Length of the treatment and number of doses per day as major determinants of child adherence to acute treatment.

OBJECTIVE: To determine the rate of aftercare adherence to prescriptions from a paediatric emergency department and to identify predictors for nonadherence. METHODS: Patients discharged from a French paediatric emergency department with at least one oral drug prescription were included. A telephone interview questionnaire was used to determine whether the child had received the treatments according to the prescription. Adherence was assessed according to three items: frequency of drug administration, length of treatment and drug administering method. Complete adherence was defined as adherence to the three items mentioned above, and nonadherent as nonadherent to at least one of the items. Influence of age, sex, pathology, language spoken at home, type of medical insurance, type of medication prescribed, diagnosis, dissatisfaction with the explanation of the medical problem, number of prescribed medications, length of the treatment and number of doses per day was assessed. RESULTS: One hundred and five telephone interviews were exploited. The children were 60 boys (57%) and 45 girls (43%). The ages of these 105 children were between 0.2 and 12 years. The most common diagnoses were asthma and pulmonary infection. Complete adherence with the prescription was 36.2%. Three factors were significantly associated with nonadherence (p < 0.05): length of treatment, number of doses per day and male sex. CONCLUSION: This study suggests that simplifying treatment schedules is an effective strategy for improving compliance in paediatric emergency departments.

[Communication, information, and roles of parents in the pediatric intensive care unit: A review article]. / Communication, informations et place des parents en réanimation polyvalente pédiatrique : revue de la littérature.

Pediatric intensive care units (PICUs), whose accessibility to parents raises controversy, often operate under their own rules. Patients are under critical and unstable conditions, often in a life-threatening situation. In this context, the communication with the parents and their participation in the unit may be difficult. Information is a legal, deontological, and moral duty for caregivers, confirmed by the parents' needs. But the ability to enforce them is a challenge, and there is a gap between the theory and the reality. The communication between the parents and the physicians starts at the admission of the child with a family conference. According to the Société de réanimation de langue française (SRLF), the effectiveness of the communication is based on three criteria: the patients' comprehension, their satisfaction and their anxiety and depression. It has been shown that comprehension depends on multiple factors, related on the parents, the physicians, and the medical condition of the child. Regarding the parents' participation in the organization of the service, the parents' presence is becoming an important factor. In the PICU, the parents' status has evolved. They become a member of the care team, as a partner. The best interest of the child is always discussed with the parents, as the person knowing the best their child. This partnership gives them a responsibility, which is complementary to the physician's one, but does not substitute it.

[Unscheduled pediatrician office visits: A national survey]. / Enquête nationale sur les consultations non programmées en pédiatrie de ville.

INTRODUCTION: Unscheduled visits (UV) are defined as visits to the family pediatrician (FP) without an appointment or when the appointment was made less than 24h before. Because the number of FPs has decreased since the 2000s, the FP might be less available for UVs and that might be one of the reasons for the increase in emergency department visits. OBJECTIVES: The main objective of the study was to evaluate the proportion of UVs among visits with a FP. The secondary objective was to describe the daily activity of FPs. METHODS: In February 2012, e-mail requests were sent to 1022 FPs, asking them to complete an anonymous questionnaire online at the website of the French Association of Pediatricians in Outpatient Practice (AFPA). The questionnaire was about 1 day of activity. RESULTS: A total of 434 FPs participated in the study (42.5%). Among the 10,263 visits a day conducted by these FPs, 4574 were UVs (44.6% [95% CI: 43.6-45.5]). Two hundred and fifty FPs (59.5%) could not conduct one or more UVs because of a lack of availability. The number of children who were not treated on the same day because of a lack of availability was 959, i.e., 2.2 children per day and pediatrician. An absence of off-hour pediatricians in outpatient practice during weekends and during the night was reported by 61% (266) and 90% (391) of the FPs, respectively. CONCLUSION: FPs' activity includes a considerable number of UVs. However, a large number of UVs could not be made because of a lack of pediatricians' availability.

[Ethics in pediatric emergencies: Care access, communication, and confidentiality]. / L'éthique dans les services d'accueil des urgences pédiatriques : accès aux soins, communication et confidentialité.

Children suffer most from today's increasing precariousness. In France, access to care is available for all children through various structures and existing measures. The support for foreign children is overseen by specific legislation often unfamiliar to caregivers. Pediatric emergencies, their location, organization, actors, and patient flow are a particular environment that is not always suitable to communication and may lead to situations of abuse. Communication should not be forgotten because of the urgency of the situation. The place of the child in the dialogue is often forgotten. Considering the triangular relationship, listening to the child and involving the parents in care are the basis for a good therapeutic alliance. Privacy and medical confidentiality in pediatric emergencies are governed by law. However, changes in treatments and medical practices along with the variety of actors involved imply both individual and collective limitations, to the detriment of medical confidentiality.

