RESUMEN
OBJECTIVE: This study aimed to evaluate the sensitivity of a digital platform to assess attentional and executive function in systemic lupus erythematosus (SLE) patients, and to evaluate the impact of an at-home interactive digital treatment to improve cognitive dysfunction in this clinical population. BACKGROUND: Deficits in attention and executive function are common in patients with SLE. Despite these cognitive difficulties, there are limited brief assessment techniques and few treatment options to improve cognitive abilities in patients with SLE. Interactive digital treatment approaches (use of video game-based software) have been successful in identifying and improving cognition in other clinical populations. METHODS: Sixty SLE patients completed baseline neuropsychological tests (of attention, psychomotor speed, and executive function), a tablet-based digital platform (EVOTM Monitor), and biobehavioral measures. The patients were randomized into treatment SLE (n = 30) or no contact control SLE (n = 30) groups, and returned 4 weeks later for follow-up cognitive, EVO Monitor, and biobehavioral testing. The SLE treatment group was trained on a tablet-based digital treatment (AKL-T01) and was instructed to complete 5 sessions at least 5 days per week for 4-weeks for a total of approximately 25 min of gameplay per day. RESULTS: Systemic lupus erythematosus patients demonstrated impairment in visuomotor and processing speed, visual attention, and cognitive flexibility/sequencing skills at baseline. The video game-like treatment group (AKL-T01) had significant improvement in visuomotor speed (Trail Making A) and cognitive flexibility/sequencing (Trail Making B) compared to the control group at 4-week follow-up. The treatment group also demonstrated significant improvement in EVO Monitor multitasking at follow-up (with no change in controls). At baseline, a multitasking metric from EVO Monitor was associated with performance on tasks of cognitive flexibility (Trail Making B) and psychomotor speed (WAIS-IV Coding). CONCLUSIONS: These findings provide evidence that SLE patients who participated in a 4-week interactive digital video game-like activity had significant improvement in motor speed and executive functions, and would benefit from participation in digital interventions designed to target frontoparietal networks of the brain. Preliminary findings also suggest specific metrics from EVO Monitor may also be useful to detect cognitive impairment and cognitive changes in patients with SLE.
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Trastornos del Conocimiento , Lupus Eritematoso Sistémico , Cognición , Trastornos del Conocimiento/psicología , Función Ejecutiva , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/terapia , Pruebas NeuropsicológicasRESUMEN
Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are both independently associated with increased cardiovascular disease (CVD) risk and impaired cognitive function. It is unknown if individuals with both COPD and OSA (i.e., overlap syndrome) have greater common carotid artery (CCA) stiffness, an independent predictor of CVD risk, and lower cognitive performance than either COPD or OSA alone. Elevated CCA stiffness is associated with cognitive impairment in former smokers with and without COPD in past studies. We compared CCA stiffness and cognitive performance between former smokers with overlap syndrome, COPD only, OSA only and former smoker controls using analysis of covariance (ANCOVA) tests to adjust for age, sex, body mass index (BMI), pack years, and postbronchodilator FEV1/FVC. We also examined the association between CCA stiffness and cognitive performance among each group separately. Individuals with overlap syndrome (n = 12) had greater CCA ß-stiffness index (P = 0.015) and lower executive function-processing speed (P = 0.019) than individuals with COPD alone (n = 47), OSA alone (n = 9), and former smoker controls (n = 21), differences that remained significant after adjusting for age, BMI, sex, pack years, and FEV1/FVC. Higher CCA ß-stiffness index was associated with lower executive function-processing speed in individuals with overlap syndrome (r = -0.58, P = 0.047). These data suggest that CCA stiffness is greater and cognitive performance is lower among individuals with overlap syndrome compared with individuals with COPD or OSA alone and that CCA stiffening may be an underlying mechanism contributing to the lower cognitive performance observed in patients with overlap syndrome.NEW & NOTEWORTHY Previous studies have demonstrated greater carotid artery stiffness and lower cognitive function among individuals with COPD alone and OSA alone. However, the present study is the first to demonstrate that individuals that have both COPD and OSA (i.e., overlap syndrome) have greater carotid artery stiffness and lower executive function-processing speed than individuals with either disorder alone. Furthermore, among individuals with overlap syndrome greater carotid artery stiffness is associated with lower executive function-processing speed.
