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BACKGROUND: Molecular biomarkers for bipolar disorder (BD) that distinguish it from other manifestations of depressive symptoms remain unknown. The aim of this study was to determine if a very sensitive tyramine-based signal-amplification technology for flow cytometry (CellPrint™) could facilitate the identification of cell-specific analyte expression profiles of peripheral blood cells for bipolar depression (BPD) versus healthy controls (HCs). METHODS: The diagnosis of psychiatric disorders was ascertained with Mini International Neuropsychiatric Interview for DSM-5. Expression levels for eighteen protein analytes previously shown to be related to bipolar disorder were assessed with CellPrint™ in CD4+ T cells and monocytes of bipolar patients and HCs. Implementation of protein-protein interaction (PPI) network and pathway analysis was subsequently used to identify new analytes and pathways for subsequent interrogations. RESULTS: Fourteen drug-naïve or -free patients with bipolar I or II depression and 17 healthy controls (HCs) were enrolled. The most distinguishable changes in analyte expression based on t-tests included GSK3ß, HMGB1, IRS2, phospho-GSK3αß, phospho-RELA, and TSPO in CD4+ T cells and calmodulin, GSK3ß, IRS2, and phospho-HS1 in monocytes. Subsequent PPI and pathway analysis indicated that prolactin, leptin, BDNF, and interleukin-3 signal pathways were significantly different between bipolar patients and HCs. LIMITATION: The sample size of the study was small and 2 patients were on medications. CONCLUSION: In this pilot study, CellPrint™ was able to detect differences in cell-specific protein levels between BPD patients and HCs. A subsequent study including samples from patients with BPD, major depressive disorder, and HCs is warranted.
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Trastorno Bipolar , Trastorno Depresivo Mayor , Humanos , Trastorno Bipolar/psicología , Monocitos/metabolismo , Proyectos Piloto , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Citometría de Flujo , Linfocitos T CD4-Positivos/metabolismo , Receptores de GABA/metabolismoRESUMEN
BACKGROUND: Response to a trial of proton pump inhibitors (PPIs) is currently accepted as a first step in the management of gastroesophageal reflux disease (GERD). However, information on the diagnostic performance of the PPI test is limited. AIM: The aim of this study was to determine the diagnostic accuracy of the PPI test in GERD and noncardiac chest pain (NCCP) and to assess the test performance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD). METHODS: Web of Science, Cochrane Controlled Register of Trials (CENTRAL), and MEDLINE were searched for studies reporting the diagnostic accuracy of the PPI test in adult patients with typical GERD and NCCP who underwent evaluation using an accepted reference standard, from January 1, 1950, through February 1, 2021. Subgroup analyses were performed, and the risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: Nineteen studies (GERD=11, NCCP=8) involving 1691 patients were included. In GERD, the PPI test had 79% pooled sensitivity [95% confidence interval (CI), 72%-84%], and 45% pooled specificity (95% CI, 40%-49%). In NCCP, pooled sensitivity and specificity were 79% (95% CI, 69%-86%) and 79% (95% CI, 69%-86%), respectively. In ERD, the PPI test had 76% pooled sensitivity (95% CI, 66%-84%) and 30% pooled specificity (95% CI, 8%-67%). In NERD, the PPI test had 79% pooled sensitivity (95% CI, 70%-86%) and 50% pooled specificity (95% CI, 39%-61%). CONCLUSIONS: The PPI test was sensitive in GERD but with suboptimal specificity. The test performed better in GERD-related NCCP. Diagnostic accuracy was comparable in ERD and NERD.
