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1.
Artigo em Inglês | MEDLINE | ID: mdl-31264800

RESUMO

AIM: Previous studies suggest that Mindfulness-Based Cognitive Therapy for Children (MBCT-C) is feasible and may improve anxiety and emotion regulation in youth with anxiety disorders at-risk for bipolar disorder. However, controlled studies are warranted to replicate and extend these findings. METHODS: In the current study, 24 youth with anxiety disorders who have at least one parent with bipolar disorder participated in a MBCT-C treatment period (n = 24; Mage = 13.6, 75% girls, 79% White) with a subset also participating in a prior psychoeducation waitlist control period (n = 19 Mage = 13.8, 68% girls, 84% White). Participants in both the waitlist and MBCT-C periods completed independently-rated symptom scales at each time point. Participants in the waitlist period received educational materials 12 weeks prior to the beginning of MBCT-C. RESULTS: There were significantly greater improvements in overall clinical severity in the MBCT-C period compared to the waitlist period, but not in clinician- and child-rated anxiety, emotion regulation or mindfulness. However, increases in mindfulness were associated with improvements in anxiety and emotion regulation in the MBCT-C period, but not the waitlist period. CONCLUSIONS: Findings suggest that MBCT-C may be effective for improving overall clinical severity in youth with anxiety disorders who are at-risk for bipolar disorder. However, waitlist controlled designs may inflate effect sizes so interpret with caution. Larger studies utilizing prospective randomized controlled designs are warranted.

2.
Bipolar Disord ; 21(6): 503-513, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31025452

RESUMO

OBJECTIVES: Bipolar disorder is marked by progressive symptomatic changes, which have been linked with episode-related structural findings-particularly in the prefrontal cortex. However, few studies have examined neurofunctional and neurochemical effects of disease burden. In this study, we compared first- and multi-episode bipolar individuals. We hypothesized that the latter would demonstrate evidence of neurophysiological differences consistent with a model of progressive functional degradation of these networks. METHODS: First- and multi-episode manic bipolar subjects participated in functional magnetic resonance imaging (fMRI) including a continuous performance task with emotional distractors, and in single-voxel (1 H) magnetic resonance spectroscopy (MRS). A priori fMRI regions-of-interest (ROI) included structures comprising prefrontal-striatal-amygdala networks; (1 H)MRS voxels were placed within bilateral ventrolateral prefrontal (VLPFC) and anterior cingulate cortex (ACC). Both ROI and voxel-based brain activation in response to emotional stimuli, and neurochemical concentrations derived from (1 H)MRS were compared across bipolar groups. RESULTS: Multi-episode bipolar subjects showed relatively lower regional activation across prefrontal-striatal-amygdala networks, including bilateral VLPFC, orbitofrontal cortex, ACC, putamen, caudate, and amygdala. Exploratory whole-brain, voxel-based analysis suggested additional areas of lower activation extending into Brodmann area 22, posterior parietal regions, and right thalamus. Glutamate and N-acetylaspartate (NAA) concentrations were also relatively lower in the ACC of multi-episode subjects. CONCLUSIONS: Disease burden, exemplified by multiple affective episodes is associated with evidence of widespread decrements in affective network activity. Lower ACC NAA concentration is similarly consistent with a model of progressive functional deficits. These findings support the functional significance of previously observed progressive structural changes throughout these regions.

3.
Bipolar Disord ; 21(4): 330-341, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30864200

RESUMO

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.

4.
BMC Nephrol ; 20(1): 24, 2019 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-30674290

RESUMO

BACKGROUND: Reproductive function in women with end stage renal disease generally improves after kidney transplant. However, pregnancy remains challenging due to the risk of adverse clinical outcomes. METHODS: We searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from date of inception through August 2017 for studies reporting pregnancy with kidney transplant. RESULTS: Of 1343 unique studies, 87 met inclusion criteria, representing 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 ± 2.4 years. The live-birth rate was 72.9% (95% CI, 70.0-75.6). The rate of other pregnancy outcomes was as follows: induced abortions (12.4%; 95% CI, 10.4-14.7), miscarriages (15.4%; 95% CI, 13.8-17.2), stillbirths (5.1%; 95% CI, 4.0-6.5), ectopic pregnancies (2.4%; 95% CI, 1.5-3.7), preeclampsia (21.5%; 95% CI, 18.5-24.9), gestational diabetes (5.7%; 95% CI, 3.7-8.9), pregnancy induced hypertension (24.1%; 95% CI, 18.1-31.5), cesarean section (62.6, 95% CI 57.6-67.3), and preterm delivery was 43.1% (95% CI, 38.7-47.6). Mean gestational age was 34.9 weeks, and mean birth weight was 2470 g. The 2-3-year interval following kidney transplant had higher neonatal mortality, and lower rates of live births as compared to > 3 year, and < 2-year interval. The rate of spontaneous abortion was higher in women with mean maternal age < 25 years and > 35 years as compared to women aged 25-34 years. CONCLUSION: Although the outcome of live births is favorable, the risks of maternal and fetal complications are high in kidney transplant recipients and should be considered in patient counseling and clinical decision making.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30522995

