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OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.
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Epilepsia , População Urbana , Humanos , Masculino , Feminino , Lactente , Criança , Incidência , Epilepsia/epidemiologia , Epilepsia/genética , Pré-Escolar , Adolescente , Cidade de Nova Iorque/epidemiologia , População Urbana/estatística & dados numéricos , Recém-Nascido , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Intravenous dihydroergotamine (DHE) has well-established efficacy for the acute treatment of migraine, but its use is limited by the need for in-hospital administration and the nausea/vomiting associated with a high maximum plasma concentration (Cmax). Inhalation is an alternative to intravenous dosing. The surface area of the lung allows for rapid absorption of a self-administered dose. OBJECTIVE: This study evaluated the safety, tolerability, and systemic pharmacokinetics (PK) of a dry powder formulation (PUR3100) DHE when delivered via inhalation compared to intravenous delivery. METHODS: In this double-blind, double-dummy Phase 1 study, healthy volunteers (N = 26) were randomized (1:1:1:1) to one of four groups: orally inhaled placebo plus intravenous DHE 1.0 mg or orally inhaled PUR3100 (0.5, 1.0, or 1.5 mg) plus intravenous placebo. Blood samples were drawn pre-dose and at time points post-dose over 48 h. Standard PK and safety parameters were assessed and values for Cmax and area under plasma concentration time curve (AUC) were used to assess comparative exposures of PUR3100 versus intravenous DHE. RESULTS: All doses of PUR3100 were associated with a lower incidence of nausea (21% vs. 86%), vomiting (0% vs. 29%), and headache (16% vs. 57%) compared to intravenous DHE. The PK profile of PUR3100 versus intravenous DHE was characterized by a similar mean time to Cmax (5 vs. 5.5 min), with reduced AUC0-2h (1120-4320 vs. 6340), and a lower Cmax (3620-14,400 vs. 45,000). Compared to intravenous DHE 1.0 mg, the highest nominal PUR3100 dose (1.5 mg), which delivers a fine-particle dose of approximately 0.9 mg to the lungs, had a geometric mean ratio percentage (90% confidence interval [CI]) for Cmax of 32% [17.2, 59.6] and AUC0-inf of 93% (62.9, 138.5), the latter of which was not significantly different. CONCLUSIONS: Inhaled PUR3100 is associated with rapid systemic PK within the therapeutic window and an improved safety profile relative to intravenous DHE.
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Administração Intravenosa , Di-Hidroergotamina , Humanos , Di-Hidroergotamina/administração & dosagem , Di-Hidroergotamina/farmacocinética , Di-Hidroergotamina/efeitos adversos , Método Duplo-Cego , Masculino , Adulto , Feminino , Administração por Inalação , Adulto Jovem , Voluntários Saudáveis , Pessoa de Meia-Idade , Inaladores de Pó Seco , AdolescenteRESUMO
OBJECTIVE: Absence seizures result from aberrant thalamocortical processing that confers synchronous, bilateral spike-and-wave discharges (SWDs) and behavioral arrest. Previous work has demonstrated that SWDs can result from enhanced thalamic tonic inhibition, consistent with the mechanism of first-line antiabsence drugs that target thalamic low-voltage-activated calcium channels. However, nearly half of patients with absence epilepsy are unresponsive to first-line medications. In this study we evaluated the role of cortical tonic inhibition and its manipulation on absence seizure expression. METHODS: We used video-electroencephalogram (EEG) monitoring to show that mice with a γ-aminobutyric acid type A (GABAA) receptor mutation (γ2R43Q) display absence seizures. Voltage-clamp recordings in brain slices from wild type and γ2R43Q mice were used to evaluate the amount of tonic inhibition and its selective pharmacological modulation. Finally, we determined whether modulating tonic inhibition controls seizure expression. RESULTS: γ2R43Q mice completely lack tonic inhibition in principal neurons of both layer 2/3 cortex and ventrobasal thalamus. Blocking cortical tonic inhibition in wild type mice is sufficient to elicit SWDs. Tonic inhibition in slices from γ2R43Q mice could be rescued in a dose-dependent fashion by the synthetic neurosteroid ganaxolone. Low-dose ganaxolone suppressed seizures in γ2R43Q mice. CONCLUSIONS: Our data suggest that reduced cortical tonic inhibition promotes absence seizures and that normal function can be restored via selective pharmacological rescue. These results, together with previous findings, suggest that deviations of tonic inhibition either above or below an optimal set point can contribute to absence epilepsy. Returning the thalamocortical system to this set point may provide a novel treatment for refractory absence epilepsy.
