Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) therapy is a clinically safe, noninvasive, nonsystemic treatment for major depressive disorder.ObjectiveWe evaluated the cost-effectiveness of rTMS versus pharmacotherapy for the treatment of patients with major depressive disorder who have failed at least two adequate courses of antidepressant medications.MethodsA 3-year Markov microsimulation model with 2-monthly cycles was used to compare the costs and quality-adjusted life-years (QALYs) of rTMS and a mix of antidepressant medications (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclics, noradrenergic and specific serotonergic antidepressants, and monoamine oxidase inhibitors). The model synthesized data sourced from published literature, national cost reports, and expert opinions. Incremental cost-utility ratios were calculated, and uncertainty of the results was assessed using univariate and multivariate probabilistic sensitivity analyses.ResultsCompared with pharmacotherapy, rTMS is a dominant/cost-effective alternative for patients with treatment-resistant depressive disorder. The model predicted that QALYs gained with rTMS were higher than those gained with antidepressant medications (1.25 vs. 1.18 QALYs) while costs were slightly less (AU $31,003 vs. AU $31,190). In the Australian context, at the willingness-to-pay threshold of AU $50,000 per QALY gain, the probability that rTMS was cost-effective was 73%. Sensitivity analyses confirmed the superiority of rTMS in terms of value for money compared with antidepressant medications.ConclusionsAlthough both pharmacotherapy and rTMS are clinically effective treatments for major depressive disorder, rTMS is shown to outperform antidepressants in terms of cost-effectiveness for patients who have failed at least two adequate courses of antidepressant medications.     

Detection of Hepatitis C virus RNA in peripheral blood mononuclear cells of patients with abnormal alanine transaminase in Ahvaz

Purpose: Hepatitis C virus (HCV) is an important agent for chronic and acute hepatitis. Occult hepatitis C remains a major health problem worldwide. Patients with chronic occult HCV may progress to cirrhosis and hepatocellular carcinoma. The aim of this study was to determine prevalence of occult hepatitis C by IS-PCR-ISH (in situ PCR in situ hybridisation) in the patients with abnormal ALT. Materials and Methods: The blood samples were taken from 53 patients including 17 females (32.1%) and 36 (67.9%) males who had abnormal alanine transaminase (ALT) for more than 1 year. The mean ALT and aspartate transaminase (AST) level were 41.02 ± 9.3 and 24.17 ± 7.3, respectively. The patients’ age were between 4 and 70-years old with mean age 38 ± 13. All the patients were negative for HCV antibody, HCV RNA and HBs Ag. The peripheral blood mononuclear cells (PBMC) were separated with ficoll gradient from each blood sample, then the cells were fixed on slides by cold acetone and followed by IS-PCR-ISH for HCV RNA detection. Results: Seventeen (32%) patients including 6 (11.3%) females and 11 (20.7%) males showed positive results for HCV RNA by in situ-PCR in situ hybridisation. Ten (18.8%) positive cases were between 20 and 40-years old and 6 (11.3%) positive patients were between 40 and 60 years old. Ten (19.6%) patients who were positive for IS-PCR-ISH also had positive anti-HBc IgG and 7 (13.2%) patients were negative for HBc-IgG. Conclusion: In the present study high rate of 32% occult hepatitis C were found among the patients with elevated ALT.     

Interference effects of choice on confidence: Quantum characteristics of evidence accumulation

