Secondary Ischemia Assessment in Murine and Rat Preclinical Subarachnoid Hemorrhage Models: A Systematic Review.

BACKGROUND: Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models. METHODS AND RESULTS: We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used. CONCLUSIONS: Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.

Pre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage: A systematic review of published prediction models with risk of bias and clinical applicability assessment.

BACKGROUND: Pre-treatment rebleeding following aneurysmal subarachnoid hemorrhage (aSAH) increases the risk of death and a poor neurological outcome. Current guidelines recommend aneurysm treatment "as early as feasible after presentation, preferably within 24 h of onset" to mitigate this risk, a practice termed ultra-early treatment. However, ongoing debate regarding whether ultra-early treatment is independently associated with reduced re-bleeding risk, together with the recognition that re-bleeding occurs even in centres practicing ultra-early treatment due to the presence of other risk-factors has resulted in a renewed need for patient-specific re-bleed risk prediction. Here, we systematically review models which seek to provide patient specific predictions of pre-treatment rebleeding risk. METHODS: Following registration on the International prospective register of systematic reviews (PROSPERO) CRD 42023421235; Ovid Medline (Pubmed), Embase and Googlescholar were searched for English language studies between 1st May 2002 and 1st June 2023 describing pre-treatment rebleed prediction models following aSAH in adults ≥18 years. Of 763 unique records, 17 full texts were scrutinised with 5 publications describing 4 models reviewed. We used the semi-automated template of Fernandez-Felix et al. incorporating the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist and the Prediction model Risk Of Bias ASsessment Tool (PROBAST) for data extraction, risk of bias and clinical applicability assessment. To further standardize risk of bias and clinical applicability assessment, we also used the published explanatory notes for the PROBAST tool and compared the aneurysm treatment practices each prediction model's formulation cohort experienced to a prespecified benchmark representative of contemporary aneurysm treatment practices as outlined in recent evidence-based guidelines and published practice pattern reports from four developed countries. RESULTS: Reported model discriminative performance varied between 0.77 and 0.939, however, no single model demonstrated a consistently low risk of bias and low concern for clinical applicability in all domains. Only the score of Darkwah Oppong et al. was formulated using a patient cohort in which the majority of patients were managed in accordance with contemporary, evidence-based aneurysm treatment practices defined by ultra-early and predominantly endovascular treatment. However, this model did not undergo calibration or clinical utility analysis and when applied to an external cohort, its discriminative performance was substantially lower that reported at formulation. CONCLUSIONS: No existing prediction model can be recommended for clinical use in centers practicing contemporary, evidence-based aneurysm treatment. There is a pressing need for improved prediction models to estimate and minimize pre-treatment re-bleeding risk.

A Nationwide Analysis of Aneurysmal Subarachnoid Hemorrhage Mortality, Complications, and Health Economics in the USA.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition. Endovascular coiling or surgical clipping have equivocal success rates, but relatively little is known regarding the health economics and complications of these procedures at the population level. We aimed to analyze the complication profiles and healthcare resource utilization (HRCU) associated with the treatment of aSAH in the USA. We performed a retrospective analysis utilizing the IBM MarketScan database between 2008 and 2015. Primary outcomes included economic analysis stratified by post-operative complication; determination of the effect of several factors on total cost by multivariable regression; and analysis of the incidence, timing, and associated HCRU of aSAH-related post-operative complications. Of the 2374 patients meeting inclusion criteria for economic analysis, 1783 (75.1%) patients had at least one of the ten complications. The most common complications included hydrocephalus (43.8%), transient cerebral ischemia (including vasospasm) (30.6%), ischemic stroke (29.1%), syndrome of inappropriate antidiuretic hormone (SIADH)/hyposmolarity/hyponatremia (22.1%), and seizures (14.9%). Patients who experienced complications had higher median 90-day total costs [$161,127 (Q1 to Q3, $101,411 to $257,662)] than those who did not [$97,376 (Q1 to Q3, $55,692 to $147,447)]. Length of stay was longest for those with pulmonary embolism and pneumonia (27 days) and shortest for those with SIADH/hyposmolarity/hyponatremia (16 days). Brain compression/herniation had the highest mortality rate (19.5%). In total, 14.6% of all patients experienced a readmission within 30 days. In conclusion, patients with aSAH have high post-operative complication rates and costs. Development of novel interventions to reduce complications and improve outcomes is crucial.