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Reflujo Gastroesofágico , Inhibidores de la Bomba de Protones , Adulto , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Reflujo Gastroesofágico/diagnóstico , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Sensibilidad y EspecificidadRESUMEN
Purpose: To determine if enhanced flow cytometry (CellPrint™) can identify intracellular proteins of lithium responsiveness in monocytes and CD4+ lymphocytes from patients with bipolar disorder. Methods: Eligible bipolar I or II patients were openly treated with lithium for 16-weeks. Baseline levels of Bcl2, BDNF, calmodulin, Fyn, phospho-Fyn/phospho-Yes, GSK3ß, phospho-GSK3αß, HMGB1, iNOS, IRS2, mTor, NLPR3, PGM1, PKA C-α, PPAR-γ, phospho-RelA, and TPH1 in monocytes and CD4+ lymphocytes of lithium responders and non-responders were measured with CellPrint™. Their utility of discriminating responders from non-responders was explored. Protein-protein network and pathway enrichment analyses were conducted. Results: Of the 24 intent-to-treat patients, 12 patients completed the 16-week study. Eleven of 13 responders and 8 of 11 non-responders were available for this analysis. The levels of the majority of analytes in lithium responders were lower than non-responders in both cell types, but only the level of GSK3ß in monocytes was significantly different (p = 0.034). The combination of GSK3ß and phospho-GSK3αß levels in monocytes correctly classified 11/11 responders and 5/8 non-responders. Combination of GSK3ß, phospho-RelA, TPH1 and PGM1 correctly classified 10/11 responders and 6/7 non-responders, both with a likelihood of ≥ 85%. Prolactin, leptin, BDNF, neurotrophin, and epidermal growth factor/epidermal growth factor receptor signaling pathways are involved in the lithium treatment response. GSK3ß and RelA genes are involved in 4 of 5 these pathways. Conclusion: CellPrint™ flow cytometry was able to detect differences in multiple proteins in monocytes and CD4+ lymphocytes between lithium responders and non-responders. A large study is warranted to confirm or refute these findings.
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Trastorno Bipolar , Biomarcadores , Trastorno Bipolar/tratamiento farmacológico , Factor Neurotrófico Derivado del Encéfalo , Linfocitos T CD4-Positivos , Estudios de Factibilidad , Citometría de Flujo , Glucógeno Sintasa Quinasa 3 beta , Humanos , Litio/farmacología , Litio/uso terapéutico , Compuestos de Litio , Monocitos , TiraminaRESUMEN
BACKGROUND: Association between irritability and depression has been frequently reported, but the nature of this association in the adult population is poorly understood. OBJECTIVES: We examined associations among irritability (e.g., a feeling of agitation), inflammatory biomarkers, and depression during chemotherapy. METHODS: Forty-four patients with nonmetastatic breast cancer were assessed at baseline and after 3 months of chemotherapy on The Irritability Scale-Initial Version, severity and new onset of depressive symptoms using the Hamilton Depression Rating Scale, and serum levels of high-sensitivity C-reactive protein and interleukin 6. RESULTS: At baseline, high-sensitivity C-reactive protein significantly correlated with physical and mood subscales of The Irritability Scale-Initial Version, but not with depression. Irritability and high-sensitivity C-reactive protein significantly predicted the severity and new onset of moderate to severe depressive symptoms over time, while irritability and interleukin 6 significantly predicted new onset of moderate to severe depressive symptoms. CONCLUSION: The findings suggest that irritability is an independent risk factor of depression and associated with increasing high-sensitivity C-reactive protein. Irritability needs to be effectively managed in patients with cancer undergoing chemotherapy to prevent them from developing depressive symptoms. These preliminary findings should be investigated in future large-sample studies.
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Neoplasias de la Mama , Interleucina-6 , Adulto , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/uso terapéutico , Depresión , Femenino , Humanos , Interleucina-6/uso terapéutico , Estudios Prospectivos , Receptores InmunológicosRESUMEN
BACKGROUND: Dyadic heart failure (HF) management can improve outcomes for patients and caregivers and can be enhanced through eHealth interventions. OBJECTIVE: To evaluate the feasibility, acceptability, and preliminary efficacy of an eHealth dyadic teamwork intervention, compared to an attention control condition. METHODS: We recruited 29 HF patient-caregiver dyads from inpatient units and randomized dyads to an intervention or a control group. We calculated enrollment and retention rates, described acceptability using interview and questionnaire data, and computed intervention effect sizes. RESULTS: 37% of eligible dyads agreed to participate and 93% of randomized participants completed follow-up questionnaires. Participants found both study conditions to be acceptable. Between-group effect sizes suggested that the intervention led to improvements in relationship quality, self-efficacy, and quality of life for patients and caregivers. CONCLUSIONS: Dyadic recruitment from acute care settings is challenging. Findings provide initial evidence that our intervention can contribute to better health outcomes for HF dyads.
