Definition of Personalized Medicine and Targeted Therapies: Does Medical Familiarity Matter?

Personalized medicine (PM) is increasingly becoming a topic of discussion in public health policies and media. However, there is no consensus among definitions of PM in the scientific literature and the terms used to designate it, with some definitions emphasizing patient-centered aspects and others emphasizing biomedical aspects. Furthermore, terms used to refer to PM (e.g., "pharmacogenomics" or, more often, "targeted therapies") are diverse and differently used. To our knowledge, no study has apprehended the differences of definition and attitudes toward personalized medicine and targeted therapies according to level of familiarity with the medical field. Our cohort included 349 French students from three different academic fields, which modulated their familiarity level with the medical field. They were asked to associate words either to "personalized medicine" or "target therapies". Then, they were asked to give an emotional valence to their associations. Results showed that nonfamiliar students perceived PM as more positive than targeted therapies (TT), whereas familiar students showed no difference. Only familiar students defined PM and TT with technical aspects such as genetics or immunology. Further studies are needed in the field in order to determine which other factors could influence the definitions of PM and TT and determine how these definitions could have an impact in a clinical setting.

[Pediatric informed consent in medical care and research]. / Consentement éclairé de l'enfant.

Pediatric informed consent in medical care and research. The obligation to obtain informed consent from a patient prior to any care does not depend solely on the personal ethics of the practitioner. It is defined and framed by law. However, innumerable legal difficulties emanate from the simple fact that the subject is a child, a vulnerable person who must be protected, and that this protection is exercised under the aegis of the parental authority. If in most cases there is an alliance with the holders of parental authority, the views sometimes diverge. The article lists the most frequently observed cases in clinical practice and the way in which the french Public Health Code plans to solve them. Problems specific to research are discussed. Difficulties for consent about off-label prescribing are briefly exposed.

Consentement éclairé de l'enfant. L'obligation de recueillir le consentement éclairé du patient avant tout soin le concernant ne relève pas seulement de l'éthique personnelle du praticien. Elle est définie et encadrée par la loi. Cependant, des difficultés juridiques innombrables émanent du simple fait que le sujet est un enfant, personne vulnérable qu'il faut protéger, et que ladite protection s'exerce sous l'égide de l'autorité parentale. Si dans l'immense majorité des cas, il y a alliance avec les détenteurs de l'autorité parentale, il arrive que les points de vue divergent. Cet article recense les cas de figure les plus fréquemment observés en pratique clinique et la façon dont le code de la santé publique prévoit de les résoudre. Les problèmes spécifiques à la recherche et à la prescription hors autorisation de mise sur le marché sont succinctement abordés.

Communication in pediatric critical care: A proposal for an evidence-informed framework.

The aim of this investigation was to conduct a comprehensive examination of communication between parents and health care professionals (HCPs) in the pediatric intensive care unit (PICU). A secondary analysis was performed on data from 3 previous qualitative studies, which included 30 physicians, 37 nurses, and 38 parents in France and Quebec (Canada). All three studies examined a mix of cases where children either survived or died. All data referring to communication between parents (and patients when applicable) and HCPs were examined to identity themes that related to communication. Thematic categories for parents and HCPs were developed. Three interrelated dimensions of communication were identified: (1) informational communication, (2) relational communication, and (3) communication and parental coping. Specific themes were identified for each of these 3 dimensions in relation to parental concerns as well as HCP concerns. This investigation builds on prior research by advancing a comprehensive analysis of PICU communication that includes (a) cases where life-sustaining treatments were withdrawn or withheld as well as cases where they were maintained, (b) data from HCPs as well as parents, and (c) investigations conducted in 4 different sites. An evidence-informed conceptual framework is proposed for PICU communication between parents and HCPs. We also outline priorities for the development of practice, education, and research.

Struggling to do what is right for the child: pediatric life-support decisions among physicians and nurses in France and Quebec.

This study examined (a) how physicians and nurses in France and Quebec make decisions about life-sustaining therapies (LSTs) for critically ill children and (b) corresponding ethical challenges. A focus groups design was used. A total of 21 physicians and 24 nurses participated (plus 9 physicians and 13 nurses from a prior secondary analysis). Principal differences related to roles: French participants regarded physicians as responsible for LST decisions, whereas Quebec participants recognized parents as formal decision-makers. Physicians stated they welcomed nurses' input but found they often did not participate, while nurses said they wanted to contribute but felt excluded. The LST limitations were based on conditions resulting in long-term consequences, irreversibility, continued deterioration, inability to engage in relationships and loss of autonomy. Ethical challenges related to: the fear of making errors in the face of uncertainty; struggling with patient/family consequences of one's actions; questioning the parental role and dealing with relational difficulties between physicians and nurses.

Prevalence of questioning regarding life-sustaining treatment and time utilisation by forgoing treatment in francophone PICUs.

