A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes

Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo ( P < 0.001). When side-effects and administration attributes were combined into an overall profile, 91% of patients selected raltitrexed as their clearly preferred regimen, versus 6% for Mayo ( P < 0.001). The administration regimen of raltitrexed was ranked most acceptable (mean rank score 1.5 compared with Mayo 2.6, De Gramont 2.7, and Lokich 3.3). Given similar palliative effects, patients with ACRC exhibit preferences for raltitrexed over other regimens, based on administration and/or side-effect attributes. Such preferences should constitute an important part of decisions relating to the choice of chemotherapy regimen in ACRC.     

Evaluation of anti-cocaine antibodies and a cocaine vaccine in a rat self-administration model

Rationale: Previous pre-clinical studies with an anti-cocaine monoclonal antibody left open several issues critical to assessing the effectiveness of a vaccine for altering cocaine self-administration behavior. Objectives: The objectives of this study were to determine, first, whether changes in self-administration behavior would be systematically related to antibody level and, second, how the antibody affected the self-administration of different doses of cocaine. Methods: Two experiments were conducted using a second-order schedule of drug delivery in rats. The first was a passive-administration study using the anti-cocaine monoclonal antibody MO240 to examine the relationship between antibody level and cocaine self-administration behavior, and the second was an active-immunization study to examine the efficacy of the cocaine vaccine IPC-1010 for blocking various doses of self-administered cocaine. Results: The passive-administration experiment with control and 4-mg or 12-mg MO240 treatments showed that antagonism of the 1 mg/kg cocaine training dose was dependent on antibody level. In animals whose serum antibody levels were sustained above 0.05 mg/ml, there was a sufficient amount of antibody to reduce drug-seeking behavior and drug intake. In the active-immunization experiment, the cocaine vaccine IPC-1010 induced average serum antibody levels of 0.08 mg/ml and reduced the reacquisition of behavior by 1 mg/kg cocaine. Antagonism of cocaine self-administration after immunization was evident across a range of doses of cocaine and was only apparent in animals whose serum antibody levels exceeded 0.05 mg/ml. Furthermore, there was no evidence that the antagonism was surmountable within the dose range examined (up to 5.6 mg/kg). Conclusions: Antagonism of cocaine self-administration across a range of doses is feasible after immunization with a cocaine vaccine as long as antibody levels are of a sufficient concentration. Received: 2 April 1999 / Final version: 25 September 1999     

不同剂量聚肌胞治疗慢性迁延性肝炎

慢性迁延性肝炎患者90例(男52,女38,年龄12-72yr,41±SD20yr)。分成4组,隔日1次分别肌注聚肌胞2mg,4mg,6mg和8mg,共3mo。经过治疗前后免疫、生化、组织学和肝穿刺的检验,以及随访1yr的观察,6mg和8mg组的治愈率明显高于2mg和4mg组.因此推荐治疗时应用较大剂量为宜。     

Ethanol drinking by rhesus monkeys with concurrent access to water.

Three monkeys were provided concurrent access to water and ethanol in concentrations of either 8, 16 or 32% (w/v) during daily 3-hr sessions. The monkeys were those for whom ethanol had been established as a reinforcer in an earlier study in which only ethanol or water was available. Ethanol was preferred to water at all concentrations and volume of ethanol consumed was inversely related to ethanol concentration. Quantity of ethanol (g/kg of body wt.) consumed remained relatively constant, and blood ethanol determinations confirmed that the monkeys were drinking ethanol. Water drinking occurred at negligible levels except by one monkey at 16 and 32% who followed ethanol drinking bouts by water bouts (chasers) in a manner similar to that reported in other studies. Two monkeys were also provided concurrent access to 8% ethanol and water during 23-hr daily sessions. Under these conditions, ethanol was consumed every few hours to the near exclusion of water. The significance of this study lies largely in its procedure; that is, the development and application of a concurrent water-ethanol preparation in which ethanol serves as a reinforcer for rhesus monkeys. This preparation should be useful in the evaluation of a wide range of factors suspected to control alcoholic drinking.     

Effects of selective D1 and D2 dopamine antagonists on cocaine self-administration in the rat

The effect of the selective D1 antagonist, SCH 23390, and the selective D2 antagonist, spiperone, was investigated in rats trained to self-administer intravenous cocaine on a fixed-ratio (FR) 5 schedule of reinforcement. Both SCH 23390 and spiperone pretreatment increased responding up to doses of 10.0 µg/kg, and decreased responding at higher doses. Since rate of responding maintained by a drug can be influenced by factors other than its reinforcing efficacy, behavior maintained by cocaine was also investigated under a progressive-ratio schedule. The breaking point obtained under this schedule is used as a measure of the efficacy of the reinforcer and this value is not exclusively determined by response rate. With the progressive-ratio schedule, both SCH 23390 and spiperone produced dose-dependent decreases in the highest ratio completed in rats self-administering cocaine. The results obtained using the FR 5 and progressive-ratio schedules suggest that both D1 and D2 receptors are involved in mediating the reinforcing effects of cocaine.     