RESUMO

BACKGROUND AND OBJECTIVES: Kidney biopsy is an essential tool for the diagnosis and treatment of patients with kidney disease; however, because of its invasive nature, bleeding complications may arise. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a meta-analysis of prospective or retrospective observational studies and randomized, controlled trials in pediatric patients undergoing native or transplant kidney biopsy in an inpatient or outpatient setting in MEDLINE-indexed studies from January 1998 to November 1, 2017 to determine the proportion of patients who develop hematoma, need blood transfusion, or need an additional intervention due to a complication after kidney biopsy. RESULTS: Twenty-three studies of 5504 biopsies met inclusion criteria. The proportion of patients developing hematoma after biopsy was between 11% (95% confidence interval, 7% to 17%) and 18% (95% confidence interval, 9% to 35%) using two analyses that included different time periods. The proportion needing blood transfusion was 0.9% (95% confidence interval, 0.5% to 1.4%). The proportion needing an additional intervention due to postbiopsy complication was 0.7% (95% confidence interval, 0.4% to 1.1%). Secondary analysis was not possible due to lack of data in the original manuscripts on laboratory values, needle gauges, number of needle passes, age of patient, or performer (attending versus trainee). Analysis with metaregression found that use of real-time ultrasound during biopsy did not modify the risk for hematoma, requirement of a blood products transfusion, or requirement of an additional procedure after biopsy. Analysis with metaregression comparing native biopsies with transplant biopsies did not reveal that biopsy type (native kidney biopsy versus transplant kidney biopsy) was associated with the need for a blood transfusion or requirement of an additional intervention after biopsy. CONCLUSIONS: The development of perinephric hematoma after kidney biopsy is not an infrequent finding. The proportion of patients requiring blood transfusion or needing an additional intervention as a result of kidney biopsy in pediatric patients is significantly smaller. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_12_06_CJASNPodcast_19_01_.mp3.

6.
J Matern Fetal Neonatal Med ; : 1-9, 2018 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-30373419

RESUMO

BACKGROUND: Women that previously had preterm labor are at an increased risk for heart disease. Because spontaneous preterm birth is an adverse pregnancy outcome that affects millions of children worldwide, our objective was to review and analyze studies that have examined associations between maternal total cholesterol (TC), LDL-C, and HDL-C concentrations during pregnancy and the risk of preterm birth to potentially define biomarkers or targets for treatment. METHOD: A search was performed and 22 articles were found that examined the association of maternal plasma cholesterol concentrations and preterm birth. A meta-analysis was performed on 10 of the articles, those that used maternal lipid concentrations as the outcome and presented results as means plus variables, and a qualitative review was performed on all 22 articles. RESULTS: The meta-analysis showed no relationship between maternal TC, LDL-C, or HDL-C and increased risk of preterm birth, although, a near significant relationship between low maternal HDL-C concentration and preterm birth (p = .055). Importantly, associations increased when cholesterol concentrations were combined with inflammatory markers or metabolic syndrome factors. CONCLUSIONS: The relationship between maternal cholesterol levels and preterm birth is heterogeneous. Associations are strengthened when maternal cholesterol concentrations are combined with other factors that may be related to more recently defined lipoprotein functions.

