41-Year-Old Male with Sub-Acute Encephalopathy, Seizures, and End Stage Renal Disease: A Unifying Diagnosis and Response to Therapy.

We describe a case of a 41-year-old male with a history of end-stage renal disease, hypertension, epilepsy, ischemic stroke, and traumatic brain injury transferred to our tertiary care center for subacute, progressive cognitive impairment. He was found to have disproportionate brain atrophy, focal seizures, and refractory hypertension. Given suspicion for an underlying genetic etiology, a genetic panel for progressive renal disease was sent, revealing two known pathogenic variants in a gene for a cobalamin metabolism disorder, Cobalamin C deficiency. He was started on targeted metabolic supplementation with subsequent improvement in his cognition. Our case highlights the crucial need to expand diagnostic workup to include genetic and metabolic causes in patients with neurologic disease, atypical features, relevant family history and multi-organ dysfunction.

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.

Behavioral "nudges" in the electronic health record to reduce waste and misuse: 3 interventions.

Electronic health records (EHRs) offer decision support in the form of alerts, which are often though not always interruptive. These alerts, though sometimes effective, can come at the cost of high cognitive burden and workflow disruption. Less well studied is the design of the EHR itself-the ordering provider's "choice architecture"-which "nudges" users toward alternatives, sometimes unintentionally toward waste and misuse, but ideally intentionally toward better practice. We studied 3 different workflows at our institution where the existing choice architecture was potentially nudging providers toward erroneous decisions, waste, and misuse in the form of inappropriate laboratory work, incorrectly specified computerized tomographic imaging, and excessive benzodiazepine dosing for imaging-related sedation. We changed the architecture to nudge providers toward better practice and found that the 3 nudges were successful to varying degrees in reducing erroneous decision-making and mitigating waste and misuse.

Development of a core outcome set for quality of life for adults with drug-resistant epilepsy: A multistakeholder Delphi consensus study.

OBJECTIVE: In 2017, the American Academy of Neurology (AAN) convened the AAN Quality Measurement Set working group to define the improvement and maintenance of quality of life (QOL) as a key outcome measure in epilepsy clinical practice. A core outcome set (COS), defined as an accepted, standardized set of outcomes that should be minimally measured and reported in an area of health care research and practice, has not previously been defined for QOL in adult epilepsy. METHODS: A cross-sectional Delphi consensus study was employed to attain consensus from patients and caregivers on the QOL outcomes that should be minimally measured and reported in epilepsy clinical practice. Candidate items were compiled from QOL scales recommended by the AAN 2017 Quality Measurement Set. Inclusion criteria to participate in the Delphi study were adults with drug-resistant epilepsy diagnosed by a physician, no prior diagnosis of psychogenic nonepileptic seizures or a cognitive and/or developmental disability, or caregivers of patients meeting these criteria. RESULTS: A total of 109 people satisfied inclusion/exclusion criteria and took part in Delphi Round 1 (patients, n = 95, 87.2%; caregivers, n = 14, 12.8%), and 55 people from Round 1 completed Round 2 (patients, n = 43, 78.2%; caregivers, n = 12, 21.8%). One hundred three people took part in the final consensus round. Consensus was attained by patients/caregivers on a set of 36 outcomes that should minimally be included in the QOL COS. Of these, 32 of the 36 outcomes (88.8%) pertained to areas outside of seizure frequency and severity. SIGNIFICANCE: Using patient-centered Delphi methodology, this study defines the first COS for QOL measurement in clinical practice for adults with drug-resistant epilepsy. This set highlights the diversity of factors beyond seizure frequency and severity that impact QOL in epilepsy.

Real-World Midazolam Use and Outcomes With Out-of-Hospital Treatment of Status Epilepticus in the United States.

STUDY OBJECTIVE: Guidelines recommend 10-mg intramuscular midazolam as the first-line treatment option for status epilepticus. However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower. Therefore, we used conventional and instrumental variable approaches to examine the effectiveness of midazolam in a national out-of-hospital cohort. METHODS: This retrospective cohort study of adults with status epilepticus used the ESO Data Collaborative research dataset (January 1, 2019, to December 31, 2019). The exposures were the route and dose of midazolam. We performed hierarchical logistic regression and 2-stage least squares regression using agency treatment patterns as an instrument to examine our outcomes, rescue therapy, and ventilatory support. RESULTS: There were 7,634 out-of-hospital encounters from 657 EMS agencies. Midazolam was administered intranasally in 20%, intravenously in 46%, and intramuscularly in 35% of the encounters. Compared with intramuscular administration, intranasal midazolam increased (risk difference [RD], 6.5%; 95% confidence interval [CI], 2.4% to 10.5%) and intravenous midazolam decreased (RD, -11.1%; 95% CI, -14.7% to -7.5%) the risk of rescue therapy. The differences in ventilatory support were not statistically significant (intranasal RD, -1.5%; 95% CI, -3.2% to 0.3%; intravenous RD, -0.3%; 95% CI, -1.9% to 1.2%). Higher doses were associated with a lower risk of rescue therapy (RD, -2.6%; 95% CI, -3.3% to -1.9%) and increased ventilatory support (RD, 0.4%; 95% CI, 0.1% to 0.7%). The instrumental variable analysis yielded similar results, except that dose was not associated with ventilatory support. CONCLUSION: The route and dose of midazolam affect clinical outcomes. Compared with intramuscular administration, intranasal administration may be less effective and intravenous administration more effective in terminating status epilepticus, although the differences between these and previous results may reflect the nature of real-world data as opposed to randomized data.