Baby's first bites: association between observed maternal feeding behavior and infant vegetable intake and liking

Positive experiences with the introduction of solid food in infancy may lead to positive associations with feeding in both parent and infant. During this transitional period, parental feeding behavior and infant eating behavior might mutually reinforce each other. A feeding style that is found to be associated with positive child eating behavior, is sensitive feeding. In the present study we tested bidirectional prospective relations between mother and infant behavior in a cross-lagged model using observations of two feeds on two consecutive days on which the first bites of solid food were offered. The sample consisted of 246 first-time mothers and their infants, whose feeding interactions were videotaped during two home visits. Maternal sensitive feeding behavior (consisting of responsiveness to child feeding cues, general sensitivity and non-intrusiveness) and maternal positive and negative affect were coded. In addition, infant vegetable intake was weighed and vegetable liking was reported by mother. Results showed at least some stability of maternal feeding behavior and infant vegetable intake and liking from the first to the second feed. In addition, during the second feed maternal sensitive feeding and positive affect were associated with infant vegetable intake (r=.34 and r=.14) and liking (r=.33 and r=.39). These associations were mostly absent during the first feed. Finally, infant vegetable liking during the first feed positively predicted maternal sensitive feeding behavior during the second feed (β=.25), suggesting that the infant's first response might influence maternal behavior. Taken together, mother and infant seem more attuned during the second feed than during the first feed. Future studies might include multiple observations over a longer time period, or micro-coding. Such insights can inform prevention programs focusing on optimizing feeding experiences during the weaning period.Education and Child Studie

The baby's first bites RCT: evaluating a vegetable-exposure and a sensitive-feeding intervention in terms of child health outcomes and maternal feeding behavior during toddlerhood

Education and Child Studie

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

Pharmacometrics for treatment optimization and drug development in oncology

This thesis describes the application of pharmacometrics to optimize treatment with existing therapies and to support development of novel drugs in the area of oncology. In the field of pharmacometrics, data on pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs are characterized using a combination of mathematical and statistical models. These properties give insight in the fate of a drug in the body (PK) and in its desired and undesired (toxic) effects (PD). Quantification of PK-PD relationships in mathematical and statistical models allows for understanding the characteristics of a drug. Additionally, these models can help answer questions to improve clinical application of drugs and supports decision making in drug development. This thesis describes various examples of applying modeling and simulation methods to improve current treatments and support development of new drugs in oncology. Chapter 1 focuses on the pharmacology of tamoxifen and strategies to individualize dosing of tamoxifen by applying dose adjustments based on endoxifen concentrations. In chapter 2 a pharmacometric approach is used to determine a first-in-human dose for a novel monoclonal antibody and to evaluate its pharmacokinetic properties. In chapter 3 PK-PD modeling is performed to describe pharmacodynamic properties (i.e. toxicity) of different anti-cancer drugs, such as anthracyclines, trastuzumab and docetaxel.This thesis demonstrates that pharmacometrics provides powerful techniques to answer (clinical) pharmacological questions that are often impossible to answer using conventional statistical methods. The examples in this thesis, are applied to the therapeutic area of oncology, though can in part also be applied to answer pharmacological questions in other therapeutic fields and contribute to improved and safer drug treatment in patients

Interacties tussen monoklonale antistoffen en het immuunsysteem

Monoclonal antibodies have different pharmacological and immunological modes of actions and targets and can be used to treat many diseases. In auto-immune diseases monoclonal antibodies can be used to disrupt pro-inflammatory pathways and thereby suppressing auto-immune reactions. Because of this, patients have an increased infection risk during treatment with these biologicals. Infectious complications of monoclonal antibodies in oncology predominantly occur in hemato102 oncology patients where monoclonal antibodies are used to deplete immune cells. Monoclonal antibodies that interfere in allergy pathways can also cause infections. For the safe application of these biologicals a risk assessment of potential infectious complications is required since a part of these complications can be mitigated by adequate screening and antimicrobial prophylaxis. Conversely, the (composition of the) gut microbiome can also affect efficacy of monoclonal antibody therapy, predominantly for antibodies in which Fc-effector functions are required for therapeutic efficacy. Infusion reactions to monoclonal antibodies are also immunological adverse events since these are mostly due to the cytokine-release syndrome. Routine prophylaxis is recommended for drugs with a high incidence of infusion reactions

Stability of colistimethate sodium in a disposable elastomeric infusion device

Infections of the respiratory tract with Pseudomonas aeruginosa in cystic fibrosis patients are frequently treated with colistimethate sodium (CMS). For the intravenous administration of CMS a disposable elastomeric pump is a convenient option. To date, there are no data available on the chemical stability of CMS solutions stored in elastomeric pumps. We evaluated the chemical stability of 0.8 mg/mL solutions of CMS by measuring the degradation over a period of 7 days. Test samples were prepared by diluting CMS with saline solution (0.9%). The preparations were transferred to 100-mL elastomeric pumps and stored at 4 degrees C. The chemical stability was measured by a high-performance liquid chromatography method with UV detection. There was no degradation of CMS (<0.5% of CMS present as colistin) for at least 3 day at 4 degrees C, and after 7 days all test samples remained chemically stable (<5% of CMS present as colistin). Since colistin formed in pharmacy-compounded CMS solutions prior to administration may cause toxicity, we advise that the solution should be used before the hydrolysis of CMS occurs. Therefore, we recommend that the 0.8 mg/mL solution of CMS can be stored for up to 3 days at 4 degrees C in an elastomeric pump. (C) 2015 Elsevier B.V. All rights reserved

Therapeutic Drug Monitoring of endoxifen as an alternative for CYP2D6 genotyping in individualizing tamoxifen therapy

Different strategies have been proposed to individualize tamoxifen treatment in order to improve recurrence-free survival in estrogen receptor (ER)-positive breast cancer. To date, the debate remains on which strategy should be used. The objective of this viewpoint is to highlight Therapeutic Drug Monitoring of endoxifen, the active tamoxifen metabolite, as the preferred methodology compared to CYP2D6 genotyping for individualizing tamoxifen therapy for ER-positive breast cancer patients treated in the adjuvant setting