Cost-analysis of treatment of childhood acute lymphoblastic leukemia with asparaginase preparations: the impact of expensive chemotherapy.

Asparaginase is an expensive drug, but important in childhood acute lymphoblastic leukemia. In order to compare costs of PEGasparaginase, Erwinia asparaginase and native E. coli asparaginase, we performed a cost-analysis in the Dutch Childhood Oncology Group ALL-10 medium-risk group intensification protocol. Treatment costs were calculated based on patient level data of 84 subjects, and were related to the occurrence of allergy to PEGasparaginase. Simultaneously, decision tree and sensitivity analyses were conducted. The total costs of the intensification course of 30 weeks were $57,893 in patients without PEGasparaginase allergy (n=64). The costs were significantly higher ($113,558) in case of allergy (n=20) necessitating a switch to Erwinia asparaginase. Simulated scenarios (decision tree analysis) using native E. coli asparaginase in intensification showed that the costs of PEGasparaginase were equal to those of native E. coli asparaginase. Also after sensitivity analyses, the costs for PEGasparaginase were equal to those of native E. coli asparaginase. Intensification treatment with native E. coli asparaginase, followed by a switch to PEGasparaginase, and subsequently to Erwinia asparaginase in case of allergy had similar overall costs compared to the treatment with PEGasparaginase as the first-line drug (followed by Erwinia asparaginase in the case of allergy). PEGasparaginase is preferred over native E. coli asparaginase, because it is administered less frequently, with less day care visits. PEGasparaginase is less immunogenic than native E. coli asparaginase and is not more expensive. Asparaginase costs are mainly determined by the percentage of patients who are allergic and require a switch to Erwinia asparaginase.

Screening for post-miscarriage psychiatric morbidity.

OBJECTIVE: The purpose of this study was to evaluate 12-item General Health Questionnaire (GHQ-12) in screening for psychiatric morbidity after miscarriage. STUDY DESIGN: A prospective cohort study was carried out involving 222 patients. Six weeks after miscarriage, the GHQ-12 was applied. Psychiatric "case" or "non-case" was diagnosed by the psychiatrist with use of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-R. The patients were computer randomized into Groups A or B. A receiver operating characteristic (ROC) curve was constructed for Group A. The optimal cutoff value of GHQ-12 was determined, and this value was applied to Group B. The test characteristics were assessed. RESULTS: Twenty-seven patients were found to be psychiatric cases. An ROC with area under curve of 0.93 (95% CI 0.87-0.99, P<.001) was constructed. The best GHQ-12 cutoff score was > or =4 in detecting psychiatric caseness. A sensitivity of 83%, specificity of 90%, positive predictive value of 50%, and negative predictive value of 98% were obtained. CONCLUSION: GHQ-12 is an effective screening tool in detecting psychiatric morbidity after miscarriage.

Determination of local statistical significance of patterns in Markov sequences with application to promoter element identification.

High-level eukaryotic genomes present a particular challenge to the computational identification of transcription factor binding sites (TFBSs) because of their long noncoding regions and large numbers of repeat elements. This is evidenced by the noisy results generated by most current methods. In this paper, we present a p-value-based scoring scheme using probability generating functions to evaluate the statistical significance of potential TFBSs. Furthermore, we introduce the local genomic context into the model so that candidate sites are evaluated based both on their similarities to known binding sites and on their contrasts against their respective local genomic contexts. We demonstrate that our approach is advantageous in the prediction of myogenin and MEF2 binding sites in the human genome. We also apply LMM to large-scale human binding site sequences in situ and found that, compared to current popular methods, LMM analysis can reduce false positive errors by more than 50% without compromising sensitivity. This improvement will be of importance to any subsequent algorithm that aims to detect regulatory modules based on known PSSMs.

Focus on sustainability.

PIP: In recent years, sustainability has become one of the most critical concepts in international development and is having a dramatic impact on the way development is conceptualized and carried out. The US Agency for International Development (USAID) is incorporating this concept into its programs and projects. Factors encouraging sustainability of projects and programs include host government policies that support or constrain program objectives, national and/or local commitment to project goals, managerial leadership that helps shape improved policies, collaboration at all staff levels in program management, financial resources that cover program operational costs, appropriate program technology, integration of the program with the social and cultural setting of the country, community involvement in the program, sound environmental management, technical assistance oriented to transferring skills and increasing institutional capacity, perception by the host country that the project is "effective," training provided by the project to transfer skill needed for capacity-building, integration of the program into existing institutional framework, and external political, economic and environmental factors. Impediments to sustainability are often inherent in the donor agency's programming process. This includes the implicit assumption that program objectives can be accomplished in a relatively short time frame, when in fact capacity-building requires a lengthy commitment. USAID professionals are pressured to show near-term results which emphasize outputs rather than purpose and goal-level accomplishments achievable only after extensive effort. The emphasis on obligating money and on the project paper as a sales document leads project designers to talk with a great deal more certainty about project results than is warranted by the complex development situation. Uncertainty and flexibility should be designed into projects so activities and objects can change as more information and on-site experience is gained. Instead of outputs, success should be measured in processes that will continue to produce long-term results. Emphasis should be placed on establishing policymaking processes and decision making procedures in the recipient country that will lead to sound economic policymaking on a continuing basis. Sustainable efforts in agriculture, health, rural development and their evaluation are examined for several USAID projects.^ieng