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Insuficiencia Cardíaca , Calidad de Vida , Cuidadores , Insuficiencia Cardíaca/terapia , Humanos , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
BACKGROUND: In 2019, the United States Food and Drug Administration detected above-regulation levels of the human carcinogen N-nitrosodimethylamine (NDMA) in ranitidine, resulting in a complete removal of the medication from the market. NDMA is known to cause gastrointestinal malignancies in animal models. AIM: To determine if patients who were receiving ranitidine have a higher risk of developing cancers of the digestive tract compared to patients taking other anti-reflux medications. METHODS: Using the nationwide database IBM Explorys, patients taking ranitidine were compared to patients on either famotidine or omeprazole. Incidence data of new malignancies of the oesophagus, stomach, liver, pancreas, and colon/rectum were obtained in 1-year intervals for up to 10 years. Two multivariable logistic regression models were used to calculate odds ratios (ORs), one adjusting for common risk factors for each cancer studied, and the other for demographic factors. RESULTS: Patients on ranitidine who were compared to patients on famotidine had ORs of 0.51(95% CI 0.43-0.60), 0.43(95% CI 0.36-0.51), 0.39(95% CI 0.36-0.41), 0.54(95% CI 0.49-0.62), and 0.46(95% CI 0.43-0.49) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers, respectively (P < 0.001). Patients on ranitidine compared to omeprazole had ORs of 0.62(95% CI 0.52-0.72), 0.58(95% CI 0.49-0.68), 0.81 (95% CI 0.76-0.86), 0.68(95% CI 0.60-0.76), and 0.66(95% CI 0.62-0.70) of developing oesophageal, gastric, hepatocellular, pancreatic, and colorectal cancers respectively (P < 0.001). CONCLUSIONS: Use of ranitidine was not associated with an increased odds of developing gastrointestinal malignancies compared to omeprazole or famotidine use.
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Reflujo Gastroesofágico , Neoplasias Gastrointestinales , Animales , Famotidina/efectos adversos , Humanos , Omeprazol/efectos adversos , Ranitidina/efectos adversos , Estados UnidosRESUMEN
Mental health wellbeing is a critical element in the overall wellbeing of an individual. Severe mental health issues are directly connected with the individual's functioning and negatively impacts the quality of life. Inpatient psychiatric hospitalization does help significantly in stabilizing the acute serious mental health problems; however, the utility of community partial hospitalization program (PHP) has not been studied extensively. We undertook this study to assess the usefulness of community partial hospitalization program (PHP) in reducing severity of psychosomatic symptoms of patients; to study the epidemiology of the referred patients; and to elucidate the characteristics and predictors of psychosomatic symptom response. 164 patients were assessed by a baseline Behavioral and Symptom Identification Scale-32 (BASIS-32) at a tertiary healthcare center, out of which 82 patients subsequently followed up and were assessed using the same scale and the data was then stratified and compiled. Out of the initial 164 patients, at a 50% adherence rate, 13 patients showed an improvement greater than 30% with a significant co-relation to the race of the patients. Partial Hospitalization Program proved to be moderately effective in improving psychosomatic symptoms, with better results noticed in the White/Caucasian race. We need to consider several variables before generalizing this finding and more studies are needed in this area. However, we are able to highlight this valuable tool in addressing the severe mental health issues in a community-based populations.