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Epilepsia Tipo Ausência , Humanos , Camundongos , Animais , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Tipo Ausência/genética , Convulsões , Encéfalo , Tálamo , EletroencefalografiaRESUMO
PURPOSE: Amyloid positron emission tomography (PET) with [18F]florbetaben (FBB) is an established tool for detecting Aß deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification. METHODS: This is a retrospective analysis of FBB PET images from 589 subjects. PET scans were quantified with 15 analytical methods using nine software packages (MIMneuro, Hermes BRASS, Neurocloud, Neurology Toolkit, statistical parametric mapping (SPM8), PMOD Neuro, CapAIBL, non-negative matrix factorization (NMF), AmyloidIQ) that used several metrics to estimate Aß load (SUVR, centiloid, amyloid load, and amyloid index). Six analytical methods reported centiloid (MIMneuro, standard centiloid, Neurology Toolkit, SPM8 (PET only), CapAIBL, NMF). All results were quality controlled. RESULTS: The mean sensitivity, specificity, and accuracy were 96.1 ± 1.6%, 96.9 ± 1.0%, and 96.4 ± 1.1%, respectively, for all quantitative methods tested when compared to histopathology, where available. The mean percentage of agreement between binary quantitative assessment across all 15 methods and visual majority assessment was 92.4 ± 1.5%. Assessments of reliability, correlation analyses, and comparisons across software packages showed excellent performance and consistent results between analytical methods. CONCLUSION: This study demonstrated that quantitative methods using both CE marked software and other widely available processing tools provided comparable results to visual assessments of FBB PET scans. Software quantification methods, such as centiloid analysis, can complement visual assessment of FBB PET images and could be used in the future for identification of early amyloid deposition, monitoring disease progression and treatment effectiveness.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Estudos Retrospectivos , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/metabolismo , Compostos de Anilina , Tomografia por Emissão de Pósitrons/métodos , Amiloide , Software , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologiaRESUMO
OBJECTIVE: Administrative codes to identify people with rare epilepsies in electronic health records are limited. The current study evaluated the use of keyword search as an alternative method for rare epilepsy cohort creation using electronic health records data. METHODS: Data included clinical notes from encounters with International Classification of Diseases, Ninth Revision (ICD-9) codes for seizures, epilepsy, and/or convulsions during 2010-2014, across six health care systems in New York City. We identified cases with rare epilepsies by searching clinical notes for keywords associated with 33 rare epilepsies. We validated cases via manual chart review. We compared the performance of keyword search to manual chart review using positive predictive value (PPV), sensitivity, and F-score. We selected an initial combination of keywords using the highest F-scores. RESULTS: Data included clinical notes from 77 924 cases with ICD-9 codes for seizures, epilepsy, and/or convulsions. The all-keyword search method identified 6095 candidates, and manual chart review confirmed that 2068 (34%) had a rare epilepsy. The initial combination method identified 1862 cases with a rare epilepsy, and this method performed as follows: PPV median = .64 (interquartile range [IQR] = .50-.81, range = .20-1.00), sensitivity median = .93 (IQR = .76-1.00, range = .10-1.00), and F-score median = .71 (IQR = .63-.85, range = .18-1.00). Using this method, we identified four cohorts of rare epilepsies with over 100 individuals, including infantile spasms, Lennox-Gastaut syndrome, Rett syndrome, and tuberous sclerosis complex. We identified over 50 individuals with two rare epilepsies that do not have specific ICD-10 codes for cohort creation (epilepsy with myoclonic atonic seizures, Sturge-Weber syndrome). SIGNIFICANCE: Keyword search is an effective method for cohort creation. These findings can improve identification and surveillance of individuals with rare epilepsies and promote their referral to specialty clinics, clinical research, and support groups.
