Transcobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

Fluorescein Angiography Findings in Susac Syndrome: A Multicenter Retrospective Case Series.

BACKGROUND: Susac syndrome is a vasculopathy, resulting in the classic triad of branch retinal artery occlusion (BRAO), inner ear ischemia, and brain ischemia. In this retrospective chart review, we characterize fluorescein angiography (FA) findings and other ancillary studies in Susac syndrome, including the appearance of persistent disease activity and the occurrence of new subclinical disease on FA. METHODS: This multicenter, retrospective case series was institutional review board-approved and included patients with the complete triad of Susac syndrome evaluated with FA, contrasted MRI of the brain, and audiometry from 2010 to 2020. The medical records were reviewed for these ancillary tests, along with demographics, symptoms, visual acuity, visual field defects, and findings on fundoscopy. Clinical relapse was defined as any objective evidence of disease activity during the follow-up period after initial induction of clinical quiescence. The main outcome measure was the sensitivity of ancillary testing, including FA, MRI, and audiometry, to detect relapse. RESULTS: Twenty of the 31 (64%) patients had the complete triad of brain, retinal, and vestibulocochlear involvement from Susac syndrome and were included. Median age at diagnosis was 43.5 years (range 21-63), and 14 (70%) were women. Hearing loss occurred in 20 (100%), encephalopathy in 13 (65%), vertigo in 15 (75%), and headaches in 19 (95%) throughout the course of follow-up. Median visual acuity at both onset and final visit was 20/20 in both eyes. Seventeen (85%) had BRAO at baseline, and 10 (50%) experienced subsequent BRAO during follow-up. FA revealed nonspecific leakage from previous arteriolar damage in 20 (100%), including in patients who were otherwise in remission. Of the 11 episodes of disease activity in which all testing modalities were performed, visual field testing/fundoscopy was abnormal in 4 (36.4%), MRI brain in 2 (18.2%), audiogram in 8 (72.7%), and FA in 9 (81.8%). CONCLUSIONS: New leakage on FA is the most sensitive marker of active disease. Persistent leakage represents previous damage, whereas new areas of leakage suggest ongoing disease activity that requires consideration of modifying immunosuppressive therapy.

Spinal epidural arteriovenous fistula with nerve root enhancement mimicking myeloradiculitis: a case report.

BACKGROUND: Gadolinium enhancement of spinal nerve roots on magnetic resonance imaging (MRI) has rarely been reported in spinal dural arteriovenous fistula (SDAVF). Nerve root enhancement and cerebrospinal fluid (CSF) pleocytosis can be deceptive and lead to a misdiagnosis of myeloradiculitis. We report a patient who was initially diagnosed with neurosarcoid myeloradiculitis due to spinal nerve root enhancement, mildly inflammatory cerebrospinal fluid, and pulmonary granulomas, who ultimately was found to have an extensive symptomatic SDAVF. CASE PRESENTATION: A 52-year-old woman presented with a longitudinally extensive spinal cord lesion with associated gadolinium enhancement of the cord and cauda equina nerve roots, and mild lymphocytic pleocytosis. Pulmonary lymph node biopsy revealed non-caseating granulomas and neurosarcoid myeloradiculitis was suspected. She had rapid and profound clinical deterioration after a single dose of steroids. Further work-up with spinal angiography revealed a thoracic SDAVF, which was surgically ligated leading to clinical improvement. CONCLUSIONS: This case highlights an unexpected presentation of SDAVF with nerve root enhancement and concurrent pulmonary non-caseating granulomas, leading to an initial misdiagnosis with neurosarcoidosis. Nerve root enhancement has only rarely been described in cases of SDAVF; however, as this case highlights, it is an important consideration in the differential diagnosis of non-inflammatory causes of longitudinally extensive myeloradiculopathy with nerve root enhancement. This point is highly salient due to the importance of avoiding misdiagnosis of SDAVF, as interventions such as steroids or epidural injections used to treat inflammatory or infiltrative mimics may worsen symptoms in SDAVF. We review the presentation, diagnosis, and management of SDAVF as well as a proposed diagnostic approach to differentiating SDAVF from inflammatory myeloradiculitis.

Predisposing and Precipitating Factors Associated With Delirium: A Systematic Review.

