• 【类风湿关节炎患者中性粒细胞的肌动蛋白聚合与非甾体类抗炎药的治疗有关。】 复制标题 收藏 收藏
    DOI:10.1016/s0009-8981(96)06505-9 复制DOI
    作者列表:De Clerck LS,Mertens AV,De Gendt CM,Bridts CH,Stevens WJ
    BACKGROUND & AIMS: There is evidence that neutrophil functions such as chemotaxis and oxygen radical formation are disturbed in rheumatoid arthritis (RA). Medication might also influence these functions. Cyclic formation and depolymerisation of actin microfilaments is crucial in cell motility, but this phenomenon has not been studied in RA. The aim of this study was to investigate basal and dynamic (formyl-methionyl-leucyl-phenylalanine (fMLP)-induced) neutrophil actin polymerisation in ten RA patients (a) during therapy with non-steroidal anti-inflammatory drugs (NSAIDS) and (b) after stopping NSAIDS> The results were compared with those of ten age-matched controls. Basal F-actin content in RA patients with NSAIDS was significantly lower than in RA patients without NSAIDS and controls35.5 (25.0-49.0), 50.5 (27.0-75.0) and 52.5 (32.0-85.0), respectively. Conversely, upon stimulation with fMLP, the actin polymerisation curve of RA patients with NSAIDS was higher than for RA patients without NSAIDS and controls. These results suggest that, in RA, the effects orf NSAIDS on neutrophil functions might be related to changes in the actin polymerisation-depolymerisation cycle.

    背景与目标: 有证据表明,类风湿关节炎(RA)中性粒细胞功能(如趋化性和氧自由基的形成)受到干扰。药物治疗也可能影响这些功能。肌动蛋白微丝的循环形成和解聚对于细胞运动至关重要,但尚未在RA中研究此现象。这项研究的目的是研究10名RA患者的基础和动态(甲酰基-甲硫基-亮氨酰-苯丙氨酸(fMLP)诱导)嗜中性白细胞肌动蛋白聚合反应(a)在使用非甾体抗炎药(NSAIDS)治疗期间和( b)停止NSAIDS后>将结果与十个年龄匹配的对照组的结果进行比较。 NSAIDS的RA患者的基础F-肌动蛋白含量显着低于非NSAIDS的RA患者和对照组,分别为35.5(25.0-49.0),50.5(27.0-75.0)和52.5(32.0-85.0)。相反,在用fMLP刺激后,患有NSAIDS的RA患者的肌动蛋白聚合曲线高于没有NSAIDS和对照的RA患者。这些结果表明,在RA中,NSAIDS对中性粒细胞功能的影响可能与肌动蛋白聚合-解聚循环的变化有关。

  • 【氟化分子在中枢神经系统中作为药物和显像剂。】 复制标题 收藏 收藏
    DOI:10.2174/156802606777951046 复制DOI
    作者列表:Sun S,Adejare A
    BACKGROUND & AIMS: :The strategic use of fluorine substitution in drug discovery and drug development is well documented. The small size and high electronegativity of fluorine are among properties of this element that lend special advantages. Applications in drugs targeted to the central nervous system (CNS) have been particularly fruitful in addition to favorable properties seen in many peripherally acting drugs. Fluorine substitution can be used to solve problems unique to the CNS, such as blood brain barrier (BBB) penetration. Likewise, use of the positron emitting isotope, (18)F, provides a unique tool for non-invasive imaging and diagnoses in the CNS. In this review, fluorine in CNS drugs and drug discovery are discussed.
    背景与目标: :氟取代在药物发现和药物开发中的战略用途已得到充分证明。氟的小尺寸和高电负性是该元素的特性之一,具有特殊的优势。除了在许多外围作用药物中看到的有利特性外,在针对中枢神经系统(CNS)的药物中的应用也特别富有成果。氟取代可用于解决CNS独有的问题,例如血脑屏障(BBB)渗透。同样,正电子发射同位素(18)F的使用为CNS中的非侵入性成像和诊断提供了独特的工具。在这篇综述中,讨论了中枢神经系统药物中的氟和药物发现。
  • 【准确衡量非法药物的消费,价格和市场的行为和经济方面的潜力。】 复制标题 收藏 收藏
    DOI:10.1016/j.drugalcdep.2006.08.005 复制DOI
    作者列表:Johnson BD,Golub A
    BACKGROUND & AIMS: :There are numerous analytic and methodological limitations to current measures of drug market activity. This paper explores the structure of markets and individual user behavior to provide an integrated understanding of behavioral and economic (and market) aspects of illegal drug use with an aim toward developing improved procedures for measurement. This involves understanding the social processes that structure illegal distribution networks and drug users' interactions with them. These networks are where and how social behaviors, prices, and markets for illegal drugs intersect. Our focus is upon getting an up close measurement of these activities. Building better measures of consumption behaviors necessitates building better rapport with subjects than typically achieved with one-time surveys in order to overcome withholding and underreporting and to get a comprehensive understanding of the processes involved. This can be achieved through repeated interviews and observations of behaviors. This paper also describes analytic advances that could be adopted to direct this inquiry including behavioral templates, and insights into the economic valuation of labor inputs and cash expenditures for various illegal drugs. Additionally, the paper makes recommendations to funding organizations for developing the mechanisms that would support behavioral scientists to weigh specimens and to collect small samples for laboratory analysis-by providing protection from the potential for arrest. The primary focus is upon U.S. markets. The implications for other countries are discussed.
