Frailty as a Predictor of Outcomes in Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using "Subarachnoid hemorrhage AND frailty" and "subarachnoid hemorrhage AND frail" as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients (p < 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model (p < 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients.

Frailty in aneurysmal subarachnoid hemorrhage: the risk analysis index.

BACKGROUND: Few studies have evaluated frailty in the setting of aneurysmal subarachnoid hemorrhage (aSAH) using large-scale data. The risk analysis index (RAI) may be implemented at the bedside or assessed retrospectively, differentiating it from other indices used in administrative registry-based research. METHODS: Adult aSAH hospitalizations were identified in the National Inpatient Sample (NIS) from 2015 to 2019. Complex samples statistical methods were performed to evaluate the comparative effect size and discriminative ability of the RAI, the modified frailty index (mFI), and the Hospital Frailty Risk Score (HFRS). Poor functional outcome was determined by the NIS-SAH Outcome Measure (NIS-SOM), shown to have high concordance with modified Rankin Scale scores > 2. RESULTS: 42,300 aSAH hospitalizations were identified in the NIS during the study period. By both ordinal [adjusted odds ratio (aOR) 3.20, 95% confidence interval (CI) 3.05, 3.36, p < 0.001] and categorical stratification [frail aOR 3.59, 95% CI 3.39, 3.80, p < 0.001; severely frail aOR 6.67, 95% CI 5.78, 7.69, p < 0.001], the RAI achieved the largest effect sizes for NIS-SOM in comparison with the mFI and HFRS. Discrimination of the RAI for NIS-SOM in high-grade aSAH was significantly greater than that of the HFRS (c-statistic 0.651 vs. 0.615). The mFI demonstrated the lowest discrimination in both high-grade and normal-grade patients. A combined Hunt and Hess-RAI model (c-statistic 0.837, 95% CI 0.828, 0.845) for NIS-SOM achieved significantly greater discrimination than both the combined models for mFI and HFRS (p < 0.001). CONCLUSION: The RAI was robustly associated with poor functional outcomes in aSAH independent of established risk factors.

An institutional report of heparin induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Heparin induced thrombocytopenia Type II (HIT-II) is a dangerous thromboembolic complication of heparin therapy. The current literature on incidence and outcomes of HIT-II in aneurysmal subarachnoid hemorrhage (aSAH) patients remains sparse. OBJECTIVE: We report our institution's incidence and outcomes of HIT-II in aSAH patients. METHODS: We performed a retrospective cohort study at an academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography. Diagnosis of HIT-II was determined by positive results on both heparin PF4-platelet antibody ELISA (anti-PF4) and serotonin release assay (SRA). RESULTS: 204 patients met inclusion criteria. Seven patients (7/204, 3.5%) underwent laboratory testing, three of whom met clinical criteria. HIT-II incidence was confirmed in two of these seven patients (2/204, 0.98%), who had high BMI and T4 scores. CONCLUSION: Our institution's report of HIT-II incidence in aSAH patients is lower than previously reported in this population and more closely parallels HIT-II incidence in the general and surgical ICU setting. Widely-accepted American College of Chest Physicians (ACCP) clinical diagnostic criteria in conjunction with anti-PF4 and SRA testing is the gold standard of clinical diagnosis of HIT-II in aSAH patients.

Utility of frailty as a predictor of acute kidney injury in patients with aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Acute kidney injury (AKI) is associated with poor outcome in aneurysmal subarachnoid hemorrhage patients (aSAH). Frailty has recently been demonstrated to correlate with elevated mortality and morbidity; its impact on predicting AKI and mortality in aSAH patients has not been investigated. OBJECTIVE: Evaluating risk factors and predictors for AKI in aSAH patients. METHODS: aSAH patients from a single-center's prospectively maintained database were retrospectively evaluated for development of AKI within 14 days of admission. Baseline demographic and clinical characteristics were collected. The effect of frailty and other risk factors were evaluated. RESULTS: Of 213 aSAH patients, 53 (33.1%) were frail and 12 (5.6%) developed AKI. Admission serum creatinine (sCr) and peak sCr within 48 h were higher in frail patients. AKI patients showed a trend towards higher frailty. Mortality was significantly higher in AKI than non-AKI aSAH patients. Frailty was a poor predictor of AKI when controlling for Hunt and Hess (HH) grade or age. HH grade ≥ 4 strongly predicted AKI when controlling for frailty. CONCLUSION: AKI in aSAH patients carries a poor prognosis. The HH grade appears to have superior utility as a predictor of AKI in aSAH patients than mFI.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

BACKGROUND: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources. METHODS: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs. RESULTS: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability. CONCLUSIONS: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability.