Importance: Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups. Objective: To conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting. Evidence Review: A literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium. Findings: A total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity. Conclusions and Relevance: In this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium's heterogeneous pathophysiology and treatment.

Potential for remote vital sign monitoring to improve hospital patient sleep: A feasibility study.

BACKGROUND: Even low-acuity patients suffer from disrupted sleep in the hospital in part due to routine overnight vital sign (VS) checks. When invasive monitoring is not needed, vital sign monitoring devices (VSMDs) similar to consumer-grade health monitors may play a role in promoting sleep, which can aid healing and recovery. METHODS: We provided one VSMD to neuroscience ward patients during their hospital stays and used surveys to assess patient and nurse attitudes toward the device and the impact of the device on patient comfort. We also compared VSMD-streamed vS data to nurse-recorded vS data in the chart to evaluate the consistency of data streaming and data concordance between the device and nurse-collected vital sign values. FINDINGS: 21 patients and 15 nurses enrolled. Overall, patients and nurses responded positively to the device and patients preferred wearing the device to receiving manual vital checks overnight. The most common device-related cause of sleep disruption per patients was device weight (29%). Device vS were concordant with nurse vS on average but there was significant variance in agreement between nurse and device values. INTERPRETATION: Patients and nurses feel positively about the use of VSMDs and their use in the hospital. The device we tested may be limited in its sleep promotion by its weight and patient comfort assessment. Further research is needed to assess the precision of the device in measuring vital signs when used in a clinical setting. Future studies should compare VSMD models and assess their impacts on patient sleep in the absence of manual vS checks overnight. FUNDING: Funding provided by the Sara & Evan Williams Foundation Endowed Neurohospitalist Chair at UCSF.

COVID-19 severity and age increase the odds of delirium in hospitalized adults with confirmed SARS-CoV-2 infection: a cohort study.

BACKGROUND: Despite recognition of the neurologic and psychiatric complications associated with SARS-CoV-2 infection, the relationship between coronavirus disease 19 (COVID-19) severity on hospital admission and delirium in hospitalized patients is poorly understood. This study sought to measure the association between COVID-19 severity and presence of delirium in both intensive care unit (ICU) and acute care patients by leveraging an existing hospital-wide systematic delirium screening protocol. The secondary analyses included measuring the association between age and presence of delirium, as well as the association between delirium and safety attendant use, restraint use, discharge home, and length of stay. METHODS: In this single center retrospective cohort study, we obtained electronic medical record (EMR) data using the institutional Epic Clarity database to identify all adults diagnosed with COVID-19 and hospitalized for at least 48-h from February 1-July 15, 2020. COVID-19 severity was classified into four groups. These EMR data include twice-daily delirium screenings of all patients using the Nursing Delirium Screening Scale (non-ICU) or CAM-ICU (ICU) per existing hospital-wide protocols. RESULTS: A total of 99 patients were diagnosed with COVID-19, of whom 44 patients required ICU care and 17 met criteria for severe disease within 24-h of admission. Forty-three patients (43%) met criteria for delirium at any point in their hospitalization. Of patients with delirium, 24 (56%) were 65 years old or younger. After adjustment, patients meeting criteria for the two highest COVID-19 severity groups within 24-h of admission had 7.2 times the odds of having delirium compared to those in the lowest category [adjusted odds ratio (aOR) 7.2; 95% confidence interval (CI) 1.9, 27.4; P = 0.003]. Patients > 65 years old had increased odds of delirium compared to those < 45 years old (aOR 8.7; 95% CI 2.2, 33.5; P = 0.003). Delirium was associated with increased odds of safety attendant use (aOR 4.5; 95% CI 1.0, 20.7; P = 0.050), decreased odds of discharge home (aOR 0.2; 95% CI 0.06, 0.6; P = 0.005), and increased length of stay (aOR 7.5; 95% CI 2.0, 13; P = 0.008). CONCLUSIONS: While delirium is common in hospitalized patients of all ages with COVID-19, it is especially common in those with severe disease on hospital admission and those who are older. Patients with COVID-19 and delirium, compared to COVID-19 without delirium, are more likely to require safety attendants during hospitalization, less likely to be discharged home, and have a longer length of stay. Individuals with COVID-19, including younger patients, represent an important population to target for delirium screening and management as delirium is associated with important differences in both clinical care and disposition.

