RESUMEN
Precision medicine (PM) requires the delivery of individually adapted medical care based on the genetic characteristics of each patient and his/her tumor. The last decade witnessed the development of high-throughput technologies such as microarrays and next-generation sequencing which paved the way to PM in the field of oncology. While the cost of these technologies decreases, we are facing an exponential increase in the amount of data produced. Our ability to use this information in daily practice relies strongly on the availability of an efficient bioinformatics system that assists in the translation of knowledge from the bench towards molecular targeting and diagnosis. Clinical trials and routine diagnoses constitute different approaches, both requiring a strong bioinformatics environment capable of (i) warranting the integration and the traceability of data, (ii) ensuring the correct processing and analyses of genomic data, and (iii) applying well-defined and reproducible procedures for workflow management and decision-making. To address the issues, a seamless information system was developed at Institut Curie which facilitates the data integration and tracks in real-time the processing of individual samples. Moreover, computational pipelines were developed to identify reliably genomic alterations and mutations from the molecular profiles of each patient. After a rigorous quality control, a meaningful report is delivered to the clinicians and biologists for the therapeutic decision. The complete bioinformatics environment and the key points of its implementation are presented in the context of the SHIVA clinical trial, a multicentric randomized phase II trial comparing targeted therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer. The numerous challenges faced in practice during the setting up and the conduct of this trial are discussed as an illustration of PM application.
RESUMEN
BACKGROUND: Rotavirus causes approximately one-third to one-half (55,000-70,000 hospitalizations per year) of hospitalizations for acute gastroenteritis (AGE) among US children <5 years of age. We forecasted the potential reduction in the number of hospitalizations for rotavirus disease and AGE in US children during 2006-2015 as a result of the new rotavirus vaccine introduced in 2006. METHODS: The mean number of hospitalizations for AGE by calendar month among US children was determined using the National Hospital Discharge Survey from the period 1993-2005. From these baseline prevaccine estimates, we forecasted the effect of vaccine in reducing the number of hospitalizations for rotavirus disease and AGE during 2006-2015 with use of estimates of vaccine effectiveness and uptake. RESULTS: During 2006-2015, approximately 313,000 (45%) of an estimated 703,190 hospitalizations for rotavirus disease would be directly prevented by vaccination. A significant reduction in the number of hospitalizations for AGE should be detectable among infants aged 0-11 months during the first quarter of 2009, followed by children aged 12-23 months during 2010, and all children <5 years of age during 2011. CONCLUSIONS: Vaccination is expected to substantially reduce the health burden of hospitalizations for rotavirus disease among US children during 2006-2015, and the impact of vaccination based on direct protective effects alone was expected to first occur for hospitalizations for AGE among infants during winter 2009.