    背景与目标: :目前对药物市场活动的度量存在许多分析和方法学限制。本文探讨了市场结构和个人用户行为,以提供对非法药物使用的行为和经济(及市场)方面的综合理解,旨在开发改进的测量程序。这涉及了解构成非法分销网络和吸毒者与之互动的社会过程。这些网络是非法毒品的社会行为,价格和市场在何处以及如何相交的地方。我们的重点是仔细衡量这些活动。要建立更好的消费行为衡量标准,就必须与受试者建立更好的融洽关系,这要比一次调查更能实现,以克服扣缴和漏报的情况,并对所涉及的过程有一个全面的了解。这可以通过反复采访和观察行为来实现。本文还描述了可用于指导这一询问的分析进展,包括行为模板,以及对各种非法药物的劳动投入和现金支出的经济估值的见解。此外,该论文还向资助组织提出了建议,以开发机制,以支持行为科学家称量样本并收集小样本进行实验室分析,从而提供保护措施以防止被捕。主要重点是美国市场。讨论了对其他国家的影响。
  • 【具有1,3,5-trioxazatriquinane骨架的新型三联体药物的合成及其药理作用。 3:合成具有双(环氧基甲烷)或双(二甲基环氧基甲烷)结构的新型三联体药物(双封端的三联体)。】 复制标题 收藏 收藏
    DOI:10.1016/j.bmcl.2012.10.023 复制DOI
    作者列表:Wada N,Fujii H,Koyano K,Hirayama S,Iwai T,Nemoto T,Nagase H
    BACKGROUND & AIMS: :Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the κ opioid receptor. On the other hand, the N-Me series exhibited selectivities for the μ opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the μ receptor independently of their N-substituents. SYK-385 (19b), one of the μ-selective double-capped triplet drugs, showed the highest selectivity for the μ receptor among the reported μ-selective nonpeptide ligands.
    背景与目标: 合成了具有一个药效团单元和两个环氧亚甲基或二甲基环氧亚甲基结构(分别称为帽或二甲基-帽结构)的新型双封端三联体药物。源自丙酮的关键中间体恶唑啉16能够有效合成双封三胞胎。具有N-环丙基甲基取代基和帽结构的SYK-134(7a)和SYK-135(8a)对κ阿片受体具有选择性。另一方面,N-Me系列对μ阿片受体具有选择性。具有diMe-cap结构的双封端三联体药物优选μ受体,而与它们的N取代基无关。微米选择性双封端三联体药物之一SYK-385(19b)在已报道的微米选择性非肽配体中显示出对微米受体的最高选择性。
  • 【达到胆固醇目标并开具更高价的他汀类药物:在一般实践中的横断面研究。】 复制标题 收藏 收藏
    DOI:10.3399/bjgp12X659286 复制DOI
    作者列表:Fleetcroft R,Schofield P,Duerden M,Ashworth M
    BACKGROUND & AIMS: BACKGROUND:There is conflicting evidence as to whether achievement of cholesterol targets at the population level is dependent on the choice and cost of statin. AIM:To investigate the practice-level relationship between cholesterol quality indicators in patients with heart disease, stroke, and diabetes and prescribing of low-cost statins. DESIGN AND SETTING:Correlations and linear regression modelling of retrospective cross-sectional practice-level data with potential explanatory variables in 7909 (96.4%) general practices in England in 2008-2009. METHOD:Quality indicator data were obtained from the Information Centre and prescribing data from the NHS Business Authority. A 'cholesterol quality indicator' score was constructed by dividing the numbers of patients achieving the target for cholesterol control of ≤5 mmol/l in stroke, diabetes, and heart disease by the numbers on each register. A 'low-cost statin' ratio score was constructed by dividing the numbers of defined daily doses of simvastatin and pravastatin by the total numbers of defined daily doses of statins. RESULTS:Simvastatin accounted for 83.3% (standard deviation [SD] = 15.7%) of low-cost statins prescribed and atorvastatin accounted for 85.7% (SD = 14.8%) of high-cost statins prescribed. The mean cholesterol score was 73.7% (SD = 6.0%). Practices using a higher proportion of the low-cost statins were less successful in achieving cholesterol targets. An increase of 10% in the prescribing of low-cost statins was associated with a decrease of 0.46% in the cholesterol quality indicator score (95% confidence interval = -0.54% to -0.38%, P<0.001). CONCLUSION:Greater use of low-cost statins was associated with a small reduction in cholesterol control.
    背景与目标: 背景:关于在人群水平上实现胆固醇目标是否取决于他汀类药物的选择和成本,有相互矛盾的证据。
    目的:探讨心脏病,中风和糖尿病患者的胆固醇质量指标与廉价他汀类药物处方之间的实践水平关系。
    设计与设置:回顾性横截面实践水平数据的相关性和线性回归模型,该数据具有2008年至2009年英格兰7909例(96.4%)常规实践中的潜在解释变量。
    方法:质量指标数据是从信息中心获得的,处方数据是从NHS商业管理局获得的。通过将实现卒中,糖尿病和心脏病中胆固醇控制目标≤5mmol / l的患者人数除以每个登记册上的人数,来构建“胆固醇质量指标”评分。通过将辛伐他汀和普伐他汀的每日定义剂量数除以他汀类药物的每日定义总数,可以构建“低成本他汀类药物”比率评分。
    结果:辛伐他汀占处方中低成本他汀类药物的83.3%(标准差[SD] = 15.7%),阿托伐他汀占处方中低成本他汀类药物的85.7%(SD = 14.8%)。平均胆固醇得分为73.7%(SD = 6.0%)。使用较高比例的低成本他汀类药物的做法在实现胆固醇目标方面不太成功。低成本他汀类药物处方的增加10%与胆固醇质量指标评分的0.46%的降低相关(95%置信区间= -0.54%至-0.38%,P <0.001)。
    结论:大量使用低成本他汀类药物与降低胆固醇控制量有关。
  • 【巴西圣保罗腹膜透析和血液透析治疗终末期肾脏疾病的成本评估。】 复制标题 收藏 收藏
    DOI:10.3747/pdi.2011.00138 复制DOI
    作者列表:de Abreu MM,Walker DR,Sesso RC,Ferraz MB
    BACKGROUND & AIMS: OBJECTIVE:Conventional hemodialysis (HD) predominates over peritoneal dialysis (PD) around the world. Prospective and comparative studies comparing the costs of these modalities are scarce. In the present prospective assessment, we describe the resources used and total patient costs for both HD and PD. ♢ METHODOLOGY:We assessed 249 patients on HD and 228 on PD. All patients were 18 years of age or older and on stable dialysis. The information was collected at three points over 1 year, using standard questionnaires. The sources for costs were the Brazilian public and private health care systems. Societal perspective was considered. ♢ STATISTICAL ANALYSIS:Core trends and dispersions were measured. Regression models assessed the impact of modality on the average total cost per patient per year. ♢ RESULTS:Of the 249 HD patients and 228 PD dialysis patients, 189 (74%) and 160 (70%) respectively completed follow-up. The mean age for women was 55.8 years; for men, it was 59.8 years (p = 0.001). The average total cost per patient-year was US$28 570 for HD and US$27 158 for PD. By category, the costs consisted of direct medical-hospital costs (82.3% for HD, 86.5% for PD), direct nonmedical costs (5.3% for HD, 3.7% for PD), and indirect costs (12.4% for HD, 9.8% for PD). Overall costs were less for PD patients than for their HD counterparts (p = 0.025). ♢ CONCLUSIONS:Maintenance dialysis represented the most important source of costs for both modalities; loss of productivity incurred significant costs. Future studies should contemplate the social consequences arising from each modality.
    背景与目标: 目的:常规血液透析(HD)优于全世界的腹膜透析(PD)。缺乏比较这些方式成本的前瞻性和比较性研究。在当前的前瞻性评估中,我们描述了HD和PD的资源使用和患者总费用。 ♢
    方法:我们评估了249例HD患者和228例PD患者。所有患者年龄均在18岁或以上,并且透析稳定。使用标准调查表在1年中的3个时间点收集了该信息。费用来源是巴西的公共和私人卫生保健系统。考虑了社会视角。 ♢
    统计分析:测量核心趋势和离散度。回归模型评估了模态对每位患者每年平均总费用的影响。 ♢
    结果:在249例HD患者和228例PD透析患者中​​,分别完成了189例(74%)和160例(70%)随访。女性的平均年龄为55.8岁;男性为59.8岁(p = 0.001)。 HD患者每位患者每年的平均总费用为28 570美元,PD患者为27 158美元。按类别,这些费用包括直接医疗-医院费用(HD的82.3%,PD的86.5%),直接非医疗费用(HD的5.3%,PD的3.7%)和间接费用(HD的12.4%,9.8%)对于PD)。 PD患者的总费用比HD患者低(p = 0.025)。 ♢
    结论:维持性透析是这两种方式最重要的费用来源。生产力的损失导致了巨大的成本。未来的研究应考虑每种方式产生的社会后果。
  • 【阿片类药物,抗癫痫药和抗胆碱能药以及65岁及65岁以上患者骨折的风险:一项基于人群的前瞻性研究。】 复制标题 收藏 收藏
    DOI:10.1093/ageing/afs178 复制DOI
    作者列表:Nurminen J,Puustinen J,Piirtola M,Vahlberg T,Lyles A,Kivelä SL
    BACKGROUND & AIMS: BACKGROUND:in men, the concomitant use of two or more benzodiazepines or two or more antipsychotics is associated with an increased risk of fracture(s). Potential associations between the concomitant use of drugs with central nervous system effects and fracture risk have not been studied. OBJECTIVE:the purpose was to describe the gender-specific risk of fractures in a population aged 65 years or over associated with the use of an opioid, antiepileptic or anticholinergic drug individually; or, their concomitant use with each other; or the concomitant use of one of these with a psychotropic drug. METHODS:this study was part of a prospective, population-based study performed in Lieto, Finland. Information about fractures in 1,177 subjects (482 men and 695 women) was confirmed with radiology reports. RESULTS:at 3 years of follow-up, the concomitant use of an opioid with an antipsychotic was associated with an increased risk of fractures in men. During the 6-year follow-up, the concomitant use of an opioid with a benzodiazepine was also related to the risk of fractures for males. No significant associations were found for females. CONCLUSION:the concomitant use of an opioid with an antipsychotic, or with a benzodiazepine may increase the risk of fractures in men aged 65 years and older.
    背景与目标: 背景:在男性中,同时使用两种或多种苯二氮杂类或两种或多种抗精神病药会增加骨折的风险。尚未研究同时使用药物与中枢神经系统作用与骨折风险之间的潜在关联。
    目的:目的是描述在65岁或65岁以上人群中因单独使用阿片类药物,抗癫痫药或抗胆碱能药物引起的骨折的性别特异性风险;或同时使用;或或将其中一种与精神药物同时使用。
    方法:本研究是在芬兰利托进行的一项基于人群的前瞻性研究的一部分。放射学报告证实了有关1,177名受试者(482名男性和695名女性)骨折的信息。
    结果:在随访的3年中,同时使用阿片类药物和抗精神病药会增加男性骨折的风险。在6年的随访期间,阿片类药物与苯二氮卓类药物同时使用也与男性骨折风险有关。没有发现与女性的显着关联。
    结论:阿片类药物与抗精神病药或苯二氮卓类药物同时使用可能会增加65岁以上男性骨折的风险。
  • 【比较24种抗菌药物对产气荚膜梭菌的体外杀菌活性。】 复制标题 收藏 收藏
    DOI:10.1159/000238758 复制DOI
    作者列表:Traub WH
    BACKGROUND & AIMS: :Twenty-four antimicrobial drugs were examined for rapidity of onset and magnitude of bactericidal activity against selected strains of Clostridium perfringens. Ceftriaxone, imipenem, metronidazole, mezlocillin, penicillin G, piperacillin, and teicoplanin reduced colony counts by at least 3 log10 units within 2-4 h after exposure. Clindamycin, fluoroquinolones, josamycin, and tetracycline caused delayed kill (greater than or equal to 99.9% reduction of viable counts at 4-22 h after exposure). Chloramphenicol and rifampin lacked bactericidal activity against 2 of 4 strains, whereas erythromycin, fusidic acid, and fosfomycin (with added glucose-6-phosphate) were merely inhibitory for all 4 strains. Imipenem and penicillin G were combined with 9 and 12 antimicrobial drugs, respectively. Essentially all drug combinations yielded indifferent effects; only penicillin G plus doxycycline resulted in an antagonistic effect against C. perfringens.
