Automated Identification of Fall-related Injuries in Unstructured Clinical Notes.

Fall-related injuries (FRIs) are a major cause of hospitalizations among older patients, but identifying them in unstructured clinical notes poses challenges for large-scale research. In this study, we developed and evaluated Natural Language Processing (NLP) models to address this issue. We utilized all available clinical notes from the Mass General Brigham for 2,100 older adults, identifying 154,949 paragraphs of interest through automatic scanning for FRI-related keywords. Two clinical experts directly labeled 5,000 paragraphs to generate benchmark-standard labels, while 3,689 validated patterns were annotated, indirectly labeling 93,157 paragraphs as validated-standard labels. Five NLP models, including vanilla BERT, RoBERTa, Clinical-BERT, Distil-BERT, and SVM, were trained using 2,000 benchmark paragraphs and all validated paragraphs. BERT-based models were trained in three stages: Masked Language Modeling, General Boolean Question Answering (QA), and QA for FRI. For validation, 500 benchmark paragraphs were used, and the remaining 2,500 for testing. Performance metrics (precision, recall, F1 scores, Area Under ROC [AUROC] or Precision-Recall [AUPR] curves) were employed by comparison, with RoBERTa showing the best performance. Precision was 0.90 [0.88-0.91], recall [0.90-0.93], F1 score 0.90 [0.89-0.92], AUROC and AUPR curves of 0.96 [0.95-0.97]. These NLP models accurately identify FRIs from unstructured clinical notes, potentially enhancing clinical notes-based research efficiency.

Centromedian region thalamic responsive neurostimulation mitigates idiopathic generalized and multifocal epilepsy with focal to bilateral tonic-clonic seizures.

OBJECTIVE: Although >30% of epilepsy patients have drug-resistant epilepsy (DRE), typically those with generalized or multifocal disease have not traditionally been considered surgical candidates. Responsive neurostimulation (RNS) of the centromedian (CM) region of the thalamus now appears to be a promising therapeutic option for this patient population. We present outcomes following CM RNS for 13 patients with idiopathic generalized epilepsy (IGE) and eight with multifocal onsets that rapidly generalize to bilateral tonic-clonic (focal to bilateral tonic-clonic [FBTC]) seizures. METHODS: A retrospective review of all patients undergoing bilateral CM RNS by the senior author through July 2022 were reviewed. Electrodes were localized and volumes of tissue activation were modeled in Lead-DBS. Changes in patient seizure frequency were extracted from electronic medical records. RESULTS: Twenty-one patients with DRE underwent bilateral CM RNS implantation. For 17 patients with at least 1 year of postimplantation follow-up, average seizure reduction from preoperative baseline was 82.6% (SD = 19.0%, median = 91.7%), with 18% of patients Engel class 1, 29% Engel class 2, 53% Engel class 3, and 0% Engel class 4. There was a trend for average seizure reduction to be greater for patients with nonlesional FBTC seizures than for other patients. For patients achieving at least Engel class 3 outcome, median time to worthwhile seizure reduction was 203.5 days (interquartile range = 110.5-343.75 days). Patients with IGE with myoclonic seizures had a significantly shorter time to worthwhile seizure reduction than other patients. The surgical targeting strategy evolved after the first four subjects to achieve greater anatomic accuracy. SIGNIFICANCE: Patients with both primary and rapidly generalized epilepsy who underwent CM RNS experienced substantial seizure relief. Subsets of these patient populations may particularly benefit from CM RNS. The refinement of lead targeting, tuning of RNS system parameters, and patient selection are ongoing areas of investigation.

Comparative Effectiveness and Safety of Seizure Prophylaxis Among Adults After Acute Ischemic Stroke.

