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.

Transcriptomic profiling of cardiac tissues from SARS-CoV-2 patients identifies DNA damage.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison with the 2009 pandemic (pH1N1), SARS-CoV-2 infection is likely to lead to more severe disease, with multi-organ effects, including cardiovascular disease. SARS-CoV-2 has been associated with acute and long-term cardiovascular disease, but the molecular changes that govern this remain unknown. In this study, we investigated the host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two pH1N1, and six control patients using targeted spatial transcriptomics approaches. Although SARS-CoV-2 was not detected in cardiac tissue, host transcriptomics showed upregulation of genes associated with DNA damage and repair, heat shock, and M1-like macrophage infiltration in the cardiac tissues of COVID-19 patients. The DNA damage present in the SARS-CoV-2 patient samples, were further confirmed by γ-H2Ax immunohistochemistry. In comparison, pH1N1 showed upregulation of interferon-stimulated genes, in particular interferon and complement pathways, when compared with COVID-19 patients. These data demonstrate the emergence of distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection supporting the need for a greater understanding of the effects on extra-pulmonary organs, including the cardiovascular system of COVID-19 patients, to delineate the immunopathobiology of SARS-CoV-2 infection, and long term impact on health.

In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 SUGGESTION FOR REPHRASING: In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

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.

Regionality in vector control: effect of fluctuating temperature in the susceptibility of Aedes aegypti (Diptera: Culicidae) larvae to Pyriproxyfen.

Using Pyriproxyfen in controlling Aedes aegypti shows great potential considering its high competence in low dosages. As an endocrine disruptor, temperature can interfere with its efficiency, related to a decrease in larval emergence inhibition in hotter environments. However, previous studies have been performed at constant temperatures in the laboratory, which may not precisely reflect the environmental conditions in the field. The aim of this study was to assess the effect of the fluctuating temperatures in Pyriproxyfen efficiency on controlling Aedes aegypti larvae. We selected maximum and minimum temperatures from the Brazilian Meteorological Institute database from September to April for cities grouped by five regions. Five fluctuating temperatures (17-26; 20-28.5; 23-32.5; 23-30.5; 19.5-31 °C) were applied to bioassays assessing Pyriproxyfen efficiency in preventing adult emergence in Aedes aegypti larvae in five concentrations. In the lowest temperatures, the most diluted Pyriproxyfen treatment (0.0025 mg/L) was efficient in preventing the emergence of almost thrice the larvae than in the hottest temperatures (61% and 21%, respectively, p value = 0.00015). The concentration that inhibits the emergence of 50% of the population was lower than that preconized by the World Health Organization (0.01 mg/L) in all treatments, except for the hottest temperatures, for which we estimated 0.010 mg/L. We concluded that fluctuating temperatures in laboratory bioassays can provide a more realistic result to integrate the strategies in vector surveillance. For a country with continental proportions such as Brazil, considering regionalities is crucial to the rational use of insecticides.

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.

Development and Evaluation of a Natural Language Processing Annotation Tool to Facilitate Phenotyping of Cognitive Status in Electronic Health Records: Diagnostic Study.

