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PURPOSE: Assessing expertise using psychometric models usually yields a measure of ability that is difficult to generalize to the complexity of diagnoses in clinical practice. However, using an item response modeling framework, it is possible to create a decision-aligned response model that captures a clinician's decision-making behavior on a continuous scale that fully represents competing diagnostic possibilities. In this proof-of-concept study, the authors demonstrate the necessary statistical conceptualization of this model using a specific electrocardiogram (ECG) example. METHOD: The authors collected a range of ECGs with elevated ST segments due to either ST-elevation myocardial infarction (STEMI) or pericarditis. Based on pilot data, 20 ECGs were chosen to represent a continuum from "definitely STEMI" to "definitely pericarditis," including intermediate cases in which the diagnosis was intentionally unclear. Emergency medicine and cardiology physicians rated these ECGs on a 5-point scale ("definitely STEMI" to "definitely pericarditis"). The authors analyzed these ratings using a graded response model showing the degree to which each participant could separate the ECGs along the diagnostic continuum. The authors compared these metrics with the discharge diagnoses noted on chart review. RESULTS: Thirty-seven participants rated the ECGs. As desired, the ECGs represented a range of phenotypes, including cases where participants were uncertain in their diagnosis. The response model showed that participants varied both in their propensity to diagnose one condition over another and in where they placed the thresholds between the 5 diagnostic categories. The most capable participants were able to meaningfully use all categories, with precise thresholds between categories. CONCLUSIONS: The authors present a decision-aligned response model that demonstrates the confusability of a particular ECG and the skill with which a clinician can distinguish 2 diagnoses along a continuum of confusability. These results have broad implications for testing and for learning to manage uncertainty in diagnosis.
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Cardiología , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico , Incertidumbre , Arritmias Cardíacas , Electrocardiografía/métodosRESUMEN
The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.).
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BACKGROUND: Little is known about baseline diastolic dysfunction and changes in diastolic dysfunction grade after transcatheter aortic valve replacement (TAVR) for aortic stenosis (AS) and its impact on overall outcomes. The aim of this study was to describe baseline diastolic dysfunction and changes in diastolic dysfunction grade that occur with TAVR and their relationship to mortality and rehospitalization. METHODS: This was a single-center study evaluating all TAVRs from January 2012 to June 2014. We compared parameters of diastolic dysfunction grade on pre-TAVR and 1 month post-TAVR echocardiograms for all patients undergoing the procedure. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. RESULTS: Of a sample size of 120 patients undergoing TAVR for symptomatic severe AS, 90 were included in the final analysis after excluding significant mitral valve disease. There were improvements in individual parameters of diastolic dysfunction grade such as lateral e' velocity, E/lateral e', and left atrial volume index (nonsignificant trend) in the setting of improvement in aortic valve area and gradients and functional class pre- and post-TAVR. Multivariate analysis revealed that baseline diastolic dysfunction grade, but not post-TAVR or changes in diastolic dysfunction grade, was associated with 1-year death (hazard ratio, 1.163; 95% CI, 1.049-1.277, P = .005) and combined death/cardiovascular hospitalization (hazard ratio, 1.174; 95% CI, 1.032-1.318; P = .018). CONCLUSIONS: In this single-center retrospective study of patients with symptomatic severe AS who underwent TAVR, several diastolic function parameters improved on echocardiography, but baseline diastolic dysfunction grade remained the most important echocardiographic factor associated with adverse 1-year outcomes.
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Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/cirugía , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias/mortalidad , Volumen Sistólico , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Disfunción Ventricular Izquierda/mortalidad , Adolescente , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Causalidad , Chicago/epidemiología , Comorbilidad , Ecocardiografía/estadística & datos numéricos , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Complicaciones Posoperatorias/diagnóstico por imagen , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Reemplazo de la Válvula Aórtica Transcatéter/estadística & datos numéricos , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/prevención & controlRESUMEN
Frailty is a syndrome of older adults associated with increased morbidity and mortality. We aimed to assess the impact of frailty status on outcomes after transcatheter aortic valve implantation (TAVI). We reviewed all 191 patients who underwent a modified Fried frailty assessment before TAVI between February 2012 and September 2015 at a single academic medical center, and we assessed the impact of preoperative frailty status on morbidity, mortality, and health care utilization after TAVI. Frailty, pre-frailty, and nonfrailty were present in 33% (n = 64), 37% (n = 70), and 30% (n = 57) of patients, respectively. Slowness (75% vs 54%, p = 0.003) and low physical activity (55% vs 31%, p = 0.001) were more common in women than men. With increasing frailty status, the proportion of women increased (35% nonfrail, 44% pre-frail, and 66% frail, p = 0.002) and stature decreased (1.68 ± 0.11 m nonfrail, 1.66 ± 0.11 m pre-frail, 1.62 ± 0.12 m frail, p = 0.028). There was no difference in post-TAVI 30-day mortality, stroke, major vascular injury, major or life-threatening bleeding, respiratory failure, mean hospital length of stay, 30-day hospital re-admission, or overall survival between groups. The rate of discharge to a rehabilitation facility increased with increasing frailty status (14% nonfrail, 22% pre-frail, and 39% frail, p = 0.005). Frailty was independently associated with discharge to a rehabilitation facility (odds ratio 4.80, 95% confidence interval 1.66 to 13.85, p = 0.004). In conclusion, the safety of TAVI is not affected by frailty status, but patients with frailty are less likely to be discharged directly home after TAVI.
