Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.     

Perugia urodynamic method of analysis (PUMA): a new advanced method of urodynamic analysis applied clinically and compared with other advanced methods.

AIMS: The aim of this study is to compare PUMA curves with different pathologic conditions causing bladder dysfunction in 158 men and 83 women. METHODS: PUMA results in terms of bladder outlet obstruction and detrusor contractility were compared in 92 men with benign prostatic hypertrophy (BPH) and p(ves) congruent with p(det) (i.e., p(abd) congruent with 0) with the results of the urodynamics operator's opinion, the provisional International Continence Society method, Abrams and Griffith's diagram, urethral resistence factor (URA), Sch?fer's diagram, and Watt factor. PUMA curves correlated reliably with different pathologic conditions such as obstructive BPH, orthotopic bladder, cystocele, the neurological bladder, and bladder diverticulum. Statistical analysis indicated excellent agreement between PUMA and URA; agreement with other methods was good in cases of obstruction and nonobstruction. In doubtful cases, as diagnosed by standard methods, PUMA agreed only with the Abrams and Griffith's diagram. PUMA and Wmax were in good agreement on detrusor con traction force. Agreement between PUMA and Sch?fer's diagram was excellent for patients with detrusor hypercontractility and good for patients with detrusor hypocontractility and normocontractility. PUMA is the only method applicable to women. It is easy to perform. When integrated with other diagnostic tests, it provides realistic data for diagnosis, medical or surgical therapy, and outcome.     

靶重建放大扫描对肺孤立性结节病变的诊断意义

目的：探讨靶重建放大扫描技术对肺孤立性结节病变的诊断价值。方法：对63例患者先行常规CT平扫，选定结节处为兴趣区，行薄层靶重建放大扫描，层厚、层距为2mm，FOV为160。结果：42例恶性病变中有37例表现为深分叶，占88．1％；21例良性病变中有15例表现为浅分叶，占71．4％。恶性结节中15例内部出现条状低密度支气管征；7例出现血管集中征；8例出现空泡征；病变内部出现液化坏死13例，其中恶性病变ll例。22例出现钙化，包括12例良性病变和10例恶性病变。2例错构瘤内均见小面积脂肪性低密度影。结论：靶重建放大扫描比普通CT扫描可提供更多的信息，对良恶性病变的鉴别诊断有一定价值。恶性病变大多数为深分叶，良性病变大多数为浅分叶或无分叶。     

Fat and water separation in balanced steady-state free precession using the Dixon method.

In this work the feasibility of separating fat and water signals using the balanced steady-state free precession (SSFP) technique is demonstrated. The technique is based on the observation (Scheffler and Hennig, Magnetic Resonance in Medicine 2003;49:395-397) that at the nominal values of TE = TR/2 in SSFP imaging, phase coherence can be achieved at essentially only two orientations (0 degrees and 180 degrees ) relative to the RF pulses in the rotating frame, under the assumption of TR < T2, and independently of the SSFP angle. This property allows in-phase and out-of-phase SSFP images to be obtained by proper choices of the center frequency offset, and thus allows the Dixon subtraction method to be utilized for effective fat-water separation. The TR and frequency offset for optimal fat-water separation are derived from theories. Experimental results from healthy subjects, using a 3.0 Tesla system, show that nearly complete fat suppression can be accomplished.     

中风毒邪论与神经保护治疗的研究

中风毒邪论是一种与传统中医中风病理有所不同的理论 ,在中风毒邪论指导下形成解毒通络方是较为理想的神经保护剂 ,可解决目前神经保护治疗的主要障碍 ,有望成为提高中医治疗中风急性期疗效的关键     

2008年连云港市“手足口病”流行特征及病原学分型

目的分析连云港市2008年手足口病的流行特征及病原学分型情况。方法应用流行病学方法对2008年该市的手足口病流行资料进行分析。结果依据疫情报告,实验室诊断病例45例,其中CoxA1638例,EV71型7例,其他肠道病毒0例。2008年该市临床报告手足口病例1067例,报告发病率为23.19/10万,比2007年上升442.34%,男女发病比为3.1∶1。发病年龄最小的为0岁组,最大的为8岁;0～5岁组,共计发病976例,占总发数的91.47%。发病数的构成以散居儿童最多,占76.66%。地区分布:全市各个区县均有手足口病病例报告,但城区的总体发病率高于县。结论连云港市手足口病发病率有上升趋势;控制传染源是有效防止该病流行的关键。     

Causes and types of health effects during the use of crop protection chemicals: data from a survey of over 6,300 smallholder applicators in 24 different countries

Purpose  The present investigation looks in detail at the causes and types of health incidents reported by 6,300 mainly smallholder agrochemical users in 24 countries during 2005 and 2006. Methods  The investigation is based on a questionnaire survey of knowledge, attitude and practice that concentrated on the sequence of events from purchasing the pesticide to disposal. Information was also collected about health problems experienced while using agrochemicals. The survey targeted mainly smallholder knapsack spray operators who were expected to be at a highest risk of exposure. Results  In the 12 months prior to interview, 1.2% of users reported an agrochemical-related incident that required hospital treatment, 5.8% reported an incident requiring at least trained medical treatment but not hospitalisation and 19.8% reported only a minor sign or symptom. Users who had experienced an incident involving agricultural equipment were 3.38 (95% CI 2.29–4.99) times more likely to experience an agrochemical-related health incident, but confident users who felt that their use of personal protective equipment while spraying was best practice were 0.60 (95% CI 0.44–0.84) times less likely to experience such an incident. Over 80% of product-related incidents were caused by insecticides and the incidence rate per spraying time for incidents linked to insecticides was significantly higher than that for fungicides or herbicides. Headache/dizziness and nausea/vomiting, often smell related, were the most common symptoms reported by users who listed agrochemical products that had caused them health problems (52 and 38% of product mentions, respectively). Conclusions  In most countries, the incidence of serious health effects was low; however, there was a high incidence of minor signs and symptoms in a few countries, especially in Africa. A disproportionate number of incidents occurred during insecticide use relative to the time that they were sprayed. Failure to exercise caution as indicated by whether users had incidents involving agricultural equipment or livestock, and lack of confidence in their practices were the most important predictors of agrochemical-related incidents.     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.