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Enfermedad Pulmonar Obstructiva Crónica , Apnea Obstructiva del Sueño , Arterias Carótidas , Arteria Carótida Común , Cognición , HumanosRESUMEN
OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. METHOD: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. RESULTS: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression. CONCLUSION: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.
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Disfunción Cognitiva , Enfermedad Pulmonar Obstructiva Crónica , Actividades Cotidianas , Disfunción Cognitiva/etiología , Estudios Transversales , Humanos , Pruebas Neuropsicológicas , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Calidad de Vida , Encuestas y CuestionariosRESUMEN
Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery ß-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (ß=-0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. ß-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.
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Arterias Carótidas/fisiopatología , Enfermedades de las Arterias Carótidas/etiología , Cognición , Disfunción Cognitiva/etiología , Ex-Fumadores , Enfermedad Pulmonar Obstructiva Crónica/etiología , Fumar/efectos adversos , Rigidez Vascular , Anciano , Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/fisiopatología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/psicología , Función Ejecutiva , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Medición de Riesgo , Factores de Riesgo , Fumar/fisiopatología , Fumar/psicologíaRESUMEN
BACKGROUND: Attention difficulties are often reported by patients with chronic obstructive pulmonary disease (COPD); however, limited research exists using objective tests designed specifically to measure attention in this population. This study aimed to (1) identify specific attention deficits in COPD and (2) determine which demographic/clinical characteristics are associated with reduced attention. METHODS: Eighty-four former smokers (53 COPD, 31 no COPD) completed questionnaires, pulmonary function testing, and the Conner's Continuous Performance Test II (CPT-II). Participants with and without COPD were compared on CPT-II measures of inattention, impulsivity, and vigilance. CPT-II measures that differed significantly between the two groups were further examined using hierarchical regression modeling. Demographic/clinical characteristics were entered into models with attention as the dependent variable. RESULTS: Participants with COPD performed worse than those without COPD on CPT measures of inattention and impulsivity (i.e., detectability [discrimination of target from non-target stimuli], perseverations [reaction time under 100 ms], omissions [target stimuli response failures], and commissions [responses to non-target stimuli]). More severe COPD (measured by greater airflow limitation) was associated with poorer ability to detect targets vs. foils and perseverative responding after adjusting for age and other covariates in the model. CONCLUSION: Former smokers with COPD experience problems with attention that go beyond slowed processing speed, including aspects of inattention and impulsivity. Clinicians should be aware that greater airflow limitation and older age are associated with attention difficulties, as this may impact functioning.
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Atención , Enfermedad Pulmonar Obstructiva Crónica/psicología , Fumadores/psicología , Fumar/psicología , Factores de Edad , Anciano , Femenino , Humanos , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Fumar/fisiopatologíaRESUMEN
BACKGROUND: Studies of the relationship between patient self-reported angina symptoms using the Seattle Angina Questionnaire (SAQ) and angiographic findings after coronary artery bypass grafting surgery (CABG) are lacking. Nested within a randomized controlled trial, this prospective observational cohort comparison study aimed to assess which clinical characteristics and angiographic findings are associated with self-reported angina 1 year after CABG. METHODS AND RESULTS: Patients from the ROOBY trial (Randomized On/Off Bypass) with protocol-specified 1-year post-CABG coronary angiography and SAQ assessments were included (n=1258). Patients reporting no angina (62.3%) within 4 weeks before the 1-year post-CABG study visit on the SAQ angina frequency domain were compared with patients reporting angina (37.7%). Multivariable modeling identified clinical variables and angiographic findings associated with angina. Sequential univariate and multivariable modeling found the following demographic and clinical factors were associated with angina after CABG: younger age, worse preoperative SAQ angina frequency score, smoking, diabetes mellitus, and pre-CABG depression. The only 1-year angiographic finding significantly associated with angina was incomplete revascularization of the left anterior descending (LAD) territory. Graft occlusions, incomplete revascularization of non-LAD territories, and ≥70% lesions in nonrevascularized native coronary arteries were not correlated with the presence or absence of angina. Further, only 30.6% of subjects reporting angina at 1 year had a residual major coronary artery stenosis of ≥70%. CONCLUSIONS: Self-reported angina 1 year after CABG is associated with younger age, worse baseline SAQ angina frequency score, smoking, diabetes mellitus, and depression. The only angiographic finding associated with angina was a poorly revascularized LAD territory. These results may help guide physicians when counseling patients on expected improvements in angina symptoms and in making decisions regarding the need for coronary angiography after CABG. Whether intensive treatment of these comorbidities improves post-CABG angina symptoms requires further study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00032630.