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Estenosis de la Válvula Aórtica/cirugía , Anciano Frágil , Medición de Riesgo/métodos , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/mortalidad , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Periodo Posoperatorio , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
The aim of this study was to determine the influence of inhospital and post-discharge worsening renal function (WRF) on prognosis after transcatheter aortic valve replacement (TAVR). Severe chronic kidney disease and inhospital WRF are both associated with poor outcomes after TAVR. There are no data available on post-discharge WRF and outcomes. This was a single-center study evaluating all TAVR from June 1, 2008, to June 31, 2014. WRF was defined as an increase in serum creatinine of ≥0.3 mg/dl. Inhospital WRF was measured from day 0 until discharge or day 7 if the hospitalization was >7 days. Post-discharge WRF was measured at 30 days after discharge. Descriptive statistics, Kaplan-Meier time-to-event analysis, and multivariate logistic regression were used. In a series of 208 patients who underwent TAVR, 204 with complete renal function data were used in the inhospital analysis and 168 who returned for the 30-day follow-up were used in the post-discharge analysis. Inhospital WRF was seen in 28%, whereas post-discharge WRF in 12%. Inhospital and post-discharge WRF were associated with lower rates of survival; however, after multivariate analysis, only post-discharge WRF remained a predictor of 1-year mortality (hazard ratio 1.18, p = 0.030 for every 1 mg/dl increase in serum creatinine). In conclusion, the rate of inhospital WRF is higher than the rate of post-discharge WRF after TAVR, and post-discharge WRF is more predictive of mortality than inhospital WRF.
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Estenosis de la Válvula Aórtica/cirugía , Creatinina/sangre , Hospitalización , Riñón/fisiopatología , Complicaciones Posoperatorias , Insuficiencia Renal/fisiopatología , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/fisiopatología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Pruebas de Función Renal , Masculino , Alta del Paciente , Pronóstico , Insuficiencia Renal/sangre , Insuficiencia Renal/etiología , Estudios Retrospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
AIMS: Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. METHODS AND RESULTS: We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). CONCLUSION: In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. TRIAL REGISTRATION: NCT01030991.
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Insuficiencia Cardíaca , Ventrículos Cardíacos , Insuficiencia Renal Crónica , Volumen Sistólico , Anciano , Anciano de 80 o más Años , Comorbilidad , Ecocardiografía/métodos , Femenino , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Estados Unidos/epidemiologíaRESUMEN
The ubiquitin-proteasome system (UPS) plays a critical role in protein degradation. The 19S regulatory particle (RP) of the 26S proteasome mediates the recognition, deubiquitylation, unfolding, and channeling of ubiquitylated substrates to the 20S proteasome. Several subunits of the 19S RP interact with a growing number of factors. The cyclophilin-like domain (CLD) of Ran-binding protein-2 (RanBP2/Nup358) associates specifically with at least one subunit, S1, of the base subcomplex of the 19S RP, but the functional implications of this interaction on the UPS activity are elusive. This study shows the CLD of RanBP2 promotes selectively the accumulation of a subset of reporter substrates of the UPS, such as the ubiquitin (Ub)-fusion yellow fluorescent protein (YFP) degradation substrate, Ub(G76V)-YFP, and the N-end rule substrate, Ub-R-YFP. Conversely, the degradation of endoplasmic reticulum and misfolded proteins, and of those linked to UPS-independent degradation, is not affected by CLD. The selective effect of CLD on the UPS in vivo is independent of, and synergistic with, proteasome inhibitors, and CLD does not affect the intrinsic proteolytic activity of the 20S proteasome. The inhibitory activity of CLD on the UPS resides in a purported SUMO binding motif. We also found two RanBP2 substrates, RanGTPase-activating protein and retinitis pigmentosa GTPase regulator interacting protein-1alpha1, whose steady-state levels are selectively modulated by CLD. Hence, the CLD of RanBP2 acts as a novel auxiliary modulator of the UPS activity; it may contribute to the molecular and subcellular compartmentation of the turnover of properly folded proteins and modulation of the expressivity of several neurological diseases.
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Ciclofilinas/química , Chaperonas Moleculares/química , Chaperonas Moleculares/fisiología , Proteínas de Complejo Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/fisiología , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas/química , Ubiquitina/química , Secuencias de Aminoácidos , Animales , Proteínas Bacterianas/química , Células COS , Bovinos , Línea Celular , Chlorocebus aethiops , Inhibidores Enzimáticos/farmacología , Proteínas Luminiscentes/química , Modelos Genéticos , Complejo de la Endopetidasa Proteasomal/química , Inhibidores de Proteasoma , Estructura Terciaria de Proteína , Proteínas Recombinantes de Fusión/químicaRESUMEN
This study examined the relation between parental coping styles, discipline, and child behavior before and after participating in a parent training program for parents of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and oppositional behavior. For mothers, use of more maladaptive and less adaptive coping styles was related to more self-reported lax and overreactive discipline, more observed coercive parenting, and more observed child misbehavior prior to parent training. No significant relations were found for mothers following parent training after controlling for pretreatment variables. For fathers, use of more maladaptive and less adaptive coping styles was related to self-reported lax discipline before and after parent training. Contrary to prediction, fathers who reported less seeking support and adaptive-focused coping showed the most improvement in their children's behavior. Most results remained significant after controlling for self-reported depression. Implications for improving parent training research and programs were discussed.