Analyse pharmacoéconomique et pharmacothérapeutique de l'efficacité des cercles de qualité médecins-pharmaciens pour la prescription médicamenteuse entre 1999 et 2009

IntroductionUn cercle de qualité médecins-pharmaciens (CQ) pour la prescription médicamenteuse repose sur une démarche systémique coordonnée par des pharmaciens d'officine visant l'amélioration continue de la sécurité et de l'efficience des prescriptions de médecins de premier recours. Les trois éléments clés de ce concept collaboratif sont 1) le travail en réseau au niveau local ; 2) les données de prescription médicale et le retour d'informations (feedback) décrivant de manière comparative les coûts, le choix et la fréquence des médicaments prescrits ; 3) le matériel standardisé de formation continue interdisciplinaire.L'objectif de la présente étude est d'évaluer sur une période de onze ans (1999-2009) l'impact pharmacoéconomique et pharmacothérapeutique de six CQs pionniers (24 médecins et 6 pharmaciens), localisés dans le canton de Fribourg.Méthode: L'étude mesure notamment l'impact sur les coûts globaux de prescription des médecins des CQs en comparaison avec un groupe contrôle de médecins omnipraticiens travaillant hors CQ entre 1999-2009. La maîtrise des coûts engendrée est détaillée pour cinq index thérapeutiques de la classe des médicaments cardiovasculaires, y compris le pourcentage des génériques et celui des emballages de sartans dans la classe dite des antihypertenseurs. Les données sont issues des données de facturation fournies par la Coopérative professionnelle pour les pharmaciens suisses (OFAC).Résultats: Concernant la maîtrise des coûts annuels des médicaments par patient, la différence cumulée entre les CQs et le groupe contrôle est en 2009 de 43% en faveur des cercles (cf. Fig. 1). Ceci représente pour 2009 uniquement une économie de 245'000 CHF par médecin. Ces résultats s'expliquent par un profil de prescription médicale plus efficient, une meilleure pénétration des génériques (cf. Fig. 2), une attitude plus pondérée vis-à-vis des stratégies marketing, une formation continue interdisciplinaire spécialisée à propos de l'usage rationnel des médicaments, une meilleure application des recommandations nationales ou internationales.Conclusion: Cette évaluation a confirmé l'intérêt des CQs comme réseau local de collaboration en médecine de premier recours. Les médecins travaillant avec les pharmaciens modifient leurs prescriptions de manière claire et durable. Ce projet interdisciplinaire de qualité des soins montre que la maîtrise des coûts médicamenteux est obtenue sans concession à la qualité des traitements.

Effects of prior repeated-sprints with different recovery duration on oxygen uptake kinetics during subsequent heavy-exercise

Introduction: Prior repeated-sprints (6) has become an interesting method to resolve the debate surrounding the principal factors that limits the oxygen uptake (V'O2) kinetics at the onset of exercise [i.e., muscle O2 delivery (5) or metabolic inertia (3)]. The aim of this study was to compare the effects of two repeated-sprints sets of 6x6s separated by different recovery duration between the sprints on V'O2 and muscular de-oxygenation [HHb] kinetics during a subsequent heavy-intensity exercise. Methods: 10 male subjects performed a 6-min constant-load cycling test (T50) at intensity corresponding to half of the difference between V'O2max and the ventilatory threshold. Then, they performed two repeated-sprints sets of 6x6s all-out separated by different recovery duration between the sprints (S1:30s and S2:3min) followed, after 7-min-recovery, by the T50 (S1T50 and S2T50, respectively). V'O2, [HHb] of the vastus lateralis (VL) and surface electromyography activity [i.e., root-mean-square (RMS) and the median frequency of the power density spectrum (MDF)] from VL and vastus medialis (VM) were recorded throughout T50. Models using a bi-exponential function for the overall T50 and a mono-exponential for the first 90s of T50 were used to define V'O2 and [HHb] kinetics respectively. Results: V'O2 mean value was higher in S1 (2.9±0.3l.min-1) than in S2 (1.2±0.3l.min-1); (p<0.001). The peripheral blood flow was increased after sprints as attested by a higher basal heart rate (HRbaseline) (S1T50: +22%; S2T50: +17%; p≤0.008). Time delay [HHb] was shorter for S1T50 and S2T50 than for T50 (-22% for both; p≤0.007) whereas the mean response time of V'O2 was accelerated only after S1 (S1T50: 32.3±2.5s; S2T50: 34.4±2.6s; T50: 35.7±5.4s; p=0.031). There were no significant differences in RMS between the three conditions (p>0.05). MDF of VM was higher during the first 3-min in S1T50 than in T50 (+6%; p≤0.05). Conclusion: The study show that V'O2 kinetics was speeded by prior repeated-sprints with a short (30s) but not a long (3min) inter-sprints-recovery even though the [HHb] kinetics was accelerated and the peripheral blood flow was enhanced after both sprints. S1, inducing a greater PCr depletion (1) and change in the pattern of the fibres recruitment (increase in MDF) compared with S2, may decrease metabolic inertia (2), stimulate the oxidative phosphorylation activation (4) and accelerate V'O2 kinetics at the beginning of the subsequent high-intensity exercise.

