Performance in population models for count data,part II: A new SAEM algorithm

Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations, including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization (SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in July 2009).     

Evaluating therapeutic outcome in epileptic patients using the changes of interval and duration

BACKGROUND: Seizure frequency is in abnormal distribution, and it is not enough to express the trend of concentration using means, and its median loses a lot of information, thus it lacks of a standard for evaluating the therapeutic effects based on seizure frequency. OBJECTIVE: To establish a method for evaluating the therapeutic effects on anti-epileptic drugs using changes of interval and duration of seizure. DESIGN: A prospective cohort study. SETTING: Zhumadian Psychiatric Hospital. PARTICIPANTS: Outpatients and inpatients suffering from epilepsy attending firstly visited Zhumadian Psychiatric Hospital from June 2001 to June 2002 were enrolled. They were diagnosed as epileptic according to the International Classification of Epileptic Seizure by International League Against Epilepsy (1981) based on the clinical history, physical examination, and investigations. The interval time was no more than 6 months. Informed consent was obtained from all the subjects, and the study was approved by the hospital ethical committee. METHODS: ① For the first visit and each follow-up, the following data were recorded, including general demographic information, seizure type, the date and time of ictus, the duration of ictus, and inducement or situation related, according to which the following indexes could be calculated, including seizure styles, interval, duration, cluster frequency and cluster duration. The information from the first review was noted as annals A. The second interview was taken at the end of the evaluating period; the information from the second review was noted as annals B. The third interview was taken within two weeks after the second one; the information from the third review was noted as annals C. The annals B or the annals C were respectively compared with the annals A in the light of the same types or the same styles of the same patient. Summation of the scores of interval change and duration change of the same type or the same style and 5 of basic score was the score of a corresponding seizure type or a corresponding style of one patient. In order to test its reliability and validity, the score of change of frequency or duration plus 5 scores respectively was the score of frequency or duration. ② Reliability and validity were tested by calculating corresponding correlation coefficient with SPSS 11.0. ROC curve was used for developing diagnostic criterion of predicting therapeutic effects with SPSS 11.0. MAIN OUTCOME MEASURES: ① Reliability and validity; ② Diagnostic criterion for predicting therapeutic effects one year later. RESULTS: Totally 28 patients were involved in the final analysis of results. ① Reliability and validity were high: rinter-rater=0.98, rtest-retest=0.99, rconstruct validity=0.83. ② A total score > 6 was the optimal diagnostic criteria for predicting therapeutic effects one year later, in other words, a patient who scored more than 6 at the evaluating period may be seizure-free one year later. CONCLUSION: It is a potential tool for evaluating epileptic therapeutic outcome, and it can be diffusely used in interrelated fields after being further validated.     

宫腔镜手术电热损伤的研究

目的探讨宫腔镜手术中各种电极在不同功率下对子宫组织电热损伤程度.方法设置电极功率为80～120 W,作用时间为3～5 s,作用于宫腔镜手术在体子宫内膜及肌层,在切下内膜组织及电极作用下方分别取材,通过HE染色观察电热损伤.结果不同电极子宫组织电热损伤有显著差异,滚球电极电热损伤最深,气化电极次之,环状电极最薄.结论子宫组织电热损伤程度与电极功率选择关系不大,而与电极形状密切相关.     

Laser photobioactivation mechanisms: in vitro studies using ascorbic acid uptake and hydroxyproline formation as biochemical markers of irradiation response

Clinical investigations of laser photobioactivation, or biostimulation, might be differently designed and more fruitful if knowledge of basic biochemical mechanisms were better understood. In this investigation, biochemical events identified as responses to 904 nm irradiation included increased ascorbic acid uptake by fibroblasts. These cells also showed increased hydroxyproline formation, and this was increased several-fold by the addition of proline to the medium. Maximum biochemical responses were observed at a pulse frequency of 67 Hz and a pulse width of 150 nsec with an energy density of approximately 7 mJ/cm2 per exposure. Elements in the mitochondrial cytochrome system are proposed as the radiation absorbing chromophore(s). Hypothetically, the energy generated is linked to ascorbic acid uptake, which in turn stimulates collagen synthesis.     

Analgesic and antipyretic effects of Ecballium elaterium (L.) A. Richard. Extract in rodents

The dried (elaterium) or fresh juice from Ecballium elaterium fruit is used in the treatment of various inflammatory conditions in popular medicine. In this study the elaterium is examined for its analgesic and antipyretic effects in several animal models. The elaterium exhibits both analgesic and antipyretic activities.     

环孢霉素A滴眼治疗角膜移植排斥反应

应用0.5％环孢霉素A(cyclosporin A,CsA)滴眼治疗穿透性角膜移植术后发生免疫排斥患者16例(16只眼),治愈9只眼,好转6只眼,无效1只眼。随访5～24个月,其中2只眼因停药复发,1只眼于拆线后复发,继续用药或增加给药次数后治愈。研究表明0.5％CsA滴眼剂治疗术前移植床条件较好,角膜移植术后发生免疫排斥的病例可得到良好疗效;而对术前移植床条件较差,角膜移植术后发生免疫排斥的病例有一定的疗效。作者对眼局部应用CsA治疗角膜移植排斥的疗效和作用机理进行了讨论。     

Nicotine discrimination and self-administration in humans as a function of smoking status

Nicotine’s discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 μg/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 μg/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 μg/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 μg/kg nicotine from placebo (≥ 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 μg/kg on the quantitative task and at 12 μg/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of “head rush”, which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use. Received: 1 October 1996/Final version: 28 January 1997     

抗癌药物对心脏毒性反应(附五例报告)

本文报道五例肿瘤患者在用抗癌药的治疗过程中,出现对心脏不同程度的毒性反应,并就有关几种抗癌药物的毒性作用机理及防治进行了讨论。