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Epilepsias Mioclônicas , Epilepsia , Síndrome de Lennox-Gastaut , Humanos , Registros Eletrônicos de Saúde , Epilepsia/diagnóstico , Epilepsia/epidemiologia , ConvulsõesRESUMO
Accurate coregistration of computed tomography (CT) and magnetic resonance (MR) imaging can provide clinically relevant and complementary information and can serve to facilitate multiple clinical tasks including surgical and radiation treatment planning, and generating a virtual Positron Emission Tomography (PET)/MR for the sites that do not have a PET/MR system available. Despite the long-standing interest in multimodality co-registration, a robust, routine clinical solution remains an unmet need. Part of the challenge may be the use of mutual information (MI) maximization and local phase difference (LPD) as similarity metrics, which have limited robustness, efficiency, and are difficult to optimize. Accordingly, we propose registering MR to CT by mapping the MR to a synthetic CT intermediate (sCT) and further using it in a sCT-CT deformable image registration (DIR) that minimizes the sum of squared differences. The resultant deformation field of a sCT-CT DIR is applied to the MRI to register it with the CT. Twenty-five sets of abdominopelvic imaging data are used for evaluation. The proposed method is compared to standard MI- and LPD-based methods, and the multimodality DIR provided by a state of the art, commercially available FDA-cleared clinical software package. The results are compared using global similarity metrics, Modified Hausdorff Distance, and Dice Similarity Index on six structures. Further, four physicians visually assessed and scored registered images for their registration accuracy. As evident from both quantitative and qualitative evaluation, the proposed method achieved registration accuracy superior to LPD- and MI-based methods and can refine the results of the commercial package DIR when using its results as a starting point. Supported by these, this manuscript concludes the proposed registration method is more robust, accurate, and efficient than the MI- and LPD-based methods.
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Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Algoritmos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: We aimed to describe how often and why clinicians counsel people with epilepsy about sudden unexpected death in epilepsy (SUDEP). Understanding counseling gaps can help design interventions. METHODS: We searched clinical notes of 77,924 patients from 2010 to 2014 from six hospitals to find examples of SUDEP counseling and seizure safety counseling. Visits were coded for patient, clinician, and visit factors, and documented reasons for counseling. We evaluated factors associated with SUDEP vs. seizure safety counseling, and reasons for counseling using bivariate and multivariable statistics. Reasons for counseling included: poor medication adherence, lifestyle factors (e.g., poor sleep, drinking alcohol), patient/family reluctance to make recommended medication adjustment, epilepsy surgery considerations, and patient education only. RESULTS: Analysis was restricted to two of six hospitals where 91% of counseling occurred. Documentation of SUDEP counseling was rare (332 of 33,821 patients, 1.0%), almost exclusively by epileptologists (98.5% of counseling), and stable over time, X2 (4, nâ¯=â¯996)â¯=â¯3.81, pâ¯=â¯0.43. Adult neurologists were more likely to document SUDEP counseling than pediatric (ORâ¯=â¯1.65, 95% CIâ¯=â¯1.12-2.44). Most SUDEP counseling was documented with a goal of seizure reduction (214 of 332, 64.5%), though some was for patient education only (118 of 332, 35.5%). By the time SUDEP counseling was documented, the majority of patients had refractory epilepsy (187 of 332, 56.3%) and/or a potentially modifiable risk factor (214 of 332, 64.5%). Neurologists with more years of clinical experience (ORâ¯=â¯2.18, 95% CIâ¯=â¯1.12-4.25) and more senior academic titles (ORâ¯=â¯2.25, 95% CIâ¯=â¯1.27-3.99) were more likely to document SUDEP counseling for patient education only. People with ≥2 anti-seizure medications (ASM) were more likely to receive counseling for patient education (ORâ¯=â¯2.72, 95% CIâ¯=â¯1.49-4.97). CONCLUSIONS: Documentation of SUDEP is rare, and varies by clinician, hospital, and patient factors. Efforts to increase SUDEP counseling should focus on junior clinicians, and emphasize starting the conversation soon after onset of epilepsy.
