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OBJECTIVE: Initial stroke severity is a potent modifier of stroke outcomes but this information is difficult to obtain from electronic health record (EHR) data. This limits the ability to risk-adjust for evaluations of stroke care and outcomes at a population level. The purpose of this analysis was to develop and validate a predictive model of initial stroke severity using EHR data elements. METHODS: This observational cohort included individuals admitted to a US Department of Veterans Affairs hospital with an ischemic stroke. We extracted 65 independent predictors from the EHR. The primary analysis modeled mild (NIHSS score 0-3) versus moderate/severe stroke (NIHSS score ≥4) using multiple logistic regression. Model validation included: (1) splitting the cohort into derivation (65%) and validation (35%) samples and (2) evaluating how the predicted stroke severity performed in regard to 30-day mortality risk stratification. RESULTS: The sample comprised 15,346 individuals with ischemic stroke (n = 10,000 derivation; n = 5,346 validation). The final model included 15 variables and correctly classified 70.4% derivation sample patients and 69.4% validation sample patients. The areas under the curve (AUC) were 0.76 (derivation) and 0.76 (validation). In the validation sample, the model performed similarly to the observed NIHSS in terms of the association with 30-day mortality (AUC: 0.72 observed NIHSS, 0.70 predicted NIHSS). CONCLUSIONS: EHR data can be used to construct a surrogate measure of initial stroke severity. Further research is needed to better differentiate moderate and severe strokes, enhance stroke severity classification, and how to incorporate these measures in evaluations of stroke care and outcomes.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Registros Eletrônicos de Saúde , Índice de Gravidade de Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Modelos LogísticosRESUMO
Apamin-sensitive small-conductance Ca2+-activated K+ (SK) current ( IKAS) is encoded by Ca2+-activated K+ channel subfamily N ( KCNN) genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT syndrome (diLQTS), we screened for KCNN variants among patients with diLQTS, determined the properties of heterologously expressed wild-type (WT) and variant KCNN channels, and determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS. We searched 2,306,335 records in the Indiana Network for Patient Care and found 11 patients with diLQTS who had DNA available in the Indiana Biobank. DNA sequencing discovered a heterozygous KCNN2 variant (p.F503L) in a 52-yr-old woman presenting with corrected QT interval prolongation at baseline (473 ms) and further corrected QT interval lengthening (601 ms) after oral administration of ondansetron. That patient was also heterozygous for the p.S38G and p.P2835S variants of the QT-controlling genes KCNE1 and ankyrin 2, respectively. Patch-clamp experiments revealed that the p.F503L KCNN2 variant heterologously expressed in human embryonic kidney (HEK)-293 cells augmented Ca2+ sensitivity, increasing IKAS density. The fraction of total F503L-KCNN2 protein retained in the membrane was higher than that of WT KCNN2 protein. Ondansetron at nanomolar concentrations inhibited WT and p.F503L SK2 channels expressed in HEK-293 cells as well as native SK channels in ventricular cardiomyocytes. Ondansetron-induced IKAS inhibition was also demonstrated in Langendorff-perfused murine hearts. In conclusion, the heterozygous p.F503L KCNN2 variant increases Ca2+ sensitivity and IKAS density in transfected HEK-293 cells. Ondansetron at therapeutic (i.e., nanomolar) concentrations is a potent IKAS blocker. NEW & NOTEWORTHY We showed that ondansetron, a 5-HT3 receptor antagonist, blocks small-conductance Ca2+-activated K+ (SK) current. Ondansetron may be useful in controlling arrhythmias in which increased SK current is a likely contributor. However, its SK-blocking effects may also facilitate the development of drug-induced long QT syndrome.
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Antiarrítmicos/farmacologia , Síndrome do QT Longo/tratamento farmacológico , Ondansetron/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Ativados por Cálcio de Condutância Baixa/antagonistas & inibidores , Animais , Antiarrítmicos/uso terapêutico , Cálcio/metabolismo , Células Cultivadas , Feminino , Células HEK293 , Humanos , Síndrome do QT Longo/genética , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Ondansetron/uso terapêutico , Bloqueadores dos Canais de Potássio/uso terapêutico , Canais de Potássio Ativados por Cálcio de Condutância Baixa/genética , Canais de Potássio Ativados por Cálcio de Condutância Baixa/metabolismoRESUMO
BACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG.
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Isquemia Encefálica/epidemiologia , Técnicas de Apoio para a Decisão , Ataque Isquêmico Transitório/epidemiologia , Apneia Obstrutiva do Sono/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sono , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.