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Angina de Pecho/diagnóstico por imagen , Angiografía Coronaria , Puente de Arteria Coronaria/efectos adversos , Oclusión de Injerto Vascular/diagnóstico por imagen , Medición de Resultados Informados por el Paciente , Anciano , Angina de Pecho/etiología , Oclusión de Injerto Vascular/etiología , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , United States Department of Veterans AffairsRESUMEN
The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.
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Encéfalo/fisiopatología , Disfunción Cognitiva/fisiopatología , Vasculitis por Lupus del Sistema Nervioso Central/fisiopatología , Autoanticuerpos/inmunología , Barrera Hematoencefálica/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/inmunología , Isquemia Encefálica/fisiopatología , Disfunción Cognitiva/inmunología , Disfunción Cognitiva/terapia , Citocinas/inmunología , Humanos , Inflamación/inmunología , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/inmunología , Vasculitis por Lupus del Sistema Nervioso Central/terapia , Imagen por Resonancia Magnética , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVE: This study examined the association of perceived cognitive difficulties with objective cognitive performance in former smokers. We hypothesized that greater perceived cognitive difficulties would be associated with poorer performance on objective executive and memory tasks. METHOD: Participants were 95 former smokers recruited from the COPDGene study. They completed questionnaires (including the Cognitive Difficulties Scale [CDS] and the Hospital Anxiety and Depression Scale [HADS]), neuropsychological assessment, and pulmonary function testing. Pearson correlations and t-tests were conducted to examine the bivariate association of the CDS (total score and subscales for attention/concentration, praxis, delayed recall, orientation for persons, temporal orientation, and prospective memory) with each domain of objective cognitive functioning (memory recall, executive functioning/processing speed, visuospatial processing, and language). Simultaneous multiple linear regression was used to further examine all statistically significant bivariate associations. The following covariates were included in all regression models: age, sex, pack-years, premorbid functioning (WRAT-IV Reading), HADS total score, and chronic obstructive pulmonary disease (COPD) status (yes/no based on GOLD criteria). RESULTS: In regression models, greater perceived cognitive difficulties overall (using CDS total score) were associated with poorer performance on executive functioning/processing speed tasks (b = -0.07, SE = 0.03, p = .037). Greater perceived cognitive difficulties on the CDS praxis subscale were associated with poorer performance on executive functioning/processing speed tasks (b = -3.65, SE = 1.25, p = .005), memory recall tasks (b = -4.60, SE = 1.75, p = .010), and language tasks (b = -3.89, SE = 1.39, p = .006). CONCLUSIONS: Clinicians should be aware that cognitive complaints may be indicative of problems with the executive functioning/processing speed and memory of former smokers with and without COPD.