BACKGROUND: Older adults occasionally receive seizure prophylaxis in an acute ischemic stroke (AIS) setting, despite safety concerns. There are no trial data available about the net impact of early seizure prophylaxis on post-AIS survival. METHODS: Using a stroke registry (American Heart Association's Get With The Guidelines) individually linked to electronic health records, we examined the effect of initiating seizure prophylaxis (ie, epilepsy-specific antiseizure drugs) within 7 days of an AIS admission versus not initiating in patients ≥65 years admitted for a new, nonsevere AIS (National Institutes of Health Stroke Severity score ≤20) between 2014 and 2021 with no recorded use of epilepsy-specific antiseizure drugs in the previous 3 months. We addressed confounding by using inverse-probability weights. We performed standardization accounting for pertinent clinical and health care factors (eg, National Institutes of Health Stroke Severity scale, prescription counts, seizure-like events). RESULTS: The study sample included 151 patients who received antiseizure drugs and 3020 who did not. The crude 30-day mortality risks were 219 deaths per 1000 patients among epilepsy-specific antiseizure drugs initiators and 120 deaths per 1000 among noninitiators. After standardization, the estimated mortality was 251 (95% CI, 190-307) deaths per 1000 among initiators and 120 (95% CI, 86-144) deaths per 1000 among noninitiators, corresponding to a risk difference of 131 (95% CI, 65-200) excess deaths per 1000 patients. In the prespecified subgroup analyses, the risk difference was 52 (95% CI, 11-72) among patients with minor AIS and 138 (95% CI, 52-222) among moderate-to-severe AIS patients. Similarly, the risk differences were 86 (95% CI, 18-118) and 157 (95% CI, 57-219) among patients aged 65 to 74 years and ≥75 years, respectively. CONCLUSIONS: There was a higher risk of 30-day mortality associated with initiating versus not initiating seizure prophylaxis within 7 days post-AIS. This study does not support the role of seizure prophylaxis in reducing 30-day poststroke mortality.

Identification of patients with epilepsy using automated electronic health records phenotyping.

OBJECTIVE: Unstructured data present in electronic health records (EHR) are a rich source of medical information; however, their abstraction is labor intensive. Automated EHR phenotyping (AEP) can reduce the need for manual chart review. We present an AEP model that is designed to automatically identify patients diagnosed with epilepsy. METHODS: The ground truth for model training and evaluation was captured from a combination of structured questionnaires filled out by physicians for a subset of patients and manual chart review using customized software. Modeling features included indicators of the presence of keywords and phrases in unstructured clinical notes, prescriptions for antiseizure medications (ASMs), International Classification of Diseases (ICD) codes for seizures and epilepsy, number of ASMs and epilepsy-related ICD codes, age, and sex. Data were randomly divided into training (70%) and hold-out testing (30%) sets, with distinct patients in each set. We trained regularized logistic regression and an extreme gradient boosting models. Model performance was measured using area under the receiver operating curve (AUROC) and area under the precision-recall curve (AUPRC), with 95% confidence intervals (CI) estimated via bootstrapping. RESULTS: Our study cohort included 3903 adults drawn from outpatient departments of nine hospitals between February 2015 and June 2022 (mean age = 47 ± 18 years, 57% women, 82% White, 84% non-Hispanic, 70% with epilepsy). The final models included 285 features, including 246 keywords and phrases captured from 8415 encounters. Both models achieved AUROC and AUPRC of 1 (95% CI = .99-1.00) in the hold-out testing set. SIGNIFICANCE: A machine learning-based AEP approach accurately identifies patients with epilepsy from notes, ICD codes, and ASMs. This model can enable large-scale epilepsy research using EHR databases.

Identifying Medicare Beneficiaries With Delirium.

BACKGROUND: Each year, thousands of older adults develop delirium, a serious, preventable condition. At present, there is no well-validated method to identify patients with delirium when using Medicare claims data or other large datasets. We developed and assessed the performance of classification algorithms based on longitudinal Medicare administrative data that included International Classification of Diseases, 10th Edition diagnostic codes. METHODS: Using a linked electronic health record (EHR)-Medicare claims dataset, 2 neurologists and 2 psychiatrists performed a standardized review of EHR records between 2016 and 2018 for a stratified random sample of 1002 patients among 40,690 eligible subjects. Reviewers adjudicated delirium status (reference standard) during this 3-year window using a structured protocol. We calculated the probability that each patient had delirium as a function of classification algorithms based on longitudinal Medicare claims data. We compared the performance of various algorithms against the reference standard, computing calibration-in-the-large, calibration slope, and the area-under-receiver-operating-curve using 10-fold cross-validation (CV). RESULTS: Beneficiaries had a mean age of 75 years, were predominately female (59%), and non-Hispanic Whites (93%); a review of the EHR indicated that 6% of patients had delirium during the 3 years. Although several classification algorithms performed well, a relatively simple model containing counts of delirium-related diagnoses combined with patient age, dementia status, and receipt of antipsychotic medications had the best overall performance [CV- calibration-in-the-large <0.001, CV-slope 0.94, and CV-area under the receiver operating characteristic curve (0.88 95% confidence interval: 0.84-0.91)]. CONCLUSIONS: A delirium classification model using Medicare administrative data and International Classification of Diseases, 10th Edition diagnosis codes can identify beneficiaries with delirium in large datasets.