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors.

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures. Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor. Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients. Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor.

A Polygenic Score for Type 2 Diabetes Improves Risk Stratification Beyond Current Clinical Screening Factors in an Ancestrally Diverse Sample.

A substantial proportion of the adult United States population with type 2 diabetes (T2D) are undiagnosed, calling into question the comprehensiveness of current screening practices, which primarily rely on age, family history, and body mass index (BMI). We hypothesized that a polygenic score (PGS) may serve as a complementary tool to identify high-risk individuals. The T2D polygenic score maintained predictive utility after adjusting for family history and combining genetics with family history led to even more improved disease risk prediction. We observed that the PGS was meaningfully related to age of onset with implications for screening practices: there was a linear and statistically significant relationship between the PGS and T2D onset (-1.3 years per standard deviation of the PGS). Evaluation of U.S. Preventive Task Force and a simplified version of American Diabetes Association screening guidelines showed that addition of a screening criterion for those above the 90th percentile of the PGS provided a small increase the sensitivity of the screening algorithm. Among T2D-negative individuals, the T2D PGS was associated with prediabetes, where each standard deviation increase of the PGS was associated with a 23% increase in the odds of prediabetes diagnosis. Additionally, each standard deviation increase in the PGS corresponded to a 43% increase in the odds of incident T2D at one-year follow-up. Using complications and forms of clinical intervention (i.e., lifestyle modification, metformin treatment, or insulin treatment) as proxies for advanced illness we also found statistically significant associations between the T2D PGS and insulin treatment and diabetic neuropathy. Importantly, we were able to replicate many findings in a Hispanic/Latino cohort from our database, highlighting the value of the T2D PGS as a clinical tool for individuals with ancestry other than European. In this group, the T2D PGS provided additional disease risk information beyond that offered by traditional screening methodologies. The T2D PGS also had predictive value for the age of onset and for prediabetes among T2D-negative Hispanic/Latino participants. These findings strengthen the notion that a T2D PGS could play a role in the clinical setting across multiple ancestries, potentially improving T2D screening practices, risk stratification, and disease management.

Association of baseline frailty status with clinical outcome following aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent neurosurgical condition associated with high morbidity and mortality. The prognostic significance of baseline frailty status in aSAH patients has not been previously evaluated in a large, nationally representative sample. MATERIALS AND METHODS: Clinical outcomes data from the National Inpatient Sample from 2010-2018 were compared among sub-cohorts stratifying admissions by increasing frailty thresholds [(assessed using the 11-point modified frailty index (mFI-11)]. The previously validated NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM) were utilized. Complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess adjusted associations and discrimination of frailty for endpoints. RESULTS: Among 64,102 aSAH hospitalizations (mean age 55.4 years), 20.4% of admissions were classified as robust (mFI=0), 43.4% as pre-frail (mFI = 1), 24.9% as frail (mFI = 2), and 11.2% as severely frail (mFI ≥ 3). Following multivariable analysis adjusting for age and aSAH severity, increasing frailty was independently associated with NIS-SOM (OR = 1.15, 95% CI 1.09-1.21; p < 0.001), extended length of hospital stay (eLOS) (OR = 1.08, 1.02-1.13; p = 0.008), neurological complications (OR = 1.08, 1.03-1.13; p < 0.001), and medical complications (OR = 1.14, 1.08-1.21; p < 0.001). Based on ROC curve analysis, frailty achieved an AUC of 0.59 (0.58-0.60) and 0.54 (0.53-0.55) for NIS-SOM and eLOS, respectively. Age and NIS-SSS demonstrated significantly greater discrimination for NIS-SOM [AUC 0.69 (0.68-0.70) and 0.79 (0.78-0.80), respectively), while NIS-SSS achieved significantly greater discrimination for eLOS [(AUC 0.74 (0.73-0.75)] in comparison to both age and frailty. CONCLUSIONS: This national database evaluation of frailty in aSAH patients demonstrates an independent association between increasing frailty and poor functional outcome. Age and aSAH severity, however, may be more robust prognostic factors.