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Centros de Día , Trastornos Mentales , Adulto , Hospitalización , Humanos , Pacientes Internos , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Salud Mental , Calidad de VidaRESUMEN
Background/Aims: A number of inflammatory mediators have been documented to be elevated in gastroesophageal reflux disease (GERD). Similar inflammatory mediators are involved in coronary artery disease. Thus, the aim of the study is to determine if GERD is a risk factor for developing acute myocardial infarction (AMI). Methods: We used Explorys, a private cloud-based data store to which a number of health care systems feed information. We identified a cohort of GERD patients who have undergone an esophagogastroduodenoscopy compared to those without GERD. Incidence of AMI was studied after statistically controlling for known AMI risk factors. Results: Total of 200 400 patients were included in the GERD group and 386 800 patients in non-GERD group. The primary event of AMI occurred in 17 200 patients in the GERD group (8.6%) vs 24 300 in non-GERD group (6.3%). Using logistic regression analysis and controlling for 6 major risk factors which included male gender (OR, 1.09; 95% CI, 1.07-1.11; P < 0.001), hypertension (OR, 6.53; 95% CI, 6.21-6.88; P < 0.001), hyperlipidemia (OR, 3.08; 95% CI, 2.96-3.20; P < 0.001), diabetes mellitus (OR, 1.72; 95% CI, 1.69- 1.76; P < 0.001), obesity (OR, 1.02; 95% CI, 1.00-1.04; P = 0.044), and smoking (OR, 1.38; 95% CI, 1.35-1.41; P < 0.001). The odds of developing AMI in the GERD population was 1.11 (95% CI, 1.08-1.13; P < 0.001). GERD had higher odds of developing AMI than male gender or obesity in our study. Conclusions: This study demonstrated that GERD is a risk factor for AMI, higher than male gender and obesity. However, the increased risk may be clinically insignificant.
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BACKGROUND: Body fluids are rich in histiocytes and may mimic atypical epithelial cells morphologically. Histiocytes can pose a significant challenge in serous fluid cytology as they tend to appear atypical due to prolonged accumulation in serous fluids in vivo and processing by liquid-based cytology in vitro. Not many studies have documented the utilization of histiocytic marker such as CD68 in serous fluid cytology, which can subsequently reduce the "atypical" diagnostic category. METHODS: One thousand one hundred and twenty-nine cases of serous fluid cytology from 2016 to 2019 were reviewed and reclassified based on proposed classification of the international system for reporting serous fluid cytology. There were 133 cases with atypical diagnoses, out of which 51 cases had cellblocks. An immunohistochemistry (IHC) panel, including two mesothelial markers, two epithelial markers, and one histiocytic marker was applied to the atypical samples. Same IHC panel was utilized to evaluate 15 cases each from negative for malignancy (NFM), suspicious for malignancy (SFM), and malignant (MAL) categories for further comparison. RESULTS: After reevaluation of the cytology material with IHC stains, 924 (82%), 133 (12%), 23 (2%), and 49 (4%) of the cases were reclassified as NFM, atypia of uncertain significance, SFM, and MAL, respectively. Twenty-five out of 51 atypical cases (49%) were downgraded to "benign" after reevaluation with CD68 IHC. CONCLUSION: Histiocytes can mimic atypical epithelial cells in body fluids. Effective utilization of CD68 IHC will be beneficial in further refining the "atypical" diagnostic category in serous fluid cytology.
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Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Líquidos Corporales/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Biomarcadores de Tumor/metabolismo , Citodiagnóstico/métodos , Técnicas Citológicas/métodos , Diagnóstico Diferencial , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Irritability is common among people who are physically ill, but a physical underpinning of irritability is not assessed by existing measures. A measure that assesses multidimensionality of irritability can help nurses and clinicians provide better care for people with cancer and, thus, reduce a risk for developing depression during cancer treatment. OBJECTIVES: We pilot tested a new measure, The Irritability Scale-Initial Version (TISi), for assessing irritability of cancer patients on three dimensions: physical, affective, and behavioral. METHODS: We conducted thee pilot studies to develop the 35-item TISi on a 5-point Likert scale. TISi was tested in 48 early-stage, nonmetastasized breast cancer patients at baseline (before) and 3 months (during chemotherapy). Of these patients, 62.5% received neoadjuvant and 37.5% received adjuvant chemotherapy, but none received hormonal treatment before or during the study. Measures of other correlates, including depression, anxiety, symptom distress, and social disconnectedness, were also administered, and biomarkers of hsCRP, TNF-α, IL-6, and BDNF were obtained from blood draws at both assessments. RESULTS: TISi has