Nutritional assessment of patients with aneurysmal subarachnoid hemorrhage using the modified "Nutrition Risk in the Critically Ill" score, and its association with outcomes.

Introduction: Introduction: subarachnoid hemorrhage (SAH) is a rare and life-threatening cerebrovascular disease. Mitigating the factors that compromise patient recovery during neurocritical care due to SAH is of clinical benefit. Objectives: to evaluate the nutritional risk of patients with aneurysmal subarachnoid hemorrhage using "The Modified Nutrition Risk in the Critically Ill" (mNUTRIC) score, and examine its association with outcomes such as mortality, time of mechanical ventilation, and functional status among survivors. Methods: we designed a cross-sectional study. Patients with SAH admitted to the neurointensive critical care unit (neuroICU) in a tertiary care public hospital were eligible. The inclusion criteria were a minimum stay in the intensive care unit (ICU) of 24 hrs for subarachnoid hemorrhage from a nontraumatic, spontaneously ruptured cerebral aneurysm, and hospital admission within 24 hrs after the onset of symptoms. Results: high nutritional risk as stratified by the mNUTRIC score was associated with discharge type (OR = 0.346; 95 % CI = 0.182-0.650; p = 0.001), acute hypertensive hydrocephalus (OR = 4.371; 95 % CI = 2.283-8.549; p < 0.001), and functional outcome (OR = 0.106; 95 % CI = 0.025-0.0388; p < 0.001). The mNUTRIC score was significantly different among median age (p < 0.001), length of stay in the neuroICU (p = 0.005), SOFA score (p < 0.001), and APACHE II score (p < 0.001) categories. Conclusions: this study demonstrated an association between nutritional risk assessment and outcomes such as length of stay in the neuroICU, type of discharge, functional status, and mortality prediction accuracy.

Introducción: Introducción: la hemorragia subaracnoidea es una forma rara de enfermedad cerebrovascular que pone en peligro la vida del paciente. Reducir los factores que comprometen la recuperación de los pacientes durante los cuidados neurocríticos tiene benefício clínico. Objetivo: evaluar el riesgo nutricional de los pacientes con hemorragia subaracnoidea por aneurisma utilizando la puntuación "The Modified Nutrition Risk in the Critically Ill" (mNUTRIC) y su asociación con resultados como la mortalidad, el tiempo de ventilación mecánica y el estado funcional entre los supervivientes. Método: diseñamos un estudio transversal. Fueron elegibles los pacientes con hemorragia subaracnoidea ingresados en la unidad de cuidados críticos neurointensivos (neuroUCI) de un hospital público de atención terciaria. Los criterios de inclusión fueron una permanencia mínima de 24 horas en la UCI, hemorragia subaracnoidea por rotura espontánea no traumática de aneurisma cerebral, e ingreso hospitalario en las 24 horas siguientes al inicio de los síntomas. Resultados: el alto riesgo nutricional estratificado por la puntuación mNUTRIC se asoció con el tipo de alta (OR = 0,346; IC 95 % = 0,182-0,650; p = 0,001), la hidrocefalia hipertensiva aguda (OR = 4,371; IC 95 % = 2,283-8,549; p < 0,001) y el resultado funcional (OR = 0,106; IC 95 % = 0,025-0,0388; p < 0,001). La puntuación mNUTRIC presentó diferencias estadísticamente significativas entre las medianas de edad (p < 0,001), duración de la permanencia en la neuroUCI (p = 0,005), puntuación SOFA (p < 0,001) y puntuación APACHE II (p < 0,001). Conclusión: este estudio demuestra una asociación de la evaluación del riesgo nutricional con resultados como la necesidad de ventilación mecánica, la duración de la permanencia en la neuroUCI, el tipo de alta, el estado funcional y la precisión en la predicción de la mortalidad.

Comparison between rupture/growth risk scores and treatment recommendation scores application to aneurysmal subarachnoid hemorrhage patients: A multicenter cross-reliability assessment study.

