Neonatal health care is provided with medication and protocols for almost all morbidities. Before the use of these medicines is allowed, they are extensively studied and tested for efficacy and... Show moreNeonatal health care is provided with medication and protocols for almost all morbidities. Before the use of these medicines is allowed, they are extensively studied and tested for efficacy and safety. As patient population and knowledge on specific diseases changes with time, repeated evaluation of efficacy and safety of current used policies is of paramount importance. In this thesis six __Neonatal Pearls__ are presented: six relatively rare clinical conditions, of which a retrospective study evaluates the efficacy, safety and/or long term consequences of the current protocol. Despite their retrospective design and relatively small sample size, they are all of significant value and may serve as potential foundations for future protocol adjustments and randomized controlled trials. The evaluated clinical conditions and policies include: -Fetal, neonatal and developmental outcomes of lithium exposed pregnancies -Neonatal outcome in allo-immune thrombocytopenia after maternal treatment with antenatal intravenous immunoglobulin - Repeated courses of ibuprofen for closure of a patent ductus arteriosus - Use of rifampin in persistent coagulase negative staphylococcal bacteremia in neonates - Outcome and management in neonatal thrombocytopenia due to maternal idiopathic thrombocytopenic purpura - Short and long term outcome of neonatal hyperglycemia in very preterm infants Show less
In this project we investigated the difference between efficacy (treatment outcome investigated in randomized clinical trials, RCTs) and effectiveness (treatment outcome when these treatments are... Show moreIn this project we investigated the difference between efficacy (treatment outcome investigated in randomized clinical trials, RCTs) and effectiveness (treatment outcome when these treatments are applied in daily psychiatric practice) for major depressive disorder. Treatment outcome and patient features in daily practice were assessed with routine outcome monitoring. We found that effectiveness is significantly lower than efficacy. In RCTs, a stringent patient selection is applied bij inclusion/exclusion criteria. We found that patients in daily practice do differ significantly from participants in RCTs with respect to baseline severity, comorbid disorders, suicidality and employment status. However, we found that these differences have very little influence on treatment outcome. In other words, if, hypothetically, only patients who are eligible for participation in RCTs for major depressive disorder would be tre ated, treatment success would not improve dramatically. Show less
Lem, R. van der; Wee, N.J.A. van der; Veen, T. van; Zitman, F.G. 2012
In this thesis, we focus on the palliative treatment of advanced colorectal carcinoma with capecitabine, irinotecan and oxaliplatin. We investigated the potential associations of germline genetic... Show moreIn this thesis, we focus on the palliative treatment of advanced colorectal carcinoma with capecitabine, irinotecan and oxaliplatin. We investigated the potential associations of germline genetic variations with the efficacy or toxicity of treatment. We genotyped a selection of SNPs in paired tumor tissue and blood samples of colorectal cancer patients (Chapter 3). Next, we present an overview of clinical and pharmacogenetic factors that have been described to influence irinotecan toxicity (Chapter 4). We investigated the association of febrile neutropenia and drug efficacy with the UGT1A1 genotype in Chapter 5. In Chapter 6, we investigated the GSTP1 Ile105Val SNP with regard to irinotecan efficacy in terms of progression-free survival. We also provide an overview of pharmacogenetic, pharmacokinetic and pharmacodynamic data on this platinum derivative (Chapter 7). In Chapter 8, we transfected ERCC1 negative cells with an ERCC1 gene, containing either the codon 118C or 118T genotype, in order to establish differences in cell survival or DNA repair. In chapter 9 we describe our investigations on the cumulative neurotoxicity and efficacy of oxaliplatin. In chapter 10, an explorative study is described that investigates associations of survival and toxicity in patients receiving oxaliplatin, using a SNP array. Show less
The objective of the investigations described in this thesis was to characterize the in vivo pharmacological and PK-PD properties of buprenorphine relative to fentanyl with respect to: 1) kinetics... Show moreThe objective of the investigations described in this thesis was to characterize the in vivo pharmacological and PK-PD properties of buprenorphine relative to fentanyl with respect to: 1) kinetics of onset and offset of the pharmacological effects at the mu-opioid receptor, 2) selectivity of action (antinociception versus respiratory depression), 3) the interspecies extrapolation of the PK-PD correlation of the antinociceptive and respiratory depressant effect, 4) the role of active metabolites, 5) kinetics of antagonism of the respiratory depressant effect. Preclinical investigations were performed to develop and validate mechanism-based PK-PD models for the effects of opioids on antinociception and respiration. These PK-PD models were subsequently applied to characterize the effects of buprenorphine and fentanyl in humans. It was shown that the developed PK-PD model can be used to predict the efficacy and safety outcome of opioids in animals. Furthermore, the PK-PD model had excellent properties to enable animal-to-human extrapolation of the efficacy and safety outcome. Show less
The present thesis deal with the diagnostic boundaries between hypochondriasis and obsessive compulsive disorder and between hypochondriasis and another somatoform disorder called non-cardiac chest... Show moreThe present thesis deal with the diagnostic boundaries between hypochondriasis and obsessive compulsive disorder and between hypochondriasis and another somatoform disorder called non-cardiac chest pain. These studies showed that hypochondriasis and both other disorders are valid disorders based on diagnosis-specific symptoms. Furthermore, in the thesis the first randomized controlled trial comparing the efficacy of cognitive behavioural therapy, and a double-blind SSRI (paroxetine) and pill-placebo is described. The short term effects (4 months) and the long term (5 years) of both treatments were compared to each other and to the placebo. It can be concluded that both are effective treatments for hypochondriasis compared to the placebo in the short term, but the significant differences between both active treatments in ameliorating hypochondriacal symptoms disappears during the follow-up, although CBT is more effective in ameliorating comorbid depressive and psychoneurotic symptoms during the follow-up period than the placebo. Furthermore, CBT results in less use of additional psychological or medical help during the follow-up. Finally, the psychometric properties of the first clinician-administered semi-structured interview, the hypochondriasis Y-BOCS, were described. This interview seemed reliable and valid addition to the assessment arsenal measuring hypochondriacal symptoms. Show less