Talking to kids about prescription drug abuse, 2007

A brochure to assist parents and other care givers when talking about drug abuse as it relates to prescription drugs.

Neuromuscular fatigue induced by whole-body vibration exercise

The aim of this study was to examine the magnitude and the origin of neuromuscular fatigue induced by half-squat static whole-body vibration (WBV) exercise, and to compare it to a non-WBV condition. Nine healthy volunteers completed two fatiguing protocols (WBV and non-WBV, randomly presented) consisting of five 1-min bouts of static half-squat exercise with a load corresponding to 50 % of their individual body mass. Neuromuscular fatigue of knee and ankle muscles was investigated before and immediately after each fatiguing protocol. The main outcomes were maximal voluntary contraction (MVC) torque, voluntary activation, and doublet peak torque. Knee extensor MVC torque decreased significantly (P < 0.01) and to the same extent after WBV (-23 %) and non-WBV (-25 %), while knee flexor, plantar flexor, and dorsiflexor MVC torque was not affected by the treatments. Voluntary activation of knee extensor and plantar flexor muscles was unaffected by the two fatiguing protocols. Doublet peak torque decreased significantly and to a similar extent following WBV and non-WBV exercise, for both knee extensors (-25 %; P < 0.01) and plantar flexors (-7 %; P < 0.05). WBV exercise with additional load did not accentuate fatigue and did not change its causative factors compared to non-WBV half-squat resistive exercise in recreationally active subjects.

Fuel metabolism during exercise in euglycaemia and hyperglycaemia in patients with type 1 diabetes mellitus--a prospective single-blinded randomised crossover trial.

Aims/hypothesis We assessed systemic and local muscle fuel metabolism during aerobic exercise in patients with type I diabetes at euglycaemia and hyperglycaemia with identical insulin levels.Methods This was a single-blinded randomised crossover study at a university diabetes unit in Switzerland. We studied seven physically active men with type I diabetes (mean +/- SEM age 33.5 +/- 2.4 years, diabetes duration 20.1 +/- 3.6 years, HbA(1c) 6.7 +/- 0.2% and peak oxygen uptake [VO2peak] 50.3 +/- 4.5 ml min(-1) kg(-1)). Men were studied twice while cycling for 120 min at 55 to 60% of VO2peak, with a blood glucose level randomly set either at 5 or 11 mmol/l and identical insulinaemia. The participants were blinded to the glycaemic level; allocation concealment was by opaque, sealed envelopes. Magnetic resonance spectroscopy was used to quantify intramyocellular glycogen and lipids before and after exercise. Indirect calorimetry and measurement of stable isotopes and counter-regulatory hormones complemented the assessment of local and systemic fuel metabolism.Results The contribution of lipid oxidation to overall energy metabolism was higher in euglycaemia than in hyperglycaemia (49.4 +/- 4.8 vs 30.6 +/- 4.2%; p<0.05). Carbohydrate oxidation accounted for 48.2 +/- 4.7 and 66.6 +/- 4.2% of total energy expenditure in euglycaemia and hyperglycaemia, respectively (p<0.05). The level of intramyocellular glycogen before exercise was higher in hyperglycaemia than in euglycaemia (3.4 +/- 0.3 vs 2.7 +/- 0.2 arbitrary units [AU]; p<0.05). Absolute glycogen consumption tended to be higher in hyperglycaemia than in euglycaemia (1.3 +/- 0.3 vs 0.9 +/- 0.1 AU). Cortisol and growth hormone increased more strongly in euglycaemia than in hyperglycaemia (levels at the end of exercise 634 52 vs 501 +/- 32 nmol/l and 15.5 +/- 4.5 vs 7.4 +/- 2.0 ng/ml, respectively; p<0.05).Conclusions/interpretation Substrate oxidation in type I diabetic patients performing aerobic exercise in euglycaemia is similar to that in healthy individuals revealing a shift towards lipid oxidation during exercise. In hyperglycaemia fuel metabolism in these patients is dominated by carbohydrate oxidation. Intramyocellular glycogen was not spared in hyperglycaemia.

