Pharmacologic

Pharmacological
  • 文章类型: Journal Article
    分娩疼痛是女性在分娩和分娩过程中最讨厌的疼痛。这样,分娩结束时的疼痛经常被神话和模棱两可地概述。因此,在包括埃塞俄比亚在内的发展中国家,分娩时明显没有疼痛仍然是一个挑战。
    本系统综述和荟萃分析旨在探讨埃塞俄比亚孕妇分娩镇痛的综合患病率及相关因素。
    系统评价和荟萃分析与系统评价的首选报告项目一致使用。
    PubMed/Medline,Scopus,EMBASE,WebofScience,谷歌学者,和Cochrane图书馆,并补充了手册被故意看,直到2024年1月1日至30日。
    两位作者利用标准化的数据提取设计独立地提取了所有主要信息,分析是利用STATA版本17完成的。使用I2测量评估研究中的异质性。漏斗图和Egger加权回归检验分别用于评估主观和客观出版偏差。此外,利用随机效应模型评估了分娩疼痛管理的综合效应及其相关性.
    在本研究中,分娩镇痛的总体汇总患病率为23.3%,a(95%置信区间(CI):13.5,33.1)。产妇年龄(比值比(OR):1.91;95%CI:1.11,2.77),母亲的平价(OR:0.28;95%CI:0.06,0.63),妊娠不幸史(OR:0.12;95%CI:0.11,0.36),劳动力长度(OR:2.09;95%CI:1.06,3.13),埃塞俄比亚孕妇对分娩镇痛的认识(OR:1.91;95%CI:0.34,3.49)与分娩镇痛显着相关。
    埃塞俄比亚孕妇分娩镇痛的普遍合并患病率较低。产妇年龄,母亲的平价,妊娠流产史,劳动的长度,和分娩镇痛意识是影响埃塞俄比亚孕妇分娩镇痛的因素。这一发现提出了特殊的考虑,通过扩大策略并以符合普遍公认的标准的方式利用分娩疼痛管理,使分娩的母亲免于疼痛。
    PROSPEROCRD:42024525636。
    UNASSIGNED: Labor pain is the nastiest conceivable pain women are involved in during labor and delivery. In this way, the end of labor pain is frequently outlined by myths and equivocalness. Hence, giving a compelling absence of pain in labor remained a challenge specifically in developing countries including Ethiopia.
    UNASSIGNED: This systematic review and meta-analysis aimed to explore the pooled prevalence of labor analgesia and associated factors to pregnant women in Ethiopia.
    UNASSIGNED: A systematic review and meta-analysis were utilized in agreement with the Preferred Reporting Items for Systematic Reviews.
    UNASSIGNED: PubMed/Medline, SCOPUS, EMBASE, Web of Science, Google Scholars, and the Cochrane Library and supplemented it with manual were deliberately looked at until January 1-30, 2024.
    UNASSIGNED: Two authors independently extricated all principal information utilizing standardized data extraction designs, and the analysis was done utilizing STATA version 17. Heterogeneity over the studies was evaluated utilizing I2 measurement. The funnel plot and Egger\'s weighted regression tests were utilized to assess subjective and objective publication biases respectively. Also, the pooled effect of labor pain management and the associations were evaluated utilizing a random-effects model.
    UNASSIGNED: The general pooled prevalence of labor analgesia in the present study was 23.3% with a (95% confidence interval (CI): 13.5, 33.1). Maternal age (odds ratio (OR): 1.91; 95% CI: 1.11, 2.77), parity of the mother (OR: 0.28; 95% CI: 0.06, 0.63), history of pregnancy misfortune (OR: 0.12; 95% CI: 0.11, 0.36), length of labor (OR: 2.09; 95% CI: 1.06, 3.13), and awareness about labor analgesia (OR: 1.91; 95% CI: 0.34, 3.49) were significantly related with labor analgesia among pregnant women in Ethiopia.