Distinct clinical phenotypes for Crohn's disease derived from patient surveys.

BACKGROUND: Defining clinical phenotypes provides opportunities for new diagnostics and may provide insights into early intervention and disease prevention. There is increasing evidence that patient-derived health data may contain information that complements traditional methods of clinical phenotyping. The utility of these data for defining meaningful phenotypic groups is of great interest because social media and online resources make it possible to query large cohorts of patients with health conditions. METHODS: We evaluated the degree to which patient-reported categorical data is useful for discovering subclinical phenotypes and evaluated its utility for discovering new measures of disease severity, treatment response and genetic architecture. Specifically, we examined the responses of 1961 patients with inflammatory bowel disease to questionnaires in search of sub-phenotypes. We applied machine learning methods to identify novel subtypes of Crohn's disease and studied their associations with drug responses. RESULTS: Using the patients' self-reported information, we identified two subpopulations of Crohn's disease; these subpopulations differ in disease severity, associations with smoking, and genetic transmission patterns. We also identified distinct features of drug response for the two Crohn's disease subtypes. These subtypes show a trend towards differential genotype signatures. CONCLUSION: Our findings suggest that patient-defined data can have unplanned utility for defining disease subtypes and may be useful for guiding treatment approaches.

Glycemic indices predict outcomes after aneurysmal subarachnoid hemorrhage: a retrospective single center comparative analysis.

Although hyperglycemia is associated with worse outcomes after aneurysmal subarachnoid hemorrhage (aSAH), there is no consensus on the optimal glucose control metric, acceptable in-hospital glucose ranges, or suitable insulin regimens in this population. In this single-center retrospective cohort study of aSAH patients, admission glucose, and hospital glucose mean (MHG), minimum (MinG), maximum (MaxG), and variability were compared. Primary endpoints (mortality, complications, and vasospasm) were assessed using multivariate logistic regressions. Of the 217 patients included, complications occurred in 83 (38.2%), 124 (57.1%) had vasospasm, and 41 (18.9%) died. MHG was independently associated with (p < 0.001) mortality, MaxG (p = 0.017) with complications, and lower MinG (p = 0.015) with vasospasm. Patients with MHG ≥ 140 mg/dL had 10 × increased odds of death [odds ratio (OR) = 10.3; 95% CI 4.6-21.5; p < 0.0001] while those with MinG ≤ 90 mg/dL had nearly 2× increased odds of vasospasm (OR = 1.8; 95% CI 1.01-3.21; p = 0.0422). While inpatient insulin was associated with increased complications and provided no mortality benefit, among those with MHG ≥ 140 mg/dL insulin therapy resulted in lower mortality (OR = 0.3; 95% CI 0.1-0.9; p = 0.0358), but no increased complication risk. While elevated MHG and MaxG are highly associated with poorer outcomes after aSAH, lower MinG is associated with increased vasospasm risk. Future trials should consider initiating insulin therapy based on MHG rather than other hyperglycemia measures.

Evaluating the Impact of Neurosurgical Educational Interventions on Patient Knowledge and Satisfaction: A Systematic Review of the Literature.

