Profile of etodolac: Pharmacokinetic evaluation in special populations

The pharmacokinetics of etodolac, a new nonsteroidal anti-inflammatory drug, were compared in normal subjects, in patients with renal and hepatic disease, and in elderly patients. In 28 normal subjects, orally administered etodolac was rapidly absorbed. By 1.2 hours after ingestion of a 200 mg dose, the maximum serum concentration (C_max) averaged 15.9 g/ml, with more than 99% of the drug bound to serum protein. Clearance was primarily hepatic. The mean half-life (t_1/2) was 6 to 7 hours. There were no apparent differences in C_max, the time at which C_max occurred (t_max), area under the serum concentration/time curve (AUC_0–24), or t_1/2 between groups of young men (n=20), elderly men (n=24), and elderly men with osteoarthritis (n=20), after a single dose of etodolac or after 7 days of subchronic administration. Moreover there was no evidence of accumulation. There also were no differences in C_max, t_max, AUC_0–24 or t_1/2 between groups of normal subjects (n=10) and patients with mild-to-moderate renal impairment (n=10). Patients with end-stage renal disease who were receiving chronic hemodialysis had the same mean serum concentration of free drug as normal subjects, even though mean serum levels of protein-bound etodolac were slightly lower than those in the normal subjects. The only significant (p<0.05) difference between patients with stable hepatic cirrhosis and normal, age-matched subjects was a slightly shorter t_max in the cirrhotic subjects (1.1 vs. 1.4 hours). These findings suggest that no alteration of etodolac dosage would be necessary in these high-risk groups.Die pharmakokinetischen Parameter von Etodolac, einem neuen, nichtsteroidalen entzündungshemmenden Therapeutikum, wurden an gesunden Probanden, an Patienten mit Leber- und Nierenleiden und an Älteren Patienten untersucht. Orale Etodolac Gaben wurden von den 28 gesunden Probanden schnell resorbiert. Nach einer einmaligen Dosis von 200 mg betrug nach 1,2 Stunden die durchschnittliche maximum Serumkonzentration (C_max) 15,9 g/ml, wobei mehr als 99% des Medikaments an das Serumprotein gebunden war. Clearance erfolgte hauptsÄchlich über die Niere. Die mittlere Eliminationshalbwertszeit (t_1/2) variierte zwischen 6 und 7 Stunden. In Bezug auf C_max, dem Zeitpunkt an dem C_max auftrat (t_max), FlÄche unter der Serumkonzentrationskurve (AUC_0–24) und t_1/2 wurden keine offensichtliche Unterschiede festgestellt zwischen der Gruppe junger MÄnnern (n=20), Älterer MÄnner (n=24) und Älteren MÄnnern mit Osteoarthritis (n=20) nach einer einmaligen Etodolac-Gabe oder nach 7 tÄgiger subchronischer Dosierung. Es bestanden auch keine Anzeichen einer Kumulation. ZusÄtzlich wurden auch keine Unterschiede in C_max, t_max, AUC_0–24 und t_1/2 zwischen der Gruppe gesunder Probanden (n=10) und der Patientengruppe mit leichten bis mÄigen NierenfunktionsschÄden (n=10) beobachtet. Im mittleren Serumspiegel des nicht gebundenen Medikaments in Patienten im Endstadium der Nierenerkrankung, die mit Langzeitdialyse behandelt wurden, konnte kein Unterschied im Vergleich zu gesunden Probanden festgestellt werden, obwohl der mittlere Serumspiegel für proteingebundenes Etodolac in den Patienten etwas niedriger lag als in gesunden Probanden. Der einzige signifikante Unterschied (p<0.05) zwischen Patienten mit stabilisierter Leberzirrhose und gleichaltrigen Probanden war eine etwas kürzere t_max in den Zirrhosepatienten (1,1 versus 1,4 Stunden). Diese Ergebnisse beweisen, dakeine Notwendigkeit vorliegt, die Etodolac-Dosierung für diese Risikogruppen zu modifizieren.Se comparó la farmacocinética de etodolac, un fármaco antiinflamatorio no esteroide nuevo, en sujetos normales y en pacientes con enfermedad renal y hepática y en pacientes ancianos. Etodolac administrado por vía oral a 28 sujetos normales fue rápidamente absorbido. A las 1,2 horas siguientes a la administración de una dosis de 200 mg, la concentración sérica máxima (C_max) alcanzó un promedio de 15,9 g/ml, con más del 99% del fármaco unido a la proteína sérica. La eliminación fue principalmente hepática. La vida media (t_1/2) fue 6–7 horas. No se observaron diferencias en C_max, en el tiempo en el cual se produjo C_max, en el área bajo la curva de concentración sérica/tiempo (ABC_0–24) ni en t_1/2 entre los grupos de hombres jóvenes (n=20), de hombres ancianos (n=24) y de hombres ancianos con osteoartritis (n=20), después de la administración de una dosis Única o después de 7 días de administración subcrónica de etodolac. Además, no hubo evidencia de