TSH 在急性精神分裂症、单相抑郁症和双相障碍中的浓度水平结果分析

目的：探讨促甲状腺激素（TSH）的浓度水平在急性精神分裂症、单相抑郁症、双相抑郁症和双相躁狂症患者中的差异性。方法在1235位患者中检测T S H血清浓度水平（其中女性781位,占63．2％,平均年龄46．4岁）。结果各疾病平均血清TSH浓度为：精神分裂症（n＝563）1．71mIU／L ,单相抑郁症（n＝478）1．63 mIU／L ,双相障碍（n＝194）1．86 mIU／L ,双相抑郁症（n＝151）2．00 mIU／L ,双相躁狂（n＝53）1．38 mIU／L。根据所用的正常值范围,是高于或低于在正常范围的整体率为精神分裂症7．9％～22．3％,单相抑郁症13．9％～26．0％,双相障碍10．8％～27．6％,双相抑郁症12．2％～28．5％,双相躁狂11．4％～24．5％。我们还发现,在年龄组（≤20岁,＞20岁和≤40岁,＞40岁和≤60岁以及＞60岁）之间的T S H浓度水平差异有显著性。T S H水平与年龄（ r＝－0．23,P＜0．001）相关。随着年龄的变化,其弱相关性已经在精神分裂症（ r＝－0．21,P＜0．001）,单相抑郁症（ r＝－0．23,P＜0．001）,双相抑郁症（ r＝－0．25,P＝0．002）和双相障碍（ r＝－0．21,P＝0．005）中发现。结论甲状腺激素（TSH）的浓度水平在急性精神分裂症、单相抑郁症、双相抑郁症和双相躁狂症患者中的有一定的差异性,所以临床在诊治时要密切监测甲状腺激素（TSH）的浓度水平。     

精神分裂症与情感障碍病人并发糖尿病的临床资料分析

目的探讨精神分裂症和情感障碍病人并发糖尿病的临床特征。方法对84例发生糖尿病的精神分裂症和情感障碍病人的糖尿病资料进行回顾性分析，比较两组糖尿病的临床资料。结果精神分裂症和情感障碍并发糖尿病的病人在年龄、体重、病程、精神药物使用时间上有极显著差异（t=2．04～3．02，P〈0．01）、糖尿病药物的选择上有显著差异（χ^2=5．43，P〈0．05）。在性别、文化、家族史、糖尿病症状、血糖水平上无统计学意义（P〉0．05）。结论精神分裂症患者比情感障碍患者有更多的与易患糖尿病相关的因素，但诊断糖尿病时的血糖水平一致，情感障碍病人并发糖尿病时降糖药物的选择范围更宽。     

康复期精神病和双相情感障碍患者自知力的差异及其影响因素

目的：了解康复期精神分裂症和双相情感障碍患者自知力的差异及其影响因素。方法：对40例精神分裂症患者、30例精神病性双相障碍患者及32例非精神病性双相障碍患者的自知力及其影响因素进行评估，并作Logistic回归分析。结果：精神分裂症患者的自知力与精神病性双相障碍患者的自知力差异无显著性(X^2=0.038，P=0.812)，但两者的自知力均低于非精神病性双相障碍患者，差异有显著性意义(P&;lt;0.05)。在康复期，虽然患者的精神症状基本缓解，但仍有36％，的精神分裂症、38％的精神病性双相障碍以及10％的非精神病性双相障碍患者存在自知力损害。精神分裂症组患者的自知力损害是非精神病性双相障碍组患者的4.65倍(95％CI=1.02～20.80)，而精神病性双相障碍患者的自知力损害为非精神病性双相障碍组的5.72倍(95％CI=1.30～24.76)。并且，患者的性别、年龄、病程和住院次数均与自知力均分无关。结论：康复期大多数精神病患者的自知力恢复良好，但仍有少数患者存在自知力损害，影响患者自知力恢复的主要因素为精神病性症状。     