OBJECTIVE: In this systematic review, preoperative educational interventions for patients undergoing neurosurgical treatment are identified and their impact on patient knowledge acquisition and satisfaction is assessed. METHODS: The review was conducted in accordance with the PRISMA guidelines and used PubMed, Google Scholar, and MEDLINE databases. Studies evaluating before and after cohort or control group comparison were identified between 2007 and 2019 and were independently scored and evaluated by 3 authors. RESULTS: Eighty-one articles were assessed for eligibility and 15 met the inclusion criteria. Patient educational interventions were text-based (2 studies), multimedia/video-based (3), mobile/tablet-based (5), or used virtual reality (2) or three-dimensional printing (3). Interventions were disease-specific for cerebrovascular lesions (5), degenerative spine disease (2), concussion/traumatic brain injury (2), movement disorders (1), brain tumor (1), adolescent epilepsy (1), and other cranial/spinal elective procedures (3). Eleven studies (n = 18-175) documented patient knowledge acquisition using self-reported knowledge questionnaires (5) or more objective assessments based on true/false or multiple-choice questions (6). Most studies (10/11) reported statistically significant increases in patient knowledge after implementation of the intervention. Ten studies (n = 14-600) documented patient satisfaction using validated satisfaction surveys (2), Likert scale surveys (6), or other questionnaires (2). Although all studies reported increases in patient satisfaction after the intervention, only 4 were statistically significant. CONCLUSIONS: Patient educational interventions using various modalities are broadly applicable within neurosurgery and ubiquitously enhance patient knowledge and satisfaction. Interventions should be implemented when possible.

A comparison of frailty indices in predicting length of inpatient stay and discharge destination following angiogram-negative subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: While patients with angiogram-negative subarachnoid hemorrhages (ANSAH) have better prognoses than those with aneurysmal SAH, frailty's impact on outcomes in ANSAH is unclear. We previously showed that the modified frailty index (mFI-11) is associated with poor outcomes following ANSAH. Here, we compared the mFI-5, mFI-11, Charlson Comorbidity Index (CCI), and temporalis thickness (TMT) to determine which index was the best predictor of ANSAH outcomes and mortality rates. METHODS: In this retrospective cohort analysis between 2014 and 2018, patients with non-traumatic, angiogram negative SAH (ANSAH) were identified. The admission mFI-5, mFI-11, CCI, and TMT were calculated for each patient. Primary outcomes were mortality rate, discharge location, and prolonged length of stay (PLOS; LOS >85th percentile). Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to evaluate frailty as predictors of primary endpoints. RESULTS: We included 75 patients with a mean age of 55.4 ± 1.5 years. There were 4 patient deaths (5.3%), 53 patients (70.7%) discharged home, and 11 patients (14.7%) with PLOS. On ROC analysis, the mFI-5 had the highest discriminatory value for mortality (AUC = 0.97) while the mFI-11 was most discriminatory for discharge home (AUC = 0.85) and PLOS (AUC = 0.78). On multivariate analysis, the only independent predictor of mortality was the mFI-11 (OR = 0.46; 95%CI: 1.45-14.23; p = 0.009) while the mFI-5 was the best predictor of discharge home (OR = 0.21; 95% CI: 0.08-0.61; p = 0.004). On multivariate analysis, the only independent predictor of PLOS was the Hunt and Hess score (OR = 2.63; 95%CI: 1.38-5.00; p = 0.003). The CCI and TMT were inferior to either mFI for predicting primary endpoints. CONCLUSIONS: Increasing frailty is associated with poorer outcomes and higher mortality following ANSAH. The mFI-5 and mFI-11 were found to be superior predictors of discharge home and mortality rate. While larger prospective study is needed, frailty, as measured by mFI-11 and -5, should be considered when evaluating ANSAH prognosis.

Clinical Characteristics Predict the Yield of Head Computed Tomography Scans among Intoxicated Trauma Patients: Implications for the Initial Work-up.