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Epilepsia , Morte Súbita Inesperada na Epilepsia , Adulto , Criança , Aconselhamento , Morte Súbita/epidemiologia , Morte Súbita/prevenção & controle , Epilepsia/complicações , Epilepsia/terapia , Humanos , Fatores de Risco , ConvulsõesRESUMO
BACKGROUND: Neurologists need to be adept at disclosing prognosis and breaking bad news. Objective structured clinical examinations (OSCE) allow trainees to practice these skills. METHODS: In 2017, in conjunction with the NYU School of Medicine Simulation Center, neurology faculty designed an OSCE case in which a resident had to inform a standardized patient (SP) her father had severe global hypoxic ischemic injury. The residents were surveyed on the experience using a Likert scale from 1 (worst) to 5 (best). The SP completed a behavioral anchored checklist and marked items as "not done," "partly done," or "well done". RESULTS: 57 third and fourth year neurology residents completed the case from 2018 to 2020, 54 (95%) of whom completed the post-OSCE survey. Residents reported feeling moderately prepared for the simulation (mean Likert score 3.7/5), and thought their performance was average (3.4/5). Overall, they found the case to be very helpful (4.6/5). The residents performed well in the realms of maintaining professionalism (64% rated "well done"), developing a relationship (62% rated "well done"), and information gathering (61% rated "well done"). There was room for improvement in the realms of providing education and presenting the bad news (39% and 37% rated "partly/not done," respectively). CONCLUSIONS: OSCE cases can be used to teach neurology trainees how to discuss prognosis and break bad news. Feedback about this simulation was positive, though its efficacy has yet to be evaluated and could be a future direction of study.
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Educação de Pós-Graduação em Medicina , Avaliação Educacional , Hipóxia-Isquemia Encefálica/terapia , Internato e Residência , Neurologistas/educação , Neurologia/educação , Relações Profissional-Família , Treinamento por Simulação , Revelação da Verdade , Adulto , Idoso , Atitude do Pessoal de Saúde , Lista de Checagem , Comunicação , Currículo , Escolaridade , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/fisiopatologia , Masculino , Neurologistas/psicologia , Núcleo Familiar , Papel do Médico , Prognóstico , Análise e Desempenho de TarefasRESUMO
BACKGROUND AND PURPOSE: The aim of this study was to evaluate an automatic multi-atlas-based segmentation method for generating prostate, peripheral (PZ), and transition zone (TZ) contours on MRIs with and without fat saturation (±FS), and compare MRIs from different vendor MRI systems. METHODS: T2-weighted (T2) and fat-saturated (T2FS) MRIs were acquired on 3T GE (GE, Waukesha, WI, USA) and Siemens (Erlangen, Germany) systems. Manual prostate and PZ contours were used to create atlas libraries. As a test MRI is entered, the procedure for atlas segmentation automatically identifies the atlas subjects that best match the test subject, followed by a normalized intensity-based free-form deformable registration. The contours are transformed to the test subject, and Dice similarity coefficients (DSC) and Hausdorff distances between atlas-generated and manual contours were used to assess performance. RESULTS: Three atlases were generated based on GE_T2 (nâ¯= 30), GE_T2FS (nâ¯= 30), and Siem_T2FS (nâ¯= 31). When test images matched the contrast and vendor of the atlas, DSCs of 0.81 and 0.83 for T2⯱ FS were obtained (baseline performance). Atlases performed with higher accuracy when segmenting (i) T2FS vs. T2 images, likely due to a superior contrast between prostate vs. surrounding tissue; (ii) prostate vs. zonal anatomy; (iii) in the mid-gland vs. base and apex. Atlases performance declined when tested with images with differing contrast and MRI vendor. Conversely, combined atlases showed similar performance to baseline. CONCLUSION: The MRI atlas-based segmentation method achieved good results for prostate, PZ, and TZ compared to expert contoured volumes. Combined atlases performed similarly to matching atlas and scan type. The technique is fast, fully automatic, and implemented on commercially available clinical platform.