    UNASSIGNED: The generally pooled prevalence of labor analgesia among pregnant women in Ethiopia was low. Maternal age, parity of the mother, history of pregnancy loss, length of labor, and awareness of labor analgesia were factors influencing labor analgesia among pregnant women in Ethiopia. This finding proposes exceptional consideration to make laboring mothers free of pain by scaling up the strategies and utilizing labor pain administration in a way that universally recognized standards are met.
    UNASSIGNED: PROSPERO CRD: 42024525636.
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  • 文章类型: Journal Article
    呼吸机相关性肺炎(VAP)导致发病率增加,死亡率和医疗费用。除了来自最新的欧洲和美国指南(分别于2017年和2022年发布)的更多证据外,在过去的两年里,一些重要的临床经验增加了新的预防工具,以改善VAP的管理.
    本文是对VAP预防新证据的叙述性综述。我们将VAP预防措施分为药理学,非药物和呼吸机护理捆绑。
    已被证明可以降低并发症发生率的大多数有效策略易于实施且价格低廉。实施护理捆绑,伴随着教育措施和多学科团队应该是优化管理的一部分。除了用于预防VAP的呼吸机护理捆绑外,使用呼吸机护理束预防非感染性呼吸机相关事件可能是有益的.
    UNASSIGNED: Ventilator associated pneumonia (VAP) leads to an increase in morbidity, mortality, and healthcare costs. In addition to increased evidence from the latest European and American guidelines (published in 2017 and 2022, respectively), in the last two years, several important clinical experiences have added new prevention tools to be included to improve the management of VAP.
    UNASSIGNED: This paper is a narrative review of new evidence on VAP prevention. We divided VAP prevention measures into pharmacological, non-pharmacological, and ventilator care bundles.
    UNASSIGNED: Most of the effective strategies that have been shown to decrease the incidence of complications are easy to implement and inexpensive. The implementation of care bundles, accompanied by educational measures and a multidisciplinary team should be part of optimal management. In addition to ventilator care bundles for the prevention of VAP, it could possibly be beneficial to use ventilator care bundles for the prevention of noninfectious ventilator associated events.
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  • 文章类型: Journal Article
    目标:肥胖与心血管(CV)疾病有关,包括但不限于动脉粥样硬化疾病,心力衰竭,和心房颤动。尽管如此,对于肥胖者和已确定的CV状况,有意减重对CV结局的影响仍缺乏研究.用于减肥的新的和新兴的药物疗法主要针对肠促胰岛素/营养感应轴,可引起实质性和持续的体重减轻。胰高血糖素样肽1受体激动剂(GLP-1RA)利拉鲁肽和司马鲁肽已获得美国FDA批准用于治疗肥胖症,GLP-1/葡萄糖依赖性促胰岛素多肽(GIP)双重受体激动剂替拉肽的肥胖适应症申请目前正在FDA审查中。正在进行广泛的II期和IIIa期随机对照试验,以评估GLP-1RA的组合排列。GIP受体激动剂,GIP受体拮抗剂,和胰高血糖素受体激动剂。这些疗法在具有确定的CV条件的高风险的肥胖者中的临床结果试验应该可以估计有意减肥在通过这些药物管理CV风险中的作用。
    结果:在射血分数保持的肥胖和心力衰竭患者中,每周一次大剂量可注射司马鲁肽(2.4mg/周)可有效减轻体重和改善健康状况;运动能力也得到改善。正在进行的口服司马鲁肽和每周一次可注射的替利西帕肽的CV结果试验将有助于确定这些疗法在患有其他CV疾病的人中的作用。除了这两种针对CV主张或适应症的疗法外,许多其他减肥新疗法,经审查,目前正在发展中。目前正在研究多种药物对肥胖和已确定的CV状况的人的药理学诱导的体重减轻对CV状况的影响。这些疗法可以提供新的途径来管理患有肥胖症和已经建立或处于CV疾病高风险的人的CV风险。
    Obesity is associated with cardiovascular (CV) conditions, including but not limited to atherosclerotic disease, heart failure, and atrial fibrillation. Despite this, the impact of intentional weight loss on CV outcomes for persons with obesity and established CV conditions remains poorly studied. New and emerging pharmacologic therapies for weight loss primarily targeting the incretin/nutrient sensing axes induce substantial and sustained weight loss. The glucagon-like-peptide 1 receptor agonists (GLP-1 RA) liraglutide and semaglutide have US FDA approval for the treatment of obesity, and the application for an obesity indication for the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide is presently under FDA review. Extensive phase II and IIIa randomized controlled trials are underway evaluating permutations of combined GLP-1 RA, GIP receptor agonist, GIP receptor antagonist, and glucagon receptor agonists. Clinical outcome trials of these therapies in persons with obesity at high risk of established CV conditions should make it possible to estimate the role of intentional weight loss in managing CV risk via these medications.
