Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression

Background Patients with anxious major depressive disorder(MDD)are more likely to have poorer outcomes than those with non-anxious MDD.However,the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown.Aims We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation,both anxious and non-anxious.Methods Fifty-four adolescents with anxious(n=33)and non-anxious(n=21)MDD received three infusions of esketamine 0.25mg/kg or active-placebo(midazolam 0.045 mg/kg)over 5 days,with routine inpatient care and treatment.Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Asberg Depression Rating Scale.Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion(day 6,primacy efficacy endpoint)and throughout the 4-week post-treatment(days 12,19 and 33).Results In subjects who received esketamine,a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6(72.7%vs 18.8%,p=0.015)and day 12(90.9%vs 43.8%,p=0.013),and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33(72.7%vs 26.7%,p=0.045).No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points.Conclusions Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD;however,this benefit was temporary and was not maintained over time.

Treatment Resistant Depression, Ketamine versus ECT

Recent studies have highlighted the increase in treatment resistant depression. Of particular concern is the rising trend of depression and suicide rates among Young Adults. Ketamine was approved for treatment resistant depression in 2019 by the US Food and Drug Administration. It received an additional indication for treatment of suicidality. While intranasal Ketamine is approved for depression, recent data about intravenous infusion of Ketamine in controlled inpatient settings has been promising. ECT has a long-standing trend for being used for resistant depression and recent comparison trials have revealed positive results when head-to-head comparisons are made with Ketamine. Future studies need to focus on patient selection and wherein treatment algorithm should Ketamine be selected as treatment modality.

Virtual Reality as an Adjunct to Ketamine Infusion Therapy Increases Patient Satisfaction in the Management of Chronic Pain and Depression: A Retrospective Pilot Study

The management of patients with concomitant chronic pain (CP) and Major Depressive Disorder (MDD) remains challenging for clinicians. Current chronic pharmacologic management is often unsuccessful, or has intolerable side effects to the patients. While not restricted to patients with chronic pain, these patients are often diagnosed with depression, presenting with symptoms such as poor mood, anhedonia, and altered cognitive processes. It is estimated that a substantial proportion of treated patients do not derive a substantive benefit from traditional pharmacological treatments for depression. The present study involved a retrospective review of cases, exploring the patient-reported satisfaction with and tolerability of a novel use of virtual reality (VR), coined KVR, as an adjunct to intravenous ketamine infusion therapies. Specifically, the ketamine-virtual reality protocol was employed as a potential adjunctive intervention for patients suffering from chronic pain and depression. Visual Analog Scores (VAS) associated with pain were significantly lower on the third than on the first assessment day. Montgomery-?sberg Depression Rating Scale (MADRS) scores improved following infusion and across days (i.e., sessions). Lastly, 2/3 of patients preferred the use of VR with their ketamine infusion. The results are considered in terms of implementing prospective studies to examine whether the combination therapies have a synergistic benefit and the nature and magnitude of clinically meaningful treatment effects, if any.

Administration of Nebulised Ketamine for Managing Pain in the Intensive Care Unit of Obstetrics and Gynaecology

Introduction: The use of inhaled ketamine to manage a variety of painful conditions has been endorsed by the American College of Emergency Physicians and the American Academy of Emergency Medicine. Nebulized analgesia has multiple benefits, including rapid, effective and titratable analgesic delivery. The aim of our study is to assess the efficacy and safety of intranasal analgesic-dose ketamine compared to multimodal analgesia in patients presenting with acute postoperative pain or headache after a spinal anaesthetic in the intensive care unit of obstetrics and gynaecology. Materials and Methods: This was a prospective descriptive study, with hospital Ethics Committee approval and written informed consent from study participants. We compared the effect of nebulized ketamine and multimodal analgesia postoperatively in 120 patients belonging to the physical status I - II of the American Society of Anesthesiologists, in the intensive care unit of obstetrics and gynaecology, at the Ibn Rochd University Hospital Center in Casablanca from June 2021 to June 2022. Results: We included 120 patients in our study divided into two groups of 60 patients: the average age was 35 years, with extremes ranging from 18 to 45 years, All patients were hospitalized for postoperative care: all women underwent locoregional anaesthesia with a standard dose according to the service protocol (10 mg of bupivacaine, 25γ of fentanyl, 100γ of morphine), where pain was the common denominator. Among these patients, 59 were admitted for management of postpartum haemorrhage, 43 for postoperative monitoring, 15 for post-spinal anaesthesia headache and 3 for pelviperitonitis. The results of the pain assessment 30 minutes after the ketamine nebulization were marked by a request for analgesia in 12 patients, which is 20% of group A, including 5 patients, whose visual analogue scale (VAS) on admission was between 5 and 7, and 7 patients whose VAS at admission was ≥8;all these patients received a second dose of ketamine by nebulization;the evaluation 30 min after the second dose was marked by a request for analgesia in 4 patients, which is 7% of Group A;in all these patients the VAS at admission was ≥8. Of the total number of patients of Group A, only 4 received morphine when they were requested for analgesia after the second dose of nebulized ketamine. Conclusion: The primary outcome of nebulized ketamine use is a significant reduction in VAS pain score. We believe that nebulized ketamine has a potential effect of reducing pain in the intensive care unit of obstetrics and gynaecology;this may be an additional analgesic modality for clinicians to provide rapid, effective and non-invasive pain relief.