Increasing lactate turnover rate during exercise by means of altitude training and fructose ingestion : effects on substrate metabolism and endurance performance

Summary : With regard to exercise metabolism, lactate was long considered as a dead-end waste product responsible for muscle fatigue and a limiting factor for motor performance. However, a large body of evidence clearly indicates that lactate is an energy efficient metabolite able to link the glycolytic pathway with aerobic metabolism and has endocrine-like actions, rather than to be a dead-end waste product. Lactate metabolism is also known to be quickly upregulated by regular endurance training and is thought to be related to exercise performance. However, to what extent its modulation can increase exercise performance in already endurance-trained subjects is unknown. The general hypothesis of this work was therefore that increasing either lactate metabolic clearance rate or lactate availability could, in turn, increase endurance performance. The first study (Study I) aimed at increasing the lactate clearance rate by means of assumed interaction effects of endurance training and hypoxia on lactate metabolism and endurance performance. Although this study did not demonstrate any interaction of training and hypoxia on both lactate metabolism and endurance performance, a significant deleterious effect of endurance training in hypoxia was shown on glucose homeostasis. The methods used to determine lactate kinetics during exercise exhibited some limitations, and the second study did delineate some of the issues raised (Study 2). The third study (Study 3) investigated the metabolic and performance effects of increasing plasma lactate production and availability during prolonged exercise in the fed state. A nutritional intervention was used for this purpose: part of glucose feedings ingested during the control condition was substituted by fructose. The results of this study showed a significant increase of lactate turnover rate, quantified the metabolic fate of fructose; and demonstrated a significant decrease of lipid oxidation and glycogen breakdown. In contrast, endurance performance appeared to be unmodified by this dietary intervention, being at odds with recent reports. Altogether the results of this thesis suggest that in endurance athletes the relationship between endurance performance and lactate turnover rate remains unclear. Nonetheless, the result of the present study raises questions and opens perspectives on the rationale of using hypoxia as a therapeutic aid for the treatment of insulin resistance. Moreover, the results of the second study open perspectives on the role of lactate as an intermediate metabolite and its modulatory effects on substrate metabolism during exercise. Additionally it is suggested that the simple nutritional intervention used in the third study can be of interest in the investigation on the aforementioned roles of lactate. Résumé : Lorsque le lactate est évoqué en rapport avec l'exercice, il est souvent considéré comme un déchet métabolique responsable de l'acidose métabolique, de la fatigue musculaire ou encore comme un facteur limitant de la performance. Or la littérature montre clairement que le lactate se révèle être plutôt un métabolite utilisé efficacement par de nombreux tissus par les voies oxydatives et, ainsi, il peut être considéré comme un lien entre le métabolisme glycolytique et le métabolisme oxydatif. De plus on lui prête des propriétés endocrines. Il est connu que l'entraînement d'endurance accroît rapidement le métabolisme du lactate, et il est suggéré que la performance d'endurance est liée à son métabolisme. Toutefois la relation entre le taux de renouvellement du lactate et la performance d'endurance est peu claire, et, de même, de quelle manière la modulation de son métabolisme peut influencer cette dernière. Le but de cette thèse était en conséquence d'investiguer de quelle manière et à quel degré l'augmentation du métabolisme du lactate, par l'augmentation de sa clearance et de son turnover, pouvait à son tour améliorer la performance d'endurance de sujets entraînés. L'objectif de la première étude a été d'augmenter la clearance du lactate par le biais d'un entraînement en conditions hypoxiques chez des cyclistes d'endurance. Basé sur la littérature scientifique existante, on a fait l'hypothèse que l'entraînement d'endurance et l'hypoxie exerceraient un effet synergétique sur le métabolisme du lactate et sur la performance, ce qui permettrait de montrer des relations entre performance et métabolisme du lactate. Les résultats de cette étude n'ont montré aucun effet synergique sur la performance ou le métabolisme du lactate. Toutefois, un effet délétère sur le métabolisme du glucose a été démontré. Quelques limitations de la méthode employée pour la mesure du métabolisme du lactate ont été soulevées, et partiellement résolues dans la seconde étude de ce travail, qui avait pour but d'évaluer la sensibilité du modèle pharmacodynamique utilisé pour le calcul du turnover du lactate. La troisième étude a investigué l'effet d'une augmentation de la lactatémie sur le métabolisme des substrats et sur la performance par une intervention nutritionnelle substituant une partie de glucose ingéré pendant l'exercice par du fructose. Les résultats montrent que les composants dynamiques du métabolisme du lactate sont significativement augmentés en présence de fructose, et que les oxydations de graisse et de glycogène sont significativement diminuées. Toutefois aucun effet sur la performance n'a été démontré. Les résultats de ces études montrent que la relation entre le métabolisme du lactate et la performance reste peu claire. Les résultats délétères de la première étude laissent envisager des pistes de travail, étant donné que l'entraînement en hypoxie est considéré comme outil thérapeutique dans le traitement de pathologies liées à la résistance à l'insuline. De plus les résultats de la troisième étude ouvrent des perspectives de travail quant au rôle du lactate comme intermédiaire métabolique durant l'exercice ainsi que sur ses effets directs sur le métabolisme. Ils suggèrent de plus que la manipulation nutritionnelle simple qui a été utilisée se révèle être un outil prometteur dans l'étude des rôles et effets métaboliques que peut revêtir le lactate durant l'exercice.