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Doença de Alzheimer/etnologia , Negro ou Afro-Americano , Demência/etnologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/tratamento farmacológico , LDL-Colesterol/sangue , Demência/sangue , Demência/tratamento farmacológico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Objectives: To understand the impact of the coronavirus disease-2019 pandemic on sleep services within the United States Department of Veterans Affairs using separate surveys from "pre-COVID" and pandemic periods. Methods: Data from a pre-pandemic survey (September to November 2019) were combined with data from a pandemic-period survey (August to November 2020) to Veterans Affairs sleep medicine providers about their local sleep services within 140 Veterans Affairs facilities). Results: A total of 67 (47.9%) facilities responded to the pandemic online survey. In-lab diagnostic and titration sleep studies were stopped at 91.1% of facilities during the pandemic; 76.5% of facilities resumed diagnostic studies and 60.8% resumed titration studies by the time of the second survey. Half of the facilities suspended home sleep testing; all facilities resumed these services. In-person positive airway pressure clinics were stopped at 76.3% of facilities; 46.7% resumed these clinics. Video telehealth was either available or in development at 86.6% of facilities and was considered a lasting addition to sleep services. Coronavirus disease-2019 transmission precautions occurred at high rates. Sleep personnel experienced high levels of stress, anxiety, fear, and burnout because of the pandemic and in response to unexpected changes in sleep medicine care delivery. Conclusions: Sleep medicine services within the Veterans Affairs evolved during the pandemic with many key services being interrupted, including in-lab studies and in-person positive airway pressure clinics. Expansion and initiation of telehealth sleep services occurred commonly. The pandemic adversely affected sleep medicine personnel as they sought to maintain access to care.
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Introduction: The Veteran Affairs (VA) Office of Rural Health (ORH) funded the Veterans Health Administration (VHA) National TeleNeurology Program (NTNP) as an Enterprise-Wide Initiative (EWI). NTNP is an innovative healthcare delivery model designed to fill the patient access gap for outpatient neurological care especially for Veterans residing in rural communities. The specific aim was to apply the RE-AIM framework in a pragmatic evaluation of NTNP services. Materials and methods: We conducted a prospective implementation evaluation. Guided by the pragmatic application of the RE-AIM framework, we conceptualized a mixed-methods evaluation for key metrics: (1) reach into the Veteran patient population assessed as total NTNP new patient consult volume and total NTNP clinical encounters (new and return); (2) effectiveness through configurational analysis of conditions leading to high Veteran satisfaction and referring providers perceived effectiveness; (3) adoption and implementation by VA sites through site staff and NTNP interviews; (4) implementation success through perceived management, implementation barriers, facilitators, and adaptations and through rapid qualitative analysis of multiple stakeholders' assessments; and (5) maintenance of NTNP through monitoring quarterly TeleNeurology consultation volume. Results: NTNP was successfully implemented in 13 VA Medical Centers over 2 years. The total NTNP new patient consult volume in fiscal year 2021 (FY21) was 836 (58% rurally residing); this increased to 1,706 in fiscal year 2022 (FY22) (55% rurally residing). Total (new and follow-up) NTNP clinical encounters were 1,306 in FY21 and 3,730 in FY22. Overall, the sites reported positive experiences with program implementation and perceived that the program was serving Veterans with little access to neurological care. Veterans also reported high satisfaction with the NTNP program. We identified the patient level of perceived excellent teleneurologist-patient communications, reduced need to drive to get care, and that NTNP provided care that the Veteran otherwise could not access as key factors related to high Veteran satisfaction. Conclusions: The VA NTNP demonstrated substantial reach, adoption, effectiveness, implementation success, and maintenance over the first 2 years of the program. The NTNP was highly acceptable to both the clinical providers making the referrals and the Veterans receiving the referred video care. The pragmatic application of the RE-AIM framework to guide implementation evaluations is appropriate, comprehensive, and recommended for future applications.
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Background Obstructive sleep apnea ( OSA ) is common among patients with acute ischemic stroke and transient ischemic attack. We evaluated whether continuous positive airway pressure for OSA among patients with recent ischemic stroke or transient ischemic attack improved clinical outcomes. Methods and Results This randomized controlled trial among patients with ischemic stroke/transient ischemic attack compared 2 strategies (standard or enhanced) for the diagnosis and treatment of OSA versus usual care over 1 year. Primary outcomes were National Institutes of Health Stroke Scale and modified Rankin Scale scores. Among 252 patients (84, control; 86, standard; 82, enhanced), OSA prevalence was as follows: control, 69%; standard, 74%; and enhanced, 80%. Continuous positive airway pressure use occurred on average 50% of nights and was similar among standard (3.9±2.1 mean hours/nights used) and enhanced (4.3±2.4 hours/nights used; P=0.46) patients. In intention-to-treat analyses, changes in National Institutes of Health Stroke Scale and modified Rankin Scale scores were similar across groups. In as-treated analyses among patients with OSA, increasing continuous positive airway pressure use was associated with improved National Institutes of Health Stroke Scale score (no/poor, -0.6±2.9; some, -0.9±1.4; good, -0.3±1.0; P=0.0064) and improved modified Rankin Scale score (no/poor, -0.3±1.5; some, -0.4±1.0; good, -0.9±1.2; P=0.0237). In shift analyses among patients with OSA, 59% of intervention patients had best neurological symptom severity (National Institutes of Health Stroke Scale score, 0-1) versus 38% of controls ( P=0.038); absolute risk reduction was 21% (number needed to treat, 4.8). Conclusions Although changes in neurological functioning and functional status were similar across the groups in the intention-to-treat analyses, continuous positive airway pressure use was associated with improved neurological functioning among patients with acute ischemic stroke/transient ischemic attack with OSA . Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT 01446913.
