Teaching Ethics in Child and Adolescent Psychiatry: Vignette-Based Curriculum

Introduction: Ethics is an integral component of child and adolescent psychiatry. While ethics can seem abstract or philosophical, its tenets are fundamental to the practice of medicine. Understanding relevant ethical principles shapes how practitioners make decisions in all activities, including clinical, administrative, research, and scholarly. Methods: Using the American Academy of Child and Adolescent Psychiatry (AACAP) Code of Ethics as the framework, these vignettes serve as stimulus material to help teach the ethical principles relevant to child and adolescent psychiatry practice. Each vignette briefly describes a clinical situation in practice, followed by questions and possible appropriate responses. The teacher\u27s guide includes a discussion of the relevant ethical principles and perspectives on how to think about the issues involved. A supplementary overview of ethical issues in child and adolescent psychiatry and a list of resources are also provided. Results: We and other child and adolescent psychiatrists have used this curriculum at professional organizational meetings, in residency programs, and in teaching medical students with positive learner responses. Discussion: This curriculum was developed by members of the AACAP Ethics Committee with input from the entire committee in an effort to produce material that was easy to use and provided valuable content about an essential aspect of practice that is relevant to all practitioners at all levels. While designed for child and adolescent psychiatrists, the content is relevant to all physicians working with children, adolescents, and families

Pro- and Anti-inflammatory Biomarkers as Predictors of Response to Valproate in Patients with Comorbid Alcohol Use and Bipolar Disorder-Preliminary Findings

Objective/Hypothesis: Bipolar disorder (BD) has the highest association with alcohol and other substance use disorders compared to other major psychiatric disorders. This patient population is particularly challenging to treat. We have previously shown that some patients with co-occurring alcohol use and bipolar disorders respond to the GABAergic agonist valproate (VPA), which is known to modulates the dopaminergic system, and also as an epigenetic modifier. Predictors of therapeutic response to VPA in patients with AUD/BD are not known, and the subgroup which would benefit from VPA is still to be identified. Recent evidence suggests that AUD promotes a pro-inflammatory state while VPA increases levels of anti-inflammatory factors. We hypothesized that VPA has an anti-inflammatory effect and that patients with AUD/BD who respond to VPA have higher baseline inflammatory indices. Methods: Nine patients with DSM-IV-defined diagnoses of AUD and BD (AUD/BD) were enrolled in the study. Patients received a course of VPA for 3 months at an average dose of 1000 mg a day in addition to receiving either naltrexone of 50 mg daily or placebo. Blood was collected prior to the initiation of VPA and throughout the treatment study. Liver function tests and trough VPA serum concentrations were evaluated periodically. Alcohol use outcome was assessed using the Timeline Follow-Back for Recent Drinking. The use of other drugs was monitored through regular urine drug screen. The primary alcohol use outcome was changes in proportion of weekly heavy drinking days (defined as ³ 5 drinks per day for men and ³ 4 drinks per day for women). Plasma levels of cytokines were measured using Multiplex Immunoassay, in accordance to the manufacturers’ recommendations. Results: We found that about one half of enrolled patients responded to VPA. Screening of pro- and anti-inflammatory cytokines showed that responders had higher levels of the chemokine SDF-1a/CXCL12a and the pro-inflammatory marker C-reactive protein (CRP) and lower levels of anti-inflammatory factor matrix metalloproteinase-10 (MMP-10) (p \u3c 0.05). Screening of cytokines in samples before and after treatment with VPA showed that VPA increased levels of anti-inflammatory factors interleukin-10 (IL-10) and MMP-10 (p \u3c 0.05) and tended to decrease levels of pro-inflammatory CRP (p \u3e 0.05). Discussion: Pro- and anti-inflammatory biomarkers may serve as predictors of treatment response to VPA in patients with combined AUD/BD. Our preliminary results also suggest that therapeutic effect of VPA may be in part due to anti-inflammatory action of VPA. Larger studies may be indicated to validate these findings