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Anatomia Artística , Atlas como Assunto , Comércio , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Próstata/anatomia & histologia , Próstata/diagnóstico por imagem , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética/instrumentação , Masculino , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. However, there is a gap in how often providers counsel patients about SUDEP. One potential solution is to electronically prompt clinicians to provide counseling via automated detection of risk factors in electronic medical records (EMRs). We evaluated (1) the feasibility and generalizability of using regular expressions to identify risk factors in EMRs and (2) barriers to generalizability. METHODS: Data included physician notes for 3000 patients from one medical center (home) and 1000 from five additional centers (away). Through chart review, we identified three SUDEP risk factors: (1) generalized tonic-clonic seizures, (2) refractory epilepsy, and (3) epilepsy surgery candidacy. Regular expressions of risk factors were manually created with home training data, and performance was evaluated with home test and away test data. Performance was evaluated by sensitivity, positive predictive value, and F-measure. Generalizability was defined as an absolute decrease in performance by <0.10 for away versus home test data. To evaluate underlying barriers to generalizability, we identified causes of errors seen more often in away data than home data. To demonstrate how small revisions can improve generalizability, we removed three "boilerplate" standard text phrases from away notes and repeated performance. RESULTS: We observed high performance in home test data (F-measure range = 0.86-0.90), and low to high performance in away test data (F-measure range = 0.53-0.81). After removing three boilerplate phrases, away performance improved (F-measure range = 0.79-0.89) and generalizability was achieved for nearly all measures. The only significant barrier to generalizability was use of boilerplate phrases, causing 104 of 171 errors (61%) in away data. SIGNIFICANCE: Regular expressions are a feasible and probably a generalizable method to identify variables related to SUDEP risk. Our methods may be implemented to create large patient cohorts for research and to generate electronic prompts for SUDEP counseling.
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Morte Súbita/epidemiologia , Epilepsia/mortalidade , Processamento de Linguagem Natural , Morte Súbita Inesperada na Epilepsia/epidemiologia , Algoritmos , Estudos Transversais , Interpretação Estatística de Dados , Epilepsia Resistente a Medicamentos/mortalidade , Registros Eletrônicos de Saúde , Epilepsia Tônico-Clônica/mortalidade , Humanos , Neurocirurgia/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
During movement, modulation of beta power occurs over the sensorimotor areas, with a decrease just before its start (event-related desynchronization, ERD) and a rebound after its end (event-related synchronization, ERS). We have recently found that the depth of ERD-to-ERS modulation increases during practice in a reaching task and the following day decreases to baseline levels. Importantly, the magnitude of the beta modulation increase during practice is highly correlated with the retention of motor skill tested the following day. Together with other evidence, this suggests that the increase of practice-related modulation depth may be the expression of sensorimotor cortex's plasticity. Here, we determine whether the practice-related increase of beta modulation depth is equally present in a group of younger and a group of older subjects during the performance of a 30-minute block of reaching movements. We focused our analyses on two regions of interest (ROIs): the left sensorimotor and the frontal region. Performance indices were significantly different in the two groups, with the movements of older subjects being slower and less accurate. Importantly, both groups presented a similar increase of the practice-related beta modulation depth in both ROIs in the course of the task. Peak latency analysis revealed a progressive delay of the ERS peak that correlated with the total movement time. Altogether, these findings support the notion that the depth of beta modulation in a reaching movement task does not depend on age and confirm previous findings that only ERS peak latency but not ERS magnitude is related to performance indices.