A novel model of drug cue-induced behaviours in rhesus macaque subjected to chronic ketamine exposure

To the Editor,Non-human primate(NHP)models are advantageous for mimicking human addiction with high behavioural validity.1 However,current NHP drug addiction models(eg,self-administration)often require a comprehensive behavioural training paradigm,relatively expensive apparatus and invasive surgical procedures.

ADS-B信号在对流层大气波导中的传播性能

对流层大气环境存在特殊大气结构“大气波导”,可形成电波超视距传播或产生雷达盲区等。目前,通过雷达、GNSS信号等可以对大气波导进行一定程度的反演探测,但均存在一定的不足。ADS-B信号具有应用范围广、信号密度大、实时性高等特点,为此提出利用ADS-B信号受到不同大气环境影响后能量损耗不同的特点对ADS-B信号与对流层大气环境关联性进行分析研究。以武汉地区ADS-B信号数据为例,基于抛物方程传播理论对路径损耗进行仿真分析,并进行了实验验证。结果表明:ADS-B接收信号与仿真结果存在线性相关性并给出线性表述,为后续利用ADS-B信号反演大气波导提供参考依据。

基于ADE优化的IPMSM全速域无传感器控制

为了实现内置式永磁同步电机(IPMSM)全速域的无传感器控制和切换速域的平滑过渡,提出了一种基于自适应差分进化(ADE)算法优化的复合控制方法。分别在零低速域、中高速域采用旋转高频电压注入法和滑模观测器法来对电机转速和转子位置进行估算,并在切换速域采用基于ADE算法的权重系数优化法来实现上述两种控制方法的平滑切换,从而实现IPMSM全速域无传感器控制。仿真结果表明:提出的复合控制方法能够实现电机全速域的无感控制和切换速域的平滑过渡,且具有良好的稳定性。

Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.

Effect of Preemptive Ketamine Administration on Postoperative Visceral Pain after Gynecological Laparoscopic Surgery

The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. Group 3 was intravenously injected with preincisional ketamine（0.3 mg/kg） and local infiltration with 20 m L ropivacaine（4 mg/m L） at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale（VAS） scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively（P〈0.05 and P〈0.01, respectively）. At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1（P〈0.01）. Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference in the incidence of shoulder pain or adverse effects. Preemptive ketamine may reduce visceral pain in patients undergoing gynecological laparoscopic surgery.

Effects of ketamine on mouse hippocampal inflammatory cytokines IL-6,IL-1β and TNF-α levels in acute and chronic administration models

OBJECTIVE Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile,ketamine has been showed to modulate the levels of inflammatory cytokines.Therefore,we sought to investigate whether the effects of ketamine on the central nervous system is associated with the inflammatory cytokines. METHODS We established acute(single or multiple intraperitoneal injection) and chronic(six months daily intraperitoneal injection) ketamine administration models in C57BL/6 mice,evaluated the spatial recognition memory and emotional response by applying the Y maze test and open field test. We analyzed the changes of inflammatory cytokines interleukin-6(IL-6),interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) levels in mouse hippocampus,employing Western blot,quantitative reverse transcriptase-polymerase chain reaction(qR T-PCR) and immunohistochemistry. RESULTS Ketamine induced spatial recognition memory deficit,reduced anxiety-like behaviors in mice after chronic administration,and it was dose-dependent. Moreover,we found that ketamine could increase the levels of mouse hippocampal inflammatory cytokines IL-6 and IL-1β after single,multiple and long-term administration in a dose-dependent manner. However,the level of TNF-α expressed differently in mouse hippocampus under different conditions. Single administration of ketamine increased the level of TNF-α,whereas multiple and long-term administration decreased it significantly. We considered that TNF-α might exist bi-directional regulatory pathway,which was associated with the dose and duration of ketamine administration. CONCLUSION Our results suggest that the alterations of inflammatory cytokines IL-6,IL-1β and TNF-α levels may be involved in the neurotoxicity of ketamine.