    High-dose once weekly injectable semaglutide (2.4 mg/week) use among persons with obesity and heart failure with preserved ejection fraction was effective at both reducing weight and improving health status; exercise capacity was also improved. Ongoing CV outcome trials of oral semaglutide and once weekly injectable tirzepatide will help to establish the role of these therapies among persons with other CV conditions. In addition to these two therapies targeting a CV claim or indication, many other new therapeutics for weight loss, as reviewed, are currently in development. The impact of pharmacologic-induced weight loss on CV conditions for persons with obesity and established CV conditions is currently under investigation for multiple agents. These therapies may offer new avenues to manage CV risk in persons with obesity and with established or at high risk for CV disease.
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  • 文章类型: Journal Article
    这篇综述评估了药物(前列腺素,催产素,米非司酮,透明质酸酶,和一氧化氮供体)和机械方法(单球囊和双球囊导管,海带,膜剥离,和羊膜切开术)以及通常在补充医学的标题下考虑的那些(蓖麻油,乳头刺激,性交,草药,和针灸)。大量已发表的报告,包括2个大型网络荟萃分析,支持米索前列醇(PGE1)用于宫颈成熟和引产时的安全性和有效性。以50μg的剂量阴道给药的米索前列醇在24小时内实现阴道分娩的可能性最高。不管给药,路线,和管理时间表,当用于宫颈成熟和引产时,前列腺素E2在降低剖宫产率方面似乎具有相似的疗效.全球范围内,尽管催产素代表了最广泛使用的引产药物,其有效性高度依赖于胎次和宫颈状态。催产素在引产方面比期待管理更有效,与羊膜切开术联合使用时,催产素的疗效得到增强。然而,经阴道或子宫内给药的前列腺素在引产方面比催产素更有效。口服200毫克米非司酮片似乎是促宫颈成熟的最低有效剂量。评估松弛素的大量文献表明,当用于该适应症时,该药物的益处有限。尽管宫颈内注射透明质酸酶可能会导致宫颈成熟,对宫颈内给药的需要限制了这种药物的使用。关于一氧化氮供体的阴道给药,包括单硝酸异山梨酯,异山梨醇,硝酸甘油,和硝普钠,这些药物的副作用发生率较高,限制了它们的使用。已发现合成的吸湿性宫颈扩张器可有效用于预诱导宫颈成熟。尽管可以在使用合成吸湿性扩张器后施用药理学药物,为了减少阴道分娩的间隔,正在探索同时使用机械和药理学方法。将单球囊导管与地诺前列酮结合使用,米索前列醇,或催产素增强这些药物在宫颈成熟和引产中的功效。单球囊导管和双球囊导管在宫颈成熟和引产中的功效相似。迄今为止,在平衡分娩时间和安全性时,米索前列醇与宫颈导管联合使用似乎是最佳方法.尽管患者偶尔会使用补充方法,鉴于缺乏记录其有效性和安全性的数据,这些方法很少在医院使用.