24-Month adherence, tolerance and efficacy of once-a-day antiretroviral therapy with didanosine, lamivudine, and efavirenz in African HIV-1 infected children: ANRS 12103/12167.

BACKGROUND: There is no data on long-term benefit of once-a-day antiretroviral therapy (ART) with combination of DDI, 3TC and EFV to allow its use in future therapeutic strategies. OBJECTIVES: To assess 24-month immuno-virological, adherence, tolerance, and effectiveness of a once-a-day ART with DDI, 3TC and EFV. METHODS: A phase 2 open trial including 51 children aged from 30 months to 15 years, monitored a once-a-day regimen for 24 months from 2006 to 2008 in the Departement de Pediatrie du CHUSS, at Bobo-Dioulasso in Burkina Faso. We tested immunological and virological response, adherence, tolerance and resistance of the treatment. RESULTS: Children with CD4 >25% at 24 months were 67.4% (33/49) CI 95% [54%, 80%]. The proportion of children with viral plasma RNA <300 cp / ml at 24 months of treatment was 81.6 % (40/49) CI [68.0% 91.2%]. Good adherence was obtained with more than 88% adherence > 95% over the 24 months. Drugs were well tolerated. CONCLUSIONS: Given the limited number of antiretroviral drugs available in Africa and the inadequacy of laboratory monitoring in support program, once-a-day treatment and especially the DDI-based combination strategies could be an attractive operational option.

ABC drug transporter and nuclear receptor expression in human cytotrophoblasts: influence of spontaneous syncytialization and induction by glucocorticoids.

OBJECTIVES: ABC transporters in the human placenta play a major role in protecting the fetus against potential toxic drugs. The glucocorticoid dexamethasone has been shown to induce ABCB1 expression in enterocytes and hepatocytes. However, in placental cells, little data exists either for dexamethasone, betamethasone or prednisone while these three glucocorticoids may be used during pregnancy. We investigated the modulation of placental ABC transporter and nuclear receptor expression by these drugs. METHODS: Cytotrophoblasts were isolated from normal full-term placentas. We first assessed the influence of spontaneous syncytialization on transporter and nuclear receptor gene expression by taking samples of cytotrophoblasts after 24, 48 and 72 h of cell culture (n = 7 placentas). Incubations were then conducted with dexamethasone (50 nM-1 µM), betamethasone (20-400 nM) and prednisone (50 nM-1 µM) versus no drug for 24 h (n = 6). mRNA expression was determined by qRT-PCR. RESULTS: Influence of syncytialization was observed only for ABCB1, ABCC2 and ABCC5 gene expression between t = 24 and 48 h (p < 0.05). Therefore, the following induction studies were conducted between t = 48 h and 72 h. Dexamethasone and betamethasone significantly induced ABCB1 gene expression by around 4-fold (p < 0.01 and 0.001, respectively). In parallel, 100 nM betamethasone decreased the glucocorticoid receptor gene expression by 22% (p < 0.01). Prednisone showed no effect on transporter or receptor expression. CONCLUSIONS: These results suggest that dexamethasone or betamethasone administration may decrease the maternal-fetal transfer of an associated treatment being ABCB1 substrate, which may be either protective or deleterious for the fetus depending on the treatment's therapeutic aim.

[Neurological complications revealing infectious endocarditis: 2 case reports]. / Complications neurologiques révélatrices d'une endocardite infectieuse : à propos de 2 cas.

Neurological signs are reported in less than 20% of infectious endocarditis (IE) cases. The most frequent complications include cerebral infarction, intracerebral hemorrhage, meningitis, and mycotic aneurysm. We describe two patients, one with congenital heart disease and the other with normal heart, who presented neurological manifestations and fever leading to an IE diagnosis. Neurological complications may be the first symptom of infectious endocarditis and are a major factor associated with increased morbidity and mortality. Early diagnosis and early treatment will minimize cardiac and neurological morbidities.

Parental comprehension and satisfaction in informed consent in paediatric clinical trials: a prospective study on childhood leukaemia.