BACKGROUND AND AIMS: Alcohol intoxication may confound the clinical assessment of the trauma patient. Head computed tomography (h-CT) is the standard imaging technique to rule out intracranial injury in most intoxicated trauma patients. The objective of this study was to determine whether certain clinical findings (computed clinical score [CCS]) could predict the h-CT yield, admission, and neurosurgical consultation (NSC) among intoxicated trauma patients. MATERIALS AND METHODS: This is a 4-year retrospective cohort study (2013-2017) of trauma patients who presented to our level 1 trauma center emergency department with alcohol intoxication. For each patient, a computed clinical score (CCS) was generated based on the following findings: age ≥50 years, Glasgow Coma Scale <13, evidence of trauma above the clavicles, amnesia, loss of consciousness, headache, vomiting, and seizures. The primary endpoints were NSC, admission, and acute h-CT finding. Univariate and multivariate regressions were used to compare predictors of the primary endpoints. RESULTS: We identified 437 intoxicated trauma patients (median age: 35 years [interquartile range: 25-50]; 71.9% men; median blood alcohol content: 207.8 mg/dL). One hundred and twenty-four (30.4%) patients had acute findings on h-CT, 351 (80.3%) were admitted, and 112 (25.6%) received NSC. On multivariate analysis, CCS was the only predictor of acute h-CT (odds ratio [OR] =1.6; 95% confidence interval [CI]: 1.3-2.0; P < 0.0001) and the best predictor of admission (OR = 1.6; 95% CI: 1.3-1.9; P < 0.0001) and NSC (OR = 1.8; 95% CI: 1.5-2.3; P < 0.0001). CONCLUSIONS: One-third of intoxicated trauma patients have acute findings on h-CT. While the CCS was the best predictor of acute h-CT findings, hospital admission, and NSC, h-CT scanning should continue to be a standard of care.

Increasing Frailty, Not Increasing Age, Results in Increased Length of Stay Following Vestibular Schwannoma Surgery.

OBJECTIVE: Understand the frailty of vestibular schwannoma surgical patients and how frailty impacts clinical course. STUDY DESIGN: Retrospective Cohort. SETTING: Single-tertiary academic hospital. PATIENTS: All patients undergoing vestibular schwannoma surgery. INTERVENTION: The modified frailty index (mFI) was calculated for all patients undergoing surgery for vestibular schwannoma between 2011 and 2018. Patient demographics and medical history, perioperative course, and postoperative complications were obtained from the medical record. MAIN OUTCOME MEASURES: The primary endpoint was hospital length of stay (LOS). Secondary endpoint was postoperative complications. Basic statistical analysis was performed including multivariate linear regressions to determine independent predictors of LOS. RESULTS: There were 218 patients included and the mean age was 48.1 ±â€Š0.9 (range 12-77). One-hundred ten patients were male (50.5%). The mean ICU LOS was 1.6 ±â€Š0.1 days while mean total hospital LOS was 4.3 ±â€Š0.2. There were 145 patients (66.5%) who were robust (nonfrail) with an mFI of 0, while 73 (33.5%) had an mFI of ≥1. Frailty (mFI≥2) was associated with longer hospital LOS compared with the prefrail (p = 0.0014) and robust (p = 0.0004) groups, but was not associated with increased complications (OR = 1.3; 95% CI: 0.5-3.7; p = 0.5925) or ICU LOS (p > 0.05). In multivariate analysis, increased mFI, and NOT increased age, was an independent risk factor for increased hospital LOS (p = 0.027). CONCLUSION: Increasing frailty, and not increasing age, is an independent risk factor for longer hospital LOS, but not for increased postoperative complications. Patients' frailty status may be useful preoperatively in counselling patients about postoperative expectations and frail vestibular schwannoma patients may require increased health spending costs given their increased hospital LOS.

The Effect of Frailty versus Initial Glasgow Coma Score in Predicting Outcomes Following Chronic Subdural Hemorrhage: A Preliminary Analysis.

