RESUMEN
BACKGROUND: Chronic pain and opioid use disorder (OUD) individually represent a risk to health and well-being. Concerningly, there is evidence that they are frequently co-morbid. While few treatments exist that simultaneously target both conditions, preliminary work has supported the feasibility of an integrated behavioral treatment targeting pain interference and opioid misuse. This treatment combined Acceptance and Commitment Therapy (ACT) and Mindfulness-Based Relapse Prevention (ACT+MBRP). This paper describes the protocol for the adequately powered efficacy study of this integrated treatment. METHODS: A multisite randomized controlled trial will examine the efficacy of ACT+MBRP in comparison to a parallel education control condition, focusing on opioid safety and pain education. Participants include veterans (n = 160; 21-75 years old) recruited from three Veterans Administration (VA) Healthcare Systems with chronic pain who are on a stable dose of buprenorphine. Both conditions include twelve weekly 90 min group sessions delivered via telehealth. Primary outcomes include pain interference (Patient Reported Outcome Measurement Information System - Pain Interference) and hazardous opioid use (Current Opioid Misuse Measure), which will be examined at the end of the active treatment phase and through 12 months post-intervention. Secondary analyses will evaluate outcomes including pain intensity, depression, pain-related fear, and substance use, as well as treatment mechanisms. CONCLUSION: This study will determine the efficacy of an integrated behavioral treatment program for pain interference and hazardous opioid use among veterans with chronic pain and OUD who are prescribed buprenorphine, addressing a critical need for more integrated treatments for chronic pain and OUD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04648228.
Asunto(s)
Terapia de Aceptación y Compromiso , Buprenorfina , Dolor Crónico , Trastornos Relacionados con Opioides , Veteranos , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Analgésicos Opioides/uso terapéutico , Dolor Crónico/tratamiento farmacológico , Trastornos Relacionados con Opioides/tratamiento farmacológico , Buprenorfina/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Status epilepticus, refractory status epilepticus, and super-refractory status epilepticus can be life-threatening conditions. This article presents an overview of the three conditions and discusses their management and outcomes. RECENT FINDINGS: Status epilepticus was previously defined as lasting for 30 minutes or longer but now is more often defined as lasting 5 minutes or longer. A variety of potential causes exist for status epilepticus, refractory status epilepticus, and super-refractory status epilepticus, but all three ultimately involve changes at the cellular and molecular level. Management of patients with status epilepticus generally requires several studies, with EEG of utmost importance given the pathophysiologic changes that can occur during the course of status epilepticus. Status epilepticus is treated with benzodiazepines as first-line antiepileptic drugs, followed by phenytoin, valproic acid, or levetiracetam. If status epilepticus does not resolve, these are followed by an IV anesthetic and then alternative therapies based on limited data/evidence, such as repetitive transcranial magnetic stimulation, therapeutic hypothermia, immunomodulatory agents, and the ketogenic diet. Scores have been developed to help predict the outcome of status epilepticus. Neurologic injury and outcome seem to worsen as the duration of status epilepticus increases, with outcomes generally worse in super-refractory status epilepticus compared to status epilepticus and sometimes also to refractory status epilepticus. SUMMARY: Status epilepticus can be a life-threatening condition associated with multiple complications, including death, and can progress to refractory status epilepticus and super-refractory status epilepticus. More studies are needed to delineate the best management of these three entities.
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Manejo de la Enfermedad , Epilepsia Refractaria , Estado Epiléptico , Anticonvulsivantes/uso terapéutico , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/etiología , Epilepsia Refractaria/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/epidemiología , Estado Epiléptico/etiología , Estado Epiléptico/terapia , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity. MATERIALS AND METHODS: Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus. RESULTS: In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my-inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC. CONCLUSIONS: This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI.
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Terapia Cognitivo-Conductual , Trastorno Depresivo Mayor/diagnóstico por imagen , Imagen por Resonancia Magnética , Atención Plena , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Estudios de Casos y Controles , Núcleo Caudado/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Femenino , Giro del Cíngulo/diagnóstico por imagen , Humanos , Masculino , Putamen/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate the genetic contributors to cerebrovascular disease and variation in biomarkers of ischemic stroke. METHODS: The Vitamin Intervention for Stroke Prevention Trial (VISP) was a randomized, controlled clinical trial of B vitamin supplementation to prevent recurrent stroke, myocardial infarction, or death. VISP collected baseline measures of C-reactive protein (CRP), fibrinogen, creatinine, prothrombin fragments F1+2, thrombin-antithrombin complex, and thrombomodulin prior to treatment initiation. Genome-wide association scans were conducted for these traits and follow-up replication analyses were performed. RESULTS: We detected an association between CRP single nucleotide polymorphisms (SNPs) and circulating CRP levels (most associated SNP, rs2592902, p = 1.14 × 10(-9)) in 2,100 VISP participants. We discovered a novel association for CRP level in the AKR1D1 locus (rs2589998, p = 7.3 × 10(-8), approaching genome-wide significance) that also is an expression quantitative trait locus for CRP gene expression. We replicated previously identified associations of fibrinogen with SNPs in the FGB and LEPR loci. CRP-associated SNPs and CRP levels were significantly associated with risk of ischemic stroke and recurrent stroke in VISP as well as specific stroke subtypes in METASTROKE. Fibrinogen levels but not fibrinogen-associated SNPs were also found to be associated with recurrent stroke in VISP. CONCLUSIONS: Our data identify a genetic contribution to inflammatory and hemostatic biomarkers in a stroke population. Additionally, our results suggest shared genetic contributions to circulating CRP levels measured poststroke and risk for incident and recurrent ischemic stroke. These data broaden our understanding of genetic contributors to biomarker variation and ischemic stroke risk, which should be useful in clinical risk evaluation.