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Pressão Positiva Contínua nas Vias Aéreas , Ataque Isquêmico Transitório/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Ataque Isquêmico Transitório/epidemiologia , Masculino , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: The literature about the relationship between obstructive sleep apnea (OSA) and stroke location is conflicting with some studies finding an association and others demonstrating no relationship. Among acute ischemic stroke patients, we sought to examine the relationship between stroke location and the prevalence of OSA; OSA severity based on apnea-hypopnea index (AHI), arousal frequency, and measure of hypoxia; and number of central and obstructive respiratory events. METHODS: Data were obtained from patients who participated in a randomized controlled trial (NCT01446913) that evaluated the effectiveness of a strategy of diagnosing and treating OSA among patients with acute ischemic stroke and transient ischemic attack. Stroke location was classified by brain imaging reports into subdivisions of lobes, subcortical areas, brainstem, cerebellum, and vascular territory. The association between acute stroke location and polysomnographic findings was evaluated using logistic regression for OSA presence and negative binomial regression for AHI. RESULTS: Among 73 patients with complete polysomnography and stroke location data, 58 (79%) had OSA. In unadjusted models, no stroke location variable was associated with the prevalence or severity of OSA. Similarly, in multivariable modeling, groupings of stroke location were also not associated with OSA presence. CONCLUSIONS: These results indicate that OSA is present in the majority of stroke patients and imply that stroke location cannot be used to identify a group with higher risk of OSA. The results also suggest that OSA likely predated the stroke. Given this high overall prevalence, strong consideration should be given to obtaining polysomnography for all ischemic stroke patients.
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Infarto Encefálico/complicações , Isquemia Encefálica/complicações , Apneia Obstrutiva do Sono/etiologia , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Infarto Encefálico/patologia , Isquemia Encefálica/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Fatores de RiscoRESUMO
Chronic heart failure is an irremediable terminal syndrome. The inability of the heart to pump sufficient blood to meet the demands of metabolically active tissues is aggravated by reflex increases in peripheral vasoconstriction induced by the sympathoadrenal and renin-angiotensin-aldosterone systems. Vasoconstriction is partially attenuated by atrial natriuretic hormone, prostaglandin, and bradykinin. The aim of therapy is to improve the pumping performance of the heart and reduce arterial and venous constriction in the hope that this will reduce symtoms and improve the quality of life. Many drugs achieve such benefits, at least initially. Inotropic drugs increase cardiac pumping activity, and drugs acting directly on arteries and veins improve cardiac function by reducing afterload and preload. ACE inhibitors suppress angiotensin II formation, reducing its vasoconstrictive action, its ability to increase aldosterone secretion and the consequent salt retention and expansion of plasma volume. Since the proportionate role played by various hemodynamic factors in individual patients in unknown, it is likely that most benefit will be achieved by a combined therapeutic approach.
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BACKGROUND: Utilization rates (URs) for implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden cardiac death (PPSCD) are lacking in the community. OBJECTIVE: The purpose of this study was to establish the ICD UR in central Indiana. METHODS: A query run on 2 hospitals in a health information exchange database in Indianapolis identified patients between 2011 and 2012 with left ventricular ejection fraction (EF) ≤0.35. ICD eligibility and utilization were determined from chart review. RESULTS: We identified 1863 patients with at least 1 low EF study. Two cohorts were analyzed: 1672 patients without and 191 patients with International Classification of Diseases, Ninth Revision, Clinical Modification procedure code 37.94 for ICD placement. We manually reviewed a stratified (by hospital) random sample of 300 patients from the no-ICD procedure code cohort and found that 48 (16%) had no ICD but had class I indications for ICD. Eight of 300 (2.7%) actually had ICD implantation for PPSCD. Review of all 191 patients in the ICD procedure code cohort identified 70 with ICD implantation for PPSCD. The ICD UR (ratio between patients with ICD for PPSCD and all with indication) was 38% overall (95% confidence interval [CI] 28%-49%). URs were 48% for males (95% CI 34%-61%), 21% for females (95% CI 16%-26%, P = .0002 vs males), 40% for whites (95% CI 27%-53%), and 37% for blacks (95% CI 28%-46%, P = .66 vs whites). CONCLUSION: ICD UR is 38% among patients meeting class I indications, suggesting further opportunities for improving guideline compliance. This study also illustrates limitations in calculating ICD UR using large electronic repositories without hands-on chart review.