Autologous stem cell transplantation in the treatment of systemic sclerosis: report from the EBMT/EULAR Registry

OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.     

Platelet adenylyl cyclase activity as a state or trait marker in alcohol dependence: results of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence

BACKGROUND: There has been considerable interest in identifying biochemical markers indicative of a genetic predisposition to alcohol dependence ("trait markers"), as well as biochemical markers of recent alcohol drinking ("state markers"). Platelet adenylyl cyclase activity has been suggested as a trait and/or as a state marker related to alcohol dependence. We have now measured platelet adenylyl cyclase activity in more than 1400 well-characterized subjects, which allows us to investigate the influence of a broad range of factors on this activity. METHODS: Subjects were recruited as part of the WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence and were interviewed by using the WHO/ISBRA Interview Schedule. Adenylyl cyclase activity (basal, cesium fluoride [CsF]-, forskolin- and Gpp(NH)p-stimulated activities) was measured in platelet samples that were obtained at the time of interview. Data were analyzed by multivariate regression analyses. RESULTS: The multivariate analyses revealed that recent abstinence from alcohol was associated with diminutions in platelet adenylyl cyclase activities. A positive family history of alcohol dependence was associated with higher levels of adenylyl cyclase activities, and there was a significant interaction between the effect of alcohol consumption in the past month and family history of alcohol dependence; that is, the influence of alcohol consumption depended on whether the individual had a positive family history. A history of marijuana abuse also was associated with higher levels of platelet adenylyl cyclase activities, and a history of major depression was associated with lower levels of forskolin- and CsF-stimulated activities. Sex, race, and site of recruitment also affected some adenylyl cyclase activities, but there was no significant association of alcohol dependence or abuse with any of the platelet adenylyl cyclase activities. DISCUSSION: The large population and extensive characterization of subjects in this study provided an advantage over previous studies in which only the association of a few individual factors with adenylyl cyclase activity was investigated. The results demonstrate that although platelet adenylyl cyclase activity could be useful as a trait marker of alcohol dependence, its reliability in this regard is diminished by the influence of recent alcohol drinking and other variables. The associations between platelet adenylyl cyclase activities and marijuana abuse, as well as a history of depression, suggest that it may be worthwhile to study the genetic association of adenylyl cyclases (e.g., polymorphisms in the genes that code for particular adenylyl cyclase isoforms) with a predisposition to depression as well as to alcohol or marijuana abuse/dependence.     

手术室多信息系统的应用现状

【】通过对医院信息系统的发展的分析及回顾,包括建立多信息系统在手术室护理管理中的应用。通过过程监测、干预、流程重组等方法对手术护理安排、护理记录管理、手术室物流等多个环节进行优化,节省了人力和物力,提高了护理工作质量,保证手术安全。剖析了手术室信息系统建设中存在的问题,指出多手术室信息系统是数字化手术室发展的必然趋势,注重兼容性使用,认识到信息化在手术室护理中的重要性,培养复合型手术室护士的必要性,把手术室护理发展成更具有专业性、规范性和创新性。     

细胞色素P450 1A2和2C19基因多态性与抗结核药物性肝损伤的关系

 目的 探讨细胞色素P450 1A2和2C19基因多态性与抗结核药物性肝损伤的相关性。方法 采用1∶1病例对照研究,以抗结核药治疗致肝损伤的结核病患者为病例组,无肝损伤者为对照组,共179对。采用聚合酶链反应限制性片段长度多态方法检测CYP1A2基因734C/A和CYP2C19基因681G/A位点基因型。采用SPSS17.0条件Logistic回归进行数据分析。结果 CYP1A2 基因734C/A位点C、A等位基因频率在病例组和对照组频率分别为37.2%、62.8%、和47.2%、52.8%;CYP2C19基因的681G/A位点G、A等位基因频率在病例组和对照组频率分别为59.8%、40.2%和62.8%、37.2%,CYP1A2基因734C/A位点多态性与抗结核药物性肝损伤的发生有关(P＜0.05),CA、AA基因型的比值比(odds ratio,OR)分别为1.951和1.916, 而尚不能认为CYP2C19基因681G/A位点多态性与抗结核药物性肝损伤发生有关。结论 CYP1A2基因734C/A位点多态性与抗结核药物性肝损伤的发生有关,并且携带CA、AA突变基因型的个体是危险人群。     

