Time domain analog circuit simulation

AbstractRecent developments of new methods for simulating electric circuits are described. Emphasis is put on methods that fit existing datastructures for backward differentiation formulae methods. These methods can be modified to apply to hierarchically organized datastructures, which allows for efficient simulation of large designs of circuits in the electronics industry

Double disadvantage: a case control study on health-related quality of life in children with sickle cell disease

<p>Abstract</p> <p>Background</p> <p>Low health-related quality of life (HRQoL) of children with sickle cell disease (SCD) may be associated with consequences of the disease, or with the low socio-economic status (SES) of this patient population. The aim of this study was to investigate the HRQoL of children with SCD, controlling for SES by comparing them to healthy siblings (matched for age and gender), and to a Dutch norm population.</p> <p>Methods</p> <p>The HRQoL of 40 children with homozygous SCD and 36 healthy siblings was evaluated by the KIDSCREEN-52. This self-report questionnaire assesses ten domains of HRQoL. Differences between children with SCD and healthy siblings were analyzed using linear mixed models. One-sample t-tests were used to analyze differences with the Dutch norm population. Furthermore, the proportion of children with SCD with impaired HRQoL was evaluated.</p> <p>Results</p> <p>In general, the HRQoL of children with SCD appeared comparable to the HRQoL of healthy siblings, while children with SCD had worse HRQoL than the Dutch norm population on five domains (Physical Well-being, Moods & Emotions, Autonomy, Parent Relation, and Financial Resources). Healthy siblings had worse HRQoL than the Dutch norm population on three domains (Moods & Emotions, Parent Relation, and Financial Resources). More than one in three children with SCD and healthy siblings had impaired HRQoL on several domains.</p> <p>Conclusion</p> <p>These findings imply that reduced HRQoL in children with SCD is mainly related to the low SES of this patient population, with the exception of disease specific effects on the physical and autonomy domain. We conclude that children with SCD are especially vulnerable compared to other patient populations, and have special health care needs.</p

Setting the stage for individualized therapy in hemophilia: what role can pharmacokinetics play?

Replacement therapy with clotting factor concentrates (CFC) is the mainstay of treatment in hemophilia. Its widespread application has led to a dramatic decrease in morbidity and mortality in patients, with concomitant improvement of quality of life. However, dosing is challenging and costs are high. This review discusses benefits and limitations of pharmacokinetic (PK)-guided dosing of replacement therapy as an alternative for current dosing regimens. Dosing of CFC is now primarily based on body weight and based on its in vivo recovery (IVR). Benefits of PK-guided dosing include individualization of treatment with better targeting, more flexible blood sampling, increased insight into association of coagulation factor levels and bleeding, and potential overall lowering of overall costs. Limitations include a slight burden for the patient, and availability of closely collaborating, experienced clinical pharmacologists

Cost-effectiveness analysis of preoperative transfusion in patients with sickle cell disease using evidence from the TAPS trial.

The study's objective was to assess the cost-effectiveness of preoperative transfusion compared with no preoperative transfusion in patients with sickle cell disease undergoing low- or medium-risk surgery. Seventy patients with sickle cell disease (HbSS/Sß(0) thal genotypes) undergoing elective surgery participated in a multicentre randomised trial, Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS). Here, a cost-effectiveness analysis based on evidence from that trial is presented. A decision-analytic model is used to incorporate long-term consequences of transfusions and acute chest syndrome. Costs and health benefits, expressed as quality-adjusted life years (QALYs), are reported from the 'within-trial' analysis and for the decision-analytic model. The probability of cost-effectiveness for each form of management is calculated taking into account the small sample size and other sources of uncertainty. In the range of scenarios considered in the analysis, preoperative transfusion was more effective, with the mean improvement in QALYs ranging from 0.018 to 0.206 per patient, and also less costly in all but one scenario, with the mean cost difference ranging from -£813 to £26. All scenarios suggested preoperative transfusion had a probability of cost-effectiveness >0.79 at a cost-effectiveness threshold of £20 000 per QALY

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients

PURPOSE: Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. METHODS: Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t(1/2)), time to 1% (Time(1%)), and calculated weekly dose (Dose(1%)). Bias and precision of these estimates were assessed to determine which LSS was adequate. RESULTS: For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: −5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time(1%), except for t(1/2) (range: 27.1% to 44.7%) and Dose(1%) (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose(1%) using LSS with the last sample taken on day 3 (LSS 6 and 10). CONCLUSION: Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively