Etudes de stabilité de médicaments anticancéreux injectables (apports analytiques et pharmaceutiques)

La prise en charge des patients atteints de cancer fait intervenir le pharmacien hospitalier dans la préparation des médicaments anticancéreux injectables. Afin de limiter les coûts de cette prise en charge médicamenteuse, une des alternatives consiste à optimiser leur préparation en prenant en compte la stabilité physico-chimique des anticancéreux : 1-en utilisant les reliquats générés lors de la préparation. 2- en évaluant la possibilité de fabriquer à l avance les préparations d anticancéreux. L absence de données de stabilité de ces médicaments nous a conduits à l évaluer sur le pemetrexed et le methotrexate afin de répondre à cette double problématique et d étudier le gain de coût associé.Nous avons démontré, au cours de ce travail, la stabilité des reliquats de pemetrexed-Alimta® pendant14 jours permettant ainsi leur réutilisation. Nous avons également montré la stabilité de solutions de méthotrexate conditionnées en seringues pendant 28 jours.Une des conséquences de ces études est la réalisation d économie pour la sécurité sociale par l optimisation de la gestion des reliquats d anticancéreux. Cette économie représente environ 10 % du budget annuel des anticancéreux injectables soit 750 kEUR. Nous avons montré au cours de ce travail l apport de la chimie analytique et organique ainsi que l apport de la pharmacie dans la mise en place et l exploitation des études de stabilité sur les médicaments anticancéreux injectables.Hospital pharmacists are involved in the management of cancer patients through preparation of intravenous anticancer drugs. To limit the costs of the chemotherapies, an alternative is to optimize their preparation by considering the physicochemical stability of anticancer drugs. This can be done by using the leftovers generated during the preparation and by preparing in advance the devices to be used for administration. The lack of data on the stability of anticancer drugs has led us to evaluate pemetrexed and methotrexate with the aim of answering both the above issues. In parallel, we studied the associated cost savings.In this thesis, we have demonstrated the stability of leftovers of pemetrexed-Alimta® for 14 days allowing their use for subsequent preparations. We also showed the stability of solutions of methotrexate packaged in syringes for 28 days.One consequence of these studies is its translation in cost-savings for our Healthcare Funding Organization by managing leftover anticancer drugs. These cost-savings (about 750 kEUR) represent about 10 % of the total annual expenditure of anticancer drugs. Our work illustrates the contribution of analytical and organic chemistry and the role pharmacists can have in improving costs by performing stability studies of anticancer drugs.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF

Reconnaissance au travail (la)

La « reconnaissance » est devenue un nouvel enjeu de société. Le désir d’être reconnu envahit le monde du travail et imprègne les relations et les discours des individus. Reconnaissance de compétences, reconnaissance de la personne à travers son positionnement dans l’organisation, reconnaissance vis à vis de la hiérarchie et du groupe. Que revendiquet-on dans le monde du travail, quand on demande « une plus grande reconnaissance » ? quelles formes celle-ci peut-elle prendre, en particulier dans les démarches d’évaluation ou de validation de l’expérience ? Comment les entreprises abordent-elles ces attentes collectives et individuelles de reconnaissance

Smells in system user interactive tests

peer reviewedTest smells are known as bad development practices that reflect poor design and implementation choices in software tests. Over the last decade, there are few attempts to study test smells in the context of system tests that interact with the System Under Test through a Graphical User Interface. To fill the gap, we conduct an exploratory analysis of test smells occurring in System User Interactive Tests (SUIT). We thus, compose a catalog of 35 SUIT-specific smells, identified through a multi-vocal literature review, and show how they differ from smells encountered in unit tests. We also conduct an empirical analysis to assess the diffuseness and removal of these smells in 48 industrial repositories and 12 open-source projects. Our results show that the same type of smells tends to appear in both industrial and open-source projects, but they are not addressed in the same way. We also find that smells originating from a combination of multiple code locations appear more often than those that are localized on a single line. This happens because of the difficulty to observe non-local smells without tool support. Furthermore, we find that smell-removing actions are not frequent with less than 50% of the affected tests ever undergoing a smell removal. Interestingly, while smell-removing actions are rare, some smells disappear while discarding tests, i.e., these smells do not appear in follow-up tests that replace the discarded ones

Associations between peer victimization and suicidal ideation and suicide attempt during adolescence : results from a prospective population-based birth cohort