The effect of epidural anesthesia on muscle flap tolerance to venous ischemia

Background: Venous ischemia is a major cause of failure after free tissue transfers and replantations. The combination of general and epidural anesthesia leads to vasodilatation and improves tissue perfusion. Postoperative pain relief and sympathetic blockage are additional benefits of epidural anesthesia. The purpose of this study was to determine whether epidural anesthesia has benefits on microcirculation and neutrophil functions in muscle flaps subjected to venous ischemia. METHOD:: Thirty Sprague-Dawley rats were divided into three groups: group I, general anesthesia; group II, spinal anesthesia; and group III, epidural anesthesia. Cremaster flaps were prepared, postcapillary venules were selected under intravital videomicroscopy, and flaps were subjected to venous ischemia. Images were recorded from preselected postcapillary venules before venous ischemia (baseline) and following reperfusion. Neutrophil rolling and adhesion, functional capillary density, and diameters of postcapillary venules were evaluated. Results: The increase in rolling neutrophils in group III was significantly lower than in groups I and II at 60 and 120 minutes. Change of adherent neutrophils in group III was significantly lower than in groups I and II at 15, 60 and 120 minutes. There was significantly more reduction in inner diameter of postcapillary venules in groups I and II compared with group III. Functional capillary density in groups I and II was significantly lower than in group III. Conclusion: Epidural anesthesia regulated neutrophil functions, salvaged functional capillaries, and prevented vasoconstriction of postcapillary venules in cremaster muscle flaps subjected to venous ischemia. Spinal and general anesthesia, however, were found to be ineffective in improving microcirculation of muscle flaps subjected to venous ischemia. © 2009 by the American Society of Plastic Surgeons

Patient satisfaction with postmastectomy breast reconstruction

BACKGROUND. At a time when the safety and effectiveness of breast implants remains under close scrutiny, it is important to provide reliable and valid evidence regarding patient outcomes. In the setting of postmastectomy reconstruction, patient satisfaction and quality of life may be the most significant outcome variables when evaluating surgical success. The objective of the current study was to identify predictors of patient satisfaction with breast appearance, including implant type, in a large sample of women who underwent breast reconstruction surgery using implants. METHODS. A multicenter, cross-sectional study design was used. A total of 672 women who had completed postmastectomy, implant-based reconstruction at 1 of 3 centers in North America were asked to complete the BREAST-Q (Reconstruction Module). Multivariate linear regression modeling was performed. RESULTS. Completed questionnaire data were available for 482 of the 672 patients. In 176 women, silicone implants were placed and in 306, saline implants were used. The multivariate model confirmed that patients' satisfaction with their breasts was significantly higher in patients with silicone implants ( P = .016). The receipt of postmastectomy radiotherapy was found to have a significant, negative effect on breast satisfaction ( P <.000) in both silicone and saline implant recipients. In addition, for women who received either silicone or saline implants, satisfaction diminished over time ( P = .017). CONCLUSIONS. In the setting of postmastectomy reconstruction, patients who received silicone breast implants reported significantly higher satisfaction with the results of reconstruction than those who received saline implants. This information can be used to optimize shared medical decision-making by providing patients with realistic postoperative expectations. Cancer 2010. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78475/1/25552_ftp.pd

Naringenin inhibits neointimal hyperplasia following arterial reconstruction with interpositional vein graft

Vessels respond to injury by a healing process that includes the development of neointima. Stenosis secondary to neointima formation is the main cause of failure following arterial reconstructions. Vessel wall homeostasis is regulated by proinflammatory cytokines that affect smooth muscle cell proliferation, growth, migration, and death. We assessed the hypothesis that naringenin, a flavinoid possessing anti-inflammatory, antioxidant, and antiproliferative activities, reduces neointimal hyperplasia (NIH) following vascular injury.Arterial injury was created by interposition grafting of autologous right superficial epigastric vein graft into the right femoral artery (FA) in 48 male Sprague-Dawley rats. Following injury, the rats were divided into 4 groups (n = 12). Two groups were treated with naringenin (100 mg/kg intraperitoneal q daily) for 2 and 4 weeks each while 2 control groups received normal saline for the same durations. For Sham group (n = 10), the FA and vein were isolated without any additional procedure. Rats were killed at the end of treatment regimen in all groups, and FAs were harvested. Thickness of intima was measured in histologic sections, and levels of platelet derived growth factor (PDGF)-BB, TNFα, and Ki67 labeling index (Ki67 LI) were quantified in immunohistochemical analyses to assess the amount of NIH and mechanisms underlying its formation.Although there was no significant difference between the groups at 2 weeks, neointima thickness was lower in the naringenin treated group at 4 weeks (23.7 ± 2.3 vs. 35.6 ± 2.6 μm in control group; P < 0.001). The levels of PDGF-BB, and TNFα were lower in naringenin treated groups at both 2 weeks (PDGF-BB [0.21% ± 0.03% versus 0.39% ± 0.05% in control group, P < 0.001), TNFα (21.2% ± 0.8% vs. 36.1% ± 1.9% in control group, P < 0.001]) and 4 weeks (PDGF-BB [0.25% ± 0.03% vs. 0.57% ± 0.09% in control group, P < 0.001], TNFα [25.5% ± 1.8% vs. 45.0% ± 2.9% in control group, P < 0.001]). Ki67 LI was lower in naringenin treated groups at 2 weeks (13.9% ± 2.8% vs. 18.7% ± 3.7% in control group, P < 0.05), and at 4 weeks (17.5% ± 2.6% vs. 31.1% ± 4.7% in control group, P < 0.001), indicating a lower level of cellular proliferation.Naringenin reduces NIH following arterial reconstruction. This may be mediated by a decrease in PDGF-BB and TNFα levels and the resulting down-regulation of smooth muscle cells' migration and proliferation. Copyright © 2009 by Lippincott Williams & Wilkins