Drivers of US health care spending for persons with seizures and/or epilepsies, 2010-2018.

OBJECTIVE: This study was undertaken to characterize spending for persons classified with seizure or epilepsy and to determine whether spending has increased over time. METHODS: In this cross-sectional study, we pooled data from the Medical Expenditure Panel Survey (MEPS) household component files for 2010-2018. We matched cases to controls on age and sex of a population-based sample of MEPS respondents (community-dwelling persons of all ages) with records associated with a medical event (e.g., outpatient visit, hospital inpatient) for seizure, epilepsy, or both. Outcomes were weighted to be representative of the civilian, noninstitutionalized population. We estimated the treated prevalence of epilepsy and seizure, health care spending overall and by site of care, and trends in spending growth. RESULTS: We identified 1078 epilepsy cases and 2344 seizure cases. Treated prevalence was .38% (95% confidence interval [CI] = .34-.41) for epilepsy, .76% (95% CI = .71-.81) for seizure, and 1.14% (95% CI = 1.08-1.20) for epilepsy or seizure. The difference in annual spending for cases compared to controls was $4580 (95% CI = $3362-$5798) for epilepsy, $7935 (95% CI, $6237-$9634) for seizure, and $6853 (95% CI = $5623-$8084) for epilepsy or seizure, translating into aggregate costs of $5.4 billion, $19.0 billion, and $24.5 billion. From 2010 to 2018, the annual growth rate in total spending incurred for seizures and/or epilepsies was 7.6% compared to 3.6% among controls. SIGNIFICANCE: US economic burden of seizures and/or epilepsies is substantial and warrants interventions focused on their unique and overlapping causes.

Anti-seizure medication treatment and outcomes in acute ischemic stroke patients undergoing continuous EEG monitoring.

OBJECTIVES: To determine the association of anti-seizure medication (ASM) treatment with outcomes in acute ischemic stroke (AIS) patients undergoing continuous electroencephalography (cEEG). METHODS: Retrospective analysis of AIS patients admitted between 2012 and 2019. The following are the inclusion criteria: age ≥ 18 years and ≥ 16 h of cEEG within the first 7 days of admission. ASM treatment exposure was defined as > 48 h of treatment after the first 24 h of cEEG. The primary outcome measure was 90-day mortality, and the secondary outcome was 90-day functional recovery (Modified Ranking Scale 0-3). Propensity scores were used to adjust for baseline covariates and presence of epileptiform abnormalities (seizures, periodic and rhythmic patterns). RESULTS: One hundred thirteen patients met the inclusion criteria; 39 (34.5%) were exposed to ASM. ASM treatment was not associated with 90-day mortality (propensity adjusted HR 1.0 [0.31-3.27], p = 0.999) or functional outcomes (adjusted HR 0.99 [0.32-3.02], p = 0.989), compared to no treatment. CONCLUSIONS: In our study, ASM treatment in AIS patients with cEEG abnormalities was not significantly associated with a change in 90-day mortality and functional recovery. Larger comparative effectiveness studies are indicated to identify which acute ischemic stroke patients with cEEG abnormalities benefit most from ASM treatment.

Anticonvulsant Primary and Secondary Prophylaxis for Acute Ischemic Stroke Patients: A Decision Analysis.

Background and Purpose: We examined the impact of 3 anticonvulsant prophylaxis strategies on quality-adjusted life-years (QALYs) among patients with an incident acute ischemic stroke. Methods: We created a decision tree to evaluate 3 strategies: (1) long-term primary prophylaxis; (2) short-term secondary prophylaxis after an early seizure with lifetime prophylaxis if persistent or late seizures (LSs) developed; and (3) long-term secondary prophylaxis if either early, late, or persistent seizures developed. The outcome was quality-adjusted life expectancy (QALY). We created 4 base cases to simulate common clinical scenarios: (1) female patient aged 40 years with a 2% or 11% lifetime risk of an LS and a 33% lifetime risk of an adverse drug reaction (ADR); (2) male patient aged 65 years with a 6% or 29% LS risk and 60% ADR risk; (3) male patient aged 50 years with an 18% or 65% LS risk and 33% ADR risk; and (4) female patient aged 80 years with a 29% or 83% LS risk and 80% ADR risk. In sensitivity analyses, we altered the parameters and assumptions. Results: Across all 4 base cases, primary prophylaxis yielded the fewest QALYs when compared with secondary prophylaxis. For example, under scenario 1, strategies 2 and 3 resulted in 7.17 QALYs each, but strategy 1 yielded only 6.91 QALYs. Under scenario 4, strategies 2 and 3 yielded 2.85 QALYs compared with 1.40 QALYs for strategy 1. Under scenarios in which patients had higher ADR risks, strategy 2 led to the most QALYs. Conclusions: Short-term therapy with continued anticonvulsant prophylaxis only after postischemic stroke seizures arise dominates lifetime primary prophylaxis in all scenarios examined. Our findings reinforce the necessity of close follow-up and discontinuation of anticonvulsant seizure prophylaxis started during acute ischemic stroke hospitalization.