基于AD与TRIZ的加工中心主轴松拉刀机构优化设计

数控加工中心在加工过程中常出现主轴松刀力不足或无法松刀的现象。针对此问题,通过TRIZ系统组件分析明确现有松拉刀机构各组件间作用关系,利用因果链分析得出影响松刀的根本原因,最终应用TRIZ理论中的物场模型分析方法和AD独立性原理提出优化设计方案。根据新方案计算出实际工况下的主轴松刀力和螺杆强度,并对松刀杆进行建模和仿真。结果表明:最大位移量为6.995μm,最大应力为45.24 MPa,符合结构设计要求。最后,经过现场实物测试,当液压力为5 MPa时,松刀行程、松刀力以及打刀量均符合生产要求,验证了优化设计方案的合理性。

基于改进型多斜Ⅲ技术的7位半AD转换器设计

高精度测试仪器在环境试验中扮演着重要角色,而积分型AD转换器被广泛的应用在高精度测试仪器中。针对传统型积分型AD转换器转换速率较低的问题,提出了一种提高转换速率的改进型多斜ⅢAD转换器,详细的介绍了其原理和设计思路。该转换器以单片机与CPLD一同控制积分型ADC,在积分末尾利用单片机片内ADC测量积分器的残留电压,以达到提高转换速率的目的。经理论分析该AD转换器比传统型转换速率快836倍,分辨率可达到31位,在±10V直流电压测量中可实现7位半分辨率。

Early and Late Postoperative Pain and Side Effects after Mastectomy: A Comparison of Ketamine and Thiamylal Administered for Anesthetic Induction

Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA physical status I-III patients undergoing mastectomy were randomly assigned to one of two groups. Ketamine group received intravenous ketamine, 1 mg/kg, and thiamylal group received intravenous thiamylal, 4 mg/kg, at the induction of general anesthesia. Anesthesia was maintained with sevoflurane, N2O and fentanyl. The intensity of pain was assessed by using visual analog scale (VAS) 3 and 16 hr and 2, 3 and 4 weeks after surgery. Postoperative side effects, including nausea, vomiting and hallucination were also recorded. Results: At 16 hr after surgery, VAS in ketamine group was significantly lower than that in thiamylal group. However, there were no statistically significant differences between the two groups in the VAS at 3 hr and 2, 3 and 4 weeks after surgery. There were no differences in the incidence of side effects such as nausea, vomiting and hallucination between the two groups. Conclusion: Intravenous ketamine at the induction of anesthesia could reduce acute postoperative pain but not long-term pain after mastectomy.

基于FPGA与AD9786的调制解调电路的设计

谐振式光学陀螺因其高理论精度、小型化以及高稳定性受到了国内外的强烈关注。针对于谐振式光学陀螺检测信号微弱的特点,需要对该信号进行调制解调,以实现陀螺的稳定输出,设计了一种基于FPGA和AD9786的高精度模拟信号源,该信号以FPGA作为核心控制单元,AD9786作为数模转换器,实现16位的高精度DA转换,通过上位机实现指令的通信过程,可实现不同频率的交流信号。该实验结果表明,该系统符合陀螺测试系统调制解调要求,通过上位机对不同输出信号进行测试,且测试结果无纹波时输出噪声Vrms269μV,交流信号精度达到0.01%,最高频率可达到2M,稳定性高。

基于AD7616的16通道数据采集系统设计

针对传统数据采集系统因通道不足或数据量过大,无法满足多通道同步采集的问题,设计了一种基于AD7616的16通道数据采集系统。系统以Xilinx系列FPGA作为主控芯片,ADI公司的AD7616作为模数转换芯片,DDR3 SDRAM作为缓存单元。介绍了各个模块硬件的设计思路,重点介绍了FPGA控制AD7616模数转换模块、DDR3 SDRAM缓存模块的软件程序设计,并对系统的多通道采样功能、同步性能以及实际水下超声信号的采集能力进行了实验验证,结果表明,系统可以完成水下超声信号的多通道同步采集。

Comparative efficacy of ketamine,lidocaine,acetaminophen,and dexmedetomidine combined with morphine patient-controlled analgesia in treating opium-addicted patients undergoing tibia fracture surgery:A randomized clinical trial