a high internal consistency (Cronbach's α = .97), satisfactory test-retest reliability (retest r = .69, intraclass correlation coefficient = .86), and moderate correlation with other constructs over time (r ≈ .40-.70). Its physical subscale significantly correlated with hsCRP (r = .32, p = .025) at baseline and TNF-α (r = .44, p = .002) at 3 months. A confirmatory factor analysis yields three factor loadings that are in line with conceptualization of the subscales. DISCUSSION: The findings support psychometric properties of TISi and its application for assessing cancer patients' irritability in multiple dimensions. Further investigation using a large study sample is necessary for improving construct and criterion validity and reducing item redundancy. CONCLUSION: TISi can be used to measure the level of irritability in cancer patients.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Depresión/prevención & control , Genio Irritable , Psicometría , Encuestas y Cuestionarios , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: The aim of this study was to use a visual analog scale (VAS) longitudinally measuring somnolence severity in patients with bipolar disorder. METHODS: A data set of patients with bipolar spectrum disorders who were randomized to lithium or quetiapine-IR for 16 weeks was used. The somnolence severity was measured with a VAS from 0 to 100 (VAS based), and somnolence frequency was recorded according to incident report (incidence based) at each visit. The rates of VAS-based and incidence-based somnolence and changes in somnolence severity from baseline to the end of study were compared between the lithium and quetiapine groups. Longitudinal changes in somnolence severity were analyzed with linear regression analysis. RESULTS: Of 42 patients randomized, only 3 scored 0 on the VAS at baseline. The rates of incidence-based and VAS-based somnolence were similar in the lithium and quetiapine-IR groups. The VAS change scores from baseline to each visit varied in both groups with significant decreases at weeks 6 and 12 in the quetiapine-IR group only. The decrease at week 6 in the quetiapine-IR group was significantly different from that in the lithium group. Patterns of changes in somnolence severity were inconsistent in both groups. A significant interaction between time course and the decrease in VAS scores was observed in the quetiapine-IR group, but not in the lithium group. CONCLUSIONS: Baseline somnolence was highly prevalent in patients with bipolar disorder. The change in somnolence severity was different between lithium-treated and quetiapine-treated patients. Quantifying somnolence longitudinally is important in clinical trials and practice.
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Trastorno Bipolar/tratamiento farmacológico , Compuestos de Litio/administración & dosificación , Fumarato de Quetiapina/administración & dosificación , Somnolencia , Adulto , Antimaníacos/administración & dosificación , Antimaníacos/efectos adversos , Antipsicóticos/administración & dosificación , Antipsicóticos/efectos adversos , Femenino , Humanos , Compuestos de Litio/efectos adversos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fumarato de Quetiapina/efectos adversos , Índice de Severidad de la Enfermedad , Escala Visual Analógica , Adulto JovenRESUMEN
BACKGROUND: Objective of the present study was to conduct an 8-week double-blind, randomized, placebo-controlled trial to test the efficacy of pioglitazone in the treatment of bipolar depression. METHODS: 38 outpatients with bipolar disorder and current major depressive episode were randomized to pioglitazone (15-45â¯mg/day) or placebo. The use of concomitant mood stabilizers, antipsychotics, and antidepressants was permitted. The primary outcome measure was the 30-item Inventory of Depressive Symptomatology, Clinician Rated (IDS-C30) total score change from baseline to endpoint. Laboratory evaluations, including serum level of inflammatory and metabolic biomarkers, were conducted. RESULTS: 37 subjects were analyzed for efficacy (1 subject had no follow-up data). Mean reduction from baseline to week 8 in IDS-C30 score was-6.59 for pioglitazone and -11.63 for placebo. Mixed effects modeling indicated borderline statistically significant difference between the two groups (pâ¯=â¯0.056) in favor of placebo. On analysis of inflammatory and metabolic markers, a statistically significant negative correlation was noted between change in leptin levels and change in depression scores in the pioglitazone group (râ¯=â¯-0.61, pâ¯=â¯0.047) but not in the placebo group, the significance of which is unclear as the study failed to demonstrate antidepressant efficacy of pioglitazone over placebo. No serious adverse effects were reported, and pioglitazone was well-tolerated. LIMITATIONS: small sample size with inadequate power, concomitant use of other psychotropic medications, and lack of statistical adjustment for multiple testing. CONCLUSION: Current study does not support the antidepressant efficacy of pioglitazone in the treatment of bipolar depression. (240 words).