7.
J Child Adolesc Psychopharmacol ; 28(6): 379-386, 2018 Jul/Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29847157

RESUMO

OBJECTIVES: Prior studies have shown that youth with bipolar disorder demonstrate neurofunctional changes in key prefrontal and subcortical brain regions implicated in emotional regulation following treatment with pharmacological agents. We recently reported a large response rate (>60%) to quetiapine (QUET) for treating depressive symptoms in adolescents with bipolar depression. This study investigates the neurofunctional effects of QUET using functional magnetic resonance imaging (fMRI). METHODS: Thirty-three unmedicated subjects, 10-17 years of age, with a current depressive episode (Children's Depression Rating Scale-Revised [CDRS-R] > 40) associated with bipolar I or II disorder were recruited in a two-site randomized, placebo (PBO)-controlled trial of QUET monotherapy for treatment of bipolar depression in adolescents. Twenty-three of these participants (nine male) underwent an MRI scan at baseline, then were randomized to QUET or PBO, followed for 8 weeks, and at the end of their study participation underwent another MRI scan. During the fMRI scan, subjects viewed negative and neutral pictures and rated the valence of each picture. RESULTS: Sixteen subjects had usable data at both time points: 10 subjects randomized to QUET, and 6 randomized to PBO. For QUET subjects, lower baseline activation in the left dorsolateral prefrontal cortex (p < 0.005) and higher baseline activation in the left ventrolateral prefrontal cortex (p = 0.0024) predicted greater improvement in CDRS-R scores from baseline to follow-up. When QUET and PBO groups were combined (n = 16), region-of-interest activation did not significantly predict change in CDRS-R. CONCLUSIONS: Baseline activation patterns in dorsal and ventral portions of the prefrontal cortex that are critical for the regulation of emotion-predicted response, but only within the QUET group. Thus, specific medications may be more effective in the context of specific prefrontal activation patterns in youth with bipolar depression. Larger studies of these youth would help to clarify the effects of QUET on brain activation.

8.
J Am Acad Child Adolesc Psychiatry ; 57(4): 235-244.e2, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29588049

RESUMO

OBJECTIVE: To determine the trajectory and magnitude of antidepressant response as well as the effect of antidepressant class and dose on symptomatic improvement in pediatric anxiety disorders. METHOD: Weekly symptom severity data were extracted from randomized, parallel group, placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) in pediatric anxiety disorders. Treatment response was modeled for the standardized change in continuous measures of anxiety using Bayesian updating. Posterior distributions for each study served as informative conjugate prior to distributions update subsequent study posteriors. Change in symptom severity was evaluated as a function of time, class and, for SSRIs, standardized dose. RESULTS: Data from 9 trials (SSRIs: n = 5; SNRIs, n = 4) evaluating 7 medications in 1,673 youth were included. In the logarithmic model of treatment response, statistically, but not clinically, significant treatment effects emerged within 2 weeks of beginning treatment (standardized medication-placebo difference = -0.054, credible interval [CI] = -0.076 to -0.032, p = .005, approximate Cohen's d ≤ 0.2) and by week 6, clinically significant differences emerged (standardized medication-placebo difference = -0.120, CI = -0.142 to -0.097, p = .001, approximate Cohen's d = 0.44). Compared to SNRIs, SSRIs resulted in significantly greater improvement by the second week of treatment (p = .0268), and this advantage remained statistically significant through week 12 (all p values <.03). Improvement occurred earlier with high-dose SSRI treatment (week 2, p = .002) compared to low-dose treatment (week 10, p = .025), but SSRI dose did not have an impact on overall response trajectory (p > .18 for weeks 1-12). CONCLUSIONS: In pediatric patients with generalized, separation, and/or social anxiety disorders, antidepressant-related improvement occurred early in the course of treatment, and SSRIs were associated with more rapid and greater improvement compared to SNRIs.

9.
J Affect Disord ; 234: 14-19, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29522938

RESUMO

BACKGROUND: The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. METHODS: Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. RESULTS: Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. LIMITATIONS: This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. CONCLUSIONS: Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power.


Assuntos
Transtorno Bipolar/fisiopatologia , Encéfalo/fisiopatologia , Cognição/fisiologia , Emoções/fisiologia , Adulto , Afeto , Mapeamento Encefálico , Análise Fatorial , Feminino , Voluntários Saudáveis , Humanos , Imagem por Ressonância Magnética , Masculino , Adulto Jovem
10.
J Behav Med ; 41(4): 423-440, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29468532