BACKGROUND: Two score families were introduced to help clinicians about the decision-making regarding intracranial aneurysms management. The first family estimates the growth/rupture risk (GRS), whereas the second provides straightforward recommendation (RS) for treatment decisions. However, both remain poorly validated and little is known about their agreement. In this paper, we performed a retrospective concordance analysis among the two scores families through their application to a multicenter cohort of SAH patients. METHODS: Demographical, clinical and radiological data were extracted in conformance with the variables included in PHASES, UCAS, ELAPSS, Juvela's growth score (JGS), UIATS and Juvela's treatment score (JTS). Individual patients' score were calculated for both score families, and pooled data were then analyzed. RESULTS: Overall, 146 patients were included. True positive rates were: 51.4% for PHASES; 71.9% for UCAS; between 60.3% and 90.4% for JTS; and between 27.4% and 68.5% for UIATS. In patients showing UIATS unclear recommendation and low JTS score (RS), UCAS outperformed PHASES (GRS) in identifying aneurysms at higher risk of rupture. Same results we found for patients with conservative UIATS recommendation and very low JTS score. Forty-to-sixty percent of aneurysms with unclear or conservative RS recommendation would have been identified as at high risk with GRS. CONCLUSIONS: Retrospectively applied, JTS appeared outperforming UIATS in correctly recommending treatment in a higher percentage of patients. UIATS and JTS appeared agreeing more with UCAS than PHASES predictions. Around 50% of patients with unclear or conservative UIATS/JTS recommendations were been classified as at higher growth risk by ELAPSS and JGS.

Methodological assessment of guidelines for the diagnosis and management of cerebral vasospasm using the AGREE-II tool.

OBJECTIVE: Rupture of an intracranial aneurysm is the most common cause of spontaneous subarachnoid hemorrhage. Despite the recent advances in its early detection, diagnosis, and proper treatment, the outcome of patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) remains poor. It is well known that cerebral vasospasm is the most troublesome complication of aSAH, while delayed cerebral ischemia related to cerebral vasospasm constitutes the major cause of unfavorable outcomes in patients with aSAH. The need for evidence-based guidelines is of great importance for the prevention, early detection, and efficient management of aSAH-induced vasospasm. Moreover, guidelines provide young physicians with a valuable tool for practicing defensible medicine. However, the methodology, clinical applicability, reporting clarity, and biases of guidelines must be periodically assessed. In this study, the authors sought to assess the reporting clarity and methodological quality of published guidelines and recommendations. METHODS: A search was performed in the PubMed, Scopus, and Web of Science databases. The search terms used were "clinical practice guidelines," "recommendations," "stroke," "subarachnoid hemorrhage," and "vasospasm" in all possible combinations. The search period extended from 1964 to September 2021 and was limited to literature published in the English language. All published guidelines and recommendations reporting on the diagnosis and management of vasospasm were included. Studies other than those reporting guidelines and recommendations were excluded. The eligible studies were evaluated by three blinded raters, employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 10 sets of guidelines were evaluated in this study. The American Heart Association/American Stroke Association issued guidelines found to have the highest methodological quality and reporting clarity, followed by the European Stroke Organization guidelines and the English edition of the Japanese guidelines issued by the Japanese Society on Surgery for Cerebral Stroke. The interrater agreement was moderate in the current analysis. CONCLUSIONS: These findings support the idea that improvement of currently existing guidelines is feasible in the following domains: the rigor of guidelines and recommendations development, clinical applicability, editorial independence, and stakeholder involvement. Furthermore, periodic updating of published guidelines requires improvement in the future.

Outcomes after clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage among dual-eligible beneficiaries.