Establishing a learning healthcare system to improve health outcomes for people with epilepsy.

OBJECTIVE: To describe the organization of the Epilepsy Learning Healthcare System (ELHS), a network that aims to improve care outcomes for people with epilepsy (PWE). MATERIALS AND METHODS: Patients and family partners, providers, researchers, epidemiologists, and other leaders collaborated to recruit epilepsy centers and community services organizations into a novel learning network. A multidisciplinary Coordinating Committee developed ELHS governance and organizational structure, including four key planning Cores (Community, Clinical, Quality Improvement, and Data). Through Quality Improvement (QI) methodology grounded in the Institute for Healthcare Improvement (IHI) model, including iterative Plan-Do-Study-Act (PDSA) rapid learning cycles and other learning and sharing sessions, ELHS equipped epilepsy centers and community organizations with tools to standardize, measure, share, and improve key aspects of epilepsy care. The initial learning cycles addressed provider documentation of seizure frequency and type, and also screening for medication adherence barriers. Rapid learning cycles have been carried out on these initial measures in both clinical centers and community-based settings. Additional key measures have been defined for quality of life, screening, and treatment for mental health and behavioral comorbidities, transition from pediatric to adult care, counseling for women and girls living with epilepsy, referral for specialty care, and prevention and treatment of seizure clusters and status epilepticus. RESULTS: It is feasible to adopt a learning healthcare system framework in epilepsy centers and community services organizations. Through structured collaboration between epilepsy care providers, community support organizations, PWE, and their families/caregivers we have identified new opportunities to improve outcomes that are not available in traditional care models.

Patterns of anticonvulsant use and adverse drug events in older adults.

PURPOSE: To examine indications for, duration of use, and rate of adverse drug events (ADE) attributable to anticonvulsant initiation, as adjudicated by expert review of electronic health records (EHR) of older adults. METHODS: We identified a cohort of community dwelling Medicare beneficiaries with linked EHR (aged 65+, continuously enrolled with a large health system/until death between 2012 and 2014, n = 20 945) and drew a stratified EHR review sample (n = 1534). An expert reviewed all records to adjudicate anticonvulsant use, years of use, indication for use, and evidence of ADEs attributable to anticonvulsant initiation. After excluding patients with insufficient EHR data (n = 37; 2%), we reconstructed the cohort using inverse probability weights to resemble the original cohort of eligible beneficiaries (n = 20 380). Among incident users of a single anticonvulsant, we estimated the rate of ADEs and described the type and severity of ADEs. RESULTS: Overall, 12% (n = 2469) of eligible beneficiaries used at least one anticonvulsant in the 2012 to 2014 period (4% [n = 757] incident users, 8% [n = 1712] prevalent users). Incident users were most frequently prescribed gabapentin (n = 461/757, 61%), benzodiazepines (n = 122/757, 16%), and levetiracetam (n = 74/757, 10%); the most common indication was pain relief (n = 214; 28%) followed by epilepsy (n = 53; 7%). Among incident users, the overall ADE rate was 10/100 person-years (95% CI 4-20/100 person-years), of which 29% (n = 28/97) were life threatening (eg, somnolence). Most ADEs among incident monotherapy users were nervous system related (68%, n = 66/97). CONCLUSION: Many older adult community dwelling traditional Medicare beneficiaries had clinically significant ADEs likely attributable to the initiation of anticonvulsant therapy, which was begun for a range of indications.

A feasibility assessment of functioning and quality-of-life patient-reported outcome measures in adult epilepsy clinics: A systematic review.