RESUMO

Behavioral HIV prevention interventions designed to improve safer-sex communication skills with sexual partners may enhance engagement in protective behaviors and reduce HIV/STI risk. The current meta-analyses examined the efficacy of individual-based (i.e., not couples-based) HIV prevention interventions with a partner communication skills building component to increase frequency of: (a) safer-sex communication and (b) condom use with sexual partners among HIV at-risk groups (e.g., heterosexual African American females). Studies were retrieved from online bibliographic databases, a database of effective behavioral HIV prevention interventions, and an existing review of effective interventions. Eight manuscripts (k = 10 intervention vs. control comparisons) met inclusion criteria. Results indicated that compared to control conditions, at post-intervention follow-up, participants who were exposed to individual-based HIV prevention interventions with safer-sex communication skills training components had safer sex discussions with partners more frequently [drandom = 0.35 ± 0.10, p < .001, 95% CI (0.16, 0.55)], and used condoms more frequently [drandom = 0.39 ± 0.07, p < .001, 95% CI (0.25, 0.54)]. Including partner communication skills training in individual-based HIV prevention interventions may increase the frequency of both partner communication and condom use among the at-risk populations represented in the meta-analyses.

11.
Bipolar Disord ; 20(7): 658-665, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29479787

RESUMO

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

12.
FASEB J ; 32(2): 717-727, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28982731

RESUMO

Studies in humans have shown a direct association between maternal plasma cholesterol concentrations and infant birthweight. Similarly, previous studies in our laboratory have shown that chow-fed mice lacking apolipoprotein (apo) A-I, the major protein in HDL, have low HDL-cholesterol (HDL-C) concentrations and smaller fetuses in midgestation. In the current study, we measured fetal weights in mice with varying levels of apoA-I gene dose (knockout, wild-type, and transgenic) and examined metabolic pathways known to affect fetal growth. As expected, we found the differences in apoA-I expression led to changes in HDL particle size and protein cargo as well as plasma cholesterol concentrations. Fetal masses correlated directly with maternal plasma cholesterol and apoA-I concentrations, but placental masses and histology did not differ between groups of mice. There was no significant difference in glucose or amino acid transport to the fetus or in expression levels of the glucose (glucose transporter 1 and 2) or amino acid (sodium-coupled neutral amino acid transporter 1 and 2) transporters in whole placentas, although there was a trend for greater uptake of both nutrients in the whole fetal unit (fetus + placenta) of mice with greater apoA-I levels; significant differences in transport rates occurred when mice without apoA-I (knockout) vs. mice with apoA-I (wild-type and transgenic) were compared. Glucose tolerance tests were improved in the mice with the highest level of apoA-I, suggesting increased insulin-induced uptake of glucose by tissues of apoA-I transgenic mice. Thus, maternal HDL is associated with fetal growth, an effect that is likely mediated by plasma cholesterol or other HDL-cargo, including apolipoproteins or complement system proteins. A direct role of enhanced glucose and/or amino acid transport cannot be excluded.-Rebholz, S. L., Melchior, J. T., Davidson, W. S., Jones, H. N., Welge, J. A., Prentice, A. M., Moore, S. E., Woollett, L. A. Studies in genetically modified mice implicate maternal HDL as a mediator of fetal growth.


Assuntos
Apolipoproteína A-I/metabolismo , Colesterol/sangue , Desenvolvimento Fetal , Regulação da Expressão Gênica no Desenvolvimento , Lipoproteínas HDL/metabolismo , Placenta/metabolismo , Animais , Apolipoproteína A-I/genética , Feminino , Lipoproteínas HDL/genética , Camundongos , Camundongos Knockout , Gravidez
13.
J Clin Lab Med ; 2(1)2017.
Artigo em Inglês | MEDLINE | ID: mdl-29226278