acumulación. Tampoco se registraron diferencias en C_max, t_max, ABC_0–24 o t_1/2 entre los grupos de sujetos normales (n=10) y los pacientes con insuficiencia renal leve a moderada (n=10). Los pacientes con nefropatía terminal que estaban recibiendo hemodiálisis crónica tuvieron las mismas concentraciones séricas medias de fármaco libre que los sujetos normales, a pesar de que las concentraciones séricas medias de etodolac unido a proteina fueron levemente inferiores que en los sujetos normales. La Única diferencia significativa (p<0,05) entre los pacientes con cirrosis hepática estable y los sujetos normales de edad similar fue t_max ligeramente inferior en los sujetos cirróticos (1,1 vs 1,4 horas). Estos hallazgos sugieren que no es necesario modificar la dosis de etodolac para su uso en estos grupos de alto riesgo.La pharmacocinétique de l'étodolac, un anti-inflammatoire non stéroÏdien, a été comparé chez des sujets normaux et des patients présentant des affections rénales et hépatiques, et chez des malades âgés. Chez 28 sujets normaux, la résorption d'étodolac administré par voie orale a été rapide. Dès 1,2 heure suivant l'absorption d'une dose de 200 mg, la moyenne des concentration sériques maximales (C_max) était de 15,9 g/ml, plus de 99% pour cent du médicament étant liés aux protéines sériques. La clairance se fait surtout par voie hépatique. La demivie moyenne (t_1/2) était de 6 à 7 heures. Il n'y avait aucune différence apparente en ce qui concerne C_max, le temps d'apparition de C_max (t_max), l'aire sous la courbe concentration sérique/temps (AUC_0–24) ni t_1/2 entre les groupes d'hommes jeunes (n=20), d'hommes âgés (n=24), et d'hommes âgés atteints d'arthrose (n=20) à la suite d'une dose unique d'étodolac ou après 7 jours d'administration subchronique. De plus, aucune accumulation n'a été constatée. D'autre part, aucune différence de C_max, t_max, AUC_0–24 ni t_1/2 n'a été notée entre les groupes de sujets normaux (n=10) et de malades présentent des altérations rénales légères ou modérées (n=10). Les malades en insuffisance rénale terminale soumis à l'hémodialyse chronique ont présenté une concentration sérique moyenne de médicament libre analogue à celle des sujets normaux, mais la moyenne des taux sériques d'étodolac lié aux protéines était légèrement inférieure à celle observée chez les sujets normaux. La seule différence significative (p<0.05) entre les malades présentant une cirrhose hépatique stable et des sujets normaux appariés quant à l'âge était représentée par un t_max légèrement plus court chez les cirrhotiques (1,1 contre 1,4 heure). Ces données permettent de penser qu'aucune modification posologique de l'étodolac ne serait nécessaire pour ces groupes à haut risque.La farmacocinetica dell'etodolac, un nuovo farmaco anti-infiammatorio non steroidale è stata messa a confronto in gruppi normali, in pazienti affetti da malattia rénale ed epatica ed in pazienti anziani. In 28 soggetti normali l'etodolac somministrato oralmente è stato rapidamente assorbito. Dopo 1.2 ore dall'ingestione di una dose di 200 mg la massima concentrazione di siero (Cmax) presentava un valore medio di 15,9 mg/ml, con più del 99% del farmaco legato alla proteina del siero. La clearance era soprattutto a livello epatico. L'emivita media (t1/2) era di 6–7 ore. Non vi sono state evidenti differenze medie nei valori di concentrazione massima (Cmax), tempo (Tmax) al quale si aveva la Cmax, nella curva dell'area sotto concentrazione di siero/tempo (AUCo-24) oppure nel valore dell'emivita media (t1/2) tra gruppi di uomini giovani (n=20), uomini anziani (n=24) e anziani con osteoartrite (n=20), dopo una dose singola di etodolac o dopo 7 giorni di somministrazione subcronica. Inoltre non vi sono stati segni di accumulo. Per di più non vi sono state differenze nei valori di Cmax, tmax, AUCo-24 o t1/2 tra gruppi di soggetti normali (n=10) e pazienti con alterazioni renali da leggere a moderate (n=10). I pazienti con malattia renale all'ultimo stadio che ricevevano emodialisi cronica presentavano la stessa concentrazione media di siero di farmaco libero dei soggetti normali, anche se i livelli medi di siero di etodolac legato alle proteine erano leggermente inferiori a quelli di soggetti normali. L'unica differenza significativa (p<0.05) tra pazienti con cirrosi epatica stabile e soggetti normali della stessa età era nei tmax leggermente più brevi nei soggetti cirrotici (1.1. contro 1.4 ore). Questi risultati suggeriscono che nessuna alterazione del dosaggio di etodolac sarebbe necessaria in questi gruppi ad alto rischio.     

