Evaluation of population pharmacokinetic models for amikacin dosage individualization in critically ill patients

Objectives The aim of this study was to evaluate the reliability for dosage individualization and Bayesian adaptive control of several literature‐retrieved amikacin population pharmacokinetic models in patients who were critically ill. Methods Four population pharmacokinetic models, three of them customized for critically‐ill patients, were applied using pharmacokinetic software to fifty‐one adult patients on conventional amikacin therapy admitted to the intensive care unit. An estimation of patient‐specific pharmacokinetic parameters for each model was obtained by retrospective analysis of the amikacin serum concentrations measured (n = 162) and different clinical covariates. The model performance for a priori estimation of the area under the serum concentration‐time curve (AUC) and maximum serum drug concentration (C_max) targets was obtained. Key findings Our results provided valuable confirmation of the clinical importance of the choice of population pharmacokinetic models when selecting amikacin dosages for patients who are critically ill. Significant differences in model performance were especially evident when only information concerning clinical covariates was used for dosage individualization and over the two most critical determinants of clinical efficacy of amikacin i.e. the AUC and C_max values. Conclusions Only a single amikacin serum level seemed necessary to diminish the influence of population model on dosage individualization.     

“个体化方案”治疗急性坏死性胰腺炎(附31例报告)

１９７８年１月—１９９６年１２月,我院收治急性坏死性胰腺炎７３例,其中早期手术４２例（１９７８年１月—１９８８年１２月）,病死率４０．４８％;“个体化”治疗３１例（１９８９年１月—１９９６年１２月）,病死率１６．１３％。两组治疗结果具有显著性差异（Ｐ＜０．０５）。认为“个体化方案”更适合于急性坏死性胰腺炎的治疗。     

地高辛血药浓度监测及个体化给药

目的 测 定患 者 地 高 辛血 药 浓 度 ，为 临 床 合理 用 药 提 供参 考 。 方 法 采 用 荧光 偏 振 免 疫 法测 定８３例 地 高 辛 血 药 浓 度 ，分 析 血 药 浓 度 与 疗 效 的 关 系 及 其 影 响 因 素 以 及 不 同 给 药 方 案 对 测 定 结 果 的 影 响 。 结果 有 效浓 度 范围 （０．８～２．０ 滋ｇ／Ｌ）与临 床 表现 并不 完 全一 致，影响 因 素较 多，不同 给药 方 案监 测结 果 差异 较 大。结论 地 高辛 血 药浓 度监 测 必须 密切 结 合临 床，综合 考 虑各 方面 的 因素 ，实 现个 体化 给 药。     

隐球菌性脑膜炎的临床治疗及疗效附12例分析

目的:回顾性分析12例隐球菌性脑膜炎的临床资料、治疗及预后。方法:动态观察12例隐球菌性脑膜炎患者的临床表现,使用二性霉素B、氟康唑、氟胞嘧啶及鞘注二性霉素B的临床疗效及转归,以及药物的不良反应和处理措施。结果:患者均取得良好的疗效,均治愈。二性霉素B的总量在2．36～10．5g,其不良反应多、严重。结论:使用二性霉素B静滴及鞘注,联合氟康唑和／或氟胞嘧啶效果确切,使用二性霉素B须个体化,加强对症支持疗法是成功不可缺少的重要措施。     

浅谈卵巢癌的个体化治疗

卵巢癌是妇科常见的肿瘤之一，其发病率仅次于子宫颈癌和子宫体癌，而列居第三，但其至死率却占首位，成为严重威胁妇女生命的肿瘤。卵巢癌个体化治疗是根据患者的具体情况，选择适宜患者的手术和药物治疗方案，从而达到最有利于患者的治疗效果。笔者从哲学的角度对卵巢癌个体化治疗的依据、认识和措施进行综合分析。     