Decision-making relies on a process of evidence accumulation which generates support for possible hypotheses. Models of this process derived from classical stochastic theories assume that information accumulates by moving across definite levels of evidence, carving out a single trajectory across these levels over time. In contrast, quantum decision models assume that evidence develops over time in a superposition state analogous to a wavelike pattern and that judgments and decisions are constructed by a measurement process by which a definite state of evidence is created from this indefinite state. This constructive process implies that interference effects should arise when multiple responses (measurements) are elicited over time. We report such an interference effect during a motion direction discrimination task. Decisions during the task interfered with subsequent confidence judgments, resulting in less extreme and more accurate judgments than when no decision was elicited. These results provide qualitative and quantitative support for a quantum random walk model of evidence accumulation over the popular Markov random walk model. We discuss the cognitive and neural implications of modeling evidence accumulation as a quantum dynamic system.Decisions in a wide range of tasks (e.g., inferring the presence or absence of a disease, the guilt or innocence of a suspect, and the left or right direction of enemy movement) require evidence to be accumulated in support of different hypotheses. Arguably, the most successful theory of evidence accumulation in humans and other animals is Markov random walk (MRW) theory (and diffusion models, their continuous space extensions) (1, 2). MRWs can be viewed as psychological implementations of a first-order Bayesian inference process that assigns a posterior probability to each hypothesis (3). MRWs can account for choices, response times, and confidence for a variety of different decision types (2, 4). Moreover, these models of the accumulation process have been connected to neural activity during decision-making (5, 6).According to MRW models, when deciding between two hypotheses, the cumulative evidence for or against each hypothesis realizes different levels at different times to generate a single particle-like trajectory of evidence levels across time (Fig. 1). At any point in time, the decision-maker has a definite level of evidence, and choices are made by comparing the existing level of evidence against a criterion. Evidence above the criterion favors one option, and evidence below it favors the alternative. Other responses are modeled in a similar manner; for example, confidence ratings are modeled by mapping evidence states onto one or more ratings (4). However, this idea that judgments and decisions are simply read out from the existing level of evidence—henceforth referred to as the “read-out” assumption—is inconsistent with the well-established idea that preferences and beliefs are constructed rather than revealed by judgments and decisions (7).Open in a separate windowFig. 1.Diagram of a state representation of a Markov and a quantum random walk model. In the Markov model, evidence (shaded state) evolves over time by moving from state to state, occupying one definite evidence level at any given time. In the quantum model the decision-maker is in an indefinite evidence state, with each evidence level having a probability amplitude (shadings) at each point in time.We present an alternative model of choice and judgment based on quantum random walk (QRW) theory (8–11), which posits that preferences and beliefs are constructed when a judgment or decision is made. Note that this work does not make the assumption that the brain is a quantum computer; instead, we simply use the mathematics of quantum theory to explain and predict human behavior. According to QRW theory, at any point in time before a decision, the decision-maker is in a superposition state that is not located at a single level of evidence. Instead, each level of evidence has a potential to be expressed, formalized as a probability amplitude (Fig. 1). New information changes the amplitudes, producing a wavelike process that moves the amplitude distribution across time.In some ways the QRW is like a second-order Bayesian model (12). According to the latter, the decision-maker assigns a probability (rather than an amplitude) to each level of evidence for each hypothesis. However, like the MRW model, second-order Bayesian models are perfectly compatible with the read-out assumption, and as an optimal model, this would suggest that a decision should not change the probability assigned to each evidence level. In contrast, a QRW, like all quantum models of cognition (13), treats a judgment or decision as a measurement process that constructs a definite state from an indefinite (superposition) state. When a decision is made, the indefinite state collapses onto a set of evidence levels that correspond to the observed choice, producing a definite choice state. Confidence ratings work similarly, with the indefinite state collapsing onto a more specific set of levels corresponding to the observed rating.These different theories of choice and judgment have strong implications for sequences of responses. Consider the situation when decision-makers have to make a choice (e.g., decide that hypothesis A or B is true) and later rate their confidence that a given (usually the chosen) hypothesis is true. According to the read-out assumption, a choice is reported on the basis of existing evidence that does not change the internal state of evidence itself. This applies to the MRW, a second-order Bayesian model, and many other accumulation models as well. Thus, after pooling across a person’s choices, the distribution of confidence ratings should be identical to conditions in which the person makes no choice at all. By contrast, the state of the system in a QRW is changed when a choice creates a definite state. Subsequent processing starts from the definite state, and the amplitudes spread out again. Thus, if information processing continues after the initial stage, the QRW predicts an interference effect where the marginal distribution of confidence judgments following a choice will differ from a condition in which no choice is made.A proof of the predicted interference effect for QRWs is in SI Appendix. The proof shows that the interference effect of choice on confidence is the result of the interaction between the creation of a definite state and subsequent evidence accumulation after making a choice. Subsequent or second-stage processing is a necessary condition for the effect. Critically, second-stage processing occurs when people are asked to report a confidence rating following a choice, giving rise to response reversals (14) and other properties (15). We also provide a proof that MRWs predict no difference between the marginal distributions of confidence ratings (i.e., no interference) regardless of the presence of second-stage processing. This proof holds for a large range of MRWs, including ones with decay (16), leakage of evidence (17), and trial-by-trial variability in the decision process (18).     

散在型多指(趾)畸形中HOXD13基因分析

目的 通过对中国福建地区汉族散在的多指(趾)、短指畸形患者中HOXD13基因的分析,了解其是否存在基因突变.方法 采集2012年12月至2013年4月在福建医科大学附属第一医院整形外科接受治疗的多指(趾)和短指畸形患者6例,以及其父母、祖父母、外祖父母和本科室医务人员在内的正常志愿者40例外周血标本,常规提取基因组DNA;采用聚合酶链反应、琼脂糖凝胶电泳方法及DNA序列分析法,对6例散在型患者及40例正常志愿者HOXD13基因进行分析.结果 6例患者均无家族史,其中5例HOXD13基因第1外显子发生c.291C ＞T(p.A60A)杂合同义突变,1例短指患者及40例志愿者均未发现有HOXD13基因突变.结论 中国汉族散在型多指(趾)畸形的出现,可能与HOXD13基因的高频杂合同义突变c.291C＞T(p.A60A)有关.     

New advances in the pathophysiologic and radiologic basis of the exstrophy spectrum

The exstrophy–epispadias complex is a rare spectrum of anomalies affecting the genitourinary system, anterior abdominal wall, and pelvis. Recent advances in the repair of classic bladder exstrophy (CBE) and cloacal exstrophy (CE) have resulted in significant changes in outcomes of surgical management (including higher continence rate, fewer surgical complications, and better cosmesis) and health-related quality of life in these patients. These noteworthy changes resulted from advances in the pathophysiological and genetic backgrounds of this disease and better radiologic assessment of the three-dimensional anatomy of the bony pelvis and its musculature. A PubMed search was performed with the keyword exstrophy. The resulting literature pertaining to genetics, stem cells, imaging, tissue engineering, epidemiology, and endocrinology was reviewed. The following represents an overview of the advances in basic science understanding and imaging of the exstrophy–epispadias spectrum and discusses their possible and future effects on the management of CBE and CE.     

二氧化硅提取核酸用于多聚酶链反应

利用硫氰酸胍裂解病毒和二氧化硅颗粒能够特异性吸附核酸的特性，将二氧化硅悬液、裂解液及肝炎病毒感染血清共同保温，病毒裂解释放出的核酸结合在二氧化硅颗粒上，经过双蒸水洗脱，所得核酸直接作ＰＣＲ扩增。