RESUMO

World-wide, millions of women enter preterm labor or have small newborns. Effective biomarkers are needed to identify women at risk for these adverse outcomes. A time and cost effective way to examine any potentially new biomarkers in samples collected during prior studies or trials that had been assayed for other metabolites would be highly useful. Thus, the current study aimed to determine if samples that had been previously thawed and re-frozen could be re-assayed for novel biomarkers, those being lipoprotein composition (sizing, proteome, lipids) and combined cholesterol and cytokine concentrations. Fasting blood was collected from 51 young non-pregnant women and plasma was analyzed for lipoprotein composition and cytokine concentrations after multiple freeze/thaw cycles in the cold or at room temperature and after being stored for 18 months. Plasma LDL-C, HDL-C, total cholesterol, and triglyceride concentrations decreased <6-7% (cholesterols) or <20% (triglyceride) after 7 thaws in the cold, 3 thaws at room temperature, and after 18 months of storage. As these decreases were less than day-to-day reported variation of lipids, they do not appear to be physiologically significant. Cytokine (IL-6, TNF α, IL-8, IL-1ß) and hsCRP concentrations decreased by 22%, 8%, 8%, 22%, and 35%, respectively; only IL-6, IL-1ß and hsCRP concentrations showed significant decreases greater than day-to-day variations of 20%. For measured triglyceride and cytokine, but not cholesterol concentrations, decreases with freeze/thaw cycles were greater when concentrations were elevated. Multiple thaws also led to changes in lipoprotein sizing, specifically to a shift from medium- and large-sized HDL particles to small-sized HDL particles and from large LDL to IDL. No changes occurred for VLDL particle numbers. Though particle sizes changed, the HDL proteome did not change with multiple thaw cycles or after long term storage. Overall, the results demonstrate that it is possible to use previously obtained frozen samples for plasma cholesterol and triglyceride levels and the lipoprotein proteome, and lipoprotein sizing and cytokine concentrations if one knows the history of the sample as changes should be relative to one another.

14.
Bipolar Disord ; 19(4): 259-272, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28574156

RESUMO

OBJECTIVES: Individualized treatment for bipolar disorder based on neuroimaging treatment targets remains elusive. To address this shortcoming, we developed a linguistic machine learning system based on a cascading genetic fuzzy tree (GFT) design called the LITHium Intelligent Agent (LITHIA). Using multiple objectively defined functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1 H-MRS) inputs, we tested whether LITHIA could accurately predict the lithium response in participants with first-episode bipolar mania. METHODS: We identified 20 subjects with first-episode bipolar mania who received an adequate trial of lithium over 8 weeks and both fMRI and 1 H-MRS scans at baseline pre-treatment. We trained LITHIA using 18 1 H-MRS and 90 fMRI inputs over four training runs to classify treatment response and predict symptom reductions. Each training run contained a randomly selected 80% of the total sample and was followed by a 20% validation run. Over a different randomly selected distribution of the sample, we then compared LITHIA to eight common classification methods. RESULTS: LITHIA demonstrated nearly perfect classification accuracy and was able to predict post-treatment symptom reductions at 8 weeks with at least 88% accuracy in training and 80% accuracy in validation. Moreover, LITHIA exceeded the predictive capacity of the eight comparator methods and showed little tendency towards overfitting. CONCLUSIONS: The results provided proof-of-concept that a novel GFT is capable of providing control to a multidimensional bioinformatics problem-namely, prediction of the lithium response-in a pilot data set. Future work on this, and similar machine learning systems, could help assign psychiatric treatments more efficiently, thereby optimizing outcomes and limiting unnecessary treatment.


Assuntos
Sintomas Comportamentais , Transtorno Bipolar , Resistência a Medicamentos , Compostos de Lítio , Imagem por Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adolescente , Adulto , Antimaníacos/administração & dosagem , Antimaníacos/efeitos adversos , Inteligência Artificial , Sintomas Comportamentais/diagnóstico , Sintomas Comportamentais/tratamento farmacológico , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Monitoramento de Medicamentos/métodos , Feminino , Lógica Fuzzy , Humanos , Compostos de Lítio/administração & dosagem , Compostos de Lítio/efeitos adversos , Masculino , Imagem Multimodal/métodos , Projetos Piloto , Valor Preditivo dos Testes , Prognóstico
15.
J Med Virol ; 89(11): 1904-1911, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28460153

RESUMO

A beneficial impact of the Human Pegivirus (HPgV)-formerly called GB virus C (GBV-C)-on HIV disease progression has been reported previously. One possible mechanism by which HPgV inhibits HIV replication is an alteration of the cytokine/chemokine milieu. Their expression has not been specifically evaluated in women despite their influence on disease progression and the possibility of gender-based differences in expression. Moreover, the impact of HPgV genotype on cytokine/chemokine expression is unknown. Sera levels of IL-2, IL-4, IL-7, IL-8, IL-10, IL-12p70, IL-13, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 were quantified in 150 HIV-positive women based on HPgV RNA status. Cytokines/chemokines with detection rates of at least 50% included IL-2, IL-4, IL-8, IL-10, IL-12p70, IFNγ, TNFα, IP-10, MIP-1α, MIP-1ß, and TGF-ß1 . Absolute values were significantly higher for HPgV positive compared to HPgV negative women for IL-7, IL-13, IL-12p70, and IFNγ. Absolute values were significantly lower for HPgV positive women for IL-4, IL-8, TGF-ß1 , and IP-10. IFNγ values were higher for HPgV genotype 2 than for genotype 1 (P = 0.036). Further study of cytokine/chemokine regulation by HPgV may ultimately lead to the development of novel therapeutic agents to treat HIV infection and/or the design of vaccine strategies that mimic the "protective" effects of HPgV replication.


