Cost-effectiveness of a specialized oral nutritional supplementation for malnourished older adult patients in Spain

Malnutrition has been related to prolonged hospital stays, and to increases in readmission and mortality rates. In the NOURISH (Nutrition effect On Unplanned Readmissions and Survival in Hospitalized patients) study, administering a high protein oral nutritional supplement (ONS) containing beta-hydroxy-beta-methylbutyrate (HP-HMB) to hospitalised older adult patients led to a significant improvement in survival compared with a placebo treatment. The aim of this study was to determine whether HP-HMB would be cost-effective in Spain. We performed a cost-effectiveness analysis from the perspective of the Spanish National Health System using time horizons of 90 days, 180 days, 1 year, 2 years, 5 years and lifetime. The difference in cost between patients treated with HP-HMB and placebo was €332.75. With the 90 days time horizon, the difference in life years gained (LYG) between both groups was 0.0096, resulting in an incremental cost-effectiveness ratio (ICER) of €34, 700.62/LYG.With time horizons of 180 days, 1 year, 2 years, 5 years and lifetime, the respective ICERs were €13, 711.68, €3377.96, €2253.32, €1127.34 and €563.84/LYG. This analysis suggests that administering HP-HMB to older adult patients admitted to Spanish hospitals during hospitalisation and after discharge could be a cost-effective intervention that would improve survival with a reduced marginal cost

Structural insights into natural transformation and toxin-antitoxin systems

La incidència d’infeccions gonocòciques i pneumocòciques roman alta en països en vies de desenvolupament i està augmentant a moltes parts del món. La necessitat de tractaments per a l’individu i per al control de la malaltia a nivel comunitàri és punyent però escollir el tractament adequat ha esdevingut complex com a conseqüència de la capacitat de Neisseria gonorrhoeae i Streptococcus pneumoniae de desenvolupar resistència envers antibiòtics. Aquesta tesi de doctorat investiga mecanismes relacionats amb la transferència genética horitzontal i amb l’arrest del creixement a N. gonorrhoeae and S. pneumoniae. La primera part de la tesi està dedicada a l’estudi de la transformació natural a N. gonorrhoeae i descriu els procediments que han portat a l’expressió, purificació i caracterització bioquímica de ComE, ComA i DprA, tres proteïnes que tenen un paper en la presa i el processament de DNA ambiental. La segona part de la tesi descriu la caracterització estructural mitjançant cristal·lografia de rajos X de RelBE2 de S. pneumoniae, un sistema toxina-antitoxina cromosòmic de tipus II que s’ha relacionat amb la moderació de la traducció i amb l’arrest del creixement en condicions d’escassetat de nutrients, i proposa un model per a la seva regulació.The incidence of gonococcal and pneumococcal infections remains high in developing countries and is increasing in many parts of the world. The need not only for treatment of the individual but also for control of the diseases at a community level is acute but the selection of appropriate treatments has become a complicated issue by the ability of Neisseria gonorrhoeae and Streptococcus pneumoniae to develop resistance to antibiotics. This PhD thesis investigates mechanisms related to horizontal gene transfer and growth arrest in N. gonorrhoeae and S. pneumoniae. The first part of the thesis is devoted to the study of natural transformation in N. gonorrhoeae and describes the procedures that have lead to the expression, purification and biochemical characterization of ComE, ComA and DprA, three proteins involved in the uptake and processing of environmental DNA. The second part of the thesis describes the structural characterization by X-ray crystallography of S. pneumoniae RelBE2, a chromosomally-encoded type II toxin-antitoxin system that has been linked to translation moderation and growth arrest under starvation conditions, and proposes a model for its regulation

Structural insights into natural transformation and toxin-antitoxin systems : biochemical and structural characterization of Neisseria gonorrhoeae ComE, ComA and DprA and Streptococcus pneumoniae ReIBE2 /

La incidència d'infeccions gonocòciques i pneumocòciques roman alta en països en vies de desenvolupament i està augmentant a moltes parts del món. La necessitat de tractaments per a l'individu i per al control de la malaltia a nivel comunitàri és punyent però escollir el tractament adequat ha esdevingut complex com a conseqüència de la capacitat de Neisseria gonorrhoeae i Streptococcus pneumoniae de desenvolupar resistència envers antibiòtics. Aquesta tesi de doctorat investiga mecanismes relacionats amb la transferència genética horitzontal i amb l'arrest del creixement a N. gonorrhoeae and S. pneumoniae. La primera part de la tesi està dedicada a l'estudi de la transformació natural a N. gonorrhoeae i descriu els procediments que han portat a l'expressió, purificació i caracterització bioquímica de ComE, ComA i DprA, tres proteïnes que tenen un paper en la presa i el processament de DNA ambiental. La segona part de la tesi descriu la caracterització estructural mitjançant cristal·lografia de rajos X de RelBE2 de S. pneumoniae, un sistema toxina-antitoxina cromosòmic de tipus II que s'ha relacionat amb la moderació de la traducció i amb l'arrest del creixement en condicions d'escassetat de nutrients, i proposa un model per a la seva regulació.The incidence of gonococcal and pneumococcal infections remains high in developing countries and is increasing in many parts of the world. The need not only for treatment of the individual but also for control of the diseases at a community level is acute but the selection of appropriate treatments has become a complicated issue by the ability of Neisseria gonorrhoeae and Streptococcus pneumoniae to develop resistance to antibiotics. This PhD thesis investigates mechanisms related to horizontal gene transfer and growth arrest in N. gonorrhoeae and S. pneumoniae. The first part of the thesis is devoted to the study of natural transformation in N. gonorrhoeae and describes the procedures that have lead to the expression, purification and biochemical characterization of ComE, ComA and DprA, three proteins involved in the uptake and processing of environmental DNA. The second part of the thesis describes the structural characterization by X-ray crystallography of S. pneumoniae RelBE2, a chromosomally-encoded type II toxin-antitoxin system that has been linked to translation moderation and growth arrest under starvation conditions, and proposes a model for its regulation