OBJECTIVE: To evaluate the extent to which parents are satisfied with and understand the information they are given when their consent is sought for their child to participate in a phase III randomised clinical trial and the reasons for their decision. PATIENTS AND METHOD: The authors carried out a prospective study. The authors included all parents whose consent was sought for their child to participate in the FRALLE 2000A protocol (acute lymphoblastic leukaemia) at two centres. The parents were questioned twice by a qualified psychologist using a semidirected interview, 1 and 6 months after consent was sought. RESULTS: 43 first interviews were carried out. All the parents declared they were satisfied with the explanations provided by the physician. 35 (81%) parents felt that the information provided with the request for consent was appropriate. Eight (19%) parents did not realise that their child had been included in a research protocol. 16 (39%) parents did not understand the concept of randomisation. Half the parents could explain neither the aim of the clinical trial nor the potential benefit of inclusion to their child. Only one third of the parents were aware that they had an alternative. The principal factor underlying their decision, as stated by 29 parents (67%), was confidence in the medical team. CONCLUSIONS: The parents signed consent forms without having fully understood all the elements specific to the experimental protocol. Rather, the parents based their decision on their confidence in the medical team, even when their child's life was at risk.

High levels of P-glycoprotein activity in human lymphocytes in the first 6 months of life.

P-glycoprotein (P-gp) is an efflux transporter that controls the intracellular concentrations of drugs. Human development may modulate P-gp function. We investigated the effect of age on P-gp activity and MDR1 gene expression in lymphocytes. We also assessed the influence of human immunodeficiency virus (HIV) infection. We used 3,3'-diethyloxacarbocyanin iodide (DiOC(6)) efflux, estimated by flow cytometry, to quantify P-gp activity in 94 children (age range, 0-18 years) and 25 adults. MDR1 gene expression was quantified using reverse transcription-PCR (RT-PCR). In T and natural killer (NK) cell populations, P-gp activity peaked at birth, decreased between the ages of 0 and 6 months, and stabilized between the ages of 6 months and 2 years (P < 10(-6)). These maturation profiles were also strongly correlated (r = 0.67, P < 10(-6)). HIV infection did not affect P-gp activity in the lymphocytes of children. MDR1 gene expression was not influenced by age, nor was it correlated with P-gp activity. The high levels of P-gp activity observed in the lymphocytes of children ~6 months of age may affect the efficacy of intracellular drugs.

Parental consent in paediatric clinical research.

AIMS: To assess parental understanding and memorisation of the information given when seeking for consent to their child's participation to clinical research, and to identify the factors of significant influence on parents' decision making process. METHODS: Sixty eight parents who had been approached for enrolling their child in a clinical oncology or HIV study were asked to complete an interview. Their understanding was measured by a score which included items required to obtain a valid consent according to French legislation. RESULTS: Items that were best understood by parents were the aims of the study (75%), the risks (70%), the potential benefits to their child (83%), the potential benefits to other children (70%), the right to withdraw (73%), and voluntariness (84%). Items that were least understood were the procedures (44%), the possibility of alternative treatments (53%), and the duration of participation (39%). Less than 10% of the parents had understood all these points. Ten parents (15%) did not remember that they had signed up for a research protocol. Thirty three parents (48%) reported no difficulty in making their decision. Twenty four parents (38%) declared that they made their decision together with the investigator; 26 (41%) let the physician decide. Fifty four parents (78%) felt that the level of information given was satisfactory. CONCLUSION: There was an apparent discrepancy between parents' evaluation of the adequacy of the information delivered and evaluation of their understanding and memorisation. The majority of parents preferred that the physician take as much responsibility as possible in the decision making process.

Weight related differences in the pharmacokinetics of abacavir in HIV-infected patients.

AIM: To study the possible influence of patient characteristics on abacavir pharmacokinetics. METHODS: A population pharmacokinetic model for abacavir was developed using data from 188 adult patients by the use of a nonlinear mixed effects modelling method performed with NONMEM. RESULTS: Abacavir pharmacokinetics was well described by a two-compartment open model with linear absorption and elimination. Typical population estimates for the absorption rate constant (Ka), the apparent central distribution volume (Vc/F), the apparent peripheral distribution volume (Vp/F), the apparent intercompartmental clearance (Q/F) and the apparent plasma clearance (CL/F) were 1.8 h(-1), 75 l, 23.6 l, 10 l h(-1) and 47.5 l h(-1), respectively. Apparent plasma clearance was positively related to bodyweight. Individual Bayesian estimates of CL/F were used to calculate abacavir AUC. The latter decreased from 10.7 +/- 5.0 to 5.7 +/- 1.6 mgh l(-1) when bodyweight increased from 36 to 102 kg. This drop in abacavir exposure could lead to suboptimal treatment for the heaviest patients, as antiviral efficacy of abacavir is known to be related to its AUC. A 400 mg abacavir dose would be necessary to achieve adequate exposure to abacavir in patients weighing more than 60 kg. CONCLUSIONS: The apparent plasma clearance of abacavir was positively related to bodyweight. The efficacy of the current recommended abacavir dosage for patients with high bodyweight should be evaluated in further studies.