OBJECTIVE: The objective of the study was to identify functioning and quality-of-life (QOL) patient-reported outcome measurements (PROMs) feasible for use in the waiting room of adult epilepsy clinics. MATERIAL AND METHODS: We searched PubMed and Web of Science for articles on in English, Spanish, Portuguese, Italian, and French published by the end of February 15th, 2019. We screened retrieved titles and abstracts looking for publications that reported the use of PROMs to measure functioning and QOL in epilepsy. The authors, clinical experts, and patient advocates from the Epilepsy Foundation of America conceptualized a set of desirable feasibility attributes for PROMs implementation in the waiting room of adult epilepsy clinics. These attributes included brief time for completion (i.e., ≤3 min), free cost, coverage of four minimum QOL domains and respective facets, and good evidence of psychometric properties. We defined QOL domains according to the World Health Organization's classification and created psychometric appraisal criteria based on the Food and Drug Administration's (FDA) Guidance. RESULTS: Eighteen candidate instruments were identified and compared with respect to desirable attributes for use in adult epilepsy clinics. We found that the Quality-of-life in epilepsy (QOLIE)-10 and Patient-Reported Outcome Measurement Information System-10 (PROMIS-10) were the most feasible PROMs for implementation in adult epilepsy clinics based on our criteria. The QOLIE-10 and PROMIS-10 still lack ideal evidence of responsiveness in people with epilepsy. CONCLUSION: This is the first systematic review that aimed to assess feasibility properties of available functioning and QOL PROMs. The QOLIE-10 and PROMIS-10 are potentially feasible instruments for implementation in the waiting room of adult epilepsy clinics. Further studies assessing the responsiveness of these PROMs are needed and will contribute to the selection of the most appropriate instrument for longitudinal use in adult epilepsy clinical practice.

Epilepsy Among Elderly Medicare Beneficiaries: A Validated Approach to Identify Prevalent and Incident Epilepsy.

BACKGROUND: Uncertain validity of epilepsy diagnoses within health insurance claims and other large datasets have hindered efforts to study and monitor care at the population level. OBJECTIVES: To develop and validate prediction models using longitudinal Medicare administrative data to identify patients with actual epilepsy among those with the diagnosis. RESEARCH DESIGN, SUBJECTS, MEASURES: We used linked electronic health records and Medicare administrative data including claims to predict epilepsy status. A neurologist reviewed electronic health record data to assess epilepsy status in a stratified random sample of Medicare beneficiaries aged 65+ years between January 2012 and December 2014. We then reconstructed the full sample using inverse probability sampling weights. We developed prediction models using longitudinal Medicare data, then in a separate sample evaluated the predictive performance of each model, for example, area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. RESULTS: Of 20,945 patients in the reconstructed sample, 2.1% had confirmed epilepsy. The best-performing prediction model to identify prevalent epilepsy required epilepsy diagnoses with multiple claims at least 60 days apart, and epilepsy-specific drug claims: AUROC=0.93 [95% confidence interval (CI), 0.90-0.96], and with an 80% diagnostic threshold, sensitivity=87.8% (95% CI, 80.4%-93.2%), specificity=98.4% (95% CI, 98.2%-98.5%). A similar model also performed well in predicting incident epilepsy (k=0.79; 95% CI, 0.66-0.92). CONCLUSIONS: Prediction models using longitudinal Medicare data perform well in predicting incident and prevalent epilepsy status accurately.

Accuracy of claims-based algorithms for epilepsy research: Revealing the unseen performance of claims-based studies.

OBJECTIVE: To evaluate published algorithms for the identification of epilepsy cases in medical claims data using a unique linked dataset with both clinical and claims data. METHODS: Using data from a large, regional health delivery system, we identified all patients contributing biologic samples to the health system's Biobank (n = 36K). We identified all subjects with at least one diagnosis potentially consistent with epilepsy, for example, epilepsy, convulsions, syncope, or collapse, between 2014 and 2015, or who were seen at the epilepsy clinic (n = 1,217), plus a random sample of subjects with neither claims nor clinic visits (n = 435); we then performed a medical chart review in a random subsample of 1,377 to assess the epilepsy diagnosis status. Using the chart review as the reference standard, we evaluated the test characteristics of six published algorithms. RESULTS: The best-performing algorithm used diagnostic and prescription drug data (sensitivity = 70%, 95% confidence interval [CI] 66-73%; specificity = 77%, 95% CI 73-81%; and area under the curve [AUC] = 0.73, 95%CI 0.71-0.76) when applied to patients age 18 years or older. Restricting the sample to adults aged 18-64 years resulted in a mild improvement in accuracy (AUC = 0.75,95%CI 0.73-0.78). Adding information about current antiepileptic drug use to the algorithm increased test performance (AUC = 0.78, 95%CI 0.76-0.80). Other algorithms varied in their included data types and performed worse. SIGNIFICANCE: Current approaches for identifying patients with epilepsy in insurance claims have important limitations when applied to the general population. Approaches incorporating a range of information, for example, diagnoses, treatments, and site of care/specialty of physician, improve the performance of identification and could be useful in epilepsy studies using large datasets.