基于药品质量提升的价格制度性影响因素分析

 目的 探索影响药品质量提升的价格制度性因素,促进药品质量与药品价格关联的合理性回归。方法 厘清药品质量内涵、药品质量与药品价格关系,通过基于专家访谈的结果编制调查问卷并对药品价格25个制度性影响因素进行描述统计和结构方程模型分析。结果 药品价格影响药品质量提升的问题,不是完全由药品价格规制所决定,药品商业贿赂、药品流通环节多和费用多、能否进入医保报销目录、企业内部成本管理制度等问题是影响价格政策发挥作用的关键性因素。结论 价格规制政策调整的方向,要以理顺企业内部成本管理制度为重点,对企业内部培训再教育、节能减排和仿制药质量一致性评价等方面给予价格政策鼓励,可弥补医药企业提升药品质量动力不足的问题。     

Age-Concordant and Age-Discordant Sexual Behavior Among Gay and Bisexual Male Adolescents

There is evidence that risks for HIV and sexually transmitted infections among adolescent females are higher for those with older male sexual partners. Yet, little empirical research has been conducted with male adolescents who engage in sexual activity with older men. In this article, we summarize in a number of ways the range of sexual activity reported by an ethnically diverse sample of 200 gay and bisexual male youth (15–22 years old) in Chicago and Miami. A general pattern of progression from oral sex with men to both receptive and insertive anal sex with men appeared to characterize the sample during their adolescence. Further, there appeared to be a high degree of “versatile” positioning among the sexually active gay and bisexual young men, in both age-discrepant and age-concordant dyads. Risk analysis revealed having primarily age-concordant partners to be a significant predictor of sexual risk behavior. HIV risk among young gay and bisexual men engaging in sexual activity with older men may occur not only within a distinct biological context from their heterosexual counterparts, but also in a social context that may not as rigidly bound to traditional assumptions about age, gender, and power. The significant associations among participants with partners who were the same age and the risk behavior measures in this analysis have implications for HIV prevention efforts.     

Compatibility of ASO3-adjuvanted H1N1pdm09 and seasonal trivalent influenza vaccines in adults: results of a randomized, controlled trial

When Canada chose a novel adjuvanted vaccine to combat the 2009 influenza pandemic, seasonal trivalent inactivated vaccine (TIV) was also available but compatibility of the two had not been assessed. To compare responses after concurrent or sequential administration of these vaccines, adults 20-59 years old were randomly assigned (1:1) to receive ASO3-adjuvanted H1N1pdm09 vaccine (Arepanrix, GSK, Quebec City, Quebec), with TIV (Vaxigrip, Sanofi Pasteur, Toronto) given concurrently or 21 days later. Blood was obtained at baseline and 21 days after each vaccination to measure hemagglutination inhibition (HAI) titers. Adverse effects were assessed using symptom diaries and personal interviews. 282 participants completed the study (concurrent vaccines 145, sequential vaccines 137). HAI titers to H1N1pdm09 were ≥ 40 at baseline in 15-18% of participants and following vaccination in 91-92%. Initially seropositive subjects (titer ≥ 10) had lower H1N1pdm09 geometric mean HAI titers (GMT) after concurrent than separate vaccinations (320.0 vs 476.5, p=0.039) but both exceeded GM responses of initially na?ve participants, which were unaffected by concurrent TIV. Responses to TIV were not lower after concurrent than separate vaccination. Adverse event rates were not increased by concurrent vaccinations above those with H1N1pdm09 vaccine alone. This adjuvanted H1N1pdm09 vaccine was immunogenic and compatible with concurrently administered TIV.     

The incidence of unrecognized myocardial infarction in women with coronary heart disease

BACKGROUND: Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized. OBJECTIVE: To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS). DESIGN: Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up. SETTINGS: Outpatient and community settings at 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus. MEASUREMENTS: Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared. RESULTS: Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction. CONCLUSION: The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.