COVID-related school absence in prmary school:considerations of parents and the role of preventive child health care

Inleiding: Na de heropening van de scholen per 11 mei 2020 bleef 3–5 % van alle leerlingen thuis vanwege COVID-19. Vraagstelling van dit onderzoek was wat de afwegingen zijn van ouders om hun kind thuis te houden, en welke rol de jeugdgezondheidszorg (JGZ) hierbij speelt. Methode: Kwalitatief onderzoek bestaande uit semigestructureerde interviews met vijf schoolmedewerkers (van drie reguliere basisscholen en twee speciaal (basis)onderwijsscholen) en ouders van vier gezinnen die hun kind(eren) thuis hebben gehouden, in Groningen. De interviews zijn thematisch geanalyseerd. Resultaten: De gepercipieerde risico’s voor de gezondheid van een van de gezinsleden was de meest voorkomende reden om een kind niet naar school te laten gaan. Andere redenen waren zorgen over de gezondheid van het kind zelf en een algemene angst voor het virus, zonder dat er gezinsleden waren die binnen de risicogroepen vielen. De JGZ is nauwelijks bij de afweging van ouders betrokken geweest. Conclusie: Dit onderzoek naar COVID-19-gerelateerd schoolverzuim op basisscholen laat zien dat ouders angstig zijn vanwege de gezondheidsrisico’s voor hun gezin, ook in een regio met een lage besmettingsgraad, zoals Groningen in de eerste COVID-19-golf. De rol die de JGZ voor scholen en ouders kan spelen was in deze fase van de epidemie onvoldoende bij hen bekend

Effect of gastrointestinal resection on sunitinib exposure in patients with GIST

Background: GIST patients often undergo GI-surgery. Previous studies have shown that imatinib and nilotinib exposures were decreased in GIST patients with prior major gastrectomy. We investigated whether major gastrectomy influences the exposure to sunitinib and its active metabolite SU12662. Methods: Pharmacokinetic data from 305 GIST patients included in 4 phase I-III trials were analyzed. Patients were subdivided into 6 groups according to their prior GI-surgery. Apparent clearance (CL/F) and dose-corrected steady-state plasma exposures (AUC24,ss) of sunitinib and SU12662 were estimated using a population PK approach. ANCOVA was performed to test for differences in AUC24,ss and CL/F between each surgery subgroup and controls. Results: Major gastrectomy did not influence sunitinib or SU12662 exposure. The geometric mean of sunitinib and SU12662 AUC24,ss was decreased by 21% and 28% in patients with both gastrectomy and small bowel resection (n = 8) compared to controls (n = 63) for sunitinib (931 ng*hr/mL (95%-CI; 676–1283) versus 1177 ng*hr/mL (95%-CI; 1097–1263); p < 0.05) and SU12662 (354 ng*hr/mL (95%-CI; 174–720) versus 492 ng*hr/mL (95%-CI; 435–555); p < 0.05). No significant differences in exposure were observed in each of the other subgroups versus controls. Conclusion: In contrast to previous results for imatinib and nilotinib, gastrectomy alone does not influence sunitinib or SU12662 exposure. This should be taken into account for the treatment of gastrectomized GIST patients with TKIs. In patients who had undergone both gastrectomy and small bowel resection, sunitinib and SU12662 exposures are significantly, although clinically not relevantly, decreased

Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662

AIMS: Previously published pharmacokinetics (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such us correlations between sunitinib and its metabolite. The current study was to develop an improved PK model that circumvented these limitations and to prove the utility of the PK model in treatment optimisation in clinical practice. METHODS: 1205 plasma samples from 70 cancer patients were collected from three PK studies with sunitinib and SU12662. A semi-physiological PK model for sunitinib and SU12662 was developed incorporating pre-systemic metabolism using nonlinear mixed-effects modelling (NONMEM). Allometric scaling based on body weight was applied. The final model was used for simulation of the PK of different treatment regimens. RESULTS: Sunitinib and SU12662 PK were best described by one and two compartment model, respectively. Introduction of pre-systemic formation of SU12662 strongly improved model fit, compared to solely systemic metabolism. The clearance of sunitinib and SU12662 was estimated at 35.7 (relative standard error (RSE) 5.7%) L·h(-1) and 17.1 (RSE 7.4%) L·h(-1) , respectively for 70 kg patients. Correlation coefficients were estimated between inter-individual variability of both clearances, both volume of distributions, and between clearance and volume of distribution of SU12662 as 0.53, 0.48 and 0.45, respectively. Simulation of the PK model predicted correctly the ratio of patients that not reaching proposed PK targets for efficacy. CONCLUSIONS: A semi-physiological PK model for sunitinib and SU12662 in cancer patients was presented including pre-systemic metabolism. The model was superior to previous PK models in multiple aspects

Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results of a Phase II Clinical Trial

Background: Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer. Patients and Methods: Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily. The primary endpoint was disease control rate [complete (CR) + partial response (PR) + stable disease (SD). 24 weeks]. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and mutational and pharmacokinetic-related outcomes. Results: Median follow-up duration was 38 months (2-64). Seventeen patients (65%) showed SD, of which 15 (58%) showed SD>24 weeks. No CR or PR was observed. Median PFS and OS were 9 [95% confidence interval (CI): 4 to 14] and 18 (95% CI: 7 to 29) months, respectively. Survival was negatively influenced by the presence of bone metastases. Toxicity was predominantly grade 1/2 and included anemia (64%), cough (64%), stomatitis (61%), and hyperglycemia (61%). Duration of SD was related to everolimus exposure. The presence of somatic gene variants related to mTOR signaling did not clearly stratify for responses. Conclusion: Everolimus has clinically relevant antitumor activity in patients with advanced differentiated thyroid cancer. Given the observed disease control rate and the relatively low toxicity profile, further investigation of everolimus in sequential or combination therapy in these patients is warranted