Deep Brain Stimulation Compared With Contingency Management for the Treatment of Cocaine Use Disorders: A Threshold and Cost-Effectiveness Analysis

ObjectivesCocaine is the second most frequently used illicit drug worldwide (after cannabis), and cocaine use disorder (CUD)-related deaths increased globally by 80% from 1990 to 2013. There is yet to be a regulatory-approved treatment. Emerging preclinical evidence indicates that deep brain stimulation (DBS) of the nucleus accumbens may be a therapeutic option. Prior to expanding the costly investigation of DBS for treatment of CUD, it is important to ensure societal cost-effectiveness.AimsWe conducted a threshold and cost-effectiveness analysis to determine the success rate at which DBS would be equivalent to contingency management (CM), recently identified as the most efficacious therapy for treatments of CUDs.Materials and MethodsQuality of life, efficacy, and safety parameters for CM were obtained from previous literature. Costs were calculated from a societal perspective. Our model predicted the utility benefit based on quality-adjusted life-years (QALYs) and incremental-cost-effectiveness ratio resulting from two treatments on a one-, two-, and five-year timeline.ResultsOn a one-year timeline, DBS would need to impart a success rate (ie, cocaine free) of 70% for it to yield the same utility benefit (0.492 QALYs per year) as CM. At no success rate would DBS be more cost-effective (incremental-cost-effectiveness ratio <$50,000) than CM during the first year. Nevertheless, as DBS costs are front loaded, DBS would need to achieve success rates of 74% and 51% for its cost-effectiveness to exceed that of CM over a two- and five-year period, respectively.ConclusionsWe find DBS would not be cost-effective in the short term (one year) but may be cost-effective in longer timelines. Since DBS holds promise to potentially be a cost-effective treatment for CUDs, future randomized controlled trials should be performed to assess its efficacy.     

创伤后迟发性脑肿胀的临床特点与治疗

目的 探讨创伤后迟发性脑肿胀的临床特点、发病机制与治疗。方法 回顾性分析1998年1月～2005年6月年收治的17例迟发性脑肿胀患者的临床特点和救治情况。结果 所有颅脑损伤患者采用保守治疗后均有好转，但于伤后5-10d出现恶化，CT复查有脑肿胀，经加强综合脱水等治疗后16例治愈，1例死亡。结论 迟发性脑肿胀好发于对冲性额、颞叶挫裂伤伴明显蛛网膜下腔出血、硬膜下薄层血肿及早期CT有脑肿胀者。其发病机制可能与创伤后的迟发性脑血管痉挛、微循环障碍、静脉回流障碍及甘露醇作用下降等因素有关。此类患者病情隐蔽性强，应加强观察、积极行CT复查，如能早期明确诊断，保守治疗多数效果良好。     

A double-blind, placebo-controlled study of the effect of imipramine on TRH-induced urinary urgency in healthy men.

We studied the effect of imipramine (IMI) on thyroid releasing hormone (TRH)-induced urinary urgency as a way of investigating the mechanism of the beneficial effect of IMI on enuresis. In a double-blind study, 12 normal, healthy men between 21 and 39 yr of age ranked their urge to urinate at 30-sec intervals following IV injection of TRH (500 micrograms) or saline. The subjects then were randomly assigned to either IMI (1 mg/kg) or placebo groups for 10 days, and the procedure was repeated. Compared to saline, TRH produced a significant elevation in urinary urgency in all subjects. IMI did not significantly blunt TRH-induced urinary urgency. Thus, the mechanism by which IMI affects enuresis is likely not mediated at the level of the urinary urgency induced by TRH.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.     

肾移植受者血清巨细胞病毒IgE和IgA抗体检测

采用间接ＥＬＩＳＡ检测２３名肾移植受者血清巨细胞病毒（ＣＭＶ）抗体，共检出１８名（７８％）活动性ＣＭＶ感染，其中１０名（４４％）为原发性感染。结果证实ＣＭＶ－ＩｇＥ和－ＩｇＡ具有较好的血清学诊断价值，优于ＣＭＶ－ＩｇＭ。     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.