Objective:To compare the effect of ketamine,lidocaine,acetaminophen,and dexmedetomidine combined with morphine patient-controlled analgesia for opium addicts after tibial fracture surgery.Methods:This double-blind clinical trial included opium-addicted patients undergoing tibia fracture surgery.Patients were recruited and randomized to four different groups including the ketamine group,the lidocaine group,the acetaminophen group,and the dexmedetomidine group.The hemodynamic parameters such as heart rate(HR),mean arterial pressure,and arterial SaO2,alongside visual analog scale pain scores,sedation assessed by Ramsay score,nausea and vomiting,and opioid use were recorded and compared among the four groups.Results:This study included 140 patients,aged 37(32,41)years,with 92 males and 48 females,and each group had 35 patients.Dexmedetomidine-sedated subjects had the lowest blood pressure from 1 to 24 h after surgery,decreased HR at 12 and 24 h after surgery,and more satisfactory sedation(P<0.05).Notwithstanding no significant difference was noted in the pain scores,or nausea and vomiting among the groups(P>0.05).Conclusions:Dexmedetomidine has a better sedation effect compared to ketamine,lidocaine,and acetaminophen for pain control,but the final choice hinges on the patients’physical condition and the anesthesiologist's preference.Clinical registration:It is registered in Iranian Registry Clinical Trial by code IRCT20141209020258N146.

基于动态离散模型的机场ADS-B攻击威胁影响研究

随着航空业信息技术的发展,空中交通管制系统面临着多种网络攻击的威胁。广播式自动相关监视(ADS-B)系统因其明文广播的数据传输方式,存在着被网络攻击的安全问题。依据“等待降落-降落-停泊-排队起飞-起飞”的航班运行全流程,建立了WLPQD动态离散模型,研究机场流量和航班延误。模型引入了系统冗余能力、处理速率等参数,模拟了攻击场景;通过受影响飞机数量和延误时间等指标研究了机场航班延误的传播影响。模型展示了ADS-B消息注入攻击对降落、起飞航班造成的延误,提出了两种攻击缓解方法。结果表明,延误规模的大小与攻击强度呈现正相关,且攻击对起飞航班的延误影响更大;提升对“幽灵飞机”和合法飞机的处理速率都可提升机场系统的抗毁性,但前者对提升机场系统冗余能力的效果更加显著。所做研究为机场系统抵御网络攻击、增强抗毁性提供了决策分析的参考依据。

采用AD654芯片的直流电压传感器及其温度漂移补偿

提出一种基于电压-频率变换的光电式电压传感器及电压传感信号温度漂移的补偿方法。电压传感系统主要包括电阻分压器、电压-频率变换芯片、发光二极管、光纤、光电探测与信号处理单元等。利用两块AD654型芯片分别作为被测电压和温度传感单元,通过对两路光传感信号进行非线性数据拟合等方式实现了对电压传感信号温度漂移的实时补偿。实验测量了0.6 kV~5.0 kV范围内的直流电压,并实现了电压传感信号的温度漂移补偿,在-40℃~+60℃的温度范围内,电压传感信号温度漂移的平均相对误差约为±0.7%。

面向Ad-Hoc协作的局部观测重建方法

在多智能体强化学习的研究中,如何进行Ad-Hoc协作,也就是说如何适应种类和数量变化的队友,是一个关键问题。现有方法或者有很强的先验知识假设,或者使用硬编码的规则进行合作,缺乏通用性,无法泛化到更一般的Ad-Hoc协作场景。为解决该问题,提出一种面向Ad-Hoc协作的局部观测重建算法,利用注意力机制和采样网络对局部观测进行重建,使得算法认识到并充分利用不同局面中的高维状态表征,实现了在Ad-Hoc协作场景下的零样本泛化。在星际争霸微操环境和Ad-Hoc协作场景上与代表性算法的性能进行对比与分析,验证了算法的有效性。

情境目标和Ad hoc关联影响言语产生的语义效应

干扰词与目标词之间的语义关联性是影响言语产生中语义效应性质的关键因素。相比其他语义关联类型,Ad hoc关联是一种较为特殊的概念联系类型。考察情境目标和Ad hoc关联对语义效应的影响,结果表明:与其他语义关联性相比,Ad hoc关联对语义效应的影响既有共性,又有差异。共性表现在:Ad hoc关联抑制图片命名,产生语义干扰效应,这种效应发生在图片命名早期(SOA从-200ms至0ms)。差异表现在:Ad hoc关联的语义干扰效应的产生要以情境目标提示为前提,有情境目标提示时,Ad hoc关联效应非常显著;无情境目标提示时,Ad hoc关联效应消失。不同语义关联类型产生不同语义效应的根源在于类别概念结点是否得到激活。