KIBRA, MTNR1B, and FKBP5 genotypes are associated with decreased odds of incident delirium in elderly post-surgical patients.

Despite the association between cognitive impairment and delirium, little is known about whether genetic differences that confer cognitive resilience also confer resistance to delirium. To investigate whether older adults without postoperative delirium, compared with those with postoperative delirium, are more likely to have specific single nucleotide polymorphisms (SNPs) in the FKBP5, KIBRA, KLOTHO, MTNR1B, and SIRT1 genes known to be associated with cognition or delirium. This prospective nested matched exploratory case-control study included 94 older adults who underwent orthopedic surgery and screened for postoperative delirium. Forty-seven subjects had incident delirium, and 47 age-matched controls were not delirious. The primary study outcome was genotype frequency for the five SNPs. Compared with participants with delirium, those without delirium had higher adjusted odds of KIBRA SNP rs17070145 CT/TT [vs. CC; adjusted odds ratio (aOR) 2.80, 95% confidence interval (CI) 1.03, 7.54; p = 0.04] and MTNR1B SNP rs10830963 CG/GG (vs. CC; aOR 4.14, 95% CI 1.36, 12.59; p = 0.01). FKBP5 SNP rs1360780 CT/TT (vs. CC) demonstrated borderline increased adjusted odds of not developing delirium (aOR 2.51, 95% CI 1.00, 7.34; p = 0.05). Our results highlight the relevance of KIBRA, MTNR1B, and FKBP5 in understanding the complex relationship between delirium, cognition, and sleep, which warrant further study in larger, more diverse populations.

Postoperative delirium prediction using machine learning models and preoperative electronic health record data.

BACKGROUND: Accurate, pragmatic risk stratification for postoperative delirium (POD) is necessary to target preventative resources toward high-risk patients. Machine learning (ML) offers a novel approach to leveraging electronic health record (EHR) data for POD prediction. We sought to develop and internally validate a ML-derived POD risk prediction model using preoperative risk features, and to compare its performance to models developed with traditional logistic regression. METHODS: This was a retrospective analysis of preoperative EHR data from 24,885 adults undergoing a procedure requiring anesthesia care, recovering in the main post-anesthesia care unit, and staying in the hospital at least overnight between December 2016 and December 2019 at either of two hospitals in a tertiary care health system. One hundred fifteen preoperative risk features including demographics, comorbidities, nursing assessments, surgery type, and other preoperative EHR data were used to predict postoperative delirium (POD), defined as any instance of Nursing Delirium Screening Scale ≥2 or positive Confusion Assessment Method for the Intensive Care Unit within the first 7 postoperative days. Two ML models (Neural Network and XGBoost), two traditional logistic regression models ("clinician-guided" and "ML hybrid"), and a previously described delirium risk stratification tool (AWOL-S) were evaluated using the area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, positive likelihood ratio, and positive predictive value. Model calibration was assessed with a calibration curve. Patients with no POD assessments charted or at least 20% of input variables missing were excluded. RESULTS: POD incidence was 5.3%. The AUC-ROC for Neural Net was 0.841 [95% CI 0. 816-0.863] and for XGBoost was 0.851 [95% CI 0.827-0.874], which was significantly better than the clinician-guided (AUC-ROC 0.763 [0.734-0.793], p < 0.001) and ML hybrid (AUC-ROC 0.824 [0.800-0.849], p < 0.001) regression models and AWOL-S (AUC-ROC 0.762 [95% CI 0.713-0.812], p < 0.001). Neural Net, XGBoost, and ML hybrid models demonstrated excellent calibration, while calibration of the clinician-guided and AWOL-S models was moderate; they tended to overestimate delirium risk in those already at highest risk. CONCLUSION: Using pragmatically collected EHR data, two ML models predicted POD in a broad perioperative population with high discrimination. Optimal application of the models would provide automated, real-time delirium risk stratification to improve perioperative management of surgical patients at risk for POD.

Approach to Altered Mental Status and Inpatient Delirium.

Altered mental status is a nonspecific diagnosis that encompasses a wide spectrum of disease and is frequently cited as a reason for both hospital admission and inpatient neurologic consultation. There are numerous etiologies of altered mental status, and so although many are facile with the workup of this potentially life-threatening entity, it can nevertheless be overwhelming. Our goal was to provide a practical framework embedded in a current, comprehensive review of the epidemiology, clinical evaluation, and management of undifferentiated altered mental status. We pay particular attention to the management of a critical yet underdiagnosed subtype of altered mental status: delirium.

Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid.

Importance: Cerebrospinal fluid (CSF) cytologic testing and flow cytometry are insensitive for diagnosing neoplasms of the central nervous system (CNS). Such clinical phenotypes can mimic infectious and autoimmune causes of meningoencephalitis. Objective: To ascertain whether CSF metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, in difficult-to-diagnose cases of CNS malignant neoplasm. Design, Setting, and Participants: Two case-control studies were performed at the University of California, San Francisco (UCSF). The first study used CSF specimens collected at the UCSF Clinical Laboratories between July 1, 2017, and December 31, 2019, and evaluated test performance in specimens from patients with a CNS malignant neoplasm (positive controls) or without (negative controls). The results were compared with those from CSF cytologic testing and/or flow cytometry. The second study evaluated patients who were enrolled in an ongoing prospective study between April 1, 2014, and July 31, 2019, with presentations that were suggestive of neuroinflammatory disease but who were ultimately diagnosed with a CNS malignant neoplasm. Cases of individuals whose tumors could have been detected earlier without additional invasive testing are discussed. Main Outcomes and Measures: The primary outcome measures were the sensitivity and specificity of aneuploidy detection by CSF mNGS. Secondary subset analyses included a comparison of CSF and tumor tissue chromosomal abnormalities and the identification of neuroimaging characteristics that were associated with test performance. Results: Across both studies, 130 participants were included (median [interquartile range] age, 57.5 [43.3-68.0] years; 72 men [55.4%]). The test performance study used 125 residual laboratory CSF specimens from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases. The neuroinflammatory disease study enrolled 12 patients and 17 matched control participants. The sensitivity of the CSF mNGS assay was 75% (95% CI, 63%-85%), and the specificity was 100% (95% CI, 96%-100%). Aneuploidy was detected in 64% (95% CI, 41%-83%) of the patients in the test performance study with nondiagnostic cytologic testing and/or flow cytometry, and in 55% (95% CI, 23%-83%) of patients in the neuroinflammatory disease study who were ultimately diagnosed with a CNS malignant neoplasm. Of the patients in whom aneuploidy was detected, 38 (90.5%) had multiple copy number variations with tumor fractions ranging from 31% to 49%. Conclusions and Relevance: This case-control study showed that CSF mNGS, which has low specimen volume requirements, does not require the preservation of cell integrity, and was orginally developed to diagnose neurologic infections, can also detect genetic evidence of a CNS malignant neoplasm in patients in whom CSF cytologic testing and/or flow cytometry yielded negative results with a low risk of false-positive results.

Outcomes Following Implementation of a Hospital-Wide, Multicomponent Delirium Care Pathway.

BACKGROUND: Delirium is associated with poor clinical outcomes that could be improved with targeted interventions. OBJECTIVE: To determine whether a multicomponent delirium care pathway implemented across seven specialty nonintensive care units is associated with reduced hospital length of stay (LOS). Secondary objectives were reductions in total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. METHODS: This retrospective cohort study included 22,708 hospitalized patients (11,018 preintervention) aged ≥50 years encompassing seven nonintensive care units: neurosciences, medicine, cardiology, general and specialty surgery, hematology-oncology, and transplant. The multicomponent delirium care pathway included a nurse-administered delirium risk assessment at admission, nurse-administered delirium screening scale every shift, and a multicomponent delirium intervention. The primary study outcome was LOS for all units combined and the medicine unit separately. Secondary outcomes included total direct cost, odds of 30-day hospital readmission, and rates of safety attendant and restraint use. RESULTS: Adjusted mean LOS for all units combined decreased by 2% post intervention (proportional change, 0.98; 95% CI, 0.96-0.99; P = .0087). Medicine unit adjusted LOS decreased by 9% (proportional change, 0.91; 95% CI, 0.83-0.99; P = .028). For all units combined, adjusted odds of 30-day readmission decreased by 14% (odds ratio [OR], 0.86; 95% CI, 0.80-0.93; P = .0002). Medicine unit adjusted cost decreased by 7% (proportional change, 0.93; 95% CI, 0.89-0.96; P = .0002). CONCLUSION: This multicomponent hospital-wide delirium care pathway intervention is associated with reduced hospital LOS, especially for patients on the medicine unit. Odds of 30-day readmission decreased throughout the entire cohort.

