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Udgivelsesdato: 2008/1

Udgivelsesdato: 2008/3/21

Udgivelsesdato: 2008/2/29

Udgivelsesdato: 2008/8

Udgivelsesdato: 2008/12/5

Udgivelsesdato: 2008/1/14

The primary objective of this double-blind, randomised, controlled trial was to determine if implanting gold beads at five acupuncture points around the knee joint improves 1-year outcomes for patients with osteoarthritis (OA) of the knee. Participants were 43 adults aged 18-80 years with pain and stiffness from non-specific OA of the knee for over a year. The intervention was blinded implantation of gold beads at five acupuncture points around the affected knee through a hypodermic needle, or needle insertion alone. Primary outcome measures were knee pain, stiffness and function assessed by the patient at 0, 1, 3, 6, 9 and 12 months and knee score and knee function assessed by an orthopaedic surgeon at 0, 6 and 12 months. Within the first month, three patients dropped out. The remaining 21/19 patients in the intervention/control groups generally improved, but there was no statistically significant difference between the groups. The improvement was shown in the patients' self-assessment scores that decreased from randomisation until 1 year later (intervention/control group, medians): pain -1.92/-2.18 (P = 0.95, F test, general linear mixed model); stiffness -0.93/-0.43 (P = 0.11); function -7.23/-3.36 (P = 0.63). The surgeon's scores also generally improved, i.e. increased: knee score +16.4/+8.2 (P = 0.65); knee function +10.5/+5.8 (P = 0.79). In the protocol-based subgroup analysis, the 15 intervention patients of the 32 patients who had a positive response to the initial conventional acupuncture had greater relative improvements in self-assessed outcomes. The treatment was well tolerated. This 1-year pilot study indicates that extraarticular gold bead implantation is a promising treatment modality for patients with OA of the knee. The new treatment should be tested in a larger trial including only patients who respond positively to initial conventional acupuncture.

Grey-box pharmacokinetic/pharmacodynamic (PK/PD) modelling is presented as a promising way of modelling PK/PD systems. The concept behind grey-box modelling is based on combining physiological knowledge along with information from data in the estimation of model parameters. Grey-box modelling consists of using stochastic differential equations (SDEs) where the stochastic term in the differential equations represents unknown or incorrectly modelled dynamics of the system. The methodology behind the grey-box PK/PD modelling framework for systematic model improvement is illustrated using simulated data and furthermore applied to Bergman's minimal model of glucose kinetics using clinical data from an intravenous glucose tolerance test (IVGTT). The grey-box estimates of the stochastic system noise parameters indicate that the glucose minimal model is too simple and should preferably be revised in order to describe the complicated in vivo system of insulin and glucose following an IVGTT.