精神分裂症与双相情感障碍患者认知功能的比较

[目的]精神分裂症和双相情感障碍都存在某些认知功能障碍,由于临床症状的重叠,这两类患者的鉴别较困难。本研究对两类疾病的认知功能障碍进行比较,探讨认知功能对临床鉴别诊断的价值。[方法]对30例阳性症状为主的精神分裂症患者、22例阴性症状为主的精神分裂症患者、27例双相情感障碍(躁狂状态)患者和28例正常对照者行相关认知心理试验(COGLAB)。[结果]COGLAB区别阴性精神分裂症和双相情感障碍的正确率达到了73．5％,其中分类测验、持续操作测验和倒行掩蔽测验判别作用最大。[结论]本研究的结果提示．阴性精神分裂症和双相障碍患者的认知作业反应的特征不同,威斯康星卡片分类、持续操作测验、倒行掩蔽测验对于临床上鉴别某些精神分裂症和双相情感障碍有一定参考意义。     

奥氮平联用丙戊酸钠治疗男性双相障碍躁狂发作的疗效对照研究

目的探讨奥氮平联用丙戊酸钠治疗男性双相障碍躁狂发作的疗效与安全性。方法选择在我院住院的、符合美国精神疾病诊断和统计手册(DSM-IV)中双相障碍急性躁狂发作的男性患者88例,随机分为两组。观察组使用奥氮平联用丙戊酸钠治疗,对照组使用喹硫平联用丙戊酸钠治疗。对两组在治疗前及治疗6周后进行Bech.Rafaelsen躁狂量表(BRMS)评定评价疗效,及进行治疗后副作用量表(TESS)评定评价安全性。结果观察组治疗6周后,BRMS减分明显,显效率高于对照组;且副作用少而轻。结论奥氮平联用丙戊酸钠治疗双相障碍躁狂发作的疗效与安全性,不亚于已经达到公认的喹硫平对双相障碍的治疗作用。     

阳性症状为主型精神分裂症和伴有精神病性症状双相障碍患者MMPI对照研究

目的探讨阳性症状为主型精神分裂症和伴有精神病性症状的躁狂或抑郁的双相障碍患者的个性特征,为其鉴别诊断提供线索。方法采用MMPI测试软件,评估24例精神分裂症阳性症状为主型患者(精神分裂症组)和37例伴有精神病性症状的躁狂或抑郁的双相障碍患者(双相障碍组)人格特征,分别计算临床量表10个因子分值。采用SPSS 13.0进行统计处理,比较两组患者之间的差异。结果精神分裂症阳性症状为主型男性患者的社会内向因子分高于女性患者,差异有统计学意义(t=2.186,P=0.040);双相障碍男、女性患者之间的临床量表10个因子分均未见差异。两组患者的临床量表10个因子分差异无统计学意义(P>0.05),但精神分裂症阳性症状为主型患者的精神病态、偏执性人格、精神分裂症、轻躁狂因子分高于中国常模划界的T分,双相障碍患者的偏执性人格因子分高于中国常模划界的T分,其余均低于中国常模标准。结论精神分裂症阳性症状为主型与伴精神病性症状的双相障碍患者存在人格特征改变,两组患者MMPI无明显差异,精神分裂症阳性症状为主型患者的社会内向人格可能存在性别差异。     

康复期精神病和双相情感障碍患者自知力的差异及其影响因素

目的:了解康复期精神分裂症和双相情感障碍患者自知力的差异及其影响因素。方法:对40例精神分裂症患者、30例精神病性双相障碍患者及32例非精神病性双相障碍患者的自知力及其影响因素进行评估,并作Logistic回归分析。结果:精神分裂症患者的自知力与精神病性双相障碍患者的自知力差异无显著性(χ2=0.038,P=0.812),但两者的自知力均低于非精神病性双相障碍患者,差异有显著性意义(P<0.05)。在康复期,虽然患者的精神症状基本缓解,但仍有36%的精神分裂症、38%的精神病性双相障碍以及10%的非精神病性双相障碍患者存在自知力损害。精神分裂症组患者的自知力损害是非精神病性双相障碍组患者的4.65倍(95%CI=1.02～20.80),而精神病性双相障碍患者的自知力损害为非精神病性双相障碍组的5.72倍(95%CI=1.30～24.76)。并且,患者的性别、年龄、病程和住院次数均与自知力均分无关。结论:康复期大多数精神病患者的自知力恢复良好,但仍有少数患者存在自知力损害,影响患者自知力恢复的主要因素为精神病性症状。     