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Disfunción Cognitiva/diagnóstico , Pruebas Neuropsicológicas/estadística & datos numéricos , Psicometría/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/psicología , Fumar/efectos adversos , Fumar/psicología , Anciano , Disfunción Cognitiva/psicología , Cultura , Función Ejecutiva , Femenino , Humanos , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Tiempo de Reacción , Factores de Riesgo , Autoevaluación (Psicología)RESUMEN
BACKGROUND: Coronary-artery bypass grafting (CABG) surgery may be performed either with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). We report the 5-year clinical outcomes in patients who had been included in the Veterans Affairs trial of on-pump versus off-pump CABG. METHODS: From February 2002 through June 2007, we randomly assigned 2203 patients at 18 medical centers to undergo either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The two primary 5-year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous coronary intervention), or nonfatal myocardial infarction. Secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less. RESULTS: The rate of death at 5 years was 15.2% in the off-pump group versus 11.9% in the on-pump group (relative risk, 1.28; 95% confidence interval [CI], 1.03 to 1.58; P=0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off-pump group versus 27.1% in the on-pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P=0.046). For the 5-year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off-pump group and 9.6% in the on-pump group (P=0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P=0.29); for repeat revascularization, the rate was 13.1% and 11.9%, respectively (P=0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P=0.02). CONCLUSIONS: In this randomized trial, off-pump CABG led to lower rates of 5-year survival and event-free survival than on-pump CABG. (Funded by the Department of Veterans Affairs Office of Research and Development Cooperative Studies Program and others; ROOBY-FS ClinicalTrials.gov number, NCT01924442 .).
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Puente de Arteria Coronaria Off-Pump/efectos adversos , Puente de Arteria Coronaria/métodos , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Factores de Confusión Epidemiológicos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/mortalidad , Puente de Arteria Coronaria Off-Pump/mortalidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , VeteranosRESUMEN
Cognitive disorders have frequently been described in the field of antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Nevertheless, the relationship between those disorders and antiphospholipid antibodies (aPL) remains unclear and seems to involve various mechanisms. Overlap with systemic lupus erythematosus, the small sample size of studies, and discrepancies in antiphospholipid antibodies and cognitive impairment determinations complicate analyses of the literature data. In this paper, we summarize current knowledge on epidemiologic, clinical data, imaging findings and treatment of cognitive dysfunction associated with aPL. We separately analyzed data on aPL-positive carriers without history of clinical feature of APS, APS patients without overlaps autoimmune disease, and SLE-associated aPL patients.
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Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/complicaciones , Trastornos del Conocimiento/etiología , Lupus Eritematoso Sistémico/complicaciones , Síndrome Antifosfolípido/inmunología , Trastornos del Conocimiento/complicaciones , Humanos , Lupus Eritematoso Sistémico/inmunologíaRESUMEN
Thrombotic manifestations of antiphospholipid syndrome (APS) are well known, and various non-stroke neuro-psychiatric manifestations (NPMs) have also been consistently described, but their place in APS remains unclear. Some syndromes, such as migraine or cognitive dysfunction, are frequently described in APS, whereas others, like seizure, multiple sclerosis-like symptoms, transverse myelitis, movement disorders, or psychiatric symptoms, are rarely found. Overlap with other autoimmune diseases, in particular with systemic lupus erythematosus, the lack of large sample size prospective studies, and discrepancies in antiphospholipid antibody (aPL) determinations complicate the study of the relationship between those disorders and aPL/APS. This review article aimed to summarize updated data on pathophysiologic, epidemiologic, and radiologic findings about non-stroke NPM described in primary APS and aPL-positive patients without overlap of other autoimmune diseases.