Dual-eligible beneficiaries, individuals with both Medicare and Medicaid coverage, represent a high-cost and vulnerable population; however, literature regarding outcomes is sparse. We characterized outcomes in dual-eligible beneficiaries treated for aneurysmal subarachnoid hemorrhage (aSAH) compared to Medicare only, Medicaid only, private insurance, and self-pay. A 10-year cross-sectional study of the National Inpatient Sample was conducted. Adult aSAH emergency admissions treated by neurosurgical clipping or endovascular coiling were included. Multivariable regression was used to adjust for confounders. A total of 57,666 patients met inclusion criteria. Dual-eligibles comprised 2.8% of admissions and were on average younger (62.4 years) than Medicare (70.0 years), older than all other groups, and had higher mean National Inpatient Sample-Subarachnoid Hemorrhage Severity Scores than all other groups (p ≤ 0.001). Among patients treated by clipping, dual-eligibles were less often discharged to home compared to Medicare (adjusted odds ratio (aOR) = 0.51, 95% CI = 0.30-0.87, p < 0.05) and all other insurance groups, p < 0.01. Likewise, those who received coiling were less often discharged to home compared to Medicaid (aOR = 0.41, 95% CI = 0.23-0.73), private (aOR = 0.42, 95% CI = 0.23-0.76) and self-pay patients (aOR = 0.24, 95% CI = 0.12-0.46). They also had increased odds of poor National Inpatient Sample-Subarachnoid Hemorrhage Outcome Measures compared to Medicaid, private, and self-pay patients, all p < 0.05. There were no differences in inpatient mortality or total complications. In conclusion, dual-eligible patients had higher aSAH severity scores, less often discharged home, and among patients who received coiling, dual-eligibles had increased odds of poor outcome. Dual-eligible patients with aSAH represent a vulnerable population that may benefit from targeted clinical and public policy initiatives.

Trends in Hospital-to-Hospital Transfers for Aneurysmal Subarachnoid Hemorrhage: A Single-Institution Experience from 2006 to 2017.

BACKGROUND: Despite evidence to support that aneurysmal subarachnoid hemorrhage (aSAH) is best treated at high-volume centers, it is unknown whether clinical practice reflects these findings. METHODS: We analyzed patients transferred to our high-volume center for aSAH between 2006 and 2017. Data collection included number of transfers, demographic data, Hunt and Hess score, Fisher score, comorbid conditions, length of stay (LOS), discharge disposition, in-hospital mortality rates, insurance status, and hospital charges. Comparisons were made across 3 time periods (2006-2009, 2010-2013, and 2014-2017) and included subgroup analyses by treatment modality (endovascular vs. microsurgical). RESULTS: aSAH transfers declined from 213 in 2006-2009 to 160 in 2014-2017. While there was no change in presenting Hunt and Hess scores, the percentage of modified Fisher scores of 4 increased from 2006-2009 to 2014-2017. Transferred patients had a greater comorbidity index and decreased predicted 10-year survival. Despite this, the average LOS decreased. In-hospital mortality decreased from 2006-2009 to 2014-2017, especially in the endovascular cohort. The proportions of patients who were either self-pay or Medicaid did not change. Overall inflation-adjusted hospital charges decreased from $76,975 in 2006-2009 to $59,870 in 2014-2017. CONCLUSIONS: Between 2006 and 2017, transfers to our center for aSAH declined. However, transferred patients had greater levels of complexity, more comorbidities, and were at greater risk for vasospasm based on their presenting Fisher score. Nonetheless, average LOS, in-hospital mortality, and cost declined. These changing referral patterns have implications for outcome data, quality reporting, resident education, and developing systems of care to optimize outcomes.

Predicting Long-Term Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage Using Decision Tree Modeling.

BACKGROUND: Despite advances in the treatment of poor-grade aneurysmal subarachnoid hemorrhage (aSAH), predicting the long-term outcome of aSAH remains challenging, although essential. OBJECTIVE: To predict long-term outcomes after poor-grade aSAH using decision tree modeling. METHODS: This was a retrospective analysis of a prospective multicenter observational registry of patients with poor-grade aSAH with a World Federation of Neurosurgical Societies (WFNS) grade IV or V. Outcome was assessed by the modified Rankin Scale (mRS) at 12 mo, and an unfavorable outcome was defined as an mRS of 4 or 5 or death. Long-term prognostic models were developed using multivariate logistic regression and decision tree algorithms. An additional independent testing dataset was collected for external validation. Overall accuracy, sensitivity, specificity, and area under receiver operating characteristic curves (AUC) were used to assess model performance. RESULTS: Of the 266 patients, 139 (52.3%) had an unfavorable outcome. Older age, absence of pupillary reactivity, lower Glasgow coma score (GCS), and higher modified Fisher grade were independent predictors of unfavorable outcome. Modified Fisher grade, pupillary reactivity, GCS, and age were used in the decision tree model, which achieved an overall accuracy of 0.833, sensitivity of 0.821, specificity of 0.846, and AUC of 0.88 in the internal test. There was similar predictive performance between the logistic regression and decision tree models. Both models achieved a high overall accuracy of 0.895 in the external test. CONCLUSION: Decision tree model is a simple tool for predicting long-term outcomes after poor-grade aSAH and may be considered for treatment decision-making.