Objective:To test whether adolescents who are victim-ized by peers are at heightened risk for suicidal ideationand suicide attempt, using both cross-sectional andprospective investigations.Method:Participants are from the Quebec LongitudinalStudy of Child Development, a general population sampleof children born in Quebec in 1997 through 1998 andfollowed up until 15 years of age. Information aboutvictimization and serious suicidal ideation and suicideattempt in the past year was obtained at ages 13 and15 years from self-reports (N¼1,168).Results:Victims reported concurrently higher rates ofsuicidal ideation at age 13 years (11.6–14.7%) and suicideattempt at age 15 years (5.4–6.8%) compared to those whohad not been victimized (2.7–4.1% for suicidal ideationand 1.6–1.9% for suicide attempt). Being victimized bypeers at 13 years predicted suicidal ideation (odds ratio[OR]¼2.27; 95% CI¼1.25–4.12) and suicideattempt (OR¼3.05, 95% CI¼1.36–6.82) 2 years later,even after adjusting for baseline suicidality andmental health problems and a series of confounders(socioeconomic status, intelligence, family’s functioningand structure, hostile-reactive parenting, maternal lifetimesuicidal ideation/suicide attempt). Those who werevictimized at both 13 and 15 years had the highest risk ofsuicidal ideation (OR¼5.41, 95% CI¼2.53–11.53) andsuicide attempt (OR¼5.85, 95% CI¼2.12–16.18) at15 years.Conclusion:Victimization is associated with an increasedrisk of suicidal ideation and suicide attempt over andabove concurrent suicidality and prior mental healthproblems. The longer the history of victimization, thegreater the risk

Contribution of genes and environment to the longitudinal association between childhood impulsive‐aggression and suicidality in adolescence

Background Population‐based and family studies showed that impulsive‐aggression predicts suicidality; however, the underlying etiological nature of this association is poorly understood. The objective was to determine the contribution of genes and environment to the association between childhood impulsive‐aggression and serious suicidal ideation/attempt in young adulthood. Methods N = 862 twins (435 families) from the Quebec Newborn Twin Study were followed up from birth to 20 years. Repeated measures of teacher‐assessed impulsive‐aggression were modeled using a genetically informed latent growth model including intercept and slope parameters reflecting individual differences in the baseline level (age 6 years) and in the change (increase/decrease) of impulsive‐aggression during childhood (6 to 12 years), respectively. Lifetime suicidality (serious suicidal ideation/attempt) was self‐reported at 20 years. Associations of impulsive‐aggression intercept and slope with suicidality were decomposed into additive genetic (A) and unique environmental (E) components. Results Additive genetic factors accounted for an important part of individual differences in impulsive‐aggression intercept (A = 90%, E = 10%) and slope (A = 65%, E = 35%). Genetic (50%) and unique environmental (50%) factors equally contributed to suicidality. We found that 38% of the genetic factors accounting for suicidality were shared with those underlying impulsive‐aggression slope, whereas 40% of the environmental factors accounting for suicidality were shared with those associated with impulsive‐aggression intercept. The genetic correlation between impulsive‐aggression slope and suicidality was 0.60, p = .027. Conclusions Genetic and unique environmental factors underlying suicidality significantly overlap with those underlying childhood impulsive‐aggression. Future studies should identify putative genetic and environmental factors to inform prevention

A collaborative model to implement flexible, accessible and efficient oncogenetic services for hereditary breast and ovarian cancer : the C-MOnGene study

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants' understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics

Awareness Tool for Safe and Responsible Driving (OSCAR) : A Potential Educational Intervention for Increasing Interest, Openness and Knowledge About the Abilities Required and Compensatory Strategies Among Older Drivers

Abstract : Objective: This pilot study aimed to verify the impact of the awareness tool for safe and responsible driving (OSCAR) on older adults’ (1) interest, openness, and knowledge about the abilities and compensatory strategies required for safe driving; (2) awareness of changes that have occurred in their own driving abilities; and (3) actual utilization of compensatory strategies. Methods: A preexperimental design, including a pretest (T0) and posttest (T1) 8 to 10 weeks after exposure to the intervention, was used with 48 drivers aged between 67 and 84. The participants had a valid driving license and drove at least once a week. Results: Overall, the results demonstrate that OSCAR increased interest, openness, and knowledge about the abilities and compensatory strategies of older drivers (P < .01). After exposure to OSCAR, the majority of the participants confirmed that changes had occurred in at least one of their abilities. Moreover, half of the older drivers reported having started using 6 or more compensatory strategies. Conclusion: In summary, in addition to increasing older adults’ interest, openness, and knowledge to discussion about driving, OSCAR also improved awareness of the changes that could negatively impact safe driving and enhanced utilization of compensatory strategies. While promoting safe driving and the prevention of crashes and injuries, this intervention could ultimately help older adults maintain or increase their transportation mobility. More studies are needed to further evaluate OSCAR and identify ways to improve its effectiveness

Population genomics of the Viking world.

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals