Pedal : identification of models for duodenal administration of levodopa

Backgound and aims: The main purpose of the PEDAL study is to identify and estimate sample individual pharmacokinetic- pharmacodynamic (PK/PD) models for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Other objectives are to study the absorption of Duodopa® and to form a basis for power calculation for a future larger study. PK/PD based on oral levodopa is problematic because of irregular gastric emptying. Preliminary work with data from [Gundert-Remy U et al. Eur J Clin Pharmacol 1983;25:69-72] suggested that levodopa infusion pharmacokinetics can be described by a two-compartment model. Background research led to a hypothesis for an effect model incorporating concentration-unrelated fluctuations, more complex than standard E-max models. Methods: PEDAL involved a few patients already on Duodopa®. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Data collection continued until the clinical effect was back at baseline. The procedure was repeated on two non-consecutive days per patient. The following data were collected in 5 to 15 minutes intervals: i) Accelerometer data. ii) Three e-diary questions about ability to walk, feelings of “off” and “dyskinesia”. iii) Clinical assessment of motor function by a physician. iv) Plasma concentrations of levodopa, carbidopa and the metabolite 3-O-methyldopa. The main effect variable will be the clinical assessment. Results: At date of abstract submission, lab analyses were currently being performed. Modelling results, simulation experiments and conclusions will be presented in our poster.

Psychometric properties of the Swedish version of the Fear of Complications Questionnaire

Objectives: To translate and evaluate the psychometric properties of the Swedish version of the Fear of Complications Questionnaire. Design: Cross-sectional study design and scale development. Settings: Totally, 469 adults (response rate 63.5%) with Type 1 diabetes completed the questionnaires. Participants were recruited from two university hospitals in Sweden. Participants: Eligible patients were those who met the following inclusion criteria: diagnosed with Type 1 diabetes, diabetes duration of at least 1 year and aged at least 18 years. Methods: The Fear of Complications Questionnaire was translated using the forward-backward translation method. Factor analyses of the questionnaire were performed in two steps using both exploratory and confirmatory factor analysis. Convergent validity was examined using the Hospital Anxiety and Depression Scale and the Fear of Hypoglycaemia Fear Survey. Internal consistency was estimated using Cronbach’s alpha.Results: Exploratory factor analysis supported a two-factor solution. One factor contained three items having to do with fear of kidney-related complications and one factor included the rest of items concerning fear of other diabetes-related complications, as well as fear of complications in general. Internal consistency was high Cronbach’s alpha 0.96. The findings also gave support for convergent validity, with significant positive correlations between measures (r = 0.51 to 0.54). Conclusion: The clinical relevance of the identified two-factor model with a structure of one dominant subdomain may be considered. We suggest, however a one-factor model covering all the items as a relevant basis to assess fear of complications among people with Type 1 diabetes.

The importance of body-mass exponent optimization for evaluation of performance capability in cross-country skiing

Introduction Performance in cross-country skiing is influenced by the skier’s ability to continuously produce propelling forces and force magnitude in relation to the net external forces. A surrogate indicator of the “power supply” in cross-country skiing would be a physiological variable that reflects an important performance-related capability, whereas the body mass itself is an indicator of the “power demand” experienced by the skier. To adequately evaluate an elite skier’s performance capability, it is essential to establish the optimal ratio between the physiological variable and body mass. The overall aim of this doctoral thesis was to investigate the importance of body-mass exponent optimization for the evaluation of performance capability in cross-country skiing. Methods In total, 83 elite cross-country skiers (56 men and 27 women) volunteered to participate in the four studies. The physiological variables of maximal oxygen uptake (V̇O2max) and oxygen uptake corresponding to a blood-lactate concentration of 4 mmol∙l-1 (V̇O2obla) were determined while treadmill roller skiing using the diagonal-stride technique; mean oxygen uptake (V̇O2dp) and upper-body power output (Ẇ) were determined during double-poling tests using a ski-ergometer. Competitive performance data for elite male skiers were collected from two 15-km classical-technique skiing competitions and a 1.25-km sprint prologue; additionally, a 2-km double-poling roller-skiing time trial using the double-poling technique was used as an indicator of upper-body performance capability among elite male and female junior skiers. Power-function modelling was used to explain the race and time-trial speeds based on the physiological variables and body mass. Results The optimal V̇O2max-to-mass ratios to explain 15-km race speed were V̇O2max divided by body mass raised to the 0.48 and 0.53 power, and these models explained 68% and 69% of the variance in mean skiing speed, respectively; moreover, the 95% confidence intervals (CI) for the body-mass exponents did not include either 0 or 1. For the modelling of race speed in the sprint prologue, body mass failed to contribute to the models based on V̇O2max, V̇O2obla, and V̇O2dp. The upper-body power output-to-body mass ratio that optimally explained time-trial speed was Ẇ ∙ m-0.57 and the model explained 63% of the variance in speed. Conclusions The results in this thesis suggest that V̇O2max divided by the square root of body mass should be used as an indicator of performance in 15-km classical-technique races among elite male skiers rather than the absolute or simple ratio-standard scaled expression. To optimally explain an elite male skier’s performance capability in sprint prologues, power-function models based on oxygen-uptake variables expressed absolutely are recommended. Moreover, to evaluate elite junior skiers’ performance capabilities in 2-km double-poling roller-skiing time trials, it is recommended that Ẇ divided by the square root of body mass should be used rather than absolute or simple ratio-standard scaled expression of power output.