Background Initial Glasgow Coma Score (iGCS) is a well-known predictor of adverse outcomes following chronic subdural hemorrhage (cSDH). Frailty, i.e. a reduced physiologic reserve, is associated with poorer outcomes across the surgical literature, however, there is no consensus on the best measure of frailty. To date, no study has compared frailty's ability to predict cSDH outcomes versus iGCS. The goal of this study was to, therefore, examine the prognostic value of the 5- (mFI-5) and 11-factor (mFI-11) modified frailty index, and Charlson Comorbidity Index (CCI) versus iGCS following cSDH. Methods Between January, 2016 and June, 2018, patients who presented to the emergency department with cSDH were retrospectively identified using the International Classification of Diseases (ICD) codes. mFI-5, mFI-11, and CCI scores were calculated using patient baseline characteristics. Primary endpoints were death and discharge home and subgroup analyses were performed among operative cSDH. Univariate and multivariate logistic regressions were used to determine predictors of primary endpoints. Results Of the 109 patients identified, the average age was 72.6±1.6 years and the majority (69/109, 63.3%) were male. The average CCI, mFI-5, and mFI-11 were 4.5 ±0.2, 1.5 ±0.1, and 2.2 ±0.1, respectively. Fifty (45.9%) patients required surgical intervention, 11 (10.1%) died, and 48 (43.4%) were discharged home. In the overall cohort, while the only multivariate predictor of mortality was iGCS (OR=0.58; 95%CI:0.44-0.77; p=0.0001), the CCI (OR=0.73; 95%CI:0.58-0.92; p=0.0082) was a superior predictor of discharge home compared to iGCS (OR=1.46; 95%CI:1.13-1.90; p=0.0041). Conversely, among those who received an operative intervention, the CCI, but not iGCS, independently predicted both mortality (OR=4.24; 95%CI:1.01-17.86; p=0.0491) and discharge home (OR=0.55; 95%CI:0.33-0.90; p=0.0170). Neither mFI nor age predicted primary outcomes in multivariate analysis. Conclusion While frailty is associated with worse surgical outcomes, the clinical utility of the mFI-5, mFI-11, and CCI in cSDH is unclear. We show that the iGCS is an overall superior predictor of mortality following cSDH but is outperformed by the CCI after operative intervention. Similarly, the CCI is the superior predictor of discharge home in cSDH patients overall and following an operative intervention. These results indicate that while the iGCS best predicts mortality overall, the CCI may be considered when prognosticating post-operative course and hospital disposition.

Low total cholesterol and high density lipoprotein are independent predictors of poor outcomes following aneurysmal subarachnoid hemorrhage: A preliminary report.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is devastating, with delayed cerebral ischemia (DCI) significantly contributing to the high morbidity and mortality rates. Cholesterol has been studied as a measure of nutritional status in other neurological pathologies, but reports examining cholesterol's effects on aSAH outcomes are sparse. This study aimed to elucidate the effect of low total cholesterol (TC) and high density lipoprotein (HDL) on mortality and DCI following aSAH. METHODS: We performed a retrospective cohort study at a quaternary academic medical center between June 2014 and July 2018. All patients had aSAH confirmed by digital subtraction angiography and had TC measured on admission. Primary outcomes were mortality and DCI. Secondary outcome was radiographic vasospasm. Univariate and multivariate logistic regressions were performed. RESULTS: There were 75 aSAH patients, with an average age of 58.7 ±â€¯1.7 (range: 14-89) and Hunt & Hess score of 2.8 ±â€¯0.1, included for analysis. Those with a low TC < 160 mg/dL had 3 times increased odds of DCI (OR = 3.4; 95 %CI: 1.3-9.0; p = 0.0175) and a nearly 5 times increased odds of death (OR = 4.9; 95 %CI: 1.1-18.3; p = 0.0339). Low HDL < 40 mg/dL was associated with 12 times increased odds of DCI (OR = 12.3; 95 %CI: 2.7-56.4; p = 0.0003) but no significant differences in death (p = 0.2205). In multivariate analysis, low TC was an independent risk factor for increased mortality (OR = 5.6; 95 %CI: 1.2-27.6; p = 0.0335) while low HDL was associated with increased risk for DCI (OR = 17.9; 95 %CI: 3.1-104.4; p = 0.0013). There was no effect of TC or HDL on radiographic vasospasm. CONCLUSIONS: Low TC and HDL are independent predictors of increased mortality and DCI, respectively, following aSAH. Low TC and HDL may be markers of poor overall health, in addition to having some pathophysiological effect on cerebral vasculature. These results may have practical implications for the improvement of aSAH prognostication and management.

The Effect of Frailty and Patient Comorbidities on Outcomes After Acute Subdural Hemorrhage: A Preliminary Analysis.