    背景与目标: :检查了二十四种抗微生物药物对产气荚膜梭状芽孢杆菌某些菌株的起效速度和杀菌活性的大小。头孢曲松,亚胺培南,甲硝唑,美洛西林,青霉素G,哌拉西林和替考拉宁在暴露后2-4小时内可将菌落数减少至少3 log10个单位。克林霉素,氟喹诺酮,乔沙霉素和四环素引起延迟杀灭(暴露后4-22 h内存活计数减少等于或大于99.9%)。氯霉素和利福平对4个菌株中的2个缺乏杀菌活性,而红霉素,夫西地酸和磷霉素(添加了6-磷酸葡萄糖)仅对全部4个菌株具有抑制作用。亚胺培南和青霉素G分别与9种和12种抗菌药物合用。基本上所有药物组合均产生无关紧要的作用。仅青霉素G加强力霉素可导致对产气荚膜梭菌的拮抗作用。
  • 【时间杀伤动力学测定作为评估抗结核药物活性的临床前建模框架的一部分,具有重要意义。】 复制标题 收藏 收藏
    DOI:10.1016/j.tube.2017.04.010 复制DOI
    作者列表:Bax HI,Bakker-Woudenberg IAJM,de Vogel CP,van der Meijden A,Verbon A,de Steenwinkel JEM
    BACKGROUND & AIMS: :Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.
    背景与目标: :迫切需要新的结核病治疗策略。目前已有许多评估抗结核药物活性的临床前模型,但尚不清楚哪种模型组合最能预测临床治疗效果。这项研究的目的是确定我们在体外时间杀伤动力学测定中作为评估抗结核药物活性的预测性临床前建模框架的一项资产的作用。在暴露于结核分枝杆菌北京基因型菌株的单药或双重,三重和四重组合暴露期间,确定了六种抗结核药物的浓度和时间依赖性分枝杆菌杀伤能力,并评估了耐药性。链霉素,利福平和异烟肼对快速增长的结核分枝杆菌最为活跃。异烟肼与利福平或大剂量乙胺丁醇是唯一的协同药物组合。在异烟肼中添加利福平或链霉素可防止异烟肼耐药。在体外排名显示,对于某些但不是全部抗结核药物,结核病患者的早期杀菌活性与之一致。时间杀灭动力学测定法提供了有关药物暴露初期抗结核药物分枝杆菌杀灭动力学的重要信息。因此,该测定是临床前建模框架的重要组成部分。
  • 【定性研究:俄罗斯注射毒品人群获得艾滋病治疗的系统性障碍。】 复制标题 收藏 收藏
    DOI:10.1093/heapol/czs107 复制DOI
    作者列表:Sarang A,Rhodes T,Sheon N
    BACKGROUND & AIMS: :Achieving 'universal access' to antiretroviral HIV treatment (ART) in lower income and transitional settings is a global target. Yet, access to ART is shaped by local social condition and is by no means universal. Qualitative studies are ideally suited to describing how access to ART is socially situated. We explored systemic barriers to accessing ART among people who inject drugs (PWID) in a Russian city (Ekaterinburg) with a large burden of HIV treatment demand. We undertook 42 in-depth qualitative interviews with people living with HIV with current or recent experience of injecting drug use. Accounts were analysed thematically, and supplemented here with an illustrative case study. Three core themes were identified: 'labyrinthine bureaucracy' governing access to ART; a 'system Catch 22' created by an expectation that access to ART was conditional upon treated drug use in a setting of limited drug treatment opportunity; and 'system verticalization', where a lack of integration across HIV, tuberculosis (TB) and drug treatment compromised access to ART. Taken together, we find that systemic factors play a key role in shaping access to ART with the potential adverse effects of reproducing treatment initiation delay and disengagement from treatment. We argue that meso-level systemic factors affecting access to ART for PWID interact with wider macro-level structural forces, including those related to drug treatment policy and the social marginalization of PWID. We note the urgent need for systemic and structural changes to improve access to ART for PWID in this setting, including to simplify bureaucratic procedures, foster integrated HIV, TB and drug treatment services, and advocate for drug treatment policy reform.
