Background: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up... Show moreBackground: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment.Aims: To report on outcomes of ETSS in a cohort of prolactinomas.Methods: Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 +/- 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation.Results: Median preoperative prolactin levels were 166 (98-837 mu g/L; males 996 [159-2145 mu g/L] vs. females 129 [84-223 mu g/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication.Conclusions: Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.(c) 2023 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved. Show less
De eetbuistoornis is de meest voorkomende eetstoornis en komt in vergelijking met anorexia en boulima veel meer onder alle lagen van de bevolking voor. Wereldwijd is er een gebrek aan kennis over... Show moreDe eetbuistoornis is de meest voorkomende eetstoornis en komt in vergelijking met anorexia en boulima veel meer onder alle lagen van de bevolking voor. Wereldwijd is er een gebrek aan kennis over de eetbuistoornis. Door gebrekkige (h)erkenning krijgen individuen met een eetbuistoornis vaak verkeerde zorg, waardoor de eetbuien juist toenemen. Daarnaast zijn er lange wachttijden voor specialistische behandeling en heeft niet iedereen toegang tot behandeling. Deze these is tweeledig: er wordt onderzoek gedaan naar risicofactoren van de eetbuistoornis in Arabische landen en twee diagnostische vragenlijsten worden gevalideerd. In Nederland wordt de werkzaamheid van een traditionele en een digitale begeleide zelfhulp behandeling onderzocht. In Arabische landen bleken een hoog BMI en lichaamsontevredenheid geassocieerd te zijn met eetstoornispathologie. De eating disorder examination questionnaire meet accuraat eetstoornisklachten en de body shape questionnaire lichaamsontevredenheid. In Nederland blijkt cognitive behavioral therapy een werkzame behandeling voor de eetbuistoornis, zowel op de traditionale manier, als digitaal aangeboden. De digitale variant vergroot de toegang tot specialistische zorg en kan mogelijk de lange wachttijden voor behandeling verkorten. Show less
BackgroundAdequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical... Show moreBackgroundAdequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing.ObjectiveThe purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort.MethodsIn this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit.ResultsA total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0–88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%).ConclusionThe long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold. Show less
Hany, M.; Aboudeeb, M.F.; Shapiro-Koss, C.; Agayby, A.S.S.; Torensma, B. 2023
Introduction Patients living with psychiatric illnesses (PIs) have a high prevalence of obesity. In a 2006 survey, 91.2% of professionals in the bariatric field identified "psychiatric issues" as... Show moreIntroduction Patients living with psychiatric illnesses (PIs) have a high prevalence of obesity. In a 2006 survey, 91.2% of professionals in the bariatric field identified "psychiatric issues" as clear contraindications to weight-loss surgery. Methods This retrospective matched case-control study investigated the impact, safety, and possible relapse after bariatric metabolic surgery (BMS) in patients with PIs. Also, we tested the incidence of patients who developed PI after BMS and compared the post-procedural weight loss with that in a matched control group without PIs. The cases were matched in a ratio of 1:4 to the control patients standardized for age, sex, preoperative BMI, and type of BMS. Results Of 5987 patients, 2.82% had a preoperative PI; postoperative de novo PI was present in 0.45%. Postoperative BMI was significantly different between the groups when compared to preoperative BMI (p < 0.001). Percentage of total weight loss (%TWL) after six months was not significantly different between the case (24.6% +/- 8.9) and control groups (24.0% +/- 8.4, p = 1.000). Early and late complications were not significantly different between the groups. The psychiatric drug use and dosage changes did not differ significantly pre- and postoperatively. Of the psychiatric patients, 5.1% were postoperatively admitted to a psychiatric hospital (p = 0.06) unrelated to BMS, and 3.4% had a prolonged absence from work after surgery. Conclusion BMS is an effective weight loss treatment and a safe procedure for patients with psychiatric disorders. We found no change in the patients' psychiatric status outside the usual disease course. Postoperative de novo PI was rare in the present study. Furthermore, patients with severe psychiatric illness were excluded from undergoing surgery and, therefore, from the study. Careful follow-up is necessary to guide and protect patients with PI. Show less
Treatment for advanced colorectal cancer (ACC) consists primarily of systemic treatment, mostly without curative intent. Systemic therapies are associated with potentially severe side effects.... Show moreTreatment for advanced colorectal cancer (ACC) consists primarily of systemic treatment, mostly without curative intent. Systemic therapies are associated with potentially severe side effects. Furthermore, treatment is not effective in all patients. Currently, pre-treatment predictors for efficacy and toxicity in systemic treatment of ACC are scarce. Germline genetic variation in genes encoding for enzymes involved in pharmacokinetics or pharmacodynamics of cytotoxic drugs could explain intra-patient differences in treatment effects. Pharmacogenetic studies aim at finding such germline genetic predictors. This thesis focusses on pharmacogenetics of capecitabine and oxaliplatin in treatment of ACC. First, it is established that results derived from DNA in archived tumor samples can be reliably compared to those using DNA from peripheral blood leukocytes. Then, germline genetic markers in MTHFR and MTRR, as well as markers derived from an in vitro genome-wide association study (GWAS) are tested for their association with capecitabine toxicity. Next, effects of ERCC1 genotype on oxaliplatin cytotoxicity in vitro and in clinical association analysis are addressed. The influence of genetic variation in organic cation transporters on oxaliplatin-induced neurotoxicity is examined. Lastly, the results of a GWAS searching for germline predictors of treatment efficacy of capecitabine, oxaliplatin and bevacizumab, with or without cetuximab, are presented. Show less
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
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