BACKGROUND: Frailty is associated with worse outcomes across a variety of neurosurgical diseases. However, its effect on acute subdural hemorrhage (aSDH) outcomes is unclear. The goal of this study is to compare 3 measures of frailty with the gold standard (i.e., initial Glasgow Coma Scale [iGCS] score) for predicting outcomes after aSDH. METHODS: Patients who presented between January 2016 and June 2018 were retrospectively identified based on International Classification of Diseases codes for aSDH. Patients' modified Frailty Index (mFI), temporalis muscle thickness (TMT), and age-adjusted Charlson Comorbidity Index (CCI) were calculated. Primary end points were death and discharge home. RESULTS: Of 167 patients included, the mean age was 63.4 ± 1.9 years, the average CCI was 3.4 ± 0.2, mFI was 1.4 ± 0.1, TMT was 7.1 ± 0.2 mm, and iGCS score was 11.9 ± 0.3. Sixty-nine patients (41.3%) were discharged home and 32 (19.2%) died during hospitalization. In multivariate analysis, decreasing iGCS score (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.74-0.96; P = 0.0112) and midline shift (OR, 1.27; 95% CI, 1.08-1.50; P = 0.0048), but not age or frailty, predicted mortality. In addition to iGCS score (OR, 1.26; 95% CI, 1.10-1.44; P = 0.0011), lower CCI (OR, 0.32; 95% CI, 0.14-0.74; P = 0.0071) and larger TMT (OR, 2.63; 95% CI, 1.16-5.99; P = 0.0210) independently predicted increased rates of discharge home. mFI was not independently associated with either primary end point in multivariate analysis. CONCLUSIONS: iGCS score predicts both mortality and discharge location after aSDH better than do age or frailty. However, CCI and TMT, but not mFI, are useful prognostic indicators of discharge to home after aSDH. The iGCS score should continue to be the primary prediction tool for patients with aSDH; however, frailty may be useful for resource allocation, especially when nearing discharge.

Identifying Ashkenazi Jewish BRCA1/2 founder variants in individuals who do not self-report Jewish ancestry.

Current guidelines recommend BRCA1 and BRCA2 genetic testing for individuals with a personal or family history of certain cancers. Three BRCA1/2 founder variants - 185delAG (c.68_69delAG), 5382insC (c.5266dupC), and 6174delT (c.5946delT) - are common in the Ashkenazi Jewish population. We characterized a cohort of more than 2,800 research participants in the 23andMe database who carry one or more of the three Ashkenazi Jewish founder variants, evaluating two characteristics that are typically used to recommend individuals for BRCA testing: self-reported Jewish ancestry and family history of breast, ovarian, prostate, or pancreatic cancer. Of the 1,967 carriers who provided self-reported ancestry information, 21% did not self-report Jewish ancestry; of these individuals, more than half (62%) do have detectable Ashkenazi Jewish genetic ancestry. In addition, of the 343 carriers who provided both ancestry and family history information, 44% did not have a first-degree family history of a BRCA-related cancer and, in the absence of a personal history of cancer, would therefore be unlikely to qualify for clinical genetic testing. These findings may help inform the discussion around broader access to BRCA genetic testing.

Validity of the cold pressor test and pain sensitivity questionnaire via online self-administration.

To determine the feasibility of complex home-based phenotyping, 1,876 research participants from the customer base of 23andMe completed an online version of a Pain Sensitivity Questionnaire (PSQ) as well as a cold pressor test (CPT) which is used in clinical assessments of pain. Overall our online version of the PSQ performed similarly to the original pen-and-paper version. Construct validity of the PSQ total was demonstrated by internal consistency and consistent discrimination between more and less painful items. Criterion validity was demonstrated by correlation with pain sensitivity as measured by the CPT. Within the same cohort we performed a cold pressor test using a layperson description and household equipment. Comparison with published reports from controlled studies revealed similar distributions of cold pain tolerance times (i.e., time elapsed before removing the hand from the water). Of those who elected to participate in the CPT, a large majority of participants did not report issues with the test procedure or noncompliance with the instructions (97%). We confirmed a large sex difference in CPT thresholds in line with published data, such that women removed their hands from the water at a median of 54.2 seconds, with men lasting for a median time of 82.7 seconds (Kruskal-Wallis statistic, p < 0.0001), but other factors like age or current pain treatment were at most weakly associated, and inconsistently between men and women. We introduce a new paradigm for performing pain testing, called testing@home, that, in the case of cold nociception, showed comparable results to studies conducted under controlled conditions and supervision of a health care professional.