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Síndrome Antifosfolípido/complicaciones , Enfermedades del Sistema Nervioso Central/etiología , Síndrome Antifosfolípido/fisiopatología , Trastornos del Conocimiento/etiología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Trastornos Mentales/etiología , Trastornos del Movimiento/etiología , Esclerosis Múltiple/etiologíaRESUMEN
BACKGROUND: Observational studies have documented an off-pump over on-pump advantage for high-risk patients, including diabetic patients. Randomized trials have not confirmed this advantage. The VA Randomization On Versus Off Bypass (ROOBY) trial randomly assigned 2,203 coronary artery bypass graft surgery (CABG) patients at 18 sites to either on-pump (n=1,099) or off-pump (n=1,104) procedures. An a priori ROOBY aim was to evaluate treatment impact on diabetic patients. METHODS: Actively treated diabetic patients (n=835, receiving oral hypoglycemic or insulin medications) received off-pump CABG (n=402) or on-pump CABG (n=433). The primary ROOBY trial endpoints were a short-term composite (30-day operative death or major complications) and a 1-year composite (death, nonfatal acute myocardial infarction, or repeat revascularization). Secondary ROOBY endpoints included 1-year all-cause death, 1-year graft patency, 1-year changes from baseline in neurocognitive status and health-related quality of life, and costs. RESULTS: Diabetic patients' risk factors at baseline were balanced across treatments. For diabetic patients, the primary short-term composite outcome rate showed a worse trend for off-pump (8.0%) than on-pump (3.9%, p=0.013), with no difference in the 1-year primary composite outcome or 1-year death rate. One-year patency was 83.1% off-pump versus 88.4% on-pump (p=0.004). No differences were found in neurocognitive, health-related quality of life, discharge cost, and 1-year cumulative cost. CONCLUSIONS: Concordant with the ROOBY trial's overall findings, off-pump CABG yielded no advantage over on-pump CABG for actively treated diabetic patients. The 1-year graft patency was lower and the short-term composite trended higher for off-pump CABG, with no other significant outcome or cost differences.
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Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Circulación Coronaria/fisiología , Diabetes Mellitus/terapia , Hipoglucemiantes/uso terapéutico , Complicaciones Posoperatorias/epidemiología , Puente de Arteria Coronaria Off-Pump , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Vasos Coronarios/cirugía , Diabetes Mellitus/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos/epidemiología , Grado de Desobstrucción VascularRESUMEN
OBJECTIVES: The aim of this study was to compare the cognitive function of antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and aPL-positive non-SLE patients. METHODS: Twenty aPL-negative SLE and 20 aPL-positive non-SLE female patients with no history of overt neuropsychiatric manifestations took standardised cognitive tests of learning and memory, attention and working memory, executive functions, verbal fluency, visuoconstruction, and motor function. The primary outcome measure was an established global cognitive impairment index (CII). Cranial magnetic resonance imaging (MRI) was also obtained on all patients. RESULTS: Twelve of 20 (60%) of the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive impairment on CII; there were no group differences on CII or on individual measures. Cognitive impairment was not associated with duration of disease, level of disease activity, or prednisone use. No correlations were found between clinical disease factors and cognitive impairment, and neither group showed an association between incidental or major MRI abnormalities and cognitive dysfunction. CONCLUSIONS: Both aPL-negative SLE and aPL-positive non-SLE patients, without other overt neuropsychiatric disease, demonstrated high levels of cognitive impairment. No clinical, serologic, or radiologic characteristics were associated with cognitive impairment. Cognitive dysfunction is common in APS and in SLE, but its mechanisms remain unknown.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/complicaciones , Trastornos del Conocimiento/etiología , Cognición , Lupus Eritematoso Sistémico/complicaciones , Adulto , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Atención , Biomarcadores/sangre , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Función Ejecutiva , Femenino , Humanos , Aprendizaje , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Imagen por Resonancia Magnética , Memoria a Corto Plazo , Persona de Mediana Edad , Destreza Motora , Pruebas Neuropsicológicas , Conducta VerbalRESUMEN
OBJECTIVE/BACKGROUND: Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy in SLE. METHODS: We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using magnetic resonance spectroscopy, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter. RESULTS: Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant when we considered disease duration and left frontal white matter Ch/Cr against total PASAT score and total dyads. CONCLUSIONS: Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.