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Biomarcadores , Isquemia Encefálica/metabolismo , Proteína C-Reactiva/metabolismo , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Accidente Cerebrovascular/metabolismo , Anciano , Isquemia Encefálica/genética , Proteína C-Reactiva/genética , Femenino , Fibrinógeno/genética , Fibrinógeno/metabolismo , Expresión Génica , Sitios Genéticos , Humanos , Masculino , Persona de Mediana Edad , Oxidorreductasas/genética , Polimorfismo de Nucleótido Simple , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Accidente Cerebrovascular/genéticaRESUMEN
This study examines the impact of a work-skills program grounded in an integrated services approach on both employment and related life domains among homeless individuals. Six hundred thirty-eight participants in a 14-week work-skills program at a large day center in New England completed assessments at intake between 1999 and 2007; a subsample of 333 also completed assessments at graduation from the program; a smaller subsample of 55 participants were re-assessed 6 months after graduation. These assessments measured work and related life skills, employment, housing status, general health status, substance use, self-esteem and self-efficacy, and legal involvement. Results revealed improvement in all types of work and related life skills, employment and income, and multiple other life domains from baseline to graduation and follow-up. Exploratory analyses suggested that improvements in work and related life skills were associated with improvement in self-esteem and self-efficacy, and that these improvements predicted stable housing situations at follow-up. Overall, these findings indicate that, for individuals struggling with the challenges of homelessness, completion of a work-skills program has a positive impact on skills and employment, and on a diverse set of life domains.
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Prestación Integrada de Atención de Salud/organización & administración , Empleo , Personas con Mala Vivienda/psicología , Evaluación de Procesos y Resultados en Atención de Salud , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , New England , Evaluación de Programas y Proyectos de Salud , Calidad de Vida , Rehabilitación Vocacional , Autoimagen , Autoeficacia , Trastornos Relacionados con Sustancias/psicología , Trastornos Relacionados con Sustancias/rehabilitaciónRESUMEN
Glutamate is the main excitatory neurotransmitter in the mammalian brain. Appropriate transmission of nerve impulses through glutamatergic synapses is required throughout the brain and forms the basis of many processes including learning and memory. However, abnormally high levels of extracellular brain glutamate can lead to neuroaxonal cell death. We have previously reported elevated glutamate levels in the brains of patients suffering from multiple sclerosis. Here two complementary analyses to assess the extent of genomic control over glutamate levels were used. First, a genome-wide association analysis in 382 patients with multiple sclerosis using brain glutamate concentration as a quantitative trait was conducted. In a second approach, a protein interaction network was used to find associated genes within the same pathway. The top associated marker was rs794185 (P < 6.44 x 10(-7)), a non-coding single nucleotide polymorphism within the gene sulphatase modifying factor 1. Our pathway approach identified a module composed of 70 genes with high relevance to glutamate biology. Individuals carrying a higher number of associated alleles from genes in this module showed the highest levels of glutamate. These individuals also showed greater decreases in N-acetylaspartate and in brain volume over 1 year of follow-up. Patients were then stratified by the amount of annual brain volume loss and the same approach was performed in the 'high' (n = 250) and 'low' (n = 132) neurodegeneration groups. The association with rs794185 was highly significant in the group with high neurodegeneration. Further, results from the network-based pathway analysis remained largely unchanged even after stratification. Results from these analyses indicated that variance in the activity of neurochemical pathways implicated in neurodegeneration is explained, at least in part, by the inheritance of common genetic polymorphisms. Spectroscopy-based imaging provides a novel quantitative endophenotype for genetic association studies directed towards identifying new factors that contribute to the heterogeneity of clinical expression of multiple sclerosis.