门诊双相情感障碍临床现象学分析

目的了解门诊双相情感障碍(BPD)患者的临床特征和药物治疗方式。方法采用自编的调查问卷对符合DSM-IV双相情感障碍诊断标准的门诊患者进行研究。结果①入组患者共203例,其中双相I型163例(80.3%),双相Ⅱ型40例(19.7%)。②最主要的治疗药物为心境稳定剂(70.4%),其次为抗精神病药物(63%)。③Ⅰ型患者使用心境稳定剂者、抗精神病药物及苯二氮类药物者多于Ⅱ型患者;Ⅱ型患者使用抗抑郁药多于Ⅰ型患者。④联合2种及以上药物治疗者占72.4%。⑤80.5%的双相情感障碍患者病情处于稳定状态。结论门诊双相情感障碍双相I型多于Ⅱ型,Ⅱ型更容易漏诊。目前临床门诊药物治疗方式与国内外指南推荐方案基本符合,联合用药多,多数患者治疗效果良好。     

小儿几种常用治疗药物监测结果分析

目的提高临床药物治疗水平，减少药物不良反应。方法高效液相色谱法及荧光偏振免疫法。结果对４３１２例小儿常用的几种治疗药物进行监测，结果表明：药物代谢的个体差异及婴幼儿药物代谢的的特点；采血时间、临床给药经验、执行医嘱情况、药品的来源及剂型的改变等因素均可影响患儿的血药浓度水平，使患儿用药后血药浓度不一定都在有效浓度范围内，其中低于有效浓度范围的例数占总数的４８．７７％，高于有效浓度范围的占４．３６％，而在有效浓度范围内的仅占４６．８７％。结论血药浓度监测十分必要，对临床用药有一定的指导作用，能帮助临床制定合理的给药方案，取得更好的疗效     

精神分裂症患者睡眠障碍的分析及护理

本文对30例伴有睡眠障碍的精神分裂症患者进行了心理分析，并采取了相应的护理措施，促进其正常睡眠，为及早康复提供必要条件。     

去甲万古霉素临床药代动力学及血药浓度监测

目的 :比较国产去甲万古霉素在老年人和年轻人中的体内过程 ,为制订去甲万古霉素在治疗老年人感染时的合理给药方案提供依据 ;建立快捷、实用的去甲万古霉素治疗药物监测 (TDM)方法。方法 :同期对照研究去甲万古霉素在 1 0名健康老年受试者 (老年组 )和 1 0名健康年轻受试者 (年轻组 )中的药代动力学。以微生物法和荧光偏振免疫法 (FPIA)测定血药浓度 ,以微生物法测定尿药浓度。结果 :老年组和年轻组静脉滴注去甲万古霉素 80 0mg后的体内过程均符合二室模型。与年轻组比较 ,老年组表观分布容积 (Vd)增大 ,总清除率 (CLt)及肾清除率 (CLr)降低 ,药时曲线下面积 (AUC)增加和消除半衰期(t1 /2 β)延长。以上各项药代参数在两组间差异均具非常显著性 (P <0 .0 1 ) ;两组血药峰浓度相近 (P >0 .0 5 )。去甲万古霉素给药后 1 2h内的累积尿排出率老年组较年轻组明显为低 ,分别为 (77.1 3± 8.95 ) %和 (83.82± 1 6 .80 ) % (P <0 .0 1 ) ,但给药后4 8h两组的累积尿排出率相近 ,分别为 (85 .38± 8.6 2 ) %和 (86 .1 2± 1 6 .85 ) % ,两组差异无显著性 (P >0 .0 5 )。以微生物法和FPIA同时测定去甲万古霉素血清标本。两种测定方法测得结果呈良好线性相关性。线性回归方程为Y =0 .75 34X - 0 .5 94 8(Y :微生物     

Optimal trough concentration of voriconazole with therapeutic drug monitoring in children: A systematic review and meta-analysis