Outcome, Return to Work and Health-Related Costs After Aneurysmal Subarachnoid Hemorrhage.

OBJECT: Data on health-related costs after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim was to evaluate outcome, return to work and costs after aSAH with focus on differences between high- and low-grade aSAH (defined as World Federation of Neurological Surgeons [WFNS] grades 4-5 and WFNS 1-3, respectively). METHODS: A cross-sectional study was performed, including all consecutive survivors of aSAH over a 4-year period. A telephone interview was conducted to assess the Glasgow Outcome Scale Extended and employment status before and after aSAH. Direct costs were calculated by multiplying the length of hospitalization by the average daily costs. Indirect costs were calculated for productivity losses until retirement age according to the human capital approach. RESULTS: Follow-up was performed 2.7 years after aSAH (range 1.3-4.6). Favorable outcome was achieved in 114 of 150 patients (76%) and work recovery in 61 of 98 patients (62%) employed prior to aSAH. High-grade compared to low-grade aSAH resulted less frequently in favorable outcome (52% vs. 85%; p < 0.001) and work recovery (39% vs. 69%; p = 0.013). The total costs were € 344.277 (95% CI 268.383-420.171) per patient, mainly accounted to indirect costs (84%). The total costs increased with increasing degree of disability and were greater for high-grade compared to low-grade aSAH (€ 422.496 vs. € 329.193; p = 0.039). The effective costs per patient with favorable outcome were 2.1-fold greater for high-grade compared to low-grade aSAH (€ 308.625 vs. € 134.700). CONCLUSION: Favorable outcome can be achieved in a considerable proportion of high-grade aSAH patients, but costs are greater compared to low-grade aSAH. Further cost-effectiveness studies in the current era of aSAH management are needed.

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.

Daily systemic energy expenditure in the acute phase of aneurysmal subarachnoid hemorrhage.

Background: Patients with subarachnoid hemorrhage often have impaired consciousness and cannot regulate nutritional intakes themselves. Previous studies have demonstrated elevated energy expenditure in the acute phase, but it is not known whether the energy demand is constant during the first week after onset of the disease. In this study, we performed daily measurements of energy expenditure with indirect calorimetry during the first 7 days after aneurysmal subarachnoid hemorrhage in mechanically ventilated patients.Methods: Metabolic measurements were performed daily with indirect calorimetry in 26 patients with aneurysmal subarachnoid hemorrhage. All patients were intubated and mechanically ventilated. The measured value was compared to the predicted values from the Harris-Benedict equation and the Penn State University 1998 equation. Urinary nitrogen excretion was measured daily.Results: There was a significant increase in energy expenditure during days 2-3 compared to days 5-6. The Harris-Benedict equation underestimated metabolic demand. The Penn State 1998 equation was closer to the measured values, but still underestimated caloric need. Urinary nitrogen excretion increased throughout the first week from initially low values.Conclusions: There is a dynamic course in energy expenditure in patients with aneurysmal subarachnoid hemorrhage, with increasing metabolic demand during the first week of the disease. Indirect calorimetry could be used more often to help provide an adequate amount of energy.

Cost Comparison of Surgical Clipping and Endovascular Coiling of Unruptured Intracranial Aneurysms: A Systematic Review.