Collaboration--a new IT-service in the next generation of regional health care networks

During the past 10–15 years, Regional Health Care Networks (RHCN) have been established in many regions throughout the world. RHCN build on well-known techniques, methodologies and appropriate standards. Most of the European Countries today have set up IT strategic plans that focus on the establishment of RHCN. The benefits of having access to all relevant information are tremendous and contribute to cost-effective and coherent health services. By the rapid spread and use of Internet, technology has made it possible to interconnect all kinds of applications. In 2000, the most experienced regions in Europe joined PICNIC, a European project to develop the Next Generation Regional Health Care Networks and to support their new ways of providing health and social care. The previous generation of Regional Health Care Networks supported the interconnection of applications by transfer of messages. Messaging is an effective means of integration for isolated high-specialised systems that only need to exchange data. This service will continue to be one of the most important services in the future health care networks. However, tighter coupling may be desirable in some instances to avoid replicating the same functionality in several applications. In other words, certain services can be common and used by a number of applications instead of building that service inside each application. These common services are called middleware services. In PICNIC (http://www.medcom.dk/picnic), a new middleware Collaboration IT service has been identified and developed. This service allows the end users to perform real-time clinical collaboration, with exchange of text, structured data, voice and images across the limits of a single region. A clinical collaboration is associated with the shared clinical context to provide a record of relevant clinical information and facilitates synchronous as well as asynchronous collaboration. This new IT service builds on the increasing popularity of instance messaging and presence systems that facilitate smooth transition between synchronous and asynchronous interaction. The new Collaboration IT service is expected to have a strong impact on the practice of health care in the next generation of Regional Health Care Networks.     

