31 research outputs found
Clinical Decision Support in Pediatric Care
The overall aim of the studies described in this thesis was to investigate and optimize the diagnostic
process of (febrile) children presenting to the hospital emergency department (ed), and to
study aspects of this process as a base for clinical decision support systems. We discussed the use
of an electronic medical record with structured data entry, the development of clinical prediction
rules for specific diagnostic problems in febrile children attending the hospital ed, the validity of
a triage system used for pediatric patients, and the evaluation of a clinical decision support system
for diagnostic management of children with fever without apparent source
Why are structured data different? Relating differences in data representation to the rationale of OpenSDE
OpenSDE is an application that supports clinicians with structured recording of narrative patient data to enable use of data in both clinical practice and research. OpenSDE is based on a rationale and requirements for structured data entry. In this study, we analyse the impact of the rationale and the requirements on data representation using OpenSDE. Three paediatricians transcribed 20 paper patient records using OpenSDE. The transcribed records were compared; the findings that were the same in content but differed in representation (e.g. recorded as free text instead of in a structured manner) were categorized in one of three categories of difference in representation. The transcribed records contained 1764 findings in total. The medical content of 302 of these findings was represented differently by at least one clinician and was thus included in this study. In OpenSDE, clinicians are free to determine the degree of detail at which patient data are described. This flexibility accounts for 87% of the differences in data representation. Thirteen per cent of the differences are due to clinicians interpreting and translating phrases from the source text and transcribing these to (different) concepts in OpenSDE. The differences in data representation largely result from initial design decisions for OpenSDE
Manchester triage system in paediatric emergency care: prospective observational study
Objective To validate use of the Manchester triage system in paediatric emergency care
Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation
Contains fulltext :
229853.pdf (Publisher’s version ) (Closed access)BACKGROUND: The natural food supplements curcumin and genistein, and the drug ivacaftor were found effective as CFTR potentiators in the organoids of individuals carrying a S1251N gating mutation, possibly in a synergistic fashion. Based on these in vitro findings, we evaluated the clinical efficacy of a treatment with curcumin, genistein and ivacaftor, in different combinations. METHODS: In three multi-center trials people with CF carrying the S1251N mutation were treated for 8 weeks with curcumin+genistein, ivacaftor and ivacaftor+genistein. We evaluated change in lung function, sweat chloride concentration, CFQ-r, BMI and fecal elastase to determine the clinical effect. We evaluated the pharmacokinetic properties of the compounds by evaluating the concentration in plasma collected after treatment and the effect of the same plasma on the intestinal organoids. RESULTS: A clear clinical effect of treatment with ivacaftor was observed, evidenced by a significant improvement in clinical parameters. In contrast we observed no clear clinical effect of curcumin and/or genistein, except for a small but significant reduction in sweat chloride and airway resistance. Plasma concentrations of the food supplements were low, as was the response of the organoids to this plasma. CONCLUSIONS: We observed a clear clinical effect of treatment with ivacaftor, which is in line with the high responsiveness of the intestinal organoids to this drug. No clear clinical effect was observed of the treatment with curcumin and/or genistein, the low plasma concentration of these compounds emphasizes that pharmacokinetic properties of a compound have to be considered when in vitro experiments are performed
Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression
RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences
Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis
In vitro drug tests using patient-derived stem cell
cultures offer opportunities to individually select
efficacious treatments. Here, we provide a study
that demonstrates that in vitro drug responses in
rectal organoids from individual patients with cystic
fibrosis (CF) correlate with changes in two in vivo
therapeutic endpoints. We measured individual
in vitro efficaciousness using a functional assay
in rectum-derived organoids based on forskolininduced swelling and studied the correlation with
in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and
change in sweat chloride concentration. Receiver
operating characteristic curves indicated good-toexcellent accuracy of the organoid-based test for
defining clinical responses. This study indicates
that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients
and suggests that biobanked stem cell resources
can be used to tailor individual treatments in a
cost-effective and patient-friendly manner