A matter of timing: EEG monitoring for neurological prognostication after cardiac arrest in the era of targeted temperature management.

Neuromonitoring with electroencephalography (EEG) is an essential tool in neurological prognostication post-cardiac arrest. EEG allows reliable and real-time assessment of early changes in background patterns, development of seizures and epileptiform activity, as well as testing for background reactivity to stimuli despite use of sedation or targeted temperature management. Delayed emergence of consciousness post-cardiac arrest is common, therefore longitudinal monitoring of EEG allows the detection of trends indicative of neurological improvement before coma recovery can be observed clinically. In this review, we summarize essential recent literature in EEG monitoring for neurological prognostication post-cardiac arrest in the context of targeted temperature management, with a particular focus on the importance of the evolution of EEG patterns in the first few days following resuscitation.

An Implementation-Effectiveness Study of a Perioperative Delirium Prevention Initiative for Older Adults.

BACKGROUND: Postoperative delirium is a common and serious problem for older adults. To better align local practices with delirium prevention consensus guidelines, we implemented a 5-component intervention followed by a quality improvement (QI) project at our institution. METHODS: This hybrid implementation-effectiveness study took place at 2 adult hospitals within a tertiary care academic health care system. We implemented a 5-component intervention: preoperative delirium risk stratification, multidisciplinary education, written memory aids, delirium prevention postanesthesia care unit (PACU) orderset, and electronic health record enhancements between December 1, 2017 and June 30, 2018. This was followed by a department-wide QI project to increase uptake of the intervention from July 1, 2018 to June 30, 2019. We tracked process outcomes during the QI period, including frequency of preoperative delirium risk screening, percentage of "high-risk" screens, and frequency of appropriate PACU orderset use. We measured practice change after the interventions using interrupted time series analysis of perioperative medication prescribing practices during baseline (December 1, 2016 to November 30, 2017), intervention (December 1, 2017 to June 30, 2018), and QI (July 1, 2018 to June 30, 2019) periods. Participants were consecutive older patients (≥65 years of age) who underwent surgery during the above timeframes and received care in the PACU, compared to a concurrent control group <65 years of age. The a priori primary outcome was a composite of perioperative American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use (Beers PIM) medications. The secondary outcome, delirium incidence, was measured in the subset of older patients who were admitted to the hospital for at least 1 night. RESULTS: During the 12-month QI period, preoperative delirium risk stratification improved from 67% (714 of 1068 patients) in month 1 to 83% in month 12 (776 of 931 patients). Forty percent of patients were stratified as "high risk" during the 12-month period (4246 of 10,494 patients). Appropriate PACU orderset use in high-risk patients increased from 19% in month 1 to 85% in month 12. We analyzed medication use in 7212, 4416, and 8311 PACU care episodes during the baseline, intervention, and QI periods, respectively. Beers PIM administration decreased from 33% to 27% to 23% during the 3 time periods, with adjusted odds ratio (aOR) 0.97 (95% confidence interval [CI], 0.95-0.998; P = .03) per month during the QI period in comparison to baseline. Delirium incidence was 7.5%, 9.2%, and 8.5% during the 3 time periods with aOR of delirium of 0.98 (95% CI, 0.91-1.05, P = .52) per month during the QI period in comparison to baseline. CONCLUSIONS: A perioperative delirium prevention intervention was associated with reduced administration of Beers PIMs to older adults.

Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.

OBJECTIVE: To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort. METHODS: Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p < 0.05 on DeSeq and t test) were identified as differentially regulated proteins. RESULTS: Compared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA. CONCLUSIONS: In this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.

Hospital admission and readmission among homeless patients with neurologic disease.

