Comparison of assays for determination of peptide content for lyophilized thymalfasin*

Abstract: Precise determination of the peptide content in drug substance samples depends highly upon the particular peptide compound and methodology used. Four independent methods were evaluated and compared to determine which would produce the best experimental precision for analysis of thymalfasin (thymosin α‐1). Four different methods were evaluated including elemental analysis (CHN), quantitative amino acid analysis (AAA), high‐performance liquid chromatography (HPLC), and Kjeldahl. This study demonstrates that the AAA method is highly variable in one laboratory while quite precise in another laboratory. Similarly, HPLC results depended on the laboratory conducting the study with more precise values obtained under cGMP. On the contrary, the CHN method yielded highly precise [i.e. <2% coefficient of variation (CV)] values. As precise knowledge of protein content is fundamental for the compounding of final pharmaceutical product of a specific potency, the CHN analysis is recommended for peptide content determination of the drug substance thymalfasin.     

Timing deficits in apraxia of speech

Summary This paper deals with a particular aspect of speech motor control in patients suffering from apraxia of speech. Three experiments are reported concerning the phase relations between individual speech gestures. These include the timing of laryngeal, velar and labial movements relative to lingual gestures.A total of 8 patients and 12 normal controls were examined using speech material which was designed according to appropriate phonetic paradigms. Evaluation was performed on the basis of speech signal parameters referring to the kinematics of inter-articulatory phasing. Deviations of the patient group were found in all three experiments. This suggests that disturbed phase relations of individual speech movements are a general feature of apraxic speech. It is further hypothesized that the described motor symptoms are the origin of a variety of phonemic errors. Support for this view is provided by appropriate examples which refer to the examined paradigms. By this argument, much of the disturbed phonemic structure of apraxic speech may be accounted for by timing deficits.     

急诊抗菌药物的使用调查与分析

目的考察了解急诊抗菌药物的使用情况。方法随机抽取2008年7—12月的急诊处方2700张，对其中抗菌药物的应用情况进行统计分析。结果急诊抗菌药物使用率49．1％，药物应用形式以单用为主（占66．3％）；给药途径以口服和静脉注射为主。不合理用药处方占抗菌药物处方的10．8％，分别在选药方案、给药方案、溶媒使用、联合应用等方面存在问题。结论我院急诊抗菌药物的应用基本合理，但仍存在一定问题，需进一步加强管理。     

Multivariate modelling of responses to conditional items: New possibilities for latent class analysis

Questionnaire data may contain missing values because certain questions do not apply to all respondents. For instance, questions addressing particular attributes of a symptom, such as frequency, triggers or seasonality, are only applicable to those who have experienced the symptom, while for those who have not, responses to these items will be missing. This missing information does not fall into the category ‘missing by design’, rather the features of interest do not exist and cannot be measured regardless of survey design. Analysis of responses to such conditional items is therefore typically restricted to the subpopulation in which they apply. This article is concerned with joint multivariate modelling of responses to both unconditional and conditional items without restricting the analysis to this subpopulation. Such an approach is of interest when the distributions of both types of responses are thought to be determined by common parameters affecting the whole population. By integrating the conditional item structure into the model, inference can be based both on unconditional data from the entire population and on conditional data from subjects for whom they exist. This approach opens new possibilities for multivariate analysis of such data. We apply this approach to latent class modelling and provide an example using data on respiratory symptoms (wheeze and cough) in children. Conditional data structures such as that considered here are common in medical research settings and, although our focus is on latent class models, the approach can be applied to other multivariate models. Copyright © 2009 John Wiley & Sons, Ltd.     

早期糖尿病视网膜病变药物治疗的药物经济学分析

目的：探讨不同方案治疗早期糖尿病视网膜病变的经济效果,找出既经济又有效的方案。方法：对目前临床常用的4种不同治疗方案（导升明、胰激肽原酶、复方血栓通胶囊、复方丹参滴丸,治疗时间均为90d）运用药物经济学方法进行成本-效果分析。结果：4种方案所需费用分别为1417.50元、810.00元、891.00元、656.10元;治疗有效率分别为94.25%、85.09%、85.17%、83.53%;成本-效果比分别为15.04、9.52、10.46、7.85。结论：复方丹参滴丸治疗效果较好,不良反应少,成本低廉。     

结节性甲状腺肿合并其他甲状腺疾病临床分析

目的探讨结节性甲状腺肿合并其他甲状腺疾病的临床特点。方法回顾性分析我院手术治疗的4622例结节性甲状腺肿中并存其他甲状腺疾病的临床资料。结果4622例结节性甲状腺肿中700例合并其他甲状腺疾病，1418例存在不同的诊断失误。结论在诊断结节性甲状腺肿的同时应注意其合并的其他甲状腺疾病。     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.