Papovavirus detection by electron microscopy in the brain of an elderly patient without overt progressive multifocal leukoencephalopathy

Virions resembling papovavirus were demonstrated in glial cells in the brain of an aged patient without overt progressive multifocal leukoencephalopathy. The patient was not in a severely immunocompromised state. On histological examination, only a few tiny incomplete necrotic foci were found in the subcortical area. These foci were widely dispersed. Rare, swollen oligodendroglial cells and astrocytes in which papovavirus capsid protein (VP-1) was demonstrated immunohistochemically were present around the foci. The two typical types of virus particles i.e. 35 to 40 nm round particles and elongated particles, were observed in the nuclei of the swollen glial cells. The latter were in the minority. Distinct crystals were also found in the nuclei. The centre-to-centre distance of the particles in the crystals, about 40 nm, and the electron-opaque spots of the round-shaped virions and of the elongated particles, were indicative of structural subunits of papovavirus capsids. This case provides further evidence that papovavirus, possibly JC virus, may be reactivated in the brains of aged patients who are not in an immunocompromised state.     

腹膜透析治疗老年慢性肾功能衰竭的临床分析

目的 分析持续性腹膜透析(PD)治疗老年慢性肾功能衰竭(CRF)患者的临床效果,探讨PD在老年CRF患者中的应用经验.方法 回顾性分析89例老年CRF患者接受PD(简称老年PD组)治疗后的临床表现和生化指标、主要并发症、存活率、死亡原因等,并与53例非老年PD组相比较.结果 老年PD组的原发疾病以糖尿病(37.08%)、原发性高血压(30.34%)为主,而非老年PD组则以肾小球肾炎(54.72%)为主.两组患者的1年与3年存活率差异无统计学意义,腹膜炎仍是两组患者退出PD的主要原因.老年组的病死率明显高于非老年组,感染与心脑血管病是两组患者的主要并发症和死亡原因.低钾血症在老年PD患者中非常普遍.结论 腹膜透析在老年CRF患者的治疗中有效,但长期存活仍受腹膜炎、心脑血管病并发症的影响,老年PD患者的低钾血症应引起足够的重视.     

人工肱骨头置换与肱骨近端锁定钢板治疗老年复杂肱骨近端骨折的近期临床疗效分析

[摘要] 目的 对比分析人工肱骨头置换术和肱骨近端锁定钢板治疗老年复杂肱骨近端骨折的近期疗效。方法 回顾性分析本院骨科2012年1月~2014年6月采用人工肱骨头置换术和肱骨近端锁定钢板治疗的老年（年龄>65岁）NeerⅢ、Ⅳ部分肱骨近端骨折患者54例，人工肱骨头置换治疗（置换组）30例，肱骨近端锁定钢板内固定治疗（内固定组）24例。比较分析两组手术时间、术中出血量、随访Neer评分及Constant-Murley评分来评定两组临床疗效。结果 两组随访时间相仿，平均随访时间为19.5个月（12~36个月）。内固定组手术时间（101±13）分钟，术中出血量（237.9±32.4）mL，Neer评分（82.5±3.2），Constant-Murley评分（71.7±5.0）；置换组手术时间（98±11）分钟，术中出血量（246.0±39.8）mL，Neer评分（82.9±4.5），Constant-Murley评分（73.5±5.0）。两组手术时间、术中出血量、随访Neer及Constant-Murley评分比较差异均无统计学意义（P＞0.05）。内固定组有1例出现肩关节半脱位，肱骨头置换组有2例出现肩关节半脱位，通过三角巾悬吊后关节脱位均得到纠正。有1例四部分骨折患者，行内固定术后出现内固定松动、肱骨头坏死，改行人工肱骨头置换术。结论 人工肱骨头置换术和肱骨近端锁定钢板治疗老年肱骨近端复杂骨折的近期临床疗效相似，对不可修复的肱骨近端骨折宜行肱骨头置换术。     

Psychosis as a predictor of response to lithium maintenance treatment in bipolar affective disorder

Sixty-six bipolar I lithium clinic patients were studied for a history of psychotic symptoms at some time during the course of their illness. Agreement between different sources of information was calculated, and the patient population was divided into psychotic and non-psychotic subgroups. Probability of remaining well on lithium for the different subgroups was analyzed by the life table method. Psychosis during mania appeared to be associated with especially good early lithium prophylaxis.     