Similar effects of antidepressant and non-antidepressant drugs on behavior under an interresponse-time >72-s schedule

Antidepressant drugs were reported to decrease responses and increase reinforcements in water-deprived male albino rats pressing a lever for water on a schedule requiring a pause of at least 72 s between responses (IRT >72). Subsequently other investigators, using food-deprived ovariectomized hooded rats pressing a lever for food, showed that antipsychotic drugs produced the same effect as antidepressants. Because methodologies differed somewhat, the present study was designed to replicate closely the experimental conditions of the original studies, e.g., same strain and sex, same reinforcer, similar baseline behavior. In this study the antidepressant imipramine, the antipsychotics chlorpromazine and haloperidol, and to some extent the anxiolytic buspirone produced qualitatively similar effects — decreased responses and increased reinforcements — although there were some quantitative differences. This result, and other results showing that some antidepressants increase responses and decrease reinforcements, suggest that the IRT >72-s task lacks specificity as a screening method for antidepressants.     

Serotonin,memory, and the aging brain

Six rhesus monkeys self-administered orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquids were available during three 6.5-h periods daily preceded by 1-h components when food was available under an FR 64 (lever press) schedule. After 10 days of stable behavior, water was substituted for PCP for 8 days. PCP was subsequently reinstated, and this PCP withdrawal sequence was repeated using different food FR values (64, 128, 256, 512 and 1024). Each time the food FR was changed behavior was allowed to stabilize for at least 10 days. Under all FR values food-maintained responding decreased markedly during PCP withdrawal, with a gradual recovery over the next 8 days. As the FR value increased from 64 to 1024 there was a parallel shift downward in food-maintained performance. When PCP was reinstated, food-reinforced responding generally returned to baseline rates during the first few days. In a second experiment monkeys were tested for PCP withdrawal effects under relatively food deprived or food satiated conditions under both an FR 512 and 1024 schedule of food delivery. The results showed that the decrease in food-maintained responding during withdrawal was inversely related to the total amount of food consumed during the control period. The results of these experiments indicate that manipulation of both the response requirements for food (FR) and the total amount of food available (food deprivation/satiation) alters the magnitude of response disruptions during PCP withdrawal.     

不同种EP方案治疗老年人非小细胞肺癌的临床观察

目的 :探讨不同剂量及途径用药的EP方案治疗非小细胞肺癌的疗效和不良反应。方法 :1999年 1月～ 2 0 0 2年 1月将 14 3例非小细胞肺癌患者随机分为A(35例 )、B(36例 )、C(37例 )、D(35例 ) 4组 ,分别使用静脉小剂量滴注顺铂加口服足叶乙甙或静脉滴注足叶乙甙 ,以及静脉大剂量滴注顺铂加口服足叶乙甙或静脉滴注足叶乙甙四种EP方案治疗。结果 :4例EP方案的有效率分别为 4 0 .0 % (14 / 35 )、38.9% (14 / 36 )、4 0 .5 % (15 / 37)、4 2 .9% (15 /35 ) ;中位缓解期分别为 3.8月、4月、3.7月、3.4月。A组有白细胞下降、恶心、呕吐及脱发等不良反应最少 ,D组最多。结论 :静脉小剂量滴注顺铂口服足叶乙甙组成的EP方案简便、不良反应少 ,而且经济 ,适合老年人的非小细胞肺癌患者的姑息性治疗     

Simulation-based education promoting situation awareness in undergraduate nursing students: A scoping review

AimTo examine simulation-based education (SBE) strategies on situation awareness (SA) in nursing students including the strategies of SBE, the measurement tools of SA during SBE and the effectiveness of SBE on SA.BackgroundSA has been reported as an effective way to identify and manage deteriorating patients. Researchers have suggested that SBE is more effective than other instructional modalities in improving SA. However, SA among nursing students and studies regarding the effectiveness of SBE on SA are limited.DesignThe Arksey and O'Malley scoping review framework was used to guide the review process and the PRISMA-ScR checklist was used to report on this scoping review.MethodsThe databases searched were Medline, CINAHL, EMBASE, EBSCO and Google Scholar from December 2020 to November 2021. Thematic analysis was applied to identify the main findings in the literature.ResultsNine eligible articles were included. Five major themes were identified: SBE situations used to teach SA to nursing students, SBE strategies to improve SA in nursing, effectiveness of SBE on SA in nursing, measurements of SA used during the SBE and experimental studies examining the effectiveness of SBE on SA.ConclusionThis review reveals that SBE may be useful to cultivate SA in nursing students. Future studies that use randomized clinical trials to test the effects of combining different simulation strategies on SA are suggested. Developing more reliable and valid SA global assessment queries and standardizing the query process of SA measurement is also recommended.