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Leucoencefalopatías/diagnóstico , Leucoencefalopatías/etiología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Colina/análisis , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Creatinina/análisis , Lóbulo Frontal/patología , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Memoria a Corto Plazo , Análisis de RegresiónRESUMEN
OBJECTIVE: The primary objective of this study was to evaluate the safety of rituximab in antiphospholipid antibody (aPL)-positive patients with non-criteria manifestations of antiphospholipid syndrome (APS). The secondary objectives were to evaluate the effect of rituximab on the aPL profile and to evaluate the efficacy of rituximab treatment for non-criteria manifestations of APS. METHODS: In this 12-month, phase II pilot study, adult aPL-positive patients with thrombocytopenia, cardiac valve disease, skin ulcer, aPL nephropathy, and/or cognitive dysfunction received 2 doses of rituximab (1,000 mg) on days 1 and 15. Antiphospholipid antibody profiles and clinical outcome measures, which were categorized as complete response, partial response, no response, or recurrence, were analyzed at preset time points. RESULTS: Two of 19 patients experienced infusion reactions, resulting in early termination. Twelve serious adverse events and 49 nonserious adverse events were recorded. All patients who had positive results of lupus anticoagulant, anticardiolipin, and anti-ß(2)-glycoprotein I antibody tests at baseline had positive results at 24 weeks and 52 weeks. The numbers of patients with a complete response, a partial response, no response, and recurrence for the clinical outcome measures at 24 weeks were as follows: for thrombocytopenia, 1, 1, 2, and 0, respectively; for cardiac valve disease, 0, 0, 3, and not analyzed, respectively; for skin ulcer, 3, 1, 0, and 1, respectively; for aPL nephropathy, 0, 1, 0, and 0, respectively; and for cognitive dysfunction, 3, 1, 1, and not analyzed, respectively. CONCLUSION: The results of this uncontrolled and nonrandomized pilot study suggest that the safety of rituximab in aPL-positive patients is consistent with the safety profile of rituximab. Despite causing no substantial change in aPL profiles, rituximab may be effective in controlling some but not all non-criteria manifestations of APS.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Adulto , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Rituximab , Resultado del TratamientoRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography (SPECT). METHODS: 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. RESULTS: 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% (0/23) of controls. SLE women also had significantly greater cognitive dysfunction (mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. CONCLUSIONS: A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction.
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Autoanticuerpos/sangre , Trastornos del Conocimiento/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Cognición/fisiología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/inmunología , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico por imagen , Lupus Eritematoso Sistémico/inmunología , Masculino , Análisis Multivariante , Pruebas Neuropsicológicas/estadística & datos numéricos , Prevalencia , Flujo Sanguíneo Regional , Tomografía Computarizada de Emisión de Fotón Único/métodos , Población BlancaRESUMEN
PURPOSE: This study compared visuomotor speed and cognitive flexibility in emphysema patients treated with either standard multidisciplinary medical therapy (MT) or lung volume reduction surgery (LVRS), followed over a 2-year period. METHODS: MT patients (n = 544) and 542 LVRS patients completed the Trail Making Test (TMT) Parts A and B prior to randomization (baseline). Testing was repeated at 1 and 2 years. RESULTS: There were no differences on scores for TMT Parts A and B between the LVRS and MT groups at baseline or at years 1 and 2. No significant difference between MT and LVRS was noted in terms of overall change in TMT Parts A and B over 2 years. The MT group had a significant improvement on TMT Part A at each followup time compared with baseline (P < .03) but the LVRS group did not. Both the MT and LVRS groups had a significant decline in performance (increase in time to completion) on TMT Part B when comparing year 1 with baseline (P < .0001). CONCLUSION: Emphysema patients who received LVRS or MT as treatment performed similarly on measures of visuomotor speed and flexibility at baseline and 1- and 2-year followup. Both groups showed improvement on visuomotor speed during the first year yet overall cognitive flexibility declined. By the second year neither group had any significant change from baseline. These findings suggest that improvement on visuomotor speed and flexibility, observed in a previous 6-month study of LVRS subjects, was not sustained at 1- and 2-year followup.