    This review assessed the efficacy and safety of pharmacologic agents (prostaglandins, oxytocin, mifepristone, hyaluronidase, and nitric oxide donors) and mechanical methods (single- and double-balloon catheters, laminaria, membrane stripping, and amniotomy) and those generally considered under the rubric of complementary medicine (castor oil, nipple stimulation, sexual intercourse, herbal medicine, and acupuncture). A substantial body of published reports, including 2 large network meta-analyses, support the safety and efficacy of misoprostol (PGE1) when used for cervical ripening and labor induction. Misoprostol administered vaginally at doses of 50 μg has the highest probability of achieving vaginal delivery within 24 hours. Regardless of dosing, route, and schedule of administration, when used for cervical ripening and labor induction, prostaglandin E2 seems to have similar efficacy in decreasing cesarean delivery rates. Globally, although oxytocin represents the most widely used pharmacologic agent for labor induction, its effectiveness is highly dependent on parity and cervical status. Oxytocin is more effective than expectant management in inducing labor, and the efficacy of oxytocin is enhanced when combined with amniotomy. However, prostaglandins administered vaginally or intracervically are more effective in inducing labor than oxytocin. A single 200-mg oral tablet of mifepristone seems to represent the lowest effective dose for cervical ripening. The bulk of the literature assessing relaxin suggests this agent has limited benefit when used for this indication. Although intracervical injection of hyaluronidase may cause cervical ripening, the need for intracervical administration has limited the use of this agent. Concerning the vaginal administration of nitric oxide donors, including isosorbide mononitrate, isosorbide, nitroglycerin, and sodium nitroprusside, the higher incidence of side effects with these agents has limited their use. A synthetic hygroscopic cervical dilator has been found to be effective for preinduction cervical ripening. Although a pharmacologic agent may be administered after the use of the synthetic hygroscopic dilator, in an attempt to reduce the interval to vaginal delivery, concomitant use of mechanical and pharmacologic methods is being explored. Combining the use of a single-balloon catheter with dinoprostone, misoprostol, or oxytocin enhances the efficacy of these pharmacologic agents in cervical ripening and labor induction. The efficacy of single- and double-balloon catheters in cervical ripening and labor induction seems similar. To date, the combination of misoprostol with an intracervical catheter seems to be the best approach when balancing delivery times with safety. Although complementary methods are occasionally used by patients, given the lack of data documenting their efficacy and safety, these methods are rarely used in hospital settings.
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  • 文章类型: Journal Article
    暂无摘要。
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  • 文章类型: Journal Article
    牙槽骨和牙龈是容纳牙齿的牙周组织的组成部分。它不断适应牙齿的咀嚼力和位置。然而,局部疾病,如慢性牙周炎和某些系统性疾病会破坏牙周组织,其中包括牙槽骨。正在探索各种药理学试剂的多效性以对抗牙槽骨的破坏。本文综述了药物在牙槽骨再生中的作用。
    Alveolar bone and gingiva are components of the periodontium that house the tooth. It constantly adapts itself to the masticatory forces and position of the tooth. However, localized diseases like chronic periodontitis and certain systemic diseases destroy periodontal tissues, which include the alveolar bone. Various pharmacological agents are being explored for their pleiotropic properties to combat the destruction of alveolar bone. This review focuses on the role of pharmacological agents in alveolar bone regeneration.
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  • 文章类型: Systematic Review
    背景:我们的系统评价研究了非药物和药物干预在急性护理中预防或治疗创伤性脑损伤(TBI)相关谵妄的有效性和安全性。
    方法:我们搜索了四个电子数据库(MEDLINE,EMBASE,中央/CDSR,和PsycINFO)以确定随机对照试验(RCT),准实验,和观察性研究。符合条件的研究包括患有TBI的成年人,至少一个比较器组,谵妄作为结果,并在急性护理中发生。两名评审员独立完成了所有研究筛选,数据抽象,以及使用Cochrane偏倚风险2工具评估RCT偏倚风险或非随机研究偏倚风险-用于观察性研究的干预工具。我们实施了PROGRESS-Plus框架来描述健康的社会决定因素(SDoH)报告。
    结果:我们确定了20,022次引用,全文回顾了301,并在描述性综合中包括八项研究。研究参与者的平均年龄为32至62岁。12.5%的纳入研究报告了SDoH。纳入的研究具有中度至高度的偏倚风险。研究将重新定向计划和干预捆绑与常规护理进行了比较,但在治疗TBI相关谵妄方面,这些干预措施并不优于常规治疗.个别研究发现,瑞舒伐他汀和阿立哌唑比安慰剂更有效,右美托咪定在预防TBI相关性谵妄方面比丙泊酚和氟哌啶醇更有效。没有研究报告安全性是主要结果。
    结论:我们确定了预防TBI相关谵妄的有效药物干预措施,但是这些研究有中等到高的偏倚风险,这限制了我们对这些发现的信心。未来的研究应纳入安全性结果,和多样化的研究人群,包括老年人。
    BACKGROUND: Our systematic review examines the effectiveness and safety of non-pharmacologic and pharmacologic interventions in preventing or treating traumatic brain injury (TBI)-related delirium in acute care.
