine if implementation in other stroke centers confirms the effectiveness of our protocol.

Multi-modality neuro-monitoring: conventional clinical trial design.

Multi-modal monitoring has become an integral part of neurointensive care. However, our approach is at this time neither standardized nor backed by data from randomized controlled trials. The goal of the second Neurocritical Care Research Conference was to discuss research priorities in multi-modal monitoring, what research tools are available, as well as the latest advances in clinical trial design. This section of the meeting was focused on how such a trial should be designed so as to maximize yield and avoid mistakes of the past.

Human albumin administration in subarachnoid hemorrhage: results of an international survey.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a devastating disease. Nimodipine is the only medical treatment shown to improve outcome of SAH patients. Human albumin (ALB) may exert neuroprotection in SAH. However, current usage of ALB in SAH is not known. We conducted an international survey of clinicians involved in the care of SAH patients to determine current practice of ALB administration in SAH. METHODS: We constructed a 27-question survey. Our sampling frame consisted of neurointensivists, general intensivists, neurocritical care nurses, critical care pharmacists, and neurosurgeons. The survey was available from 11/15/2012 to 12/15/2012. We performed mostly descriptive statistical analysis. RESULTS: We obtained 362 responses from a diverse range of world regions. Most respondents were intensivist physicians (88 %), who worked in academic institutions (73.5 %) with a bed capacity >500 (64.1 %) and an established institutional management protocol for SAH patients (70.2 %). Most respondents (83.5 %) indicated that their institutions do not incorporate ALB in their protocol, but half of them (45.9 %) indicated using ALB outside it. ALB administration is influenced by several factors: geographic variation (more common among US respondents); institutions with a dedicated neuroICU; and availability of SAH management protocol. Most respondents (75 %) indicated that a clinical trial to test the efficacy of ALB in SAH is needed. CONCLUSIONS: In this survey we found that ALB administration in SAH patients is common and influenced by several factors. Majority of respondents support a randomized clinical trial to determine the safety and efficacy of ALB administration in SAH patients.

Aspirin treatment failure and the risk of recurrent stroke and death among patients with ischemic stroke.

BACKGROUND: The prognostic value of occurrence of ischemic stroke in a patient despite aspirin treatment (aspirin treatment failure) is not known. Our objective was to determine if aspirin treatment failure predicts recurrent ischemic stroke and/or death. METHODS: We performed a post-hoc analysis of data from the National Institute of Neurological Disorders and Stroke (NINDS) intravenous recombinant tissue plasminogen activator (rt-PA) trial and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). Multivariate analysis was used to calculate the odds ratio (OR) of recurrent stroke and recurrent stroke or death for aspirin treatment failure patients for the duration of available follow-up (3 months for TOAST patients; 12 months for NINDS rt-PA trial patients). RESULTS: The rate of aspirin treatment failure was 40% and 35% among 1275 patients and 624 patients recruited in the TOAST and NINDS rt-PA trials, respectively. The risk of stroke and death at 3 months and 1 year was not higher among patients classified as aspirin treatment failures among the TOAST (OR 1.1; 95% confidence interval [CI] 0.8-1.6; P = .7) or NINDS rt-PA trial patients (OR 0.8; 95% CI 0.6-1.3; P = .4), respectively. In subgroup analysis, aspirin treatment failure was not found to be associated with recurrent stroke or with the combined endpoint of stroke and death among categories defined by etiologic subtype, including those with large artery atherosclerosis. CONCLUSIONS: In a post-hoc analysis of 2 randomized ischemic stroke trials, aspirin treatment failure was not found to be associated with an increased risk of recurrent stroke or death.

Intra-arterial tenecteplase for treatment of acute ischemic stroke: feasibility and comparative outcomes.

OBJECTIVE: Tenecteplase (TNK) is a third-generation thrombolytic agent. We evaluated the safety and feasibility of intra-arterial (IA) administration of TNK in patients with acute ischemic stroke. METHODS: Patients who received endovascular treatment for acute ischemic stroke were identified from prospectively collected databases at three university hospitals. We compared clinical and radiological outcomes of patients treated with TNK to those treated with other IA thrombolytics or mechanical thrombectomy alone. Primary outcome measures were favorable functional outcome at 30 days (modified Rankin Scale score of 0-2), and rate of intracranial hemorrhage (ICH). Early neurological improvement, angiographic recanalization, time to recanalization, and mortality at 30 days were additional outcome measures. RESULTS: We identified 114 patients (mean age 67 ± 15 years, 54 were women). Thirty-three patients received IA TNK, 48 received alteplase (n = 11) or reteplase (n = 37), and 33 patients had mechanical thrombectomy alone. Stroke severity was similar among the three groups. No difference between the groups was found in the secondary outcome measures and ICH. Borderline statistical significance was seen toward favorable functional outcome at 1 month in the TNK-treated patients [odds ratio (OR) = 2.8; 95% confidence interval (CI) .96-8.1, P = .063 vs. other thrombolytics, and OR = 3.0, 95% CI .97-9.5, P = .06 vs. mechanical thrombectomy alone]. CONCLUSION: Our study demonstrates that administration of IA TNK in acute stroke is safe and results in rates of favorable outcomes that are comparable to those observed with currently used drugs. Additional studies are needed to further determine the safety and efficacy of IA TNK in acute stroke treatment.

