Over the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1st, 2018 to... Show moreOver the past year many studies and clinical trials have been published in the osteoarthritis (OA) field. This review is based on systematic literature review covering the period May 1st, 2018 to April 19th , 2019; the final selection of articles was subjective. Specifically those articles considered to be presenting novel insights and of potential importance for clinical practice, are discussed.Further evidence has emerged that OA is a serious disease with increasing impact worldwide. Our understanding of development of pain in OA has increased. Detailed studies investigating widely used pharmacological treatments have shown the benefits to be limited, whereas the risks seem higher than expected, suggesting further studies and reconsideration of currently used guidelines. Promising new pharmacological treatments have been developed and published, however subsequent studies are warranted. While waiting for new treatment modalities to appear joint replacement is an effective alternative; new data have become available on how long they might last. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. Show less
Transfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC... Show moreTransfusion of red blood cells (RBCs) causes exposure to foreign antigens and, consequently, may induce alloimmunization. This research focused on identifying clinical determinants of RBC alloimmunization, eventually aiming to prevent alloimmunization by pre-emptively select extended matched blood for the predicted responder patient. Both RBC antigen intrinsic characteristics and patient-related factors were studied. Regarding antigen immunogenicity, K was confirmed to be the most potent antigen, followed by E, Cw, e, Jka and c. Of importance, anti-Jka is known to easily induce complement-mediated hemolysis. Inflammation due to severe bacterial and viral infections was associated to increased RBC alloimmunization incidences. Remarkably, although in line with murine models, Gram-negative bacteremia coincided with a twofold reduction of alloimmunization risk. In a non-hemoglobinopathy population, alloimmunization post-splenectomy was a highly unlikely event. Consequently, the Caucasian splenectomized patient does not benefit from RBC products matched beyond ABO/RhD. Patients with acute (either myeloid of lymphoblastic) leukemia, mature lymphomas, myelodysplastic syndrome, or patients post-autologous or -allogeneic stem cell transplantation demonstrated strongly reduced incidences of RBC alloimmunization, primarily explained by the intense immunosuppressive nature of treatments. Consequently, matching for the MDS population deserves renewed focus and should be based on the cumulative transfusion burden rather than on the diagnosis itself. Show less
In a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments... Show moreIn a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments at base-line, after three months, and at one-year follow-up were performed with the Anxiety Disorders Interview Schedule. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production (F = 3.2, p = 0.04) and a trend towards a decreased cortisol morning rise (F = 2.4, p = 0.09). At one-year follow-up daytime cor-tisol production was lowest in the early remitters (109.7 ± 29.2 h mmol/l), higher in the late remitters (121.0 ± 40.0 h mmol/l) and highest in the non-remitters (131.1 ± 48.9 h mmol/l). Early remitters had the highest cortisol morning rise (1.1 ± 1.5 h mmol/l), followed by the late remitters (0.8 ± 1.8 h mmol/l), the non-remitters had the lowest cortisol morning rise (0.07 ± 1.7 h mmol/l). Persistence of an anxiety disorder may thus lead to changes in HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders. Show less
For mechanism-based investigations on PK-PD relationships following intranasal administration, the use of advanced animal models and analytical techniques are crucial. As described in this thesis,... Show moreFor mechanism-based investigations on PK-PD relationships following intranasal administration, the use of advanced animal models and analytical techniques are crucial. As described in this thesis, quantitative information on distinction between extent as well as rate of absorption between nose-to-systemic and nose-to-brain distribution can now be obtained. Using plasma prolactin concentrations as a biomarker for dopamine D2 inhibition, a mechanism-based PK-PD model was developed. Most important aspects in this approach were incorporation of target site exposure (brain extracellular fluid) of remoxipride and a biological system response (positive feedback) mechanism on the synthesis of prolactin, thereby increasing the mechanistic insight in modulation of the dopaminergic system in rats. Simulating remoxipride brain extracellular fluid concentrations in humans, allometric scaling and use of independent information on interspecies differences proved that the structural model is applicable in both rats and man. Show less