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Envelhecimento/fisiologia , Ritmo beta/fisiologia , Encéfalo/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Fatores Etários , Idoso , Fenômenos Biomecânicos/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
CONTEXT: Athletes who have undergone an anterior cruciate ligament reconstruction often demonstrate more pronounced interlimb knee kinetic symmetry in comparison with uninjured athletes, even after they have completed rehabilitation. Part of the reason for the persistent asymmetry may be that sports medicine professionals are typically not able to assess knee joint kinetics within the clinic setting. Developing measures to assess knee joint kinetic symmetry could help to augment current rehabilitation practices. OBJECTIVE: The purpose of this study was to explore the extent to which interlimb vertical ground reaction force (GRF) symmetry can predict knee kinetic symmetry during a drop landing task. DESIGN: Cross-sectional study. SETTING: Motion analysis laboratory. PARTICIPANTS: A total of 21 uninjured subjects (9 males and 12 females). PROTOCOL: Three-dimensional kinematic data were collected using a multicamera system while subjects performed double-leg drop landings. GRF data were collected synchronously using 2 adjacent force plates. MAIN OUTCOME MEASURES: Knee joint moments and power were calculated for both limbs during the landing trials. An interlimb symmetry index (dominant/nondominant limb) was calculated for both the peak knee joint moment and power variables, as well as for the peak vertical GRFs. Linear regression analyses were performed to determine if the degree of symmetry in the peak vertical GRFs predicted the degree of symmetry for the kinetic variables. RESULTS: The symmetry index for the vertical GRFs was a significant predictor of the symmetry indices for the knee joint moments (r = .81; P < .001) and power (r = .88; P < .001). CONCLUSION: Interlimb symmetry in the peak vertical GRFs can be used to predict knee joint kinetic symmetry during a double-leg drop landing task.
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Fenômenos Biomecânicos , Teste de Esforço/instrumentação , Articulação do Joelho/fisiologia , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Movimento , Amplitude de Movimento Articular , Adulto JovemRESUMO
BACKGROUND: Understanding the epidemiology of injuries to athletes is essential to informing injury prevention efforts. HYPOTHESIS: The incidence and impact of basketball-related injuries among National Basketball Association (NBA) players from 2013-2014 through 2018-2019 is relatively stable over time. STUDY DESIGN: Descriptive epidemiology study. LEVEL OF EVIDENCE: Level 3. METHODS: Injuries from 2013-2014 through 2018-2019 were analyzed using the NBA Injury and Illness Database from an electronic medical record system. Descriptive statistics were calculated for injuries by season, game-loss, and onset. Incidence rates were estimated using Poisson models and linear trend tests. RESULTS: Between 552 and 606 players participated in ≥1 game per season during the study. Annual injury incidence ranged from 1550 to 1892, with 33.6% to 38.5% resulting in a missed NBA game. Game-loss injury rates ranged from 5.6 to 7.0 injuries per 10,000 player-minutes from 2014-2015 through 2018-2019 (P = 0.19); the rate was lower in 2013-2014 (5.0 injuries per 10,000 player-minutes), partly due to increased preseason injury rates and transition of reporting processes. The 6-year game-loss injury rate in preseason and regular season games was 6.9 (95% CI 6.0, 8.0) and 6.2 (95% CI 6.0, 6.5) injuries per 10,000 player-minutes; the rate in playoff games was lower (P < 0.01) at 2.8 (95% CI 2.2, 3.6). Most (73%) game-loss injuries had acute onset; 44.4% to 52.5% of these involved contact with another player. CONCLUSION: From 2013-2014 through 2018-2019, over one-third of injuries resulted in missed NBA games, with highest rates of game-loss injuries in preseason games and lowest rates in playoff games. Most game-loss injuries had acute onset, and half of those involved contact with another player. CLINICAL RELEVANCE: These findings - through reliable data reporting by team medical staff in an audited system - can guide evidence-based injury reduction strategies and inform player health priorities.
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Since response to antigen-based immunotherapy relies upon the level of tumor antigen expression we developed an antigen quantification assay using ABC values. Antigen quantification as a clinical assay requires methods for quality control and for interlaboratory and inter-cytometer platform standardization. A single lot of Cytotrol™ Lyophilized Control Cells (Beckman Coulter) used for all studies. The variability in antigen quantification across 4 different instrument platforms in 2 separate laboratories was evaluated. The effect of the antibody clone utilized, importance of custom 1:1 molar ratio (fluorophore to protein, F/P) verses off-the-shelf antibodies, and QuantiBrite PE calibration verses linearity calibration combined with a single point scale transformation with CD4 as reference were determined. Use of single lot control cells allowed validation of reproducibility between flow cytometer platforms and laboratories and allowed assessment of different antibody lots, cocktail preparation, and different antibody clones. Off the shelf antibody preparations provide reproducible estimates of antigen density, however custom 1:1 unimolar antibody preparations should be utilized for definitive measurement of antigen expression.Geometric Mean fluorescent Intensity (GeoMFI) was not comparable across instruments and inter-laboratory. The use of CD4 as the reference marker can minimize variability in ABC values. Comparable antigen quantification is vital in managing patients receiving antigen-based immunotherapy. If this assay is to be utilized in a clinical setting, quality control methods have to be instituted to assure reproducibility and allow validation across laboratories. We have demonstrated that use of a lyophilized cell control is highly valuable in achieveing these goals.
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Anticorpos , Antígenos , Humanos , Citometria de Fluxo/métodos , Reprodutibilidade dos Testes , Padrões de ReferênciaRESUMO
Importance: Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity. Objective: To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge. Design, Setting, and Participants: This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021. Exposure: Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke. Main Outcomes and Measures: The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition. Results: Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge. Conclusions and Relevance: The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.
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COVID-19 , Hospitalização , Doenças do Sistema Nervoso , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Criança , Feminino , Masculino , Pré-Escolar , Hospitalização/estatística & dados numéricos , Adolescente , Estudos Prospectivos , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/epidemiologia , Lactente , Índice de Gravidade de DoençaRESUMO
Prion formation involves the conversion of soluble proteins into an infectious amyloid form. This process is highly specific, with prion aggregates templating the conversion of identical proteins. However, in some cases non-identical prion proteins can interact to promote or inhibit prion formation or propagation. These interactions affect both the efficiency with which prion diseases are transmitted across species and the normal physiology of yeast prion formation and propagation. Here we examine two types of heterologous prion interactions: interactions between related proteins from different species (the species barrier) and interactions between unrelated prion proteins within a single species. Interestingly, although very subtle changes in protein sequence can significantly reduce or eliminate cross-species prion transmission, in Saccharomyces cerevisiae completely unrelated prion proteins can interact to affect prion formation and propagation.
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Amiloide/metabolismo , Glutationa Peroxidase/metabolismo , Príons/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Glutationa Peroxidase/química , Modelos Moleculares , Plasmídeos/genética , Príons/química , Estrutura Quaternária de Proteína , Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Especificidade da EspécieRESUMO
BACKGROUND: Neurology faculty care for complex patients, teach, and work within multidisciplinary teams. It is imperative for faculty to have strong communication skills. METHODS: We surveyed NYU neurology teaching faculty to determine levels of comfort and experience over the past year with providing negative feedback to a trainee; debriefing after an adverse clinical outcome; and assisting a struggling colleague. We examined the relationship between levels of comfort and experience with 1) faculty self-identified sex and 2) number of years since completion of medical training. RESULTS: The survey was completed by 36/83 teaching neurology faculty (43â¯%); 17 (47â¯%) respondents were female and 21 (58â¯%) were ≤10â¯years post-training. The proportions of faculty who reported feeling uncomfortable were 44â¯% (16/36) for assisting a struggling colleague, 28â¯% (10/36) for providing negative feedback, and 19â¯% (7/36) for debriefing an adverse outcome. Proportions of faculty who reported they had no experience were 75â¯% (27/36) for assisting a struggling colleague, 39â¯% (14/36) for debriefing an adverse clinical event, and 17â¯% (6/36) for providing negative feedback. Female respondents and faculty who were ≤10â¯years post-training were more likely to report feeling uncomfortable with assisting a struggling colleague and to have had no experience doing so in the past year. On multivariate analyses accounting for sex and experience, sex remained independently associated with feeling uncomfortable with assisting a struggling colleague (ORâ¯=â¯12.2, 95â¯% CI: 2.1-69.6, pâ¯=â¯0.005). CONCLUSION: Faculty development may be needed to improve comfort and experience with challenging communication-based interactions. Female faculty and faculty early in their careers may benefit most.