    METHODS: We searched four electronic databases (MEDLINE, EMBASE, CENTRAL/CDSR, and PsycINFO) to identify randomized controlled trials (RCTs), quasi-experimental, and observational studies. Eligible studies included adults with TBI, at least one comparator group, delirium as an outcome and took place in acute care. Two reviewers independently completed all study screening, data abstraction, and risk of bias assessment using the Cochrane risk of bias 2 tool for RCTs or risk of bias in non-randomized studies-of interventions tool for observational studies. We implemented the PROGRESS-Plus framework to describe social determinants of health (SDoH) reporting.
    RESULTS: We identified 20,022 citations, reviewed 301 in full text, and included eight studies in the descriptive synthesis. The mean age of study participants ranged from 32 to 62 years. 12.5% of included studies reported SDoH. Included studies had moderate-to-high risk of bias. Studies compared reorientation programs and an intervention bundle to usual care, but these interventions were not better than usual care in treating TBI-related delirium. Individual studies found that rosuvastatin and aripiprazole were more efficacious than placebo, and dexmedetomidine was more efficacious than propofol and haloperidol for preventing TBI-related delirium. No studies reported safety as the primary outcome.
    CONCLUSIONS: We identified efficacious pharmacologic interventions for preventing TBI-related delirium, but these studies were at moderate-to-high risk of bias, which limits our confidence in these findings. Future studies should incorporate safety outcomes, and a diverse study population, including older adults.
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  • 文章类型: Journal Article
    目的:心房颤动(房颤)是临床上最常见的持续性心律失常。发作可自发停止(阵发性房颤);仅可通过干预终止(持续性房颤);或可无限期持续(永久性房颤)(参见欧洲和美国指南,下面引用,更精确的定义)。最近,人们对终止房颤的方法重新产生了兴趣,该方法被称为“口袋里的药丸”(PITP)。在美国和欧洲指南中,PITP被认为是使用口服抗心律失常药物治疗急性/近期发作性AF急性转化的有效选择。然而,目前尚未系统地评估PITP的使用方式。
    结果:最近发表的抗心律失常干预治疗心房颤动(AIM-AF)调查包括关于当前PITP使用的问题,按美国与接受调查的欧洲国家,欧洲有代表性的国家,和心脏病学家vs.电生理学家。这份手稿提供了这项计划中的子研究的数据。我们的调查显示,美国和欧洲的临床医生在大约四分之一的患者中考虑PITP,主要用于轻度或无结构性心脏病的近期发作的房颤(指南适用)。然而,存在重大偏差。有关数据摘要,请参见图形摘要。
    结论:我们的研究结果强调了PITP的频繁使用,以及需要进一步的医师教育,以适当和最佳地使用该策略。
    Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as \'pill-in-the-pocket\' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated.
    The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data.
    Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy.
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  • 文章类型: Journal Article
    背景:T2MI是由心肌氧供应和需求之间的不匹配引起的。个体的一个子集是由急性出血引起的T2MI。传统的MI治疗包括抗血小板,抗凝剂,血运重建会使出血恶化.在这项研究中,我们的目的是描述和报告临床判定的因出血导致的T2MI患者的临床结局,按治疗方法分层。
    方法:在2009年至2022年期间,使用MassGeneralBrighamResearch患者数据注册,然后进行手动医师裁决,以识别由出血引起的T2MI个体。我们定义了3个治疗组:(1)侵入性管理组,(2)接受抗血小板和抗凝治疗但没有手术的药物组,和(3)未接受手术或抗凝/抗血小板治疗的保守管理组.基线特征,诊断测试,治疗方案,和30天的临床结果,死亡率,再次出血,提取再入院率,并采用卡方检验比较治疗组的结局.
    结果:我们确定了5712名患有急性出血的个体,其中1017人(17.8%)在入院期间被编码为具有T2MI。在医生手动裁定后,73例(7.2%)符合出血引起的T2MI标准。在出血引起的T2MI患者中,18个被侵入性管理,39人单独接受药物治疗,16个是保守管理的。侵入性管理组的死亡率较低(5.6%vs37.5%,p=0.021)但再入院率更高(22.2%对0%,p=0.045)比保守管理组。药物组的死亡率较低(10.3%vs37.5%,p=0.017)但再入院率更高(35.9%vs0%,p=0.005)比保守管理组。最后,3个不同组的再出血发生率无差异.
    结论:与急性出血相关的T2MI个体是高危人群。与采用保守治疗的患者相比,采用标准手术治疗的患者的再入院率较高,但死亡率较低。虽然这些结果没有风险调整,很可能反映了治疗选择偏差,他们至少提高了为这类高危人群测试缺血减少方法的可能性.未来的临床试验需要验证出血引起的T2MI的任何治疗策略。
    BACKGROUND: Type ll myocardial infarction (T2MI) is caused by a mismatch between myocardial oxygen supply and demand. One subset of individuals is T2MI caused by acute hemorrhage. Traditional MI treatments including antiplatelets, anticoagulants, and revascularization can worsen bleeding. We aim to report outcomes of T2MI patients due to bleeding, stratified by treatment approach.
    METHODS: The MGB Research Patient Data Registry followed by manual physician adjudication was used to identify individuals with T2MI caused by bleeding between 2009 and 2022. We defined 3 treatment groups: (1) invasively managed, (2) pharmacologic, and (3) conservatively managed Clinical parameters and outcomes for 30-day, mortality, rebleeding, and readmission were abstracted compared between the treatment groups.
    RESULTS: We identified 5,712 individuals coded with acute bleeding, of which 1,017 were coded with T2MI during their admission. After manual physician adjudication, 73 individuals met the criteria for T2MI caused by bleeding. 18 patients were managed invasively, 39 received pharmacologic therapy alone, and 16 were managed conservatively. The invasively managed group experienced lower mortality (P = .021) yet higher readmission (P = .045) than the conservatively managed group. The pharmacologic group also experienced lower mortality (P= .017) yet higher readmission (P = .005) than the conservatively managed group.
    CONCLUSIONS: Individuals with T2MI associated with acute hemorrhage are a high-risk population. Patients treated with standard procedures experienced higher readmission but lower mortality than conservatively managed patients. These results raise the possibility of testing ischemia-reduction approaches for such high-risk populations. Future clinical trials are required to validate treatment strategies for T2MI caused by bleeding.
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  • 文章类型: Journal Article
    创伤性脑损伤(TBI)是全球范围内导致死亡和残疾的主要原因。尽管进行了广泛的研究,迄今为止,大多数试验的单一疗法未能显示出显著的获益.有人认为这是由于TBI的复杂病理生理学,这可能通过治疗干预措施的组合来解决。在这篇文章中,我们回顾了不同药物治疗的组合,非药物干预的组合,以及TBI的联合药物和非药物干预措施。包括临床前和临床研究。虽然在动物模型中发现了有希望的结果,联合治疗的临床试验尚未显示出明显的获益.这可能是由于它们的应用而没有考虑TBI的病理生理学的发展。这种范式的改进可能来自多模式神经监测和多模式成像技术指导的新颖干预措施。以及多靶向非药物和内源性疗法的应用。在临床前和临床研究中还需要女性受试者的更大代表性。
    Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.
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