Patient perceptions of physician-documented quality care in epilepsy.

OBJECTIVE: The aim of this study was to compare physician encounter documentation with patient perceptions of quality of epilepsy care and examine the association between quality and patient assessment of provider communication. METHODS: We identified 505 adult patients with epilepsy aged 18years or older over a 3-year period in two large academic medical centers. We abstracted individual, clinical, and care measures from 2723 electronic clinical notes written by physicians. We then randomly selected 245 patients for a phone interview. We compared patient perceptions of care with the documented care for several established epilepsy quality measures. We also explored the association of patient's perception of provider communication with provider documentation of key encounter interventions. RESULTS: There were 88 patients (36%) who completed the interviews. Fifty-seven (24%) refused to participate, and 100 (40%) could not be contacted. Participants and nonparticipants were comparable in their demographic and clinical characteristics; however, participants were more often seen by epilepsy specialists than nonparticipants (75% vs. 61.9%, p<0.01). Quality scores based on patient perceptions differed from those determined by assessing the documentation in the medical record for several quality measures, e.g., documentation of side effects of antiseizure therapy (p=0.05), safety counseling (p<0.01), and counseling for women of childbearing potential with epilepsy (McNemar's p=0.03; intraclass correlation coefficient, ICC=0.07). There was a significant, positive association between patient-reported counseling during the encounter (e.g., personalized safety counseling) and patient-reported scores of provider communication (p=0.05). CONCLUSIONS: The association between the patient's recollection of counseling during the visit and his/her positive perception of the provider's communication skills highlights the importance of spending time counseling patients about their epilepsy and not just determining if seizures are controlled.

Quality care in epilepsy: Women's counseling and its association with folic acid prescription or recommendation.

OBJECTIVE: This study aimed to determine if annual counseling about contraception and pregnancy in the setting of treatment for epilepsy is associated with increased recommending or prescribing of folate. METHODS: This is a retrospective cohort study with medical record abstraction. We selected records from 77 women of childbearing age who had two or more visits for epilepsy at a neurology clinic. The assessment included a review of documentation from the first three visits for epilepsy within a 24-month follow-up window. We defined perfect adherence to annual counseling about the impact of epilepsy treatment on contraception or pregnancy as defect-free care for women (DFCW). A recommendation that the patient take over-the-counter folate or a prescription for folate was independently abstracted from the chart at each visit. RESULTS: The group of patients who received DFCW (N=28, 36.36%) and the group who did not receive DFCW (N=49, 63.63%) were comparable with respect to age, disease duration, baseline history of drug-resistant epilepsy (DRE), presence of concurrent psychiatric disease, epileptologist involvement, number of antiepileptic drugs (AEDs) prescribed, seizure type, and etiology. Twenty (71.4%) patients in the DFCW group and 42 (85.7%) in the non-DFCW group were not recommended or prescribed folic acid (p=0.12). CONCLUSIONS: Even with annual documentation of counseling about how epilepsy treatment may affect contraception and pregnancy, the "action" of prescribing or recommending folic acid during the ensuing 24months is frequently omitted.

Benzodiazepine Initiation and the Risk of Falls or Fall-Related Injuries in Older Adults Following Acute Ischemic Stroke.

Background: Benzodiazepine use in older adults following acute ischemic stroke (AIS) is common, yet short-term safety concerning falls or fall-related injuries remains unexplored. Methods: We emulated a hypothetical randomized trial of benzodiazepine use during the acute post stroke recovery period to assess incidence of falls or fall related injuries in older adults. Using linked data from the Get With the Guidelines Registry and Mass General Brigham's electronic health records, we selected patients aged 65 and older admitted for Acute Ischemic Stroke (AIS) between 2014 and 2021 with no documented prior stroke and no benzodiazepine prescriptions in the previous 3 months. Potential for immortal-time and confounding biases was addressed via separate inverse-probability weighting strategies. Results: The study included 495 patients who initiated inpatient benzodiazepines within three days of admission and 2,564 who did not. After standardization, the estimated 10-day risk of falls or fall-related injuries was 694 events per 1000 (95% confidence interval CI: 676-709) for the benzodiazepine initiation strategy and 584 events per 1000 (95% CI: 575-595) for the non-initiation strategy. Subgroup analyses showed risk differences of 142 events per 1000 (95% CI: 111-165) and 85 events per 1000 (95% CI: 64-107) for patients aged 65 to 74 years and for those aged 75 years or older, respectively. Risk differences were 187 events per 1000 (95% CI: 159-206) for patients with minor (NIHSS≤ 4) AIS and 32 events per 1000 (95% CI: 10-58) for those with moderate-to-severe AIS. Conclusions: Initiating inpatient benzodiazepines within three days of AIS is associated with an elevated 10-day risk of falls or fall-related injuries, particularly for patients aged 65 to 74 years and for those with minor strokes. This underscores the need for caution with benzodiazepines, especially among individuals likely to be ambulatory during the acute and sub-acute post-stroke period.