Estimated prevalence of acoustic cranial windows and intracranial stenosis in the US elderly population: ultrasound screening in adults for intracranial disease study.

BACKGROUND: Intracranial atherosclerosis is an important etiology of stroke in the USA, but its prevalence in the general population remains unknown. This study was performed to determine the feasibility of transcranial Doppler ultrasound (TCD) for general population screening and to estimate the prevalence of intracranial stenosis in the USA. METHODS: We used a public database to randomly select 99 subjects aged 65-84 years residing in a well-defined geographic area. For all subjects clinical history was reviewed, blood pressure was recorded and TCD examination was performed to identify intracranial stenosis. RESULTS: The mean age of subjects was 72 years, 42 were men, and 17 were African-Americans. All acoustic windows were present in 77 subjects. After multivariate adjustment, the odds of absence of a bone window were higher in African-Americans [odds ratio (OR) 6.0, 95% confidence interval (CI) 1.8-2.0], nonsmokers (OR 3.1, 95% CI 1.0-9) and those with a high BMI (9% higher odds per index point). Among 77 subjects who had all acoustic windows present, intracranial stenosis of >50% was identified in 6.5%, and intracranial stenosis of any severity was identified in 16% of the persons. Intracranial stenosis was most prevalent in the middle cerebral artery (6%). CONCLUSION: Presence of acoustic windows is associated with vascular risk factors. Based on the high prevalence of significant intracranial stenosis in the US elderly population, it is feasible and important to perform a large-scale population-based study for this disease entity.

Intravenous recombinant tissue plasminogen activator administered after 3 h following onset of ischaemic stroke: a metaanalysis.

OBJECTIVE: To assess the efficacy of intravenous recombinant tissue plasminogen activator administered after 3 h following onset of ischaemic stroke. BACKGROUND: Some recent data indicate that treatment with intravenous recombinant tissue plasminogen activator may be beneficial even when administered to ischaemic stroke patients beyond 3 h from symptom onset. METHODS: We searched the medical literature using the MEDLINE, BIOSIS, and Cochrane databases for pertinent publications from 1966 to 2008 using the keywords 'alteplase', 'tissue plasminogen activator', and 'stroke'. Among the retrieved publications, we selected randomised controlled trials that administered recombinant tissue plasminogen activator during 3-6 h after symptom onset in patients with acute ischaemic stroke. We evaluated the effect of intravenous recombinant tissue plasminogen activator (compared with placebo) on the rate of good functional outcome (determined by modified Rankin Scale of 0-1) and mortality at three-months. A subset analysis was performed according to time of administration of intravenous recombinant tissue plasminogen activator (3-4·5 and 4·5-6 h). Odds ratios of individual trials were pooled using a random effects model. RESULTS: We analysed four randomised trials totaling 2104 patients (1053 control and 1051 recombinant tissue plasminogen activator-treated patients). Patients that received intravenous recombinant tissue plasminogen activator at 3-6 h following onset of symptoms had a significantly higher rate of favourable neurological outcome over the patients that received placebo (odds ratio 1·24, 95% confidence intervals 1·04-1·47, P=0·02). Treatment within the 3-4·5 time window was significantly associated with higher rate of favourable neurological outcome (OR 1·27, 95% confidence interval 1·01-1·60), but not for the 4·5-6 time window (OR 1·10, 95% confidence interval 0·75-1·51). There was no difference in mortality between patients that received intravenous recombinant tissue plasminogen activator than the patients that received pharmacologic placebo (OR 1·14, 95% confidence interval 0·76-1·70). CONCLUSIONS: Treatment with intravenous recombinant tissue plasminogen activator from 3-4·5 h following symptom onset is associated with an increased rate of favourable outcome at 90-days in this analysis. Treatment with intravenous recombinant tissue plasminogen activator beyond 4·5 h did not show a benefit; however, improved patient selection is needed for future studies.