    背景与目标: :在较低的收入和过渡环境中实现对抗逆转录病毒HIV治疗(ART)的“普遍获得”是全球目标。然而,获得抗逆转录病毒药物的途径取决于当地的社会状况,绝不是普遍的。定性研究非常适合描述获得抗逆转录病毒疗法在社会上的位置。我们探索了在俄罗斯城市(叶卡捷琳堡)注射艾滋病毒(HIV)需求量很大的注射毒品者(PWID)中获取ART的系统性障碍。我们对具有当前或最近注射吸毒经验的艾滋病毒感染者进行了42次深入的定性访谈。对帐目进行了主题分析,并在此处补充了说明性的案例研究。确定了三个核心主题:控制获取抗逆转录病毒药物的“迷宫式官僚主义”;期望在有限的药物治疗机会的情况下获得抗病毒药物的条件是要获得抗逆转录病毒药物而创建的“系统捕​​获22”;以及“系统垂直化”,即艾滋病毒,结核病和药物治疗之间缺乏整合,影响了抗逆转录病毒疗法的获取。综上所述,我们发现系统性因素在影响获得ART的过程中起着关键作用,并具有再生治疗起始延迟和脱离治疗的潜在不利影响。我们认为影响PWID获得抗逆转录病毒疗法的中观系统性因素与更广泛的宏观结构性因素相互作用,包括那些与毒品治疗政策和PWID的社会边缘化有关的因素。我们注意到迫切需要进行系统和结构上的改革,以改善在这种情况下PWID获得抗病毒治疗的途径,包括简化官僚程序,促进艾滋病毒,结核病和药物治疗的综合服务,以及倡导药物治疗政策的改革。
  • 【在管理型医疗机构的初级医疗机构中,使用3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂治疗高胆固醇血症的初始疗法的成本效益。】 复制标题 收藏 收藏
    DOI:10.1016/s0149-2918(97)80142-7 复制DOI
    作者列表:Spearman ME,Summers K,Moore V,Jacqmin R,Smith G,Groshen S
    BACKGROUND & AIMS: From January 1994 through May 1995, Prudential HealthCare-North Texas prospectively studied 299 member patients diagnosed with hypercholesterolemia for whom pharmacotherapy with one of four 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as statins, was prescribed. The purpose of this study was to measure the relative cost-effectiveness (CE) of these drugs in a real-world setting. This study provides information to assist decision makers in managed-care organizations (MCO) in making formulary selections. The study used a prospective, randomized, balanced cohort design, examining patients who had been prescribed initial therapy with a statin drug as monotherapy. Costs (direct medical and indirect costs) and effectiveness (percent reduction in low-density lipoprotein cholesterol levels) were based on approximately the first 6 months of initial therapy. Both the MCO and patient perspectives were considered. In the base case, mean CE ratios were significantly lower for fluvastatin compared with lovastatin, pravastatin, and simvastatin from both the managed-care perspective and the patient perspective. Sensitivity analysis did not alter the CE conclusions, even under conditions of varying cost structures. Although differences were found in the effectiveness of lovastatin, pravastatin, and simvastatin measured in this study versus efficacy measured for these drugs in controlled clinical trials, sensitivity analysis suggests that these differences alone do not determine the superior CE of fluvastatin. Finally, this study supports the idea that well-designed formularies should consider drug CE (based on safety, effectiveness, and cost) and that integration of the pharmacy benefit management with other medical management is essential. These results provide evidence that fluvastatin may represent a more cost-effective formulary choice among statin products used for initial monotherapy of hypercholesterolemia.

    背景与目标: 从1994年1月到1995年5月,Prudential HealthCare-North Texas对299名被诊断患有高胆固醇血症的成员患者进行了前瞻性研究,他们开了用四种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂(也称为他汀类药物)之一进行药物治疗的处方。这项研究的目的是在现实环境中测量这些药物的相对成本效益(CE)。这项研究提供信息,以帮助管理服务组织(MCO)的决策者选择配方。该研究采用前瞻性,随机,均衡的队列设计,检查了已开始接受他汀类药物作为单一疗法的初始治疗的患者。成本(直接医疗和间接成本)和有效性(低密度脂蛋白胆固醇水平降低的百分比)基于初始治疗的前6个月。同时考虑了MCO和患者的观点。在基本病例中,从管理治疗和患者角度看,氟伐他汀的平均CE比率均比洛伐他汀,普伐他汀和辛伐他汀低。即使在成本结构变化的情况下,敏感性分析也不会改变CE的结论。尽管在这项研究中发现洛伐他汀,普伐他汀和辛伐他汀的疗效与对照临床试验中这些药物的疗效存在差异,但敏感性分析表明,仅凭这些差异并不能确定氟伐他汀的优异CE。最后,本研究支持以下观点:精心设计的配方应考虑药物CE(基于安全性,有效性和成本),并且将药房收益管理与其他医疗管理相结合是必不可少的。这些结果表明,氟伐他汀可能代表一种用于高胆固醇血症初始单一疗法的他汀类产品中更具成本效益的配方选择。

  • 12 A cost analysis of a tele-oncology practice. 复制标题 收藏 收藏

    【远程肿瘤学实践的成本分析。】 复制标题 收藏 收藏
    DOI:10.1258/1357633971930850 复制DOI
    作者列表:Doolittle GC,Harmon A,Williams A,Allen A,Boysen CD,Wittman C,Mair F,Carlson E
    BACKGROUND & AIMS: Costs were monitored for three different types of oncology practicea telemedicine clinic and a fly-in outreach clinic, both held in rural areas, and a traditional clinic held in a city hospital. Total expenses were calculated over the year May 1995 to April 1996. The average cost per telemedicine visit was $812. The average cost per outreach clinic visit was $897. Flying in oncology support for this practice was therefore about 10% more costly than telemedicine. While the outreach cost may have been inappropriately high due to a slow start-up phase, it was still less expensive during this period to be seen via telemedicine. For comparison, the average cost per traditional oncology clinic visit was $149. However, this figure does not take into account the costs of access to a city-based service by rural patients.