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Trastorno Bipolar/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Pioglitazona/uso terapéutico , Adulto , Antidepresivos/uso terapéutico , Antimaníacos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno Bipolar/psicología , Depresión , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to compare the effectiveness of lithium versus quetiapine immediate release (IR) monotherapy in patients with bipolar I, II, or subthreshold bipolar disorder at any phase. METHODS: Eligible patients were randomized to lithium or quetiapine IR for 16 weeks. The difference in the time to discontinuation from study due to "all causes" between lithium and quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression, mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory markers were compared. RESULTS: Of the 42 patients randomized to lithium (n = 18) and quetiapine IR (n = 24), the median time to discontinuation due to "all causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7 ± 1.1 weeks for lithium versus 8.4 ± 0.8 weeks for quetiapine IR (P = 0.54). There was no significant difference between lithium and quetiapine IR in changes in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or only in patients with depressive index episode. The decrease in total cholesterol was significantly larger with lithium than with quetiapine IR (P = 0.05) as a whole, but not only in patients with depression index episode. There was no other significant difference in changes in metabolic panels and inflammatory markers between the 2 groups. CONCLUSIONS: The difference in effectiveness between lithium and quetiapine IR monotherapy in a real-world bipolar population was minimal. Large-sample studies are needed to support or refute this finding.
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Antimaníacos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Litio/uso terapéutico , Fumarato de Quetiapina/uso terapéutico , Adulto , Trastorno Bipolar/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Patients with long QT syndrome (LQTS) are predisposed to polymorphic ventricular tachycardia (VT) during adrenergic stimulation. Microvolt T-wave alternans (MTWA) is linked to vulnerability to VT in structural heart disease. The prevalence of non-sustained MTWA (NS-MTWA) in LQTS is unknown. METHODS: 31 LQT1, 42 LQT2, and 80 controls underwent MTWA testing during exercise. MTWA tests were classified per standardized criteria, and re-analyzed according to the modified criteria to account for NS-MTWA. RESULTS: LQT1 and LQT2 patients had a significantly higher frequency of late NS-MTWA (26% and 12%) compared to controls (0%). There was no significant difference between the groups with respect to sustained and early NS-MTWA. Late NS-MTWA was significantly associated with QTc. CONCLUSION: LQT1 and LQT2 patients had a higher prevalence of late NS-MTWA during exercise than matched controls. NS-MTWA likely reflects transient adrenergically mediated dispersion of repolarization, and could be a marker of arrhythmic risk in LQTS.
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Síndrome de QT Prolongado/congénito , Síndrome de QT Prolongado/fisiopatología , Taquicardia Ventricular/congénito , Taquicardia Ventricular/fisiopatología , Adulto , Estudios de Casos y Controles , Electrocardiografía , Prueba de Esfuerzo , Femenino , Genotipo , Humanos , Síndrome de QT Prolongado/genética , Masculino , Taquicardia Ventricular/genéticaRESUMEN
BACKGROUND: Early predictors of response and remission in pediatric mania are lacking, requiring further study. METHODS: This was a post hoc analysis of a 3-week, randomized, placebo-controlled trial of olanzapine conducted between November 2002 and May 2005 in 161 adolescents aged 13-17 years who were diagnosed with a DSM-IV acute manic or mixed episode of bipolar I disorder. Data from the olanzapine arm were analyzed to investigate the predictive power of early response or early nonresponse (≥25% or < 25% reduction in Young Mania Rating Scale [YMRS] score, respectively) at week 1 for ultimate response or nonresponse (≥ 50% or < 50% reduction in YMRS score, respectively) and for remission (YMRS total score ≤ 12 [standard definition] or ≤ 8 [stringent definition]) at week 3. Correlates of early response and ultimate response were examined in multivariable regression models. RESULTS: By week 1, 69.2% of olanzapine-treated adolescents (n = 104, 2.5-20.0 mg/d) achieved early response, and 49.0% reached ultimate response at week 3. Patients with early response and early nonresponse were similar regarding baseline variables except higher scores for sleep and thought content were found with early response (P < .05) and higher olanzapine doses with early nonresponse (P < .01). At week 3, early response was associated with significantly greater improvements in YMRS, Clinical Global Impressions-Severity of Illness scale (both P < .001), and Overt Aggression Scale scores (P = .024). Adverse events were similar in patients with early response and early nonresponse, except for higher AIMS scores for patients with early nonresponse (P = .036). Early response significantly predicted ultimate response (OR = 5.61, P < .001; sensitivity = 86.3, specificity = 47.2, positive predictive value = 61.1, negative predictive value = 78.1). Significantly more early response than early nonresponse patients achieved ultimate response (61.1% vs 21.9%, P < .001) and remission defined by YMRS score ≤ 12 (45.8% vs 12.5%, P < .001) and YMRS score ≤ 8 (33.3% vs 3.1%, P < .001). In multivariable analyses, among other variables, early response remained an independent correlate of ultimate response and remission. CONCLUSIONS: In acute pediatric manic or mixed episodes, early response to olanzapine at week 1 was strongly associated with ultimate response and remission at week 3, while absence of early response predicted the unlikely success of further treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00050206.