Benzodiazepine Initiation Effect on Mortality Among Medicare Beneficiaries Post Acute Ischemic Stroke.

Rationale: Despite guideline warnings, older acute ischemic stroke (AIS) survivors still receive benzodiazepines (BZD) for agitation, insomnia, and anxiety despite being linked to severe adverse effects, such as excessive somnolence and respiratory depression. Due to polypharmacy, drug metabolism, comorbidities, and complications during the sub-acute post-stroke period, older adults are more susceptible to these adverse effects. We examined the impact of receiving BZDs within 30 days post-discharge on survival among older Medicare beneficiaries after an AIS. Methods: Using the Medicare Provider Analysis and Review (MedPAR) dataset, Traditional fee-for-service Medicare (TM) claims, and Part D Prescription Drug Event data, we analyzed a random 20% sample of TM beneficiaries aged 66 years or older who were hospitalized for AIS between July 1, 2016, and December 31, 2019. Eligible beneficiaries were enrolled in Traditional Medicare Parts A, B, and D for at least 12 months before admission. We excluded beneficiaries who were prescribed a BZD within 90 days before hospitalization, passed away during their hospital stay, left against medical advice, or were discharged to institutional post-acute care. Our primary exposure was BZD initiation within 30 days post-discharge, and the primary outcome was 90-day mortality risk differences (RD) from discharge. We followed a trial emulation process involving cloning, weighting, and censoring, plus we used inverse-probability-of-censoring weighting to address confounding. Results: In a sample of 47,421 beneficiaries, 826 (1.74%) initiated BZD within 30 days after discharge from stroke admission or before readmission, whichever occurred first, and 6,392 (13.48%) died within 90 days. Our study sample had a median age of 79, with an inter-quartile range (IQR) of 12, 55.3% female, 82.9% White, 10.1% Black, 1.7% Hispanic, 2.2% Asian, 0.4% American Native, 1.5% Other and 1.1% Unknown. After standardization based on age, sex, race/ethnicity, length of stay in inpatient, and baseline dementia, the estimated 90-day mortality risk was 159 events per 1,000 (95% CI: 155, 166) for the BZD initiation strategy and 133 events per 1,000 (95% CI: 132, 135) for the non-initiation strategy, with an RD of 26 events per 1,000 (95% CI: 22, 33). Subgroup analyses showed RDs of 0 events per 1,000 (95% CI: -4, 11) for patients aged 66-70, 3 events per 1,000 (95% CI: -1, 13) for patients aged 71-75, 10 events per 1,000 (95% CI: 3, 23) for patients aged 76-80, 27 events per 1,000 (95% CI: 21, 46) for patients aged 81-85, and 84 events per 1,000 (95% CI: 73, 106) for patients aged 86 years or older. RDs were 34 events per 1,000 (95% CI: 26, 48) and 20 events per 1,000 (95% CI: 11, 33) for males and females, respectively. RDs were 87 events per 1,000 (95% CI: 63, 112) for patients with baseline dementia and 18 events per 1,000 (95% CI: 13, 21) for patients without baseline dementia. Conclusion: Initiating BZDs within 30 days post-AIS discharge significantly increased the 90-day mortality risk among Medicare beneficiaries aged 76 and older and for those with baseline dementia. These findings underscore the heightened vulnerability of older adults, especially those with cognitive impairment, to the adverse effects of BZDs.

Association of Early Seizure Prophylaxis With Posttraumatic Seizures and Mortality: A Meta-analysis With Evidence Quality Assessment.