Assuntos
Quimiocinas/sangue , Citocinas/sangue , Infecções por Flaviviridae/complicações , Infecções por Flaviviridae/imunologia , Vírus GB C/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por HIV/virologia , Adulto , Quimiocinas/genética , Quimiocinas/imunologia , Citocinas/genética , Citocinas/imunologia , Progressão da Doença , Feminino , Vírus GB C/isolamento & purificação , Genótipo , Humanos , Interleucina-12/sangue , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-2/sangue , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-4/sangue , Interleucina-4/genética , Interleucina-4/imunologia , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/genética , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia , Estados Unidos
16.
Arch Phys Med Rehabil ; 98(3): 581-595, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27744025

RESUMO

OBJECTIVE: To assess the influence of dosing parameters and patient characteristics on the efficacy of aerobic exercise (AEX) poststroke. DATA SOURCES: A systematic review was conducted using PubMed, MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Physiotherapy Evidence Database, and Academic Search Complete. STUDY SELECTION: Studies were selected that compared an AEX group with a nonaerobic control group among ambulatory persons with stroke. DATA EXTRACTION: Extracted outcome data included peak oxygen consumption (V˙o2peak) during exercise testing, walking speed, and walking endurance (6-min walk test). Independent variables of interest were AEX mode (seated or walking), AEX intensity (moderate or vigorous), AEX volume (total hours), stroke chronicity, and baseline outcome scores. DATA SYNTHESIS: Significant between-study heterogeneity was confirmed for all outcomes. Pooled AEX effect size estimates (AEX group change minus control group change) from random effects models were V˙o2peak, 2.2mL⋅kg-1⋅min-1 (95% confidence interval [CI], 1.3-3.1mL⋅kg-1⋅min-1); walking speed, .06m/s (95% CI, .01-.11m/s); and 6-minute walk test distance, 29m (95% CI, 15-42m). In meta-regression, larger V˙o2peak effect sizes were significantly associated with higher AEX intensity and higher baseline V˙o2peak. Larger effect sizes for walking speed and the 6-minute walk test were significantly associated with a walking AEX mode. In contrast, seated AEX did not have a significant effect on walking outcomes. CONCLUSIONS: AEX significantly improves aerobic capacity poststroke, but may need to be task specific to affect walking speed and endurance. Higher AEX intensity is associated with better outcomes. Future randomized studies are needed to confirm these results.


Assuntos
Terapia por Exercício/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Exercício/fisiologia , Humanos , Consumo de Oxigênio , Resistência Física , Aptidão Física , Fatores de Tempo
17.
J Affect Disord ; 209: 246-253, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27936454

RESUMO

BACKGROUND: Studying youth at high risk of developing bipolar disorder may clarify neurobiological factors associated with vulnerability to this illness. We present here a baseline characterization of brain structure in youth at-risk for bipolar disorder. METHODS: Magnetic resonance images were obtained from 115 child and adolescent offspring of bipolar disorder type I subjects and 57 healthy child and adolescent offspring of healthy parents (healthy control offspring). Offspring of parents with bipolar disorder were divided into healthy bipolar offspring (n=47) or symptomatic bipolar offspring (n=68), according to presence or absence of childhood-onset psychopathology. All bipolar offspring were free of major mood and psychotic disorders. Gray (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. RESULTS: No differences in GM volumes were found across groups. Healthy bipolar offspring presented with decreased WM volumes in areas of the right frontal, temporal and parietal lobes, and in the left temporal and parietal lobes compared to healthy control offspring. Symptomatic bipolar offspring did not present with any differences in WM volumes compared to either healthy bipolar offspring or healthy control offspring. LIMITATIONS: Cross-sectional design and heterogeneous sample of symptomatic bipolar offspring. CONCLUSIONS: WM volume decreases in areas of the frontal, occipital, and parietal lobes are present in bipolar offspring prior to the development of any psychiatric symptoms, and may be a correlate of familial risk to bipolar disorder. In this large cohort, we have not found evidence for regional GM volume abnormalities as an endophenotype for bipolar disorder.