Biologic predictors of clinical improvement in rituximab-treated refractory myositis Clinical rheumatology and osteoporosis

Background: To examine the longitudinal utility of a biomarker signature in conjunction with myositis autoantibodies (autoAbs) as predictors of disease improvement in refractory myositis patients treated with rituximab. Methods: In the RIM Trial, all subjects received rituximab on 2 consecutive weeks. Using start of treatment as baseline, serum samples (n∈=∈177) were analyzed at baseline and after rituximab with multiplexed sandwich immunoassays to quantify type-1 IFN-regulated and other pro-inflammatory chemokines and cytokines. Biomarker scores were generated for the following pathways: type-1 IFN-inducible (IFNCK), innate, Th1, Th2, Th17 and regulatory cytokines. Myositis autoAbs (anti-synthetase n∈=∈28, TIF-γ n∈=∈19, Mi-2 n∈=∈25, SRP n∈=∈21, MJ n∈=∈18, non-MAA n∈=∈24, unidentified autoantibody n∈=∈9, and no autoantibodies n∈=∈33) determined by immunoprecipitation at baseline, were correlated with outcome measures. Kruskal-Wallis rank sum tests were used for comparisons. Results: The mean (SD) values for muscle disease and physician global disease activity VAS scores (0-100 mm) were 46 (22) and 49 (19). IFNCK scores (median values) were higher at baseline in subjects with anti-synthetase (43), TIF1-γ (31) and Mi-2 (30) compared with other autoAb groups (p∈30) and autoAb group (Mi-2, non-MAA, and undefined autoantibody) demonstrated the greatest clinical improvement based on muscle VAS (muscle-interaction p∈=∈0.075). Conclusion: Biomarker signatures in conjunction with autoAbs help predict response to rituximab in refractory myositis. Biomarker and clinical responses are greatest at 16 weeks after rituximab

Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature

Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases

Antigen-driven T cell-macrophage interactions mediate the interface between innate and adaptive immunity in histidyl-tRNA synthetase-induced myositis

IntroductionPrevious work in humans has demonstrated that both innate and adaptive immune signaling pathways contribute to the pathogenesis of idiopathic inflammatory myopathy (IIM), a systemic autoimmune disease targeting muscle as well as extra-muscular organs. To better define interactive signaling networks in IIM, we characterized the cellular phenotype and transcriptomic profiles of muscle-infiltrating cells in our established murine model of histidyl-tRNA synthetase (HRS)-induced myositis.MethodsMyositis was induced in wild type (WT) and various congenic/mutant strains of C57BL/6 mice through intramuscular immunization with recombinant HRS. Histopathological, immunohistochemical, flow cytometric, and transcriptomic assessments were used to characterize the functional relationship between muscle-infiltrating cell populations in these strains lacking different components of innate and/or adaptive immune signaling.ResultsRAG1 KO mice developed markedly reduced muscle inflammation relative to WT mice, demonstrating a key requirement for T cells in driving HRS-induced myositis. While the reduction of mononuclear cell infiltrates in CD4-Cre.MyD88fl/fl conditional knockout mice and OT-II TCR transgenic mice highlighted roles for both innate and TCR-mediated/adaptive immune signaling in T cells, diminished inflammation in Lyz2-Cre.MyD88fl/fl conditional knockout mice underscored the importance of macrophage/myeloid cell populations in supporting T cell infiltration. Single cell RNA sequencing-based clustering of muscle-infiltrating subpopulations and associated pathway analyses showed that perturbations of T cell signaling/function alter the distribution and phenotype of macrophages, fibroblasts, and other non-lymphoid cell populations contributing to HRS-induced myositis.DiscussionOverall, HRS-induced myositis reflects the complex interplay between multiple cell types that collectively drive a TH1-predominant, pro-inflammatory tissue phenotype requiring antigen-mediated activation of both MyD88- and TCR-dependent T cell signaling pathways