86 research outputs found
How repeated time to event (RTTE) modelling of opioid requests after surgery may improve future post-operative pain management.
No full textTitle: How Repeated Time To Event (RTTE) modelling of opioid requests after surgery may improve future post-operative pain management Author: Rasmus Vestergaard Juul (1) Sten Rasmussen (2) Mads Kreilgaard (1) Ulrika S. H. Simonsson (3) Lona Louring Christrup (1) Trine Meldgaard Lund (1) Institution: (1) Dept. of Drug Design and Pharmacology, University of Copenhagen, Denmark (2) Orthopaedic Surgery Research Unit, Aalborg University Hospital, Denmark (3) Dept. of Pharmaceutical Biosciences, Uppsala University, Sweden Type: Poster: Drug/Disease modelling – CNSObjectives: Amount of opioid (eg. morphine) required by patients after surgery is often used as a surrogate measure for pain intensity in post-operative pain. However, the dynamic development of pain intensity over time is often ignored when investigating new analgesic treatments for post-operative pain1. This work included a Repeated Time to Event (RTTE) modelling2 approach of repeated opioid request in order to increase the understanding of pain breakthrough patterns in severe surgeries and improve patients’ pain management.Methods: 68 patients (F:45,M:23, Age:76±15) were included from a population receiving surgery after hip fracture at Orthopaedic Department, Aalborg University Hospital, Denmark during the period May-Dec 2012. Morphine administration times (estimated precision: ±5mins), formulations and doses were extracted from medical journals in the hospitalization period or until 96 hours after surgery. RTTE modelling was performed in NONMEM 7.2 with Pirana, PsN and Xpose- and ggplot2 libraries for R3,4. Weibull and Gompertz distributions were investigated as hazard models. Visual Predictive Check (VPC) of Kaplan Meier survival curves as well objective function value was used to evaluate the model fit.Results: A base RTTE model based on a Weibull distribution fitted the pooled data. However, VPCs showed that morphine request was not adequately described by the base models on all surgery types. This suggests that pain events do not occur in similar patterns in different surgeries. The developed RTTE model provide a base for investigation of surgery specific, drug concentration related, population specific and/or time-varying covariates of opioid requests and pain events.Conclusions: A framework has been developed based on RTTE modelling that may help improve future pain management by 1) Identification of surgery specific patterns in pain events and 2) Evaluation of concentration related effects of opioids.References:[1] McQuay et al. 2008. Br J Anaesth. 101(1):69-76 [2] Plan et al. 2011. J Pharmacol Exp Ther. 339(3):878-85[3] Keizer et al 2013. CPT Pharmacometrics Syst Pharmacol. 26;2:e50[4] Wickham 2009. ggplot2: elegant graphics for data analysis. Springer.<br/
Det glutamaterge system:neurokemisk patologi af Alzheimers syge og medicinalkemiske studier af glutaminsyrereceptorerne
No full textStofskiftesygedomme - Fra gen til terapi
No full textFejl i stofskiftet er årsag til over 500 kendte sygdomme.Kortlægningen af det humane genom har forbedretmulighederne for at opklare årsagerne til sygdommeneog forstå deres biokemi. Udfordringen er nu at udviklebehandlingsmetoder
Precarious working lives - Migrant workers' experience of working conditions in the Danish labour market
No full textPredictive Biomarkers and Personalized Therapy:Use of Pharmacogenetic Testing in a Scandinavian Perspective
No full textPrecision medicine has significantly advanced through the development of predictive biomarkers based on pharmacogenetic (PGx) testing. These tests identify interactions between drugs and genetic variants that influence patient responses to treatments. Understanding genetic variations in drug-metabolizing enzymes, receptors and transporters and their impact on pharmacokinetics and pharmacodynamics allows for the prediction of drug effects and side effects, enabling tailored treatments for different patient groups. This review focuses on drugs metabolized by cytochrome P450 (CYP450) enzymes, for example, citalopram and clopidogrel or transported by the solute carrier organic anion transporter family member 1B1 (SLCO1B1), for example, atorvastatin and simvastatin, with PGx dosing guidelines, in the context of consumption in Scandinavian countries. A major barrier to the widespread adoption of PGx tests in clinical practice has been healthcare professionals' uncertainty about their efficacy, complexity in result interpretation and questions regarding the evidence base. However, recent studies have demonstrated PGx testing has the potential to improve treatment outcomes, reduce adverse drug reactions and achieve cost savings. These findings underscore the potential of PGx testing as a valuable tool in clinical decision making, promoting its use in a pre-emptive manner to enhance patient care.</p
Dose Finding in the Clinical Development of 60 US Food and Drug Administration-Approved Drugs Compared With Learning vs. Confirming Recommendations
No full textThis review characterizes clinical development that supported the label dose in 60 drug indications recently approved by the US Food and Drug Administration. With Lewis B. Sheiner's Learning vs. Confirming clinical drug development paradigm as a reference point, the clinical development paths, the design of dose-ranging trials, and the dose-exposure-response characterization were examined using US Food and Drug Administration approval packages. It was found that 89% of clinical development programs included several doses in the first-in-patient trial, 43% proceeded directly to confirmatory trials after the first-in-patient trial, and 52% included multiple doses in confirmatory development. A low number of doses and narrow dose ranges were generally included in dose-ranging trials, with only 20% including at least four doses over an at least 10-fold dose range. In a third of approval packages, no dose-response or exposure-response evaluation was identified, and model-based dose-exposure-response characterization was rarely alluded to, as only 2 of 60 approval packages mentioned the use of a model-based approach. The findings suggest that confirmatory development may often be guided more toward learning than confirming, and furthermore that dose exposure response is robustly assessed in only a minority of clinical drug development programs, indicating that there may be room left for optimizing the benefit/risk profile of confirmatory/marketed dose(s). Significant deviation from Learning vs. Confirming may exist in clinical development practice on several levels, and the reasons for why this may be the case are discussed in light of contemporary literature.</p
Comment on Delanaye et al: Future perspectives regarding kidney function estimates and dose adjustments
No full textThe Effect of CYP2C19 Polymorphism on the Pharmacokinetics and Pharmacodynamics of Clopidogrel when given Alone or in Combination with Proton Pump Inhibitors:A Systematic Review
No full textTo enable PROSPERO to focus on COVID-19 submissions, this registration record has undergone basic automated checks for eligibility and is published exactly as submitted. PROSPERO has never provided peer review, and usual checking by the PROSPERO team does not endorse content. Therefore, automatically published records should be treated as any other PROSPERO registration
Excitatory amino acid receptors: multiplicity and structural requirements for activation and blockade
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