OBJECTIVE: To characterize the most common neurologic diagnoses leading to hospitalization for homeless compared to housed individuals and to assess whether homelessness is an independent risk factor for 30-day readmission after an admission for a neurologic illness. METHODS: We performed a retrospective serial cross-sectional study using data from the Healthcare Cost and Utilization Project California State Inpatient Database from 2006 to 2011. Adult patients with a primary neurologic discharge diagnosis were included. The primary outcome was 30-day readmission. We used multilevel logistic regression to examine the association between homelessness and readmission after adjustment for patient factors. RESULTS: We identified 1,082,347 patients with a neurologic primary diagnosis. The rate of homelessness was 0.37%. The most common indications for hospitalization among homeless patients were seizure and traumatic brain injury, both of which were more common in the homeless compared to housed population (19.3% vs 8.1% and 31.9% vs 9.2%, respectively, p < 0.001). A multilevel mixed-effects model controlling for patient age, sex, race, insurance type, comorbid conditions, and clustering on the hospital level found that homelessness was associated with increased 30-day readmission (odds ratio 1.5, 95% confidence interval 1.4-1.6, p < 0.001). This association persisted after this analysis was repeated within specific diagnoses (patients with epilepsy, trauma, encephalopathy, and neuromuscular disease). CONCLUSION: The most common neurologic reasons for admission among homeless patients are seizure and traumatic brain injury; these patients are at high risk for readmission. Future interventions should target the drivers of readmissions in this vulnerable population.

Association between Inpatient Delirium and Hospital Readmission in Patients ≥ 65 Years of Age: A Retrospective Cohort Study.

BACKGROUND: Delirium affects more than seven million hospitalized adults in the United States annually. However, its impact on postdischarge healthcare utilization remains unclear. OBJECTIVE: To determine the association between delirium and 30-day hospital readmission. DESIGN: A retrospective cohort study. SETTING: A general community medical and surgical hospital. PATIENTS: All adults who were at least 65 years old, without a history of delirium or alcohol-related delirium, and were hospitalized from September 2010 to March 2015. MEASUREMENTS: The patients deemed at risk for or displaying symptoms of delirium were screened by nurses using the Confusion Assessment Method with a followup by a staff psychiatrist for a subset of screen-positive patients. Patients with delirium confirmed by a staff psychiatrist were compared with those without delirium. The primary outcome was the 30-day readmission rate. The secondary outcomes included emergency department (ED) visits 30 days postdischarge, mortality during hospitalization and 30 days postdischarge, and discharge location. RESULTS: The cohort included 718 delirious patients and 7,927 nondelirious patients. Using an unweighted multivariable logistic regression, delirium was determined to be significantly associated with the increased odds of readmission within 30 days of discharge (odds ratio (OR): 2.60; 95% CI, 1.96-3.44; P < .0001). Delirium was also significantly (P < .0001) associated with ED visits within 30 days postdischarge (OR: 2.18; 95% CI: 1.77-2.69) and discharge to a facility (OR: 2.52; 95% CI: 2.09-3.01). CONCLUSIONS: Delirium is a significant predictor of hospital readmission, ED visits, and discharge to a location other than home. Delirious patients should be targeted to reduce postdischarge healthcare utilization.

Yield of Emergent CT in Patients With Epilepsy Presenting With a Seizure.

BACKGROUND: Studies of emergent neuroimaging in the management of patients presenting with a breakthrough seizure are lacking. We sought to determine how often emergent computed tomography (CT) scans are obtained in patients with known epilepsy presenting with a seizure and how often acute abnormalities are found. METHODS: This multicenter retrospective cohort study was performed in the emergency department at 2 academic medical centers. The primary outcomes were percentage of visits where a CT scan was obtained, whether CT findings represented acute abnormalities, and whether these findings changed acute management. RESULTS: Of the 396 visits included, CT scans were obtained in 39%, and 8% of these scans demonstrated acute abnormalities. Patients who were older, had status epilepticus, a brain tumor, head trauma, or an abnormal examination were all significantly more likely to undergo acute neuroimaging (P < .05). In the multivariable model, only history of brain tumor (odds ratio [OR] 5.88, 95% confidence interval [CI], 1.33-26.1) and head trauma as a result of seizure (OR 3.92, 95% CI, 1.01-15.2) reached statistical significance in predicting an acutely abnormal scan. The likelihood of an acute imaging abnormality in visits for patients without a history of brain tumor or head trauma as a result of the seizure was 2.7% (2 visits). Both of these patients had abnormal neurological examinations. CONCLUSION: Obtaining an emergent CT scan for patients with epilepsy presenting with a seizure may be avoidable in most cases, but might be indicated for patients with a history of brain tumor or head trauma as a result of seizure.