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1.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 43(1): 70-74, Jan.-Feb. 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153286

RESUMO

Objective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. Results: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). Conclusions: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

2.
Bipolar Disord ; 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33354859

RESUMO

OBJECTIVES: Previous studies and meta-analyses suggested that N-acetylcysteine (NAC) was superior to placebo in improving depression in bipolar disorder. However, more recent data, including two larger trials, found that NAC was no more effective than placebo. We conducted a meta-analysis to appraise the possible efficacy of NAC in treating bipolar depression. METHODS: A systematic review and meta-analysis of double-blind, placebo-controlled trials of NAC as a treatment augmentation strategy for bipolar depression was carried out in PubMed (1966-2020). We utilized random-effect analysis to evaluate improvement in depressive symptoms from baseline to endpoint as the primary efficacy measure. RESULTS: Six trials including 248 patients were included. Treatment augmentation with NAC showed a moderate effect size favoring NAC over placebo (d = 0.45, 95% C.I.: 0.06-0.84). There was substantial heterogeneity (I2  = 49%). Meta-regression analyses did not identify any moderator that might explain variation in heterogeneity, including baseline depressive symptom scores, mean NAC dose, or duration of study. CONCLUSIONS: Results from six clinical trials suggest that treatment augmentation with NAC for bipolar depression appears to be superior to placebo, with a moderate effect size, but a large confidence interval. Larger clinical trials, investigating possible moderating factors, such as NAC dose, treatment duration, baseline depression severity, or chronicity of illness, are warranted.

3.
J Clin Anesth ; 67: 110027, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32980763

RESUMO

STUDY OBJECTIVE: This report analyzes the comparative costs, efficacy and side effects of a newer, more expensive reversal drug, sugammadex, with its generic counterpart, neostigmine combined with glycopyrrolate, or no reversal agent when used routinely to reverse rocuronium-induced neuromuscular blockade in adult patients. DESIGN: Cost analysis. METHODS: We constructed a decision model to analyze the costs associated with the choice of reversal drug and differences in reversal time, occurrence of postoperative nausea or vomiting (PONV), and residual blockade requiring unplanned postoperative mechanical ventilation (UPMV). We selected variables that demonstrated meaningful differences in meta-analyses of published studies and/or had significant associated costs. We used data from local hospital system information, meta-analysis of published studies, and the general literature to construct base-case scenarios and sensitivity analyses. We performed the analysis from the perspective of a single hospital system. Costs were in 2019 U.S. dollars. RESULTS: Cost analysis suggested that reversal with sugammadex is preferable to neostigmine or no reversal drug when operating room (OR) time was valued at ≥$8.60/min (base case $32.49/min). Net costs of sugammadex were less than no treatment or neostigmine reversal when the probability of UPMV exceeded 0.019 and 0.036, respectively. Neither sugammadex nor neostigmine reversal was preferable to no treatment in a base-case analysis that considered the effect of the reversal agent on only drug and PONV costs, disregarding costs of OR time or UPMV. CONCLUSIONS: Routine reversal with sugammadex is preferable to choosing neostigmine or no reversal drug when accounting for potential savings in OR time. Sugammadex might also be a reasonable choice for patients at high risk of UPMV. If the cost of OR time is not considered, the analysis does not support the routine use of sugammadex in patients with perceived increased risk or solely to reduce PONV.

4.
Data Brief ; 32: 106241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32944599

RESUMO

This meta-analysis was conducted to define clinical efficacy and side effects (bradycardia and post-operative nausea and vomiting [PONV]) in trials comparing sugammadex with neostigmine or placebo for reversal of rocuronium-induced neuromuscular blockade in adult patients. A search of PubMed, Google Scholar, and Cochrane Library electronic databases identified 111 clinical trials for potential inclusion. We performed a meta-analysis of 32 studies that quantitatively compared the efficacy and side effects of sugammadex with either neostigmine or placebo in adult patients requiring general anesthesia. Analyzed outcomes were reversal time, anesthesia time, duration of stay in the post-anesthesia care unit (PACU), and the occurrence of bradycardia or PONV. Odds ratios and 95% confidence intervals (CI) were calculated for binary data. Mean differences and 95% CI were calculated for continuous outcome data. Meta-analyses were performed using random and fixed-effects models. Heterogeneity across studies was assessed using Cochran's Q test and the I2 statistic. Quantification of these outcomes can better inform anesthetists and health systems of the relative costs and benefits of the two reversal agents. This information also forms a basis for a comparative cost analysis in a co-submitted manuscript [1].