ObjectivesThis systematic review and meta-analysis was designed to determine the optimal trough concentration of voriconazole for children with invasive fungal infections (IFIs).MethodsWe searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Japana Centra Revuo Medicina) for clinical studies describing the voriconazole trough concentration. We used stepwise cut-off values of 1.0–2.0 mg/L for efficacy and 3.0–6.0 mg/L for safety. The efficacy outcomes were treatment success and all-cause mortality, and the safety outcomes were hepatotoxicity, neurotoxicity and all-cause adverse events.ResultsNine studies involving 211 patients were included in the analysis. The probability of treatment success against IFIs was significantly increased at cut-off values of ≥1.0 mg/L (odds ratio [OR] = 2.65, 95% confidence interval [CI] = 1.20–5.87). Our analysis did not find any relationship between the trough concentration and survival. Concerning safety, the occurrence of any outcomes did not significantly differ according to the voriconazole trough concentrations at any cut-off value. However, in a subgroup analysis of Asian study locations, a significantly higher risk of hepatotoxicity was demonstrated at voriconazole trough cut-off values ≥ 3.0 mg/L (OR = 8.40, 95% CI = 1.36–51.92). Although a significant correlation between the voriconazole concentration and hepatotoxicity was evident in regression curve analysis, (y = 0.1198e^0.2298x), no correlation was demonstrated for neurotoxicity (y = 0.3913e^?0.008x).ConclusionOur findings suggest that the optimal trough concentration for increasing clinical success and minimizing hepatotoxicity during voriconazole therapy in children with IFIs, particularly for Asian populations, is 1.0–3.0 mg/L.     

Preferable timing of therapeutic drug monitoring in patients with impaired renal function treated with once-daily administration of vancomycin

The aim of this study was to investigate the timing of therapeutic drug monitoring (TDM) in patients with impaired renal function treated with once-daily administration of vancomycin (VCM). Once-daily administration was selected for patients whose creatinine clearance (C_cr) was <80 ml/min. TDM was conducted on day 3 or on day 4. Adult patients whose VCM dosage was not altered according to initial C _min and for whom subsequent follow-up TDM was performed within 1 week were entered into the study. Patients whose renal function deteriorated at follow-up TDM were excluded. One hundred sixty-five patients were eligible for analysis. Among patients with once-daily dosing, relative increases of C _min at follow-up TDM compared with initial TDM were 34.5 ± 39.2 % in TDM on day 3 and 16.6 ± 20.6 % in TDM on day 4 (P = 0.016). In contrast, there was no significant difference in the relative increase of C _min between TDM on days 3 and 4 (26.1 ± 39.6 vs. 18.4 ± 25.6 %, P = 0.551) in the twice-daily regimen. On multivariate analysis, TDM on day 3 alone (odds ratio, 4.93; 95 % confidence interval, 1.71–14.2) was selected as an independent risk factor associated with a relative increase of C _min by >30 % in the once-daily regimen. Steady-state VCM serum concentration was not achieved on day 3 in the once-daily regimen in patients with impaired renal function, and TDM on day 3 caused underestimation of C _min.     

Immunosuppressive drug monitoring of sirolimus and cyclosporine in pediatric patients

Sirolimus is primarily used as a rescue agent in pediatric transplant recipients, particularly in cases of cyclosporine or tacrolimus toxicity. Preliminary data indicate a higher apparent oral clearance in younger children (4-10 years of age). Various drug interactions have been described between sirolimus and drugs that are substrates/inhibitors or inducers of CYP3A and the P-glycoprotein transporter. Close monitoring of trough sirolimus blood levels is therefore recommended for pediatric transplant recipients. In de novo adult kidney transplant recipients on triple therapy with cyclosporine, corticosteroids and sirolimus, a therapeutic window of 4-12 microg/l is recommended for sirolimus trough concentrations determined by HPLC or LC/MS-MS. In maintenance adult patients after conversion to a calcineurin inhibitor-free regimen, sirolimus trough concentrations of 5-10 microg/l are proposed in combination with mycophenolate mofetil. These therapeutic ranges may also serve as a guide for pediatric renal transplant recipients. The concept of C2 monitoring still needs to be critically evaluated in pediatric patients. The crucial importance of achieving an adequate cyclosporine exposure early after transplantation has been demonstrated for adult transplant recipients. A cyclosporine concentration taken 2 h after dosing is a good surrogate marker of the AUC0-4h in adults. Various clinical studies have shown that in pediatric patients, the C2 concentration shows a substantially better correlation with cyclosporine exposure compared to the trough level (C0). In an outcome study with pediatric renal transplant recipients, it could be demonstrated that the AUC(0-4h) was a predictor of acute rejection in the first 3 weeks after transplantation, whereas C2 levels showed no significant association. Abbreviated AUC strategies may be preferable for optimization of CsA exposure in pediatric patients.     