Assuntos
Internato e Residência , Neurologia , Humanos , Feminino , Masculino , Docentes , Emoções , Comunicação , Competência ClínicaRESUMO
BACKGROUND: We summarize the history of individuals with Sturge-Weber syndrome (SWS) to inform clinical trial design and identify variations in care. METHODS: We performed retrospective chart review of individuals with SWS from centers in New York City. We characterized data quality using a novel scoring system. For 13 clinical concepts, we evaluated if data were present and if they were of high quality. RESULTS: We included 26 individuals with SWS (58% female; median age at initial visit 7 years; absolute range 1 month to 56 years]). Twenty-two had nevus flammeus, 13 glaucoma, four homonymous hemianopia, and 15 hemiparesis. Nineteen of 21 had at least one confirmed seizure with a known first seizure date, all before 24 months. Most (18 of 26, 69%) epilepsy was controlled. A plurality (10 of 23, 43%) had either normal cognitive function or mild cognitive delays. Aspirin use varied by site (P = 0.02)-at four sites, use was 0% (zero of three), 0% (zero of four), 80% (four of five), and 64% (nine of 14). Data were present for more than 75% of cases for 11 of 13 clinical concepts (missing: age of diagnosis, age of glaucoma onset). There were gaps in level of detail for motor impairments, glaucoma severity, seizure history, cognition, and medication history. CONCLUSIONS: Clinical charts have important gaps in the level of detail around core SWS clinical features, limiting value for some natural history studies. Any clinical trial in SWS designed to prevent epilepsy should begin in the first year of life. Variations in use of aspirin suggest de facto clinical equipoise and warrant a comparative effectiveness study.
Assuntos
Epilepsia , Glaucoma , Síndrome de Sturge-Weber , Humanos , Feminino , Criança , Masculino , Estudos Retrospectivos , Síndrome de Sturge-Weber/diagnóstico , Convulsões , Epilepsia/epidemiologia , Epilepsia/terapia , Epilepsia/diagnóstico , Glaucoma/diagnóstico , AspirinaRESUMO
Patient-specific dosimetry in radiopharmaceutical therapy (RPT) is impeded by the lack of tools that are accurate and practical for the clinic. Our aims were to construct and test an integrated voxel-level pipeline that automates key components (organ segmentation, registration, dose-rate estimation, and curve fitting) of the RPT dosimetry process and then to use it to report patient-specific dosimetry in 177Lu-DOTATATE therapy. Methods: An integrated workflow that automates the entire dosimetry process, except tumor segmentation, was constructed. First, convolutional neural networks (CNNs) are used to automatically segment organs on the CT portion of one post-therapy SPECT/CT scan. Second, local contour intensity-based SPECT--SPECT alignment results in volume-of-interest propagation to other time points. Third, dose rate is estimated by explicit Monte Carlo (MC) radiation transport using the fast, Dose Planning Method code. Fourth, the optimal function for dose-rate fitting is automatically selected for each voxel. When reporting mean dose, we apply partial-volume correction, and uncertainty is estimated by an empiric approach of perturbing segmentations. Results: The workflow was used with 4-time-point 177Lu SPECT/CT imaging data from 20 patients with 77 neuroendocrine tumors, segmented by a radiologist. CNN-defined kidneys resulted in high Dice values (0.91-0.94) and only small differences (2%-5%) in mean dose when compared with manual segmentation. Contour intensity-based registration led to visually enhanced alignment, and the voxel-level fitting had high R 2 values. Across patients, dosimetry results were highly variable; for example, the average of the mean absorbed dose (Gy/GBq) was 3.2 (range, 0.2-10.4) for lesions, 0.49 (range, 0.24-1.02) for left kidney, 0.54 (range, 0.31-1.07) for right kidney, and 0.51 (range, 0.27-1.04) for healthy liver. Patient results further demonstrated the high variability in the number of cycles needed to deliver hypothetical threshold absorbed doses of 23 Gy to kidney and 100 Gy to tumor. The uncertainty in mean dose, attributable to variability in segmentation, averaged 6% (range, 3%-17%) for organs and 10% (range, 3%-37%) for lesions. For a typical patient, the time for the entire process was about 25 min (â¼2 min manual time) on a desktop computer, including time for CNN organ segmentation, coregistration, MC dosimetry, and voxel curve fitting. Conclusion: A pipeline integrating novel tools that are fast and automated provides the capacity for clinical translation of dosimetry-guided RPT.
Assuntos
Tumores Neuroendócrinos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos , Radiometria/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Tumores Neuroendócrinos/tratamento farmacológico , Radioisótopos , Receptores de PeptídeosRESUMO
BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.