5.
Braz J Psychiatry ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32876131

RESUMO

OBJECTIVE: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). METHODS: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. RESULTS: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). CONCLUSIONS: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.

6.
J Child Adolesc Psychopharmacol ; 30(5): 293-305, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167792

RESUMO

Objectives: To evaluate the clinical and neurochemical effects of 12-week fish oil, a source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), in depressed adolescents with a family history of bipolar I disorder. Methods: Adolescents with a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision diagnosis of Major Depressive Disorder or Depressive Disorder not otherwise specified, a Childhood Depression Rating Scale-Revised (CDRS-R) Version raw score of ≥40, and at least one biological parent with bipolar I disorder were randomized to double-blind treatment with fish oil (2100 mg/day) or placebo for 12 weeks. The primary outcome measure was change in CDRS-R total score, and secondary outcomes measures were change in manic symptoms (Young Mania Rating Scale), global symptom and functioning measures (Clinical Global Impression-Severity [CGI-S] /CGI Improvement [CGI-I], Children's Global Assessment Scale, and Child Behavior Checklist), safety and laboratory measures, and anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex neurometabolite concentrations using proton magnetic resonance spectroscopy at 4 T. Results: Fifty-six patients were randomized, and 42 completed the 12-week trial (placebo: n = 21; fish oil, n = 21). Subjects randomized to fish oil, but not placebo, exhibited a significant baseline to endpoint increase in erythrocyte n-3 PUFAs. Reductions in CDRS-R scores did not differ between treatment groups (p = 0.15), and similar remission (p = 0.58) and response (p = 0.77) rates were observed. Fish oil produced a significantly greater decrease in CGI-S (p = 0.0042) and CGI-I (p = 0.036) scores compared with placebo. Baseline to endpoint change in ACC creatine (p = 0.004) and ACC choline (Cho) (p = 0.024) differed significantly between groups. Baseline ACC Cho levels were inversely correlated with baseline and baseline to endpoint change in CDRS-R scores, and baseline to endpoint change in ACC Cho correlated with baseline-endpoint change in CDRS-R scores and n-3 PUFA. There were no group differences in safety and tolerability ratings or laboratory measures. Conclusions: Fish oil monotherapy was not superior to placebo for reducing depressive symptoms in high-risk youth as assessed by the CDRS-R, but was safe and well tolerated and superior to placebo on clinician ratings of global symptom improvement. Associations among ACC Cho levels, depression symptom severity, and n-3 PUFA warrant additional investigation.

7.
J Child Adolesc Psychopharmacol ; 30(2): 119-122, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31851522

RESUMO

Objectives: To examine metabolic monitoring rates in commercially insured children and adolescents treated with a second-generation antipsychotic (SGA) during calendar years (CYs) 2016 and 2017. Methods: In this retrospective study, data were collected from a large national commercial health plan for the period covering January 1, 2016 to December 31, 2017. Commercially insured children and adolescents, aged 8-19 years with ≥2 SGA prescription claims during the CY, were identified for the CY2016 and CY2017 cohorts. The primary outcome of interest was the percentage of subjects with any glucose or lipid metabolism parameter monitoring. Other calculated metabolic testing rates included glucose, hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), other cholesterol (including triglycerides), and combined glucose and lipid metabolism testing (≥1 test for blood glucose or HbA1c and ≥1 test for LDL-C or other cholesterol). Results: In CY2016 and CY2017, 1502 and 1239 subjects, respectively, were identified for this study. The most common psychiatric diagnoses in CY2016 and CY2017 were major depressive disorder (57.1%, 56.5%, respectively), anxiety disorders (42.9%, 47.5%), attention-deficit/hyperactivity disorder (41.6%, 45.8%), and bipolar disorder (24.1%, 25.9%). The rate of any metabolic testing was 53.5% in CY2016 and 51.3% in CY2017. Glucose testing (50.3%, 46.9%, respectively) was most common in both CYs, followed by LDL-C testing (31.2%, 28.5%). Rates of combined glucose and lipid metabolism testing were 30.7% in CY2016 and 26.9% in CY2017. Conclusions: Given the known potential for adverse cardiometabolic effects, rates of metabolic monitoring associated with SGA use in children and adolescents urgently need to be improved. There is a critical need for understanding barriers to routine monitoring, particularly of lipids, and developing interventions to enhance metabolic monitoring.