四种下颌骨缺损修复方法临床疗效评价

目的:对分别采用自体骨煮沸回植、异体冻存骨移植、成品钛支架植入及个体定制化钛下颌植入等四种不同方法修复下颌骨缺损病例的外形、功能恢复情况,以及术后并发症情况进行综合评价。为临床合理选择下颌骨修复手段进行探索。方法:收集我院自1997年至2005年期间分别采用自体骨煮沸回植(A组)、异体冻存骨移植(B组)、成品钛支架植入(C组)、个体定制化钛下颌植入(D组)四种不同方法修复下颌骨缺损病例122例,比较外形、功能恢复效果;术后感染、植入体断裂等并发症的发生情况。结果:A组与D组外形和功能修复效果优于C组和B组(P<0.05)。C组和B组之间以及A组和D组之间均无显著性差异(P>0.05)。外形评价达到良好以上者,A组和D组优于B组和C组(P<0.05)。B组和C组之间无显著性差异(P>0.05)。感染率:A组7.5%,B组14.3%,C组11.9%,D组0,各组间无显著性差异(P>0.05)。植入体断裂率:A组5%,B组42.9%,C组19.0%,D组0,各组间无显著性差异(P>0.05)。结论:采用自体骨煮沸回植和定制化钛下颌修复下颌骨缺损的美观、功能效果明显优于采取异体冻存骨移植和成品钛支架的病例。四种方法在术后感染、植入物断裂等并发症的发病率方面无显著性差异。四种修复方法各有优缺点。决定临床下颌骨缺损功能重建疗效的关键,取决于临床适应证的掌握和手术中细节方面的处理。     

Individualization of tacrolimus dosage basing on cytochrome P450 3A5 polymorphism – a prospective,randomized, controlled study

We investigated how cytochrome P450 (CYP) 3A5 polymorphism affects pharmacokinetics of tacrolimus and its interaction with diltiazem in Chinese kidney transplant recipients. Sixty‐two CYP3A5 expressers and 58 non‐expressers were, respectively, randomized to receive diltiazem supplement or not. Their pharmacokinetic profiles were acquired on 14th day, sixth month, and 18th month post‐transplant and compared among groups. A dosing equation was fit based on above data with CYP3A5 genotype and diltiazem co‐administration as variables. Then, necessary initial doses with or without diltiazem were calculated and used in 11 CYP3A5 expressers, respectively, when another 11 expressers received routine doses as control. Trough concentration was measured on the third‐day post‐transplant and patients failed to reach target range were presented in percentage. These two parameters were compared among three groups. Patients were followed up until June 2010, kidney function, biopsy‐proved acute rejection, and other adverse events were monitored. Results showed that CYP3A5 expressers needed more tacrolimus to reach therapeutic concentration window and were more susceptible to diltiazem‐induced concentration increase than CYP3A5 non‐expressers. CYP3A5 polymorphism‐guided dosing equation helped to determine appropriate initial doses of tacrolimus in individuals. In conclusion, CYP3A5 polymorphism profoundly influences pharmacokinetics of tacrolimus and helps to individualize tacrolimus dose.     

基于个体化需求的护理随访在首发脑卒中患者恢复期的应用

目的 探究基于个体化需求的护理随访对首发脑卒中患者恢复期的作用效果。方法 采用便利取样的方法,本研究选取2017年6月——2017年12月期间纳入的30首发脑卒中患者为对照组,以2018年1月——2018年6月期间纳入的30例首发脑卒中患者为实验组,对照组接受常规随访,试验组接受基于个体化需求的护理随访。比较干预前后两组患者卒中知识知晓率、残疾接受度、医学应对方式以及焦虑抑郁程度。结果 干预后,试验组患者医学应对方式,卒中知识、残疾接受度以及焦虑抑郁情绪均显著改善,两组相比,差异有统计学意义（P<0.05);此外,就运动依从性而言,出院第一周,同基线相比两组患者的运动依从性均有所上升,但两组间相比,差异无统计学意义（P>0.05),而在一个月、三个月、六个月时,试验组患者的依从性显著优于对照组,差异有统计学意义（P>0.05)。 结论 基于个体化的护理随访可显著提高患者卒中知识掌握情况,改善患者的焦虑抑郁症状,提高患者的残疾接受度,改善患者的医学应对方式,进而加速患者康复进程。