PURPOSE: Our goal is to assess the prevalence of questioning about the appropriateness of initiating or maintaining life-sustaining treatments (LST) in French-speaking paediatric intensive care units (PICUs) and to evaluate time utilisation related to decision-making processes (DMP). METHODS: 18-month, multicentre, prospective, descriptive, observational study in 15 French-speaking PICUs. RESULTS: Among the 5,602 children admitted, 410 died (7.3%), including 175 after forgoing LST (42.7% of deaths). LST was questioned in 308 children (5.5%) with a prevalence of 13.3 per 100 patient-days. More than 30% of children survived despite the appropriateness of LST being questioned (23% despite a decision to forgo treatment). Median caregiver time spent on making and presenting the decisions was 11 h per child. CONCLUSIONS: In this study, on any given day in each 10-bed PICU, there was more than one child for whom a DMP was underway. Of children, 23% survived despite a decision to forgo LST being made, which underlines the need to elaborate a care plan for these children. Also, DMP represented a large amount of staff time that is undervalued but necessary to ensure optimal palliative practice in PICU.

Children with chronic conditions in pediatric intensive care units located in predominantly French-speaking regions: Prevalence and implications on rehabilitation care need and utilization.

OBJECTIVE: To estimate the prevalence of chronic conditions and/or disability in intensive care units admitting children (Pediatric Intensive Care Unit [PICU]) or both neonates and children (Neonatal and Pediatric Intensive Care Unit [NPICU]) and to describe available rehabilitation resources. DESIGN: A cross-sectional study on two separate days, using a web questionnaire. SETTING: NPICU/PICUs affiliated to the Groupe Francophone de Réanimation et Urgences Pédiatriques and the Réseau Mère-Enfant de la Francophonie. PATIENTS: Children >1 month of gestationally corrected age. MEASUREMENTS AND MAIN RESULTS: Disability was defined as a Pediatric Overall Performance Category >or=3 before admission and chronic conditions as hospitalization since birth or the presence before admission of any condition requiring ongoing pediatric subspecialty care that was expected to last >or=12 months. Intensivists indicated what rehabilitation services they would have ideally prescribed ("perceived needs") and those provided. Of 45 affiliated units, 8 PICUs and 15 NPICUs participated. Staff included or had access to a psychologist (11 and 5, respectively), a social worker (10 and 3), a physiotherapist (11 and 12), a "psychomotrician" (2 and 8), a child educator (1 and 6), and a speech-language pathologist (0 and 6). Among 289 recorded intensive care unit-days, 236 were analyzed (excluding those for children admitted after surgery): 57 concerned children hospitalized since birth and 179 children admitted from home. Among these 179 recorded intensive care unit-days, 107 concerned children with chronic conditions (including 50 concerning disabled children) and 72 previously healthy children. Thus, prevalence of chronic conditions, including children hospitalized since birth, was 67%. Rehabilitation services included respiratory physical therapy (552 visits), musculoskeletal physical therapy (71), neurologic physical therapy (37), rehabilitation for swallowing (11), and for speech-language disorders (1), representing 79% of perceived needs. CONCLUSIONS: Prevalence of chronic conditions in NPICU/PICU was 67%. More attention must be paid to the rehabilitation care needs of patients during their NPICU/PICU stay and after discharge.

Effects of inertance on respiratory mechanics measurements in mechanically ventilated children.

OBJECTIVE: The use of the first-order linear single compartment model when studying respiratory mechanics classically neglects inertance (Irs). We hypothesized that Irs would affect compliance (Crs) and resistance (Rrs) estimates in mechanically ventilated young children. DESIGN: Prospective study; single-center evaluation. SETTING: University-affiliated tertiary pediatric intensive care unit. PATIENTS: Forty-four patients with and without respiratory disease. INTERVENTIONS: Patients were studied during volume-controlled constant inspiratory flow ventilation. MEASUREMENTS AND MAIN RESULTS: Pressure (PaO) and flow (V') were analyzed according to two different models: a one-compartment first-order linear model according to PaO = (1/Crs) x V + Rrs x V' and a one-compartment second-order linear model according to PaO = (1/Crs) x V + Rrs x V' + Irs x V''. Irs was higher in children with vs. those without respiratory disease (median 0.00224 cm H2O/L/sec2, Q1-Q3 0.00180-0.00321 vs. median 0.00133 cm H2O/L/sec2, Q1-Q3 0.00072-0.00210; p < .001)). A positive correlation between Irs and the difference of Crs estimates between the first- and the second-order model was found in both groups (r = .84, p < .05 and r = .67, p < .05). Rrs estimates were similar in both groups. CONCLUSIONS: This study showed that the linear single-compartment model may not adequately estimate the respiratory mechanical properties in mechanically ventilated children, particularly in the presence of respiratory disease. Including an Irs term significantly diminished Crs estimates. A one-compartment second-order linear model might be a useful clinical tool in more adequately measuring respiratory mechanics and optimizing ventilatory settings in children with respiratory disease.

Parental involvement in treatment decisions regarding their critically ill child: a comparative study of France and Quebec.