8.
J Matern Fetal Neonatal Med ; 33(13): 2291-2299, 2020 Jul.
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.

9.
Radiol Imaging Cancer ; 2(6): e200033, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33778749

RESUMO

Purpose: To determine whether MR spectroscopic assessment of fine-needle aspiration (FNA) biopsy specimens from suspicious breast lesions could be used to improve the diagnostic utility of FNA biopsies for the characterization of breast lesions. Materials and Methods: In this prospective study, a previously reported technique using high-spatial-resolution proton MR spectroscopy was modified and used to examine the utility of FNA biopsies in the evaluation of suspicious breast lesions. Tissue samples from 115 lesions (from 102 women; average age, 54 years) were excised by using FNA and core biopsies and were collected between September 7, 2012, and April 11, 2014. Histologic results from core biopsy specimens determined the lesions to be benign (n = 55), invasive ductal carcinoma (n = 51), invasive lobular carcinoma (n = 5), or ductal carcinoma in situ (n = 4). Measures of phosphocholine (PC), glycerophosphocholine, and choline relative to each other and to total creatine (tCr) were obtained from usable spectra. Planned comparisons among lesion groups were carried out using t test contrasts, and differences of each contrast level from zero were judged significant when the two-tailed P value was less than .05. Results: Of the 115 samples, 69 (60%) yielded no usable MR spectra. Analysis of the 46 with usable spectra found that only the difference in PC/tCr between benign and cancer lesions was statistically significant (P = .028). Conclusion: Given that 60% of FNA biopsy specimens yielded no usable spectra and that results were largely inconclusive when derived from usable spectra, the combined MR and FNA technique, as modified and implemented in this study, is of little value for detection and diagnosis of breast cancer.Keywords: Breast, MR-Spectroscopy, Neoplasms-Primary© RSNA, 2020.

10.
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.


Assuntos
Afeto/fisiologia , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Adulto , Tonsila do Cerebelo/fisiopatologia , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Atenção/fisiologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Testes Neuropsicológicos , Córtex Pré-Frontal/fisiopatologia , Tálamo/fisiopatologia
11.
Clin J Am Soc Nephrol ; 14(1): 57-65, 2019 01 07.
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.


Assuntos
Biópsia/efeitos adversos , Hematoma/etiologia , Nefropatias/patologia , Rim/patologia , Adolescente , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Complicações Pós-Operatórias/etiologia , Reoperação/estatística & dados numéricos , Adulto Jovem
12.
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
13.
J Am Acad Child Adolesc Psychiatry ; 57(4): 235-244.e2, 2018 04.
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.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/administração & dosagem , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adolescente , Humanos , Inibidores de Captação de Serotonina/farmacologia , Inibidores da Recaptação de Serotonina e Norepinefrina/farmacologia
14.
Bipolar Disord ; 20(7): 658-665, 2018 11.
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.


Assuntos
Transtorno Bipolar , Ácidos Graxos Ômega-3 , Síndrome Metabólica , Psicotrópicos/uso terapêutico , Triglicerídeos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Índice de Massa Corporal , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricos , Triglicerídeos/sangue , Triglicerídeos/metabolismo
15.
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
16.
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.

17.
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
18.
J Med Virol ; 89(11): 1904-1911, 2017 11.
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
19.
J Affect Disord ; 209: 246-253, 2017 Feb.
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
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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