Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1ß, tumor necrosis factor-, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1ß by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=.65; P<.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1ß by stimulated monocytes. Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required

Impact of climate change on low-flows in the river Meuse

In this study observed precipitation, temperature, and discharge records from the Meuse basin for the period 1911-2003 are analysed. The primary aim is to establish which meteorological conditions generate (critical) low-flows of the Meuse. This is achieved by examining the relationships between observed seasonal precipitation and temperature anomalies, and low-flow indices. Secondly, the possible impact of climate change on the (joint) occurrence of these low-flow generating meteorological conditions is addressed. This is based on the outcomes of recently reported RCM climate simulations for Europe given a scenario with increased atmospheric greenhouse-gas concentrations. The observed record (1911-2003) hints at the importance of multi-seasonal droughts in the generation of critical low-flows of the river Meuse. The RCM simulations point to a future with wetter winters and drier summers in Northwest Europe. No increase in the likelihood of multi-seasonal droughts is simulated. However, the RCM scenario runs produce multi-seasonal precipitation and temperature anomalies that are out of the range of the observed record for the period 1911-2003. The impact of climate change on low-flows has also been simulated with a hydrological model. This simulation indicates that climate change will lead to a decrease in the average discharge of the Meuse during the low-flow season. However, the model has difficulties to simulate critical low-flow conditions of the Meuse

Two types of liposomal formulations improve the therapeutic ratio of prednisolone phosphate in a zebrafish model for inflammation

Glucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to improve their therapeutic ratio. We used zebrafish embryos to visualize the biodistribution of liposomes and to determine the anti-inflammatory and adverse effects of the GC prednisolone phosphate (PLP) encapsulated in these liposomes. Our results showed that PEGylated liposomes remained in circulation for long periods of time, whereas a novel type of liposomes (which we named AmbiMACs) selectively targeted macrophages. Upon laser wounding of the tail, both types of liposomes were shown to accumulate near the wounding site. Encapsulation of PLP in the PEGylated liposomes and AmbiMACs increased its potency to inhibit the inflammatory response. However, encapsulation of PLP in either type of liposome reduced its inhibitory effect on tissue regeneration, and encapsulation in PEGylated liposomes attenuated the activation of glucocorticoid-responsive gene expression throughout the body. Thus, by exploiting the unique possibilities of the zebrafish animal model to study the biodistribution as well as the anti-inflammatory and adverse effects of liposomal formulations of PLP, we showed that PEGylated liposomes and AmbiMACs increase the therapeutic ratio of this GC drug.Supramolecular & Biomaterials ChemistryAnimal science

Age-related difference in health care use and costs of patients with chronic kidney disease and matched controls

_Background_ The financial burden of chronic kidney disease (CKD) is increasing due to the ageing population and increased prevalence of comorbid diseases. Our aim was to evaluate age-related differences in health care use and costs in Stage G4/G5 CKD without renal replacement therapy (RRT), dialysis and kidney transplant patients and compare them to the general population. _Methods_ Using Dutch health care claims, we identified CKD patients and divided them into three groups: CKD Stage G4/G5 without RRT, dialysis and kidney transplantation. We matched them with two controls per patient. Total health care costs and hospital costs unrelated to CKD treatment are presented in four age categories (19–44, 45–64, 65–74 and ≥75 years). _Results_ Overall, health care costs of CKD patients ≥75 years of age were lower than costs of patients 65–74 years of age. In dialysis patients, costs were highest in patients 45–64 years of age. Since costs of controls increased gradually with age, the cost ratio of patients versus controls was highest in young patients (19–44 years). CKD patients were in greater need of additional specialist care than the general population, which was already evident in young patients. _Conclusion_ Already at a young age and in the earlier stages of CKD, patients are in need of additional care with corresponding health care costs far exceeding those of the general population. In contrast to the general population, the oldest patients (≥75 years) of all CKD patient groups have lower costs than patients 65–74 years of age, which is largely explained by lower hospital and medication costs

Healthcare costs of patients on different renal replacement modalities – Analysis of Dutch health insurance claims data

Background The aim of this study is to present average annual healthcare costs for Dutch renal replacement therapy (RRT) patients for 7 treatment modalities. Methods Health insurance claims data from 2012–2014 were used. All patients with a 2014 claim for dialysis or kidney transplantation were selected. The RRT related and RRT unrelated average annual healthcare costs were analysed for 5 dialysis modalities (in-centre haemodialysis (CHD), home haemodialysis (HHD), continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and multiple dialysis modalities in a year (Mix group)) and 2 transplant modalities (kidney from living and deceased donor, respectively). Results The total average annual healthcare costs in 2014 ranged from €77,566 (SD = €27,237) for CAPD patients to €105,833 (SD = €30,239) for patients in the Mix group. For all dialysis modalities, the vast majority (72–84%) of costs was RRT related. Patients on haemodialysis 4x/week had significantly higher average annual costs compared to those dialyzing 3x/ week (Δ€19,122). Costs for kidney transplant recipients were €85,127 (SD = €39,679) in the year of transplantation and rapidly declined in the first and second year after successful transplantation (resp. €29,612 (SD = €34,099) and €15,018 (SD = €16,186)). Transplantation with a deceased donor kidney resulted in higher costs (€99,450, SD = €36,036)) in the year of transplantation compared to a living donor kidney transplantation (€73,376, SD = €38,666). Conclusions CAPD patients have the lowest costs compared to other dialysis modalities. Costs in the year of transplantation are 25% lower for patients with kidneys from living vs. deceased donor. After successful transplantation, annual costs decline substantially to a level that is approximately 14–19% of annual dialysis costs

The phenotype of Floating-Harbor syndrome: Clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome. Methods and results. Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Een archeologisch inventariserend veldonderzoek door middel van een proefsleuf (IVO-P) op de vermoedelijke locatie van de laatmiddeleeuwse Mariakapel te Kropswolde, gemeente Hoogezand-Sappemeer (Gr.)

Lit.opg., bijl

Een aanvullend archeologisch onderzoek op het AZC te Leek, gemeente Leek

Met lit. op

Een archeologisch inventariserend veldonderzoek (IVO) door middel van proefsleuven op het voormalig kasteelterrein 'De Burght' te Geldrop, gemeente Geldrop-Mierlo (N.-Br.)

Met lit. op