OBJECTIVES: Rupture of unruptured intracranial aneurysms (UIA) is the main cause for subarachnoid hemorrhage. UIA are widespread among the population. Advanced technology enables us to diagnose UIAs with increasing reliability and subsequently treat them. There are 2 main treatment options: surgical clipping and endovascular treatment of the aneurysm. This article aims to analyze costs of neurosurgical clipping and the endovascular approach to treat UIA, and to give an overview over the existing literature. METHODS: A systematic literature search was conducted using the databases Ovid MEDLINE, PubMed, and NHS EED. Articles were divided into 2 groups based on the perspective from which costs were evaluated (health care provider or payer). Costs were inflated to the year 2015 and converted to international dollars. RESULTS: The literature search yielded 137 different articles out of which 15 have been considered relevant and have been included in this review. Not only absolute numbers but also the cost ratio of both treatment modalities showed substantial variations. The coiling procedure tends to be more expensive for health care providers but cheaper for cost bearers. Without any exception, the authors determined shorter lengths of stay for patients who underwent the coiling procedure. CONCLUSIONS: Due to different definitions of hospital costs and hardly reproducible calculations, comparability of the stated numbers is limited. Besides the economic impact, outcomes must be considered when making a treatment decision. The 2 treatment modalities are not equally suitable in every patient nor for every aneurysm location.

Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system.

BACKGROUND: Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking. METHOD: Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH. RESULT: The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH. CONCLUSION: The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage.

Treatment at Safety-Net Hospitals Is Associated with Delays in Coil Embolization in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Successful endovascular management of aneurysmal subarachnoid hemorrhage (aSAH) requires timely access to substantial resources. Prior studies suggest an association between time to treatment and patient outcome. Patients treated at safety-net hospitals are thought to be particularly vulnerable to disparities in access to interventions that require substantial technologic resources. We hypothesized that patients with aSAH treated at safety-net hospitals are at greater risk for delayed access to endovascular treatment. METHODS: Adults undergoing endovascular coiling procedures between 2002 and 2011 in the Nationwide Inpatient Sample were included. Hospitals in the quartile with the highest proportion of Medicaid or uninsured patients were defined as safety-net hospitals. A multivariate model including patient-level and hospital-level factors was constructed to permit analysis of delays in endovascular treatment (defined as time to treatment >3 days). RESULTS: Analysis included 7109 discharges of patients with aSAH undergoing endovascular coil embolization procedures from 2002 to 2011. Median time to coil embolization in all patients was 1 day; 10.1% of patients waited >3 days until treatment. In multivariate analysis, patients treated at safety-net hospitals were more likely to have a prolonged time to coil embolization (odds ratio = 1.32, P < 0.01) compared with patients treated at low-burden hospitals. CONCLUSIONS: After controlling for patient and hospital factors, individuals with aSAH treated at safety-net hospitals from 2002 to 2011 were more likely to have a delay to endovascular coil embolization than individuals treated at non-safety-net hospitals. This disparity could affect patient outcomes.

Incidence and outcome of subarachnoid haemorrhage in the general and emergency department populations in Queensland from 2010 to 2014.

OBJECTIVES: To determine: (i) incidence and outcome of subarachnoid haemorrhage (SAH) in the general population; and (ii) proportions of SAH in both the general ED population and in ED patients presenting with headache. METHODS: A population-based study in Queensland from January 2010 to December 2014 was conducted. Data were sourced from the Australian Bureau of Statistics, Queensland Hospital Admitted Patient Data Collection linked to the Queensland death registry and ED Information System. Admitted patients with SAH were identified from ICD-10-AM codes. Inter-hospital transfers and repeat admissions for previously diagnosed SAH were excluded. Pre-hospital deaths from SAH were included. ED patients with headache were identified from ICD-10-AM codes and finding 'headache' in the triage free-text entry. The incidence of SAH, in-hospital mortality, proportions of SAH in the general ED population and ED patients with headache were calculated. RESULTS: There were 1975 incident cases of SAH in admitted patients and 294 pre-hospital deaths from SAH. The incidence of SAH was 9.9 (95% confidence interval [CI] 9.5-10.4) per 100 000 person-years. The incidence standardised to the 'World Standard Population' was 7.0 per 100 000 person-years. The in-hospital mortality was 23.8% (95% CI 22.0-25.8%). SAH was found in 1407 (1.9%, 95% CI 1.8-2.0) of ED patients with headache. Overall, there were 2.4 (95% CI 2.3-2.5) SAH per 10 000 of all ED attendances. CONCLUSIONS: The incidence of SAH was similar to that previously reported for Australia. One in 50 ED patients with headache had SAH. Ten in 50 000 ED attendances had a SAH. These estimates can assist in the risk assessment for SAH.