BACKGROUND: Electronic health records (EHRs) with large sample sizes and rich information offer great potential for dementia research, but current methods of phenotyping cognitive status are not scalable. OBJECTIVE: The aim of this study was to evaluate whether natural language processing (NLP)-powered semiautomated annotation can improve the speed and interrater reliability of chart reviews for phenotyping cognitive status. METHODS: In this diagnostic study, we developed and evaluated a semiautomated NLP-powered annotation tool (NAT) to facilitate phenotyping of cognitive status. Clinical experts adjudicated the cognitive status of 627 patients at Mass General Brigham (MGB) health care, using NAT or traditional chart reviews. Patient charts contained EHR data from two data sets: (1) records from January 1, 2017, to December 31, 2018, for 100 Medicare beneficiaries from the MGB Accountable Care Organization and (2) records from 2 years prior to COVID-19 diagnosis to the date of COVID-19 diagnosis for 527 MGB patients. All EHR data from the relevant period were extracted; diagnosis codes, medications, and laboratory test values were processed and summarized; clinical notes were processed through an NLP pipeline; and a web tool was developed to present an integrated view of all data. Cognitive status was rated as cognitively normal, cognitively impaired, or undetermined. Assessment time and interrater agreement of NAT compared to manual chart reviews for cognitive status phenotyping was evaluated. RESULTS: NAT adjudication provided higher interrater agreement (Cohen κ=0.89 vs κ=0.80) and significant speed up (time difference mean 1.4, SD 1.3 minutes; P<.001; ratio median 2.2, min-max 0.4-20) over manual chart reviews. There was moderate agreement with manual chart reviews (Cohen κ=0.67). In the cases that exhibited disagreement with manual chart reviews, NAT adjudication was able to produce assessments that had broader clinical consensus due to its integrated view of highlighted relevant information and semiautomated NLP features. CONCLUSIONS: NAT adjudication improves the speed and interrater reliability for phenotyping cognitive status compared to manual chart reviews. This study underscores the potential of an NLP-based clinically adjudicated method to build large-scale dementia research cohorts from EHRs.

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.

Counting Enchytraeus crypticus Juveniles in Chronic Exposures: An Alternative Method for Ecotoxicity Studies Using Tropical Artificial Soil.

Soil toxicity tests are commonly applied using Enchytraeus crypticus to analyze reproductive outputs. However, the traditional method for counting potworms takes a long time due to the significant number of offspring. This paper compares the conventional total counting of E. crypticus juveniles (M1) and an alternative methodology (M2). The proposed methodology (M2) uses a simple random counting method (1/4) for the partial counting of juveniles and total estimation. Chronic bioassays (21 days of exposure) were performed in tropical artificial soil (TAS) using sugarcane vinasse as a hazardous substance. Comparing the final density of juveniles recorded in M1 and M2, no statistical differences were pointed out in either one. Applying analyses based on effective concentration (EC10 and EC50), no statistical differences were identified there either. The t-test showed that there was no statistical difference between the counting methods (M1 and M2) in each treatment (control and dilutions). Moreover, we ran the Tukey test for M1 and M2 methods separately and observed that 100 % of the vinasse showed a statistical difference compared to the control treatment in both (p ≤ 0.05), affirming that independent of the counting method, the ecotoxicological outputs were similar. Therefore, the proposed alternative is a suitable method for bioassay using. E. crypticus in tropical artificial soil, decreasing to 1/4 the total time required for counting.

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.

Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial.

AIMS: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting. METHODS AND RESULTS: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0). CONCLUSIONS: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02689180.

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.

Chironomus sancticaroli (Diptera, Chironomidae) as a Sensitive Test Species: Can We Rely on Its Use After Repeated Generations, Under Laboratory Conditions?

In ecotoxicological assays, previously selected and standardized organism tests are exposed to an environmental sample. Some species of the Chironomus genus have been extensively used in ecotoxicological assays. Among these, Chironomus tentans is usually utilized in the USA and Chironomus sancticaroli in Brazil. We conducted ecotoxicological bioassays to compare a population of C. sancticaroli, kept for 6 years under laboratory conditions, with a sylvatic population of the same species, collected in the field. The aim was to test the hypothesis that populations of C. sancticaroli, maintained in the laboratory for long periods, could have a different response to stressors/substances. We analyzed the responses of C. sancticaroli for potassium chloride, zinc chloride, potassium dichromate, linear alkylbenzene sulphonate (LAS) and caffeine. The results showed no significant differences between the two populations in the analyses and seems to indicate the possible use of C. sancticaroli from populations kept in the laboratory for long periods.

Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: The ReBIC-1 trial.

AIMS: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals. METHODS: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned. PERSPECTIVE: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.

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.