Formulation predictive dissolution (fPD) testing to advance oral drug product development: an introduction to the US FDA funded ‘21st Century BA/BE’ project

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions

Autism spectrum disorder diagnosis in young children: A clinical-ethical study on the experiences of parents and physicians [Hoe ouders en hulpverleners een diagnose autismespectrumstoornis van een jong kind ervaren: Een klinisch-ethische studie]

ACHTERGROND Na tientallen jaren van onderzoek en klinische ervaring is duidelijk dat de autismespectrumstoornis (ass) heterogeen is in al haar aspecten, zoals fenotype en etiologie. Hoe kunnen we deze heterogene bevindingen over ass vertalen in informatie die bruikbaar en betekenisvol is voor ouders en clinici? DOEL Aanbevelingen formuleren voor de klinische zorg voor jonge kinderen met ass. METHODE We onderzochten met diepte-interviews hoe ouders (11 moeders en 6 vaders van 11 kinderen) en artsen (n = 16) een ass-diagnose bij een jong kind ervaren. De interviews werden in Nvivo 11 geanalyseerd volgens de richtlijnen van interpretatieve fenomenologische analyse. RESULTATEN De geïnterviewde ouders en artsen bleken evenveel belang te hechten aan psychorelationele als aan handelingsgerichte implicaties van een ass-diagnose. Een jaar nadat bij hun kind de diagnose ass gesteld werd, bracht een zekere ontnuchtering over deze implicaties de ouders tot een pragmatisch begrip van de diagnose. CONCLUSIE Zowel voor clinici als beleidsmakers bieden de resultaten handvatten voor de klinische praktijk voor jonge kinderen met ass. Een ass-diagnose blijkt op zich ouders en clinici beperkt te helpen. Wel kan deze zinvol zijn bij een hulpvraaggericht diagnostisch proces dat gebaseerd is op een communicatiemodel van gedeelde besluitvorming en waarbij een descriptief profiel van het kind opgemaakt wordt dat bruikbaar is in het verdere hulpverleningstraject

Unique approach to secondary cleft-lip rhinoplasty in facial plastic surgery

Rhinoplasty occupies a unique position in facial plastic surgery due to the central position of the nose in the face and the vital functions of the nose. Among facial plastic surgeons, secondary rhinoplasty in adult cleft-lip patients is considered to be one of the most challenging surgical interventions due to the congenital distortion of the cartilaginous and bony nasal pyramid, with consequences for both nasal aesthetics and breathing. In spite of the challenging nature of the procedure, post-operative satisfaction is high, matching that of non-cleft-lip patients, as long as appropriate surgical techniques are applied. Specific rhinoplasty methods are used in unilateral or bilateral cleft-lip patients with extensive grafting, combined efforts for aligning the nasal dorsum and the creation of symmetry in the nasal tip, medialisation of the anterior nasal spine with augmentation of the premaxilla, correction of nasal vestibulum stenosis and specific post-operative care with a nasal vestibulum device. This review aims to address some specific surgical issues relating to cleft-lip rhinoplasty, resulting in the high subjective satisfaction rate reported by cleft patients operated upon in the University Hospitals Leuven.status: publishe

Surgery for velopharyngeal insufficiency: The outcomes of the University Hospitals Leuven

We reviewed the outcomes of patients who underwent a velopharyngoplasty and subsequent speech therapy for velopharyngeal insufficiency (VPI) to determine possible prognostic variables.publisher: Elsevier articletitle: Surgery for velopharyngeal insufficiency: The outcomes of the University Hospitals Leuven journaltitle: International Journal of Pediatric Otorhinolaryngology articlelink: http://dx.doi.org/10.1016/j.ijporl.2015.10.007 content_type: article copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.status: publishe

High patient satisfaction after secondary rhinoplasty in cleft lip patients

We surveyed the subjective outcome of secondary rhinoplasty in cleft lip patients. Questionnaires were sent to 38 patients who had undergone a secondary rhinoplasty. A total of 30 questionnaires were returned and analyzed. Patients were asked to score their preoperative and postoperative nasal function and form. The validated Rhinoplasty Outcome Evaluation (ROE) questionnaire was supplemented with questions on the subjective burden of the procedure and general satisfaction. In parallel, the objective aesthetic outcome was judged by 2 surgeons using preoperative and postoperative photographs. There was a significant subjective improvement in ROE scores (from 39.3 ± 3.1 to 73.1 ± 2.0, p <0.001), and in specific scores for nasal aesthetical appearance (from 3.6 ± 0.3 to 7.9 ± 0.2, p <0.0001) and breathing capacity (from 4.9 ± 0.4 to 6.8 ± 0.3, p <0.01). Subjective improvement in nasal aesthetics was generally evaluated to be better than improvement in nasal breathing. In retrospect, all patients would undergo the procedure again. Patient satisfaction did not correlate with the surgeon's appreciation of the aesthetic outcome of the rhinoplasty. Patient satisfaction after secondary rhinoplasty in cleft lip patients is high and comparable to that of non-cleft lip rhinoplasty patient