    背景与目标: 监视了三种不同类型的肿瘤科诊所,远程医疗诊所和飞入式外展诊所(均在农村地区,以及传统诊所在城市医院中)的成本。计算的总费用是从1995年5月至1996年4月。每次远程医疗就诊的平均费用为812美元。每次门诊就诊的平均费用为897美元。因此,为这种做法提供肿瘤支持的费用比远程医疗的费用高出约10%。尽管由于启动阶段缓慢,外展费用可能过高,但在此期间通过远程医疗可以看到费用仍然较低。相比之下,传统肿瘤诊所的平均每次访问费用为149美元。但是,该数字未考虑到农村患者获得城市服务的成本。

  • 【经皮气管切开术:一种替代标准开放式气管切开术的经济有效的选择。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:McHenry CR,Raeburn CD,Lange RL,Priebe PP
    BACKGROUND & AIMS: Percutaneous tracheostomy was initiated as an alternative to open tracheostomy at our institution in December 1993. To assess safety, operative time, and cost, a comparative analysis of percutaneous and open tracheostomies was performed. A retrospective evaluation of all patients who underwent percutaneous tracheostomy (P) from December 1993 to March 1996 was completed. Patients were evaluated for indications for tracheostomy, length of operation, morbidity, and cost. The results were compared with patients who underwent open tracheostomy (O) during the 12 months prior to introduction of the percutaneous technique. Tracheostomy was performed percutaneously in 74 patients and by a standard open technique in 109 patients. Indications for tracheostomy includedchronic ventilator dependence (P, 49 vs O, 58); airway protection (P, 19 vs O, 42); laryngeal dysfunction (P, 2 vs O, 7); and facial trauma (P 6 vs O, 2). The length of operation was 21 +/- 6 minutes and 46 +/- 21 minutes for percutaneous and open tracheostomy, respectively (P < 0.05). Perioperative morbidity occurred in 2 patients (3%) following percutaneous tracheostomy compared to 10 patients (9%) following open tracheostomy (P > 0.05). The mean operating room costs per patient were $1093 and $1370 for percutaneous and open tracheostomy, respectively. Percutaneous tracheostomy is a safe procedure that can be performed in less time and at a lower cost than standard open tracheostomy.

    背景与目标: 我们的机构于1993年12月开始采用经皮气管切开术代替开放式气管切开术。为评估安全性,手术时间和成本,对经皮和开放式气管切开术进行了比较分析。对1993年12月至1996年3月所有行经皮气管切开术(P)的患者进行了回顾性评估。对患者进行气管切开术,手术时间,发病率和费用的指征进行评估。将结果与在引入经皮技术之前的12个月内接受开放气管切开术(O)的患者进行比较。 74例患者经皮气管切开术,109例患者采用标准开放技术进行气管切开术。气管切开术的适应症包括慢性呼吸机依赖性(P,49 vs O,58);气道保护(P,19 vs O,42);喉功能不全(P,2 vs O,7);和面部创伤(P 6 vs O,2)。对于经皮气管切开术和开放式气管切开术,手术时间分别为21/6分钟和46 / 2-21分钟(P <0.05)。经皮气管切开术后2例(3%)发生围手术期发病,相比之下,开放气管切开术后10例(9%)发生围手术期发病(P> 0.05)。经皮气管切开术和开放式气管切开术每名患者的平均手术室费用分别为$ 1093和$ 1370。经皮气管切开术是一种安全的方法,与标准的开放式气管切开术相比,可在更短的时间内完成,且成本更低。

  • 【疾病改良抗风湿药与类风湿关节炎患者的心血管疾病风险降低相关:一项病例对照研究。】 复制标题 收藏 收藏
    DOI:10.1186/ar2045 复制DOI
    作者列表:van Halm VP,Nurmohamed MT,Twisk JW,Dijkmans BA,Voskuyl AE
    BACKGROUND & AIMS: :Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.
