Feasibility of chemosensitivity testing in soft tissue sarcomas

BACKGROUND: Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes. METHODS: The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested. RESULTS: The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples. CONCLUSION: Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet

Effectiveness of chemoprophylaxis and other determinants of malaria in travellers to Kenya.

OBJECTIVE: To investigate the effectiveness of chemoprophylaxis and the determinants of malaria importation from Kenya. METHOD: In a population-based case-control study, 51 travellers from Bavaria diagnosed with falciparum malaria imported from Kenya (cases) and a sample of 383 healthy Bavarian travellers returning from Kenya (controls) were interviewed. Data were analysed by multiple logistic regression. RESULTS: Mefloquine (OR = 0.055; 95% CI 0.019-0.16) and chloroquine combined with proguanil (OR = 0.128; 95% CI 0.039-0.419) were highly protective against P. falciparum malaria, whereas other drugs were ineffective (OR = 1.225; 95% CI 0.536-2.803). Ineffective prophylaxis (10.4%) and non-prophylaxis (11.2%) were the main reasons for malaria importation. Travelling alone or with friends, male sex, and travel duration over 4 weeks could be identified as additional risk factors. The main reason for inadequate chemoprophylaxis was inappropriate medical advice (87.5%). Prophylaxis refusal occurred frequently despite correct advice (58.1%). Diagnosis was often delayed unnecessarily (27.5%). CONCLUSION: Malaria importation from Kenya could be reduced substantially (34%) by eliminating inappropriate medical advice

A Hardware/Software Codesign Methodology for Power-Aware Smart Cards *

Abstract – Power and energy consumption is an essential design constraint for passive embedded mobile devices. These devices, e.g. smart cards, do not contain an integrated power supply and often provide only limited resources. Such devices can be designed with traditional methods due to their low complexity, but integrated HW/SW co-design methodologies enable the gain of system-level optimization. This paper presents the abstraction of smart card designs to optimize system architecture and memory system. Functiona-level, transactional-level, and cycle-accurate models are presented and discussed. The proposed design flow and results of the evaluation are depicted. Keywords: Smart Card, HW/SW Co-design, Low Power, Transaction-level, Java Card Power and energy consumption has been an important design constraint for embedded devices for more than one decade. Embedded systems powered by batteries are designed for minimized energy dissipation to increase stand-by and active times. Passive mobile devices, for instance contact-less smart cards, are often powered by some sort of RF field with constrained field energy. This field doe

The Benefit-Harm Frontier of Different Primary Screening Strategies for Cervical Cancer in Germany

Sroczynski G, Esteban E, Engel J, et al. The Benefit-Harm Frontier of Different Primary Screening Strategies for Cervical Cancer in Germany. In: Value in Health. Value in Health. Vol 16. New York: Elsevier; 2013: A574-A575

Cost-effectiveness of primary HPV screening for cervical cancer in Germany - a decision analysis

Sroczynski G, Schnell-Inderst P, Muehlberger N, et al. Cost-effectiveness of primary HPV screening for cervical cancer in Germany - a decision analysis. European Journal of Cancer. 2011;47(11):1633-1646.Objectives: To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. Methods: A Markov-model for HPV-infection and cervical cancer was developed for the German health care context, and applied to evaluate various screening strategies that differ by screening interval and test algorithms, including HPV-testing alone or in combination with cytology. German clinical, epidemiological, and economic data, and test accuracy data from international meta-analyses were used. Outcomes predicted included the reduction in cervical cancer cases and deaths, life expectancy and discounted incremental cost-effectiveness ratios (ICER). The analysis was performed from the perspective of the healthcare system adopting a 3% annual discount rate for costs and outcomes. Extensive sensitivity analyses were performed. Results: HPV-based screening is more effective than cytology alone. It results in a 71-97% reduction in cervical cancer cases as compared to 53-93% for cytology alone. The ICER range from 2600 Euro/LYG (cytology, 5-year-interval) to 155,500 Euro/LYG (annual HPV-testing starting at age 30 years, cytology age 20-29 years). Annual cytology alone, the current recommended screening strategy in Germany, is dominated by HPV-strategies. Increasing the age at screening initiation from 20 to 25 years does not result in a relevant loss in effectiveness but results in lower costs. Conclusions: Based on our analyses, HPV-based cervical cancer screening is more effective than cytology alone and could be cost-effective if performed at intervals of two years or longer. In the German context, an optimal screening strategy may be biennial HPV screening starting at age 30 years preceded by biennial cytology for women aged 25-29 years. Longer screening intervals may be considered in low-risk women with good screening adherence and in populations with low HPV-incidence. (C) 2011 Elsevier Ltd. All rights reserved

HPV-BASED PRIMARY CERVICAL CANCER SCREENING IN GERMANY. COST-EFFECTIVENESS RESULTS FROM A DECISION-ANALYTIC MODELING STUDY

Sroczynski G, Schnell-Inderst P, Muehlberger N, et al. HPV-BASED PRIMARY CERVICAL CANCER SCREENING IN GERMANY. COST-EFFECTIVENESS RESULTS FROM A DECISION-ANALYTIC MODELING STUDY. In: Value in Health. Value in Health. Vol 13. Wiley Blackwell (Blackwell Publishing); 2010: A239

From the third sector to the big society: how changing UK Government policies have eroded third sector trust

This article draws on concepts of trust to analyse recent policies affecting public/third sector relationships, examining competition, ‘command and control’ mechanisms and the community turn in shaping cultures of relationships. Drawing on examples from empirical studies in two English inner-city areas we explore ways in which power and controls exerted through dominant organisational cultures and arrangements undermine independent approaches, innovation and organisational learning across sectors. State bodies have taken trust in their actions as given while shifting responsibilities for service delivery and risks of failure to others. We argue that increasing market cultures and regulation have damaged cross-sector trust promoting divisive interests and risk-averse behaviours, restricting the local autonomy, innovation and community action presumed in the Big Society agenda. We conclude by highlighting issues that need to be addressed to ensure future collaboration with community-based providers; these include a focus on the processes and relational spaces which enable alternatives