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Antipsicóticos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Olanzapina/uso terapéutico , Adolescente , Trastorno Bipolar/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Inducción de Remisión , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aims to compare treatment response in bipolar I or II depression and generalized anxiety disorder (GAD) with and without recent alcohol and/or cannabis use disorder (ALC/CAN) to quetiapine-XR (extended release) or placebo. METHODS: A randomized, double-blind, 8-week study of quetiapine-XR versus placebo in patients with bipolar I or II depression and GAD with or without a recent ALC/CAN was used to compare changes in Hamilton Depression Rating Scale-17, Hamilton Anxiety Rating Scale, the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR-16), Clinical Global Impression for Bipolar Disorder-Severity (CGI-BP-S), and Timeline Follow Back within and between groups. RESULTS: In the quetiapine-XR group, patients with a recent ALC/CAN (n = 22) had significant decreases in QIDS-SR-16 (-9.6 ± 1.6 vs. -3.7 ± 1.7) and CGI-BP-S (-1.6 ± 0.4 vs. -0.8 ± 0.03) than those without a recent ALC/CAN (n = 24). In the placebo group, both patients with a recent ALC/CAN (n = 23) and those without (n = 21) had similar reductions in these measures. The reduction of QIDS-SR-16 scores in patients with a recent ALC/CAN was also significantly different from that of their counterparts in the placebo group. Patients who received quetiapine-XR had larger decreases in the number of drinking days/week (p = 0.17) and number of cannabis joints/week (p = 0.09) compared to those who received placebo. CONCLUSION: Quetiapine-XR was superior to placebo in reducing QIDS-SR-16 total score in patients with a recent ALC/CAN. Patients taking quetiapine-XR used less alcohol and cannabis than patients on placebo, suggesting that quetiapine-XR may be of use in patients with bipolar disorder accompanied by GAD and other comorbidities.
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Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Antipsicóticos/administración & dosificación , Trastornos de Ansiedad/tratamiento farmacológico , Trastorno Bipolar/tratamiento farmacológico , Fumar Marihuana/tratamiento farmacológico , Fumarato de Quetiapina/administración & dosificación , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/psicología , Trastornos de Ansiedad/epidemiología , Trastornos de Ansiedad/psicología , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Cannabis , Comorbilidad , Preparaciones de Acción Retardada/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Masculino , Fumar Marihuana/epidemiología , Fumar Marihuana/psicología , Persona de Mediana Edad , Autoinforme , Resultado del TratamientoRESUMEN
OBJECTIVES: To pilot efficacy and safety data of quetiapine-XR monotherapy or adjunctive therapy to antidepressant(s) in the acute treatment of MDD with current generalized anxiety disorder (GAD). METHODS: The Mini International Neuropsychiatric Interview was used to ascertain the diagnosis of DSM-IV Axis I disorders. Eligible patients were randomly assigned to quetiapine-XR or placebo for up to 8 weeks. Changes from baseline to endpoint in Hamilton Depression Rating Scale-17 items (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression-Severity (CGI-S), Quick Inventory of Depression Symptomatology-16 items Self-Report (QIDS-16-SR) total scores, and other outcome measures were analyzed with the last observation carried forward strategy and/or mixed-effects modeling for repeated measures. RESULTS: Of the 34 patients screened, 23 patients were randomized to receive quetiapine-XR (n = 11) or placebo (n = 12), with 5 and 4 completing the study, respectively. The mean dose of quetiapine-XR was 154 ± 91 mg/d. The change from baseline to endpoint in the total scores of HAMD-17, HAM-A, QIDS-16-SR, and CGI-S were significant in the quetiapine-XR group, but only the change in HAM-A total score was significant in the placebo group. The differences in these changes between the two groups were only significant in CGI-S scores, with the rest of numerical larger in the quetiapine-XR group. The most common side effects from quetiapine-XR were dry mouth, somnolence/sedation, and fatigue. CONCLUSIONS: In this pilot study, quetiapine-XR was numerically superior to placebo in reducing depressive and anxiety symptoms in patients with MDD and current GAD. Large sample studies are warranted to support or refute these preliminary findings.