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Encéfalo/metabolismo , Variación Genética/genética , Ácido Glutámico/metabolismo , Esclerosis Múltiple/genética , Esclerosis Múltiple/patología , Sulfatasas/genética , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Simulación por Computador , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos Genéticos , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro , Polimorfismo de Nucleótido Simple/genética , Estadística como AsuntoRESUMEN
To assess incidence and degree of regrowth in glioblastoma between surgery and radiation therapy (RT) and to correlate regrowth with presurgical imaging and survival, we examined images of 32 patients with newly diagnosed glioblastoma who underwent MR spectroscopic imaging (MRSI), perfusion-weighted imaging (PWI), and diffusion-weighted imaging (DWI) prior to surgery, after surgery, and prior to RT/temozolomide. Contrast enhancement (CE) in the pre-RT MR image was compared with postsurgical DWI to differentiate tumor growth from postsurgical infarct. MRSI and PWI parameters were analyzed prior to surgery and pre-RT. Postsurgical MRI indicated that 18 patients had gross total and 14 subtotal resections. Twenty-one patients showed reduced diffusion, and 25 patients showed new or increased CE. In eight patients (25%), the new CE was confined to areas of postsurgical reduced diffusion. In the other 17 patients (53%), new CE was found to be indicative of tumor growth or a combination of tumor growth and surgical injury. Higher perfusion and creatine within nonenhancing tumor in the presurgery MR were associated with subsequent tumor growth. High levels of choline and reduced diffusion in pre-RT CE suggested active metabolism and tumor cell proliferation. Median survival was 14.6 months in patients with interim tumor growth and 24 months in patients with no growth. Increased volume or new onset of CE between surgery and RT was attributed to tumor growth in 53% of patients and was associated with shorter survival. This suggests that reducing the time between surgery and adjuvant therapy may be important. The acquisition of metabolic and physiologic imaging data prior to adjuvant therapy may also be valuable in assessing regions of new CE and nonenhancing tumor.
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Neoplasias Encefálicas/patología , Glioblastoma/patología , Radioterapia Adyuvante , Adulto , Anciano , Mapeo Encefálico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirugía , Medios de Contraste , Imagen de Difusión por Resonancia Magnética , Glioblastoma/radioterapia , Glioblastoma/cirugía , Humanos , Procesamiento de Imagen Asistido por Computador , Técnicas para Inmunoenzimas , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Cuidados Preoperatorios , Planificación de la Radioterapia Asistida por Computador , Tasa de Supervivencia , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Purpose Glioblastoma Multiforme (GBM) is the most common and lethal primary brain tumor in adults. The goal of this study was to test the predictive value of MR parameters in relation to the survival of patients with newly diagnosed GBM who were scanned prior to receiving adjuvant radiation and chemotherapy. Methods The study population comprised 68 patients who had surgical resection and were to be treated with fractionated external beam radiation therapy and chemotherapy. Imaging scans included anatomical MRI, diffusion and perfusion weighted imaging and (1)H MRSI. The MR data were acquired 3-5 weeks after surgery and approximately 1 week before treatment with radiation therapy. The diffusion, perfusion and spectroscopic parameter values were quantified and subjected to proportional hazards analysis that was adjusted for age and scanner field strength. Results The patients with larger lesion burden based upon volumes of anatomic lesions, volume of CNI2 (number of voxels within the T2 lesion having choline to NAA index >2), volume of CBV3 (number of pixels within the T2 lesion having relative cerebral blood volume >3), and volume of nADC1.5 (number of pixels within the T2 lesion having normalized apparent diffusion coefficient <1.5) had a higher risk for poor outcome. High intensities of combined measures of lactate and lipid in the T2 and CNI2 regions were also associated with poor survival. Conclusions Our study indicated that several pre-treatment anatomic, physiological and metabolic MR parameters are predictive of survival. This information may be important for stratifying patients to specific treatment protocols and for planning focal therapy.
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Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Glioblastoma/mortalidad , Glioblastoma/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Asparagina/análogos & derivados , Asparagina/metabolismo , Mapeo Encefálico , Neoplasias Encefálicas/terapia , Colina/metabolismo , Medios de Contraste , Creatina/metabolismo , Quimioterapia/métodos , Femenino , Glioblastoma/terapia , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radioterapia/métodos , Análisis Espectral , Análisis de SupervivenciaRESUMEN
Traditional attribution theory conceptualizes explanations of behavior as referring to either dispositional or situational causes. An alternative approach, the folk-conceptual theory of behavior explanation, distinguishes multiple discrete modes of explanation and specific features within each mode. Because attribution theory and the folk-conceptual theory carve up behavior explanations in distinct ways, they offer very different predictions about actor-observer asymmetries. Six studies, varying in contexts and methodologies, pit the 2 sets of predictions against each other. There was no evidence for the traditional actor-observer hypothesis, but systematic support was found for the actor-observer asymmetries hypothesized by the folk-conceptual theory. The studies also provide initial evidence for the processes that drive each of the asymmetries: impression management goals, general knowledge, and copresence.
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Conducta , Motivación , Teoría de Construcción Personal , Autoimagen , Percepción Social , Formación de Concepto , Cultura , Emociones , Humanos , Control Interno-Externo , Personalidad , Medio SocialRESUMEN
Concepts such as intention, motive, or forethought have generated a great deal of doubt, dispute, and confusion in legal decision making. Here we argue for an empirically based strategy of defining and using such mens rea concepts. Instead of the standard approach of settling these concepts by theoretical argument and the debaters' own intuitions, we rely on social psychological research to determine the meaning and significance of folk concepts concerning mens rea. We demonstrate the reliable and systematic use of people's concept of intentionality, contrast it with the bewildering variety of related legal concepts, and apply the folk model of intentionality to debated distinctions between intention and intentionality, desire and intention, and belief and intention. This folk-conceptual approach promises clarity of mens rea concepts and a reconciliation of the legal and layperson's view of human behavior.