Teicoplanin and therapeutic drug monitoring: An update for optimal use in different patient populations

Individualization of antimicrobial treatment based on real-time therapeutic drug monitoring (TDM) and dosing adaptation may represent an important tool in the antimicrobial stewardship programs. Teicoplanin is a glycopeptide hydrophilic antibiotic whose pharmacokinetic behavior may consistently vary among different patient populations. Nowadays it is generally recognized that the effective trough (C_min) plasma level of tecoplanin should be of at least 10–15 mg/L for the treatment of mild infections, and of 15–30 mg/L for the treatment of deep-seated infections and/or of severe infections. The aim of this viewpoint is to provide an update for optimal use of teicoplanin TDM in different patient populations. Available literature supports TDM of C_min as a helpful approach in addressing appropriate treatment with teicoplanin, with a frequency of assessment that should be guided by the severity of the infection and/or by the complexity of the pathophysiological status of the patient.     

Recommended initial loading dose of teicoplanin, established by therapeutic drug monitoring, and outcome in terms of optimal trough level

Teicoplanin has a long serum half-life, and therefore it takes time to reach a steady-state concentration. An initial loading procedure has been recommended for teicoplanin to enable prompt reaching of the optimal serum trough level (10–15 μg/ml). However, the dose of teicoplanin that should be administered to patients with varying renal function levels remains inconclusive. In this study, we monitored the serum concentrations of teicoplanin in patients with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and compared different teicoplanin serum concentrations and their clinical efficacy, investigating the significance of the mean dose administered during the initial 3 days. The study included 48 patients with MRSA pneumonia. The peak and trough concentrations of teicoplanin were determined utilizing a fluorescence polarization immunoassay and a two-compartment Bayesian population model. Teicoplanin was given at a loading dose of 400 or 800 mg on the first day, followed by maintenance doses of 200 or 400 mg. The mean initial dose (MID) over the first 3 days was calculated as: (loading dose + dose on 2nd day + dose on 3rd day)/3. Patients with an MID of 266.7 mg or less (400 mg for loading, 200 mg over the 2nd and 3rd days) did not have a trough level that exceeded 10 μg/ml at the point before the injection on the 4th day. Even in patients with hemodialysis (HD), an MID of 266.7 mg was not enough to provide a trough level of 10 μg/ml. Patients with an MID than 533.3 mg had significantly elevated trough levels, showing better outcomes. A multiple regression formula for predicting trough level before the fourth day of administration is given as: 0.034 + 0.030 × (MID; mg) − 0.057 × creatinine clearance (Ccr; ml/min). These findings suggest that 800 mg as an initial dose, followed by 400 mg maintenance doses over the following 2 days, makes it possible to safely attain an optimal trough level, even in the patients with HD.     

治疗药物浓度监测用质控物的制备及其质控方法的应用

目的自行制备室内质控物,用于检测治疗药物监测（TDM）系统的内部质量控制。方法将适量的甲氨喋呤标准品加入正常人体检的血清中配制成所需浓度,置-80℃保存。采用反相高效液相色谱法（RP-HPLC）测定其浓度。结果经过长期观察测定,其测定均值在1年内的差异无统计学意义（在靶值的±15％允许误差范围内）。结论自行制备的室内质控物具有良好的稳定性,可满足室内质控的要求。     

The current role of liquid chromatography-tandem mass spectrometry in therapeutic drug monitoring of immunosuppressant and antiretroviral drugs

Therapeutic drug monitoring of critical dose immunosuppressant drugs is established clinical practice and there are similar good reasons to monitor antiretrovirals. The aim of this article is to review the recent literature (last five years), with particular reference to the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS offers many potential advantages. The superior selectivity of LC-MS/MS over immunoassays for immunosuppressant drugs has been widely reported. Simultaneous measurement of a number of drugs can be performed. It is currently routine practice for the four major immunosuppressants (cyclosporin, tacrolimus, sirolimus and everolimus) to be simultaneously measured in whole blood. While up to 17 antiretroviral drugs have been simultaneously measured in plasma. The exquisite sensitivity of LC-MS/MS also provides the opportunity to measure these drugs in alternative matrices, such as dried blood spots, saliva, peripheral blood mononuclear cells and tissue. However, the clinical utility of measuring these classes of drugs in alternative matrices is still to be determined.