Decision tree analysis in subarachnoid hemorrhage: prediction of outcome parameters during the course of aneurysmal subarachnoid hemorrhage using decision tree analysis.

OBJECTIVEThe aim of this study was to create prediction models for outcome parameters by decision tree analysis based on clinical and laboratory data in patients with aneurysmal subarachnoid hemorrhage (aSAH).METHODSThe database consisted of clinical and laboratory parameters of 548 patients with aSAH who were admitted to the Neurocritical Care Unit, University Hospital Zurich. To examine the model performance, the cohort was randomly divided into a derivation cohort (60% [n = 329]; training data set) and a validation cohort (40% [n = 219]; test data set). The classification and regression tree prediction algorithm was applied to predict death, functional outcome, and ventriculoperitoneal (VP) shunt dependency. Chi-square automatic interaction detection was applied to predict delayed cerebral infarction on days 1, 3, and 7.RESULTSThe overall mortality was 18.4%. The accuracy of the decision tree models was good for survival on day 1 and favorable functional outcome at all time points, with a difference between the training and test data sets of < 5%. Prediction accuracy for survival on day 1 was 75.2%. The most important differentiating factor was the interleukin-6 (IL-6) level on day 1. Favorable functional outcome, defined as Glasgow Outcome Scale scores of 4 and 5, was observed in 68.6% of patients. Favorable functional outcome at all time points had a prediction accuracy of 71.1% in the training data set, with procalcitonin on day 1 being the most important differentiating factor at all time points. A total of 148 patients (27%) developed VP shunt dependency. The most important differentiating factor was hyperglycemia on admission.CONCLUSIONSThe multiple variable analysis capability of decision trees enables exploration of dependent variables in the context of multiple changing influences over the course of an illness. The decision tree currently generated increases awareness of the early systemic stress response, which is seemingly pertinent for prognostication.

Subarachnoid Hemorrhage and Readmissions: National Rates, Causes, Risk Factors, and Outcomes in 16,001 Hospitalized Patients.

INTRODUCTION: The acute complications of aneurysmal subarachnoid hemorrhage (aSAH) often lead to readmissions, which are linked to hospital reimbursement. The national rates, causes, risk factors, and outcomes associated with 30-day and 90-day readmission after aSAH have not previously been reported. METHODS: The Nationwide Readmissions Database was queried from January to September 2013 for all patients (age ≥18 years) with a diagnosis of aSAH. Data points included demographics, comorbidities, complications, and discharge outcomes. Causes and risk factors for 30-day and 90-day readmission were identified in univariate and multivariable analysis. RESULTS: In 12,777 patients discharged alive after hospitalization for aSAH, 962 (7.5%) were readmitted within 30 days and 2153 (16.7%) within 90 days. Common causes of readmission included stroke, hydrocephalus, septicemia, and headache. At 30-day and 90-day readmission, 39.7% and 51.2% of patients with diagnosis of hydrocephalus underwent ventriculoperitoneal shunt placement, respectively. In multivariable analysis, cannabis use and diabetes were predictors of both 30-day and 90-day readmission and older patients were uniquely susceptible to 30-day readmissions. Risk factors for 90-day readmission included Medicare insurance, hypothyroidism, initial discharge to skilled nursing facility, and several index complications including bowel obstruction, gastrostomy, acute lung injury, and cerebral edema. Average cost and length of stay were calculated at 30-day ($16.647, 7.1 days) and 90-day readmission ($17,926, 6.7 days). Mortality was 2.8% within 30 days and 3.8% within 90 days. CONCLUSIONS: Many readmissions occur outside the 30-day follow-up period in patients subarachnoid hemorrhage and possess unique risk factors, which may help identify high-risk patients.