Purpose of the Review: To evaluate the quality of evidence about the association of primary seizure prophylaxis with antiseizure medication (ASM) within 7 days postinjury and the 18- or 24-month epilepsy/late seizure risk or all-cause mortality in adults with new-onset traumatic brain injury (TBI), in addition to early seizure risk. Results: Twenty-three studies met the inclusion criteria (7 randomized and 16 nonrandomized studies). We analyzed 9,202 patients, including 4,390 in the exposed group and 4,812 in the unexposed group (894 in placebo and 3,918 in no ASM groups). There was a moderate to serious bias risk based on our assessment. Within the limitations of existing studies, our data revealed a lower risk for early seizures in the ASM prophylaxis group compared with placebo or no ASM prophylaxis (risk ratio [RR] 0.43, 95% confidence interval [CI] 0.33-0.57, p < 0.00001, I 2 = 3%). We identified high-quality evidence in favor of acute, short-term primary ASM use to prevent early seizures. Early ASM prophylaxis was not associated with a substantial difference in the 18- or 24-month risk of epilepsy/late seizures (RR 1.01, 95% CI 0.61-1.68, p = 0.96, I 2 = 63%) or mortality (RR 1.16, 95% CI 0.89-1.51, p = 0.26, I 2 = 0%). There was no evidence of strong publication bias for each main outcome. The overall quality of evidence was low and moderate for post-TBI epilepsy risk and all-cause mortality, respectively. Summary: Our data suggest that the evidence showing no association between early ASM use and 18- or 24-month epilepsy risk in adults with new-onset TBI was of low quality. The analysis indicated a moderate quality for the evidence showing no effect on all-cause mortality. Therefore, higher-quality evidence is needed as a supplement for stronger recommendations.

Improving Seizure Frequency Documentation and Classification.

Background and Objectives: Accurate and reliable seizure data are essential for evaluating treatment strategies and tracking the quality of care in epilepsy clinics. This quality improvement project aimed to increase seizure documentation (i.e., documentation of seizure frequency from 80% to 100%, date of last seizure from 35% to 50%, and International League Against Epilepsy (ILAE) seizure classification from 35% to at least 50%) over 6 months. Methods: We surveyed 7 epileptologists to determine their perceived seizure frequency, ILAE classification, and date of last seizure documentation habits. Baseline data were collected weekly from September to December 2021. Subsequently, we implemented a newly created flowsheet in our Electronic Health Record (EHR) based on the Epilepsy Learning Healthcare System (ELHS) Case Report Forms to increase seizure documentation in a standardized way. Two epileptologists tested this flowsheet tool in their epilepsy clinics between February 2022 and July 2022. Data were collected weekly and compared with documentation from other epileptologists within the same group. Results: Epileptologists at our center believed they documented seizure frequency for 84%-87% of clinic visits, which aligned with baseline data collection, showing they recorded seizure frequency for 83% of clinic visits. Epileptologists believed they documented ILAE classification for 47%-52% of clinic visits, and baseline data showed this was documented in 33% of clinic visits. They also reported documenting the date of the last seizure for 52%-63% of clinic visits, but this occurred in only 35% of clinic visits. After implementing the new flowsheet, documentation increased to nearly 100% for all fields being completed by the providers who tested the flowsheet. Discussion: We demonstrated that by implementing an easy-to-use standardized EHR documentation tool, our documentation of critical metrics, as defined by the ELHS, improved dramatically. This shows that simple and practical interventions can substantially improve clinically meaningful documentation.

No short-term mortality from benzodiazepine use post-acute ischemic stroke after accounting for bias.

BACKGROUND AND OBJECTIVES: Older adults receive benzodiazepines for agitation, anxiety, and insomnia after acute ischemic stroke (AIS). No trials have been conducted to determine if benzodiazepine use affects poststroke mortality in the elderly. METHODS: We examined the association between initiating benzodiazepines within 1 week after AIS and 30-day mortality. We included patients ≥65 years, admitted for new nonsevere AIS (NIH-Stroke-Severity[NIHSS]≤ 20), 2014-2020, with no recorded benzodiazepine use in the previous 3 months and no contraindication for use. We linked a stroke registry to electronic health records, used inverse-probability weighting to address confounding, and estimated the risk difference (RD). A process of cloning, weighting, and censoring was used to avoid immortal time bias. RESULTS: Among 2,584 patients, 389 received benzodiazepines. The crude 30-day mortality risk from treatment initiation was 212/1,000 among patients who received benzodiazepines, while the 30-day mortality was 34/1,000 among those who did not. When follow-up was aligned on day of AIS admission and immortal time was assigned to the two groups, the estimated risks were 27/1,000 and 22/1,000, respectively. Upon further adjustment for confounders, the RD was 5 (-12 to 19) deaths/1,000 patients. CONCLUSION: The observed higher 30-day mortality associated with benzodiazepine initiation within 7 days was largely due to bias.