Parents' preferences for the organisation of long-term follow-up of childhood cancer survivors

Parents take an important role in follow-up of young cancer survivors. We aimed to investigate (1) parents' preferences for organisation of follow-up (including content, specialists involved and models of care), and (2) parents' and children's characteristics predicting preference for generalist vs. specialist-led follow-up. We sent a questionnaire to parents of childhood cancer survivors aged 11-17 years. We assessed on a 4-point Likert scale (1-4), parents' preferences for organisation of long-term follow-up. Proposed models were: telephone/questionnaire, general practitioner (GP) (both categorised as generalist for regression analysis); and paediatric oncologist, medical oncologist or multidisciplinary team (MDT) (categorised as specialists). Of 284 contacted parents, 189 responded (67%). Parents welcomed if visits included checking for cancer recurrence (mean = 3.89), late effects screening (mean = 3.79), taking patients seriously (mean = 3.86) and competent staff (mean = 3.85). The preferred specialists were paediatric oncologists (mean = 3.73). Parents valued the paediatric oncologist model of care (mean = 3.49) and the MDT model (mean = 3.14) highest. Parents of children not attending clinic-based follow-up (OR = 2.97, p = .009) and those visiting a generalist (OR = 4.23, p = .007) favoured the generalist-led model. Many parents preferred a clinic-based model of follow-up by paediatric oncologists or a MDT. However, parents also valued the follow-up care model according to which their child is followed up

An innovative ethosuximide granule formulation designed for pediatric use: Comparative pharmacokinetics, safety, tolerability, and palatability profile versus reference syrup.

Ethosuximide, the first-line therapy for childhood absence epilepsy, is currently formulated as a syrup (Zarontin®, Pfizer) with a bitter taste and high sugar content, poorly adapted to children, and a ketogenic diet. The collaborative European FP7 project KIEKIDS aimed at developing an innovative sugar-free, tasteless formulation convenient for pediatric use. This dual Phase-I study evaluated two granule formulations based on lipid multiparticulate (LMP) technology. Two panels of 6 healthy adult volunteers underwent a randomized, placebo-controlled, partly blinded, 3-way cross-over trial, comparing ethosuximide granules A or B with placebo granules and syrup at single 10 mg/kg doses. Corresponding plasma pharmacokinetic profiles of ethosuximide were compared, along with palatability, safety, and tolerability. The LMP granule A proved suboptimal due to bitterness and adherence to beaker walls, while the optimized granule B revealed excellent palatability, similar to placebo granules, and low adherence to glass. The relative bioavailability of granules A versus syrup, based on dose-normalized C <sub>max</sub> and AUC <sub>0-∞</sub> was 93.7% [90% CI: 76.3-115.1] and 96.1% [91.0-101.5], respectively. For granules B it was 87.6% [81.6-94.0] and 92.5% [88.5-96.6], respectively, with slightly delayed t <sub>max</sub> of 0.75 h [0.5-4.05] compared to syrup 0.5 h [0.3-0.8]. Tolerability visual analog scales revealed a trend for statistically non-significant improvement versus syrup at peak (30 min) for transient dizziness (both granules), fatigue (granules A), and anxiety (granules B). The innovative ethosuximide granule formulation B achieves a suitable profile for pediatric use, being sugar-free, tasteless, bioequivalent, and well-tolerated while enabling precise adjustment to body weight

Parents' preferences for the organisation of long-term follow-up of childhood cancer survivors.

Parents take an important role in follow-up of young cancer survivors. We aimed to investigate (1) parents' preferences for organisation of follow-up (including content, specialists involved and models of care), and (2) parents' and children's characteristics predicting preference for generalist vs. specialist-led follow-up. We sent a questionnaire to parents of childhood cancer survivors aged 11-17 years. We assessed on a 4-point Likert scale (1-4), parents' preferences for organisation of long-term follow-up. Proposed models were: telephone/questionnaire, general practitioner (GP) (both categorised as generalist for regression analysis); and paediatric oncologist, medical oncologist or multidisciplinary team (MDT) (categorised as specialists). Of 284 contacted parents, 189 responded (67%). Parents welcomed if visits included checking for cancer recurrence (mean = 3.89), late effects screening (mean = 3.79), taking patients seriously (mean = 3.86) and competent staff (mean = 3.85). The preferred specialists were paediatric oncologists (mean = 3.73). Parents valued the paediatric oncologist model of care (mean = 3.49) and the MDT model (mean = 3.14) highest. Parents of children not attending clinic-based follow-up (OR = 2.97, p = .009) and those visiting a generalist (OR = 4.23, p = .007) favoured the generalist-led model. Many parents preferred a clinic-based model of follow-up by paediatric oncologists or a MDT. However, parents also valued the follow-up care model according to which their child is followed up

Use of GLP1 receptor agonists in early pregnancy and reproductive safety: a multicentre, observational, prospective cohort study based on the databases of six Teratology Information Services.

OBJECTIVES Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING Data were collected from the databases of six Teratology Information Services. PARTICIPANTS This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings

N-of-1 trials ou essais thérapeutiques individuels : un test probant pour diagnostiquer l’efficacité thérapeutique [N-of-1 trials or single-patient therapeutic tests: evidence-based tests to diagnose therapeutic efficacy]

N-of-1 trials therapeutic tests allow an objective evaluation of treatment efficacy in a single patient. Thereby, they can support off-label prescriptions, or promote treatment safety and efficiency in chronic patients through the deprescription of useless drugs. They also encourage active participation of patients in their medical care. Practically a treatment is compared to a placebo in double blind during a series of randomly alternating periods. Statistical analysis comparing measurements performed in the patient throughout the test enable to evaluate objectively treatment efficacy. The performance of this type of test is now offered to patients and practitioners by the Service of Clinical Pharmacology in the University Hospital of Lausanne

Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!

Introduction: Broad-spectrum beta-lactams are commonly prescribed for empirical or selective treatment of bacterial infections in children with malignancies. In the immunocompromised, appropriate concentration exposure is crucial to ensure antimicrobial efficacy. Augmented renal clearance (ARC) is increasingly recognized in this population, and raises concern for unmet concentration targets. We conducted a retrospective evaluation of meropenem and piperacillin exposure in our hospital's pediatric hematology-oncology patients. Materials and Methods: We compared trough levels of meropenem and piperacillin in a cohort of unselected pediatric hematology-oncology patients stratified based on their estimated renal function as decreased, normal or with ARC, and on their neutrophil count. Results: Thirty-two children provided a total of 51 meropenem and 76 piperacillin samples. On standard intermittent intravenous regimen, 67% of all trough plasma concentrations were below targeted concentrations. In neutropenic children with bacterial infection, all meropenem and 60% of piperacillin levels were below target. Nearly two-thirds of total samples came from children with ARC. In these patients, antimicrobial exposure was insufficient in 85% of cases (compared to 36% in the decreased or normal renal function groups), despite a dosage sometimes exceeding the maximum recommended daily dose. Under continuous infusion of piperacillin, only 8% of plasma levels were insufficient. Discussion: Intermittent administration of meropenem and piperacillin often fails to ensure sufficient concentration exposure in children treated for malignancies, even at maximal recommended daily dosage. This can in part be attributed to ARC. We recommend thorough assessment of renal function, resolute dosage adjustment, continuous infusion whenever possible and systematic therapeutic drug monitoring