RESUMEN
INTRODUCTION: Microvolt T-wave alternans (MTWA) analysis can identify patients at low risk of sudden cardiac death who might not benefit from an implantable cardioverter-defibrillator (ICD). Current spectral methodology for performing MTWA analysis may "miss" part of the T-wave in patients with QT prolongation. The value of T-wave window adjustment in patients with structural heart disease has not been studied. METHODS: We assembled MTWA data from 5 prior prospective studies including 170 patients with reduced left ventricular ejection fraction, adjusted the T-wave window to include the entire T-wave, and reanalyzed MTWA. RESULTS: Of 170 patients, 43% required T-wave window adjustment. Only 3 of 170 patients (1.8%) had a clinically significant change in MTWA results. CONCLUSIONS: In 98.2% of patients, T-wave window adjustment did not improve the accuracy of MTWA analysis. Spectral MTWA as currently implemented remains effective for identifying patients with structural heart disease unlikely to benefit from ICD therapy.
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Algoritmos , Cardiomiopatías/diagnóstico , Cardiomiopatías/epidemiología , Electrocardiografía/métodos , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ohio/epidemiología , Pronóstico , Reproducibilidad de los Resultados , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Research exploring spirituality in military populations is a relatively new field with limited published reports. This study used the Spiritual Well-Being Scale to examine the association of spiritual well-being with suicidal ideation/behavior, posttraumatic stress disorder (PTSD), and depression and alcohol use disorders in a randomized sample of Ohio Army National Guard soldiers. The participants were 418 soldiers, mostly white and male, with nearly three-quarters indicating that they had been deployed at least once during their careers. Higher spirituality, especially in the existential well-being subscale, was associated with significantly less lifetime PTSD, depression, and alcohol use disorders and with less suicidal ideation over the past year. Future research in this area may benefit from a longitudinal design that can assess spirituality and mental health behaviors in addition to diagnoses at different time points, to begin to explore spirituality in a larger context.
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Depresión/psicología , Personal Militar/psicología , Satisfacción Personal , Espiritualidad , Trastornos por Estrés Postraumático/psicología , Ideación Suicida , Intento de Suicidio/psicología , Adolescente , Adulto , Trastornos Relacionados con Alcohol , Depresión/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Personal Militar/estadística & datos numéricos , Ohio , Trastornos por Estrés Postraumático/epidemiología , Intento de Suicidio/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVE: To examine the personal financial impact of atopic dermatitis (AD) and attempt to correlate cost of AD with emotional impact. STUDY DESIGN: Between March 2011 and December 2013, 82 caretakers of children 6 months to 12 years of age with moderate-to-severe AD were recruited at the time of dermatology clinic visits in Cleveland, Ohio, to complete surveys. The response rate was >95%. Participants were asked questions about direct expenses (medical visits, medications, and other products) and indirect expenses (time missed from work, childcare costs) related to AD in the past 4 weeks. Emotional impact was measured by the Childhood Atopic Dermatitis Impact Scale. RESULTS: The mean monthly personal cost of AD in the month before the office visit was $274 (median $114; IQR $29, $276), with $75 from direct costs (median $45; IQR $20, $110) and $199 from indirect costs (median $0; IQR $0, $208). An average of 34.8% of available monthly money was spent on AD care in the month before the office visit. For patients with Medicaid, there was a significant correlation between monthly adjusted personal cost and Childhood Atopic Dermatitis Impact Scale score (r = 0.548; P < .001); however, this correlation did not exist for patients who had commercial insurance (r = 0.269; P = .166). CONCLUSIONS: Our results illustrate the high emotional and financial burden of childhood AD and provide insight into spending patterns. In addition, our study correlate costs with emotional burden of AD for lower-income patients.