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Cognición , Neumonectomía , Enfisema Pulmonar/cirugía , Prueba de Secuencia Alfanumérica/estadística & datos numéricos , Anciano , Femenino , Estudios de Seguimiento , Volumen Espiratorio Forzado , Humanos , Estudios Longitudinales , Pulmón/cirugía , Masculino , Estudios Prospectivos , Desempeño Psicomotor , Resultado del TratamientoRESUMEN
BACKGROUND: The Randomized On versus Off Bypass trial reported conversion of 12.4% (n = 137) off-pump coronary artery bypass (OPCAB) patients and 3.6% (n = 40) on-pump cardiopulmonary bypass (CPB) patients. This paper explored outcomes after conversions. METHODS: Elective and urgent CABG patients (n = 2,203) at 18 sites were studied. Randomization within 54 participating surgeons occurred preoperatively, after which conversion occurred if clinically indicated. Conversion reasons and outcomes were captured prospectively with additional details retrospectively extracted from patient records by a core clinical group. RESULTS: Conversion rates varied considerably across participating surgeons. Converted OPCAB patients had more right coronary disease and coronary targets less than 1.5 mm. Conversions were elective in 49.3% of cases, urgent in 27.2%, or emergent in 23.5%. Elective conversions were mainly for poor exposure-intramyocardial vessel (35.8%). Urgent and emergent conversions were usually for hemodynamic instability (89.2% and 75.0%, respectively). Compared with CPB and OPCAB patients, OPCAB-converted patients had more 30-day complications and deaths (composite outcome rate of 5.7% and 5.5% vs 17.5% respectively, p < 0.001). Thirty-day outcomes for OPCAB-converted patients trended worse for emergent versus elective conversions (31.3% vs 13.4%, respectively, p = 0.05). One-year composite outcome rate (death, nonfatal myocardial infarction or revascularization) in OPCAB-converted patients was worse than in CPB patients (13.5% vs 7.1%, p = 0.02), but similar to OPCAB-nonconverted (9.4%). CONCLUSIONS: The OPCAB patients requiring conversion had worse 30-day and 1-year outcomes. The OPCAB patients with right coronary artery disease or small targets were more often converted. The 30-day composite outcome trended worst for emergent OPCAB conversions.
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Puente Cardiopulmonar , Puente de Arteria Coronaria Off-Pump , Anciano , Puente de Arteria Coronaria Off-Pump/mortalidad , Humanos , Persona de Mediana Edad , Método Simple Ciego , Tasa de Supervivencia , Resultado del Tratamiento , Estados Unidos , United States Department of Veterans Affairs , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: Although prior research indicates that religious and spiritual coping is associated with positive health outcomes, few studies have examined religious and spiritual coping among patients with emphysema. OBJECTIVE: To describe the utilization of religious and spiritual coping and its relationship to quality of life among patients with emphysema, in a 2-year longitudinal follow-up study. METHODS: Forty patients with emphysema (mean age 63.5 ± 6.0 y, 8 women) who participated in the National Emphysema Treatment Trial were matched on age, sex, race, and education with 40 healthy individuals recruited from the community. We conducted baseline assessment of overall coping strategies, psychological functioning, quality of life, pulmonary function, and exercise capacity, and we assessed overall coping strategies and religious and spiritual coping at 2-year follow-up. RESULTS: Ninety percent of the patients with emphysema considered themselves at least slightly religious and spiritual. The patients reported using both negative religious coping (eg, questioning God) and positive religious coping (eg, prayer) more than the healthy control subjects at follow-up. However, greater use of religious and spiritual coping was associated with poorer illness-related quality of life. CONCLUSIONS: Patients with emphysema appear to use various coping strategies in responding to their illness. Future research should investigate if patients using religious and spiritual coping would benefit from interventions to address emotional distress and reduced quality of life.
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Adaptación Psicológica , Calidad de Vida , Anciano , Enfisema , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Religión , EspiritualismoRESUMEN
BACKGROUND: Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR's effects on certain important outcomes is lacking. METHODS: We conducted a pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program. RESULTS: Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status. CONCLUSIONS: PR improves functional capacity and fatigue in patients with IPF. (Clinical Trials.gov registration NCT00692796.)