Effects of aerobic exercise conditioning at intensities corresponding to lactate threshold in the elderly

Summary In this study we attempted to determine the effects of exercise training at the intensity corresponding to lactate threshold (Th_la ^–) on various health-related variables in sedentary but apparently healthy elderly subjects. Six men and five women volunteers [mean age 68.9 (SD 3.4) years] performed supervised endurance-type training on stationary cycle ergometers for 30 min and recreational activities for 30 min, 3 days a week for 12 weeks. Four men and four women served as the control group [68.8 (SD 4.4) years]. As a result of the training programme, statistically significant increases in maximal oxygen consumption (10%), oxygen consumption at Th_la ^–(18%), distance covered in 12-min walk, side step, and leg extensor power were found in the training group, while no changes occurred in the control group. The changes in serum cholesterol and triglyceride concentrations from the pre- to post-training period were statistically significant. High-density lipoprotein cholesterol remained unchanged, and low-density lipoprotein cholesterol tended to decrease following the training programme. These data would indicate that exercise training at the intensity corresponding to Th_la ^–may have favourable effects on overall physical fitness and some serum lipid variables in older individuals.     

农村老年人心理健康状况的调查分析

随着经济的发展和社会的进步 ,人口老龄化已经成为当今世界人口发展的一种必然趋势。因此 ,老龄问题日益受到关注。研究老年人的心理健康状况及其影响因素对如何提高老年人的生活质量具有重要的指导意义。国内已有一些学者对老年人的心理健康状况进行了研究[1- 7] ,但研究的对象主要是城市老年人 ,关于农村老年人的心理健康状况的研究极少。因此 ,本文想就这一问题作些探讨。1　对象与方法1.1　对象在湖州市所辖三县三区各抽取 9个行政村 ,每个行政村随机抽取 13～ 14个年龄在 6 0岁以上 (包括 6 0岁 )的老年农民进行调查 ,其中有 16人资料…     

老年患者日间手术全程质量管理模式研究

目的探索老年患者日间手术全程质量管理模式。方法通过医院病历系统采集2015年-2020年应用老年患者日间手术全程质量管理模式前后患者信息,进行对比分析。结果老年患者应用日间手术全程质量管理模式后,≥65岁老年患者日间手术人数逐年上升,占比从13.52%上升至18.62%,差异有统计学意义（χ2=6.450,P=0.011）;日间手术住院时间＞5 d的比例从0.72%下降至0.50%,差异有统计学意义（χ2=338.088,P<0.001）;不良事件发生率从3.77‰下降至1.56‰,差异有统计学意义（χ2=5.156,P=0.023）,其中严重不良事件发生率从2.08‰下降至0.35‰,差异有统计学意义（χ2=7.019,P=0.008）。结论应用日间手术全程质量管理模式能够有效提高老年患者日间手术的安全性,值得借鉴与推广。     

老年髋部骨折患者围术期“2P-3R”营养管理模式构建

目的构建老年髋部骨折患者围术期营养管理模式,促进患者早手术、早下地、早康复。方法针对老年髋部骨折患者营养管理现状,采用课题研究型品管圈活动进行改进。经过科学循证、专家指导等,从术前、术后及家庭三个环节,骨科、营养科、家庭三个维度,人员、制度、材料设备、方法、信息五个方面,制定三大对策群组并予以实施,包括组建营养支持团队、构建营养管理策略、搭建多维信息交互平台等。结果老年髋部骨折患者首次下地时间缩短为26.7 h,平均住院日缩短为5.6 d,实现了早手术、早下地、早康复的目标。结论对老年髋部骨折患者实施个性化、全流程的序贯性营养干预具有重要意义。后续还需开展大样本多中心研究以进一步验证成效,数据自动采集与智能反馈也是今后研究重点。