OBJECTIVE: To examine whether physicians or parents assume responsibility for treatment decisions for critically ill children and how this relates to subsequent parental experience. A significant controversy has emerged regarding the role of parents, relative to physicians, in relation to treatment decisions for critically ill children. Anglo-American settings have adopted decision-making models where parents are regarded as responsible for such life-support decisions, while in France physicians are commonly considered the decision makers. DESIGN: Grounded theory qualitative methodology. SETTING: Four pediatric intensive care units (two in France and two in Quebec, Canada). PATIENTS: Thirty-one parents of critically ill children; nine physicians and 13 nurses who cared for their children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Semistructured interviews were conducted. In France, physicians were predominantly the decision makers for treatment decisions. In Quebec, decisional authority practices were more varied; parents were the most common decision maker, but sometimes it was physicians, while for some decisional responsibility depended on the type of decision to be made. French parents appeared more satisfied with their communication and relationship experiences than Quebec parents. French parents referred primarily to the importance of the quality of communication rather than decisional authority. There was no relationship between parents' actual responsibility for decisions and their subsequent guilt experience. CONCLUSIONS: It was remarkable that a certain degree of medical paternalism was unavoidable, regardless of the legal and ethical norms that were in place. This may not necessarily harm parents' moral experiences. Further research is required to examine parental decisional experience in other pediatric settings.

Severe selenium deficiency secondary to chylous loss.

Selenium deficiency is observed in patients with poor intake. We report the first case of a child with lymphangiomatosis who presented a myopathy associated with severe cardiomyopathy secondary to selenium deficiency due to selenium loss in chylous fluid.

Does taking endurance into account improve the prediction of weaning outcome in mechanically ventilated children?

INTRODUCTION: We conducted the present study to determine whether a combination of the mechanical ventilation weaning predictors proposed by the collective Task Force of the American College of Chest Physicians (TF) and weaning endurance indices enhance prediction of weaning success. METHOD: Conducted in a tertiary paediatric intensive care unit at a university hospital, this prospective study included 54 children receiving mechanical ventilation (> or = 6 hours) who underwent 57 episodes of weaning. We calculated the indices proposed by the TF (spontaneous respiratory rate, paediatric rapid shallow breathing, rapid shallow breathing occlusion pressure [ROP] and maximal inspiratory pressure during an occlusion test [Pimax]) and weaning endurance indices (pressure-time index, tension-time index obtained from P(0.1) [TTI1] and from airway pressure [TTI2]) during spontaneous breathing. Performances of each TF index and combinations of them were calculated, and the best single index and combination were identified. Weaning endurance parameters (TTI1 and TTI2) were calculated and the best index was determined using a logistic regression model. Regression coefficients were estimated using the maximum likelihood ratio (LR) method. Hosmer-Lemeshow test was used to estimate goodness-of-fit of the model. An equation was constructed to predict weaning success. Finally, we calculated the performances of combinations of best TF indices and best endurance index. RESULTS: The best single TF index was ROP, the best TF combination was represented by the expression (0.66 x ROP) + (0.34 x Pimax), and the best endurance index was the TTI2, although their performance was poor. The best model resulting from the combination of these indices was defined by the following expression: (0.6 x ROP) - (0.1 x Pimax) + (0.5 x TTI2). This integrated index was a good weaning predictor (P < 0.01), with a LR+ of 6.4 and LR+/LR- ratio of 12.5. However, at a threshold value < 1.3 it was only predictive of weaning success (LR- = 0.5). CONCLUSION: The proposed combined index, incorporating endurance, was of modest value in predicting weaning outcome. This is the first report of the value of endurance parameters in predicting weaning success in children. Currently, clinical judgement associated with spontaneous breathing trials apparently remain superior.

Can generic paediatric mortality scores calculated 4 hours after admission be used as inclusion criteria for clinical trials?

INTRODUCTION: Two generic paediatric mortality scoring systems have been validated in the paediatric intensive care unit (PICU). Paediatric RISk of Mortality (PRISM) requires an observation period of 24 hours, and PRISM III measures severity at two time points (at 12 hours and 24 hours) after admission, which represents a limitation for clinical trials that require earlier inclusion. The Paediatric Index of Mortality (PIM) is calculated 1 hour after admission but does not take into account the stabilization period following admission. To avoid these limitations, we chose to conduct assessments 4 hours after PICU admission. The aim of the present study was to validate PRISM, PRISM III and PIM at the time points for which they were developed, and to compare their accuracy in predicting mortality at those times with their accuracy at 4 hours. METHODS: All children admitted from June 1998 to May 2000 in one tertiary PICU were prospectively included. Data were collected to generate scores and predictions using PRISM, PRISM III and PIM. RESULTS: There were 802 consecutive admissions with 80 deaths. For the time points for which the scores were developed, observed and predicted mortality rates were significantly different for the three scores (P < 0.01) whereas all exhibited good discrimination (area under the receiver operating characteristic curve >or=0.83). At 4 hours after admission only the PIM had good calibration (P = 0.44), but all three scores exhibited good discrimination (area under the receiver operating characteristic curve >or=0.82). CONCLUSIONS: Among the three scores calculated at 4 hours after admission, all had good discriminatory capacity but only the PIM score was well calibrated. Further studies are required before the PIM score at 4 hours can be used as an inclusion criterion in clinical trials.