    背景与目标: 类风湿关节炎(RA)的特征在于炎症和心血管疾病(CVD)的风险增加。这项研究调查了CVD与RA中使用传统疾病缓解风湿药(DMARDs)之间的可能联系。使用病例对照设计,研究了613名RA患者(5,649患者-年),其中72例患有CVD,541例没有CVD。从RA诊断到首次心血管事件或随访期结束,评估了RA,CVD和药物治疗的数据。数据集根据DMARD使用进行了分类:柳氮磺胺吡啶(SSZ),羟氯喹(HCQ)或甲氨蝶呤(MTX)。每个DMARD组均计算出经年龄,性别,吸烟和RA持续时间校正后的CVD的赔率(OR)。从未使用过SSZ,HCQ或MTX的患者被用作参考组。 MTX治疗可显着降低CVD风险,OR为(95%CI):“仅MTX”,0.16(0.04至0.66); ``MTX和SSZ曾经'',0.20(0.08至0.51);和“ MTX,SSZ和HCQ”,0.20(0.08至0.54)。在对类风湿因子和糜烂的存在进行了进一步校正后,风险降低仍然很显着。在校正了高血压,糖尿病和高胆固醇血症后,“曾经有过MTX或SSZ”以及“曾经有过MTX,SSZ和HCQ”显示出可显着降低CVD风险。类风湿因子阳性和糜烂均增加了CVD的风险,OR分别为2.04(1.02至4.07)和2.36(0.92至6.08)。与从未使用过SSZ,HCQ或MTX的RA患者相比,MTX和较小程度的SSZ与较低的CVD风险相关。我们假设使用DMARD,尤其是使用MTX可以有效抑制炎症,从而减少动脉粥样硬化的发展,进而减少临床上明显的CVD的发生。
  • 【纳米医学:聚乙二醇结合蛋白和药物的临床应用。】 复制标题 收藏 收藏
    DOI:10.2165/00003088-200645100-00002 复制DOI
    作者列表:Parveen S,Sahoo SK
    BACKGROUND & AIMS: :The intricate problems associated with the delivery and various unnecessary in vivo transitions of proteins and drugs needs to be tackled soon to be able to exploit the myriad of putative therapeutics created by the biotechnology boom. Nanomedicine is one of the most promising applications of nanotechnology in the field of medicine. It has been defined as the monitoring, repair, construction and control of human biological systems at the molecular level using engineered nanodevices and nanostructures. These nanostructured medicines will eventually turn the world of drug delivery upside down. PEGylation (i.e. the attachment of polyethylene glycol to proteins and drugs) is an upcoming methodology for drug development and it has the potential to revolutionise medicine by drastically improving the pharmacokinetic and pharmacodynamic properties of the administered drug. This article provides a total strategy for improving the therapeutic efficacy of various biotechnological products in drug delivery. This article also presents an extensive analysis of most of the PEGylated proteins, peptides and drugs, together with extensive clinical data. Nanomedicines and PEGylation, the latest offshoots of nanotechnology will definitely pave a way in the field of drug delivery where targeted delivery, formulation, in vivo stability and retention are the major challenges.
    背景与目标: :与蛋白质和药物的递送以及各种不必要的体内过渡相关的复杂问题需要尽快解决,以便能够利用由生物技术繁荣发展而来的无数推定疗法。纳米医学是纳米技术在医学领域最有前途的应用之一。它已被定义为使用工程化的纳米器件和纳米结构在分子水平上监测,修复,构建和控制人类生物系统。这些纳米结构药物最终将颠覆药物输送的世界。聚乙二醇化(即聚乙二醇与蛋白质和药物的连接)是药物开发的一种新方法,它具有通过彻底改善所给药药物的药代动力学和药效学性质来革新药物的潜力。本文提供了用于提高各种生物技术产品在药物输送中的治疗功效的总体策略。本文还对大多数PEG化的蛋白质,肽和药物进行了广泛的分析,并提供了广泛的临床数据。纳米药物和聚乙二醇化是纳米技术的最新分支,无疑将在药物递送领域铺平道路,在这些领域中,靶向递送,制剂,体内稳定性和保留性是主要挑战。

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