Assuntos
Transtorno Bipolar , Encéfalo/diagnóstico por imagem , Filho de Pais Incapacitados , Pais , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Transtorno Bipolar/diagnóstico , Criança , Estudos Transversais , Endofenótipos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Tamanho do Órgão/fisiologia
18.
JCO Clin Cancer Inform ; 1: 1-14, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-30657399

RESUMO

PURPOSE: Drug development in oncology is resource intensive, time consuming, and frequently unsuccessful. Here, we hypothesized that therapeutic benefit of published phase I studies of antimyeloma investigational agents was associated with advancement to phase II and future regulatory approval. PATIENTS AND METHODS: Seventy four phase I trials that treated patients with multiple myeloma (n = 2,408) conducted from 2004 to 2015 were analyzed to assess drug safety, efficacy, phase advancement, and regulatory approval. RESULTS: The median overall response rate (ORR) for all single-agent trials evaluated was 13.2%. However, the ORR in trials that advanced to phase II was 19%, whereas it was only 4% in trials that failed to advance. The median ORR was 23% for trials testing agents that were ultimately approved by the US Food and Drug Administration compared with only 8% for trials testing agents that were not approved (hazard ratio, 2.21; 95% CI, 2.01 to 2.61; P = .012). Importantly, the absolute number of phase I trials in multiple myeloma, but not the success rate, significantly increased over the period studied. The proportion of industry-sponsored trials also steadily increased over that same period. The ratio of initial dose to maximum tolerated dose was 0.29, suggesting that many patients were undertreated. CONCLUSION: Investigational agents with higher ORRs in phase I trials were more likely to advance to phase II trials and achieve US Food and Drug Administration approval. Our results suggest that designing phase I trials to maximize the antimyeloma efficacy of a given compound may lead to more successful and cost-effective drug development.


Assuntos
Antineoplásicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Antineoplásicos/administração & dosagem , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Aprovação de Drogas , Drogas em Investigação/administração & dosagem , Feminino , Humanos , Masculino , Prognóstico , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
19.
J Am Acad Child Adolesc Psychiatry ; 55(11): 980-989, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27806866

RESUMO

OBJECTIVE: To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. METHOD: Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. RESULTS: Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. CONCLUSION: During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Filho de Pais Incapacitados , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Risco , Adulto Jovem
20.
Respir Med ; 120: 1-9, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27817804

RESUMO

BACKGROUND: The predictive characteristics of different screening surveys for the recognition of individuals at risk for airflow obstruction (AFO) have not been evaluated simultaneously in the same population. PURPOSE: To compare five AFO/COPD screening questionnaires. METHODS: 383 individuals completed the Veterans Airflow Obstruction Screening Questionnaire, Personal Level Screener for COPD (VAFOSQ), the 11-Q COPD Screening Questionnaire (11-Q), the COPD Population Screener (COPD-PS) and the Lung Function Questionnaire (LFQ) and performed spirometry. AFO was defined as forced expiratory volume in one second divided by the forced vital capacity (FEV1/FVC) < 0.7, fixed ratio (FR) or FEV1/FVC < lower limit of normal (LLN). The predictive characteristics of the five questionnaires were calculated and non-parametric receiver operating characteristic (ROC) curves estimated by logistic regression. RESULTS: 376 participants completed at least two of the questionnaires and performed technically acceptable spirometry. AFO was present in 102 (27.1%) and 150 (39.9%) based on LLN and FR, respectively. The number of individuals positively selected by the VAFOSQ was 227, PLS 128, 11-Q 236, COPD-PS 217, and LFQ 328. The area under the ROC curves for the questionnaires was between 0.60 and 0.66 (LLN) and 0.58 and 0.66 (FR). CONCLUSIONS: Although these screening surveys have acceptable and similar predictive ability for the identification of AFO, their published thresholds lead to substantially different classification rates. The choice of an appropriate threshold for the identification of individuals with possible AFO/COPD should consider the underlying prevalence of AFO/COPD in the target population and the relative costs of misclassifying affected and unaffected cases. CLINICAL TRIAL REGISTRATION: None. PRIMARY SOURCE OF FUNDING: Veterans Health Administration.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Inquéritos e Questionários , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Testes de Função Respiratória/métodos , Fatores de Risco , Espirometria/métodos , Veteranos , Saúde dos Veteranos , Capacidade Vital
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