Weight-bearing bones are more sensitive to physical exercise in boys than in girls during pre- and early puberty: a cross-sectional study.

We carried out a cross-section study of the sex-specific relationship between bone mineral content and physical activity at sites with different loading in pre- and early pubertal girls and boys. There was significant sensitivity of bone mineral content of the hip to physical exercise in boys, but not in girls. BACKGROUND: Since little is known whether there are sex differences in sensitivity of bone to loading, we investigated sex differences in the cross-sectional association between measures of physical activity (PA) and bone mass and size in pre- and early pubertal children of both sexes. METHODS: We measured bone mineral content/density (BMC/BMD) and fat-free mass (FFM) in 269 6- to 13-year-old children from randomly selected schools by dual-energy X-ray absorptiometry. Physical activity (PA) was measured by accelerometers and lower extremity strength by a jump-and-reach test. RESULTS: Boys (n = 128) had higher hip and total body BMC and BMD, higher FFM, higher muscle strength and were more physically active than girls (n = 141). Total hip BMC was positively associated with time spent in total and vigorous PA in boys (r = 0.20-0.33, p < 0.01), but not in girls (r = 0.02-0.04, p = ns), even after adjusting for FFM and strength. While boys and girls in the lowest tertile of vigorous PA (22 min/day) did not differ in hip BMC (15.62 vs 15.52 g), boys in the highest tertile (72 min/day) had significantly higher values than the corresponding girls (16.84 vs 15.71 g, p < 0.05). CONCLUSIONS: Sex differences in BMC during pre- and early puberty may be related to a different sensitivity of bone to physical loading, irrespective of muscle mass.

Exaggerated exercise-induced pulmonary hypertension causes lung water accumulation and right ventricular dysfunction in patients with chronic mountain sickness

Background: Chronic mountain sickness (CMS) is characterized by exaggerated exercise-induced pulmonary hypertension. Evidences suggests that exercise may cause lung fluid accumulation at high altitude. We hypothesized that, in patients with CMS, exercise causes lung fluid accumulation.Methods: In 21 male CMS patients and 20 matched healthy controls born and permanently living in La Paz (Bolivia, 3600m) we assessed with echocardiogram, pulmonary artery pressure (PASP), right and left ventricular function and ultrasoundlung comets (ULCs, a marker of lung fluid accumulation) at rest and during mild bicycle exercise (10 min at 50W).Results: CMS patients presented a more than 2-fold greater exercise-induced increase in pulmonary artery pressure than controls (17.1±8.3 vs 7.2±7.9 mmHg, P=0.003). This exaggerated PASP response to exercise was associated with a roughly 3-fold greater increase in UCLs in patients with CMS than in controls (6.3±5.1 vs. 2.1±5.3, p<0.05), and there existed a significant relationship between PASP and UCLs (r=0.44, p<0.001). Finally, TDI on lateral tricuspid annulus decreased during exercise in patients with CMS (from 13.2±3.2 to 11.5±2.1 cm s-1, p=0.03), but increased in controls (from 13.1±2.9 to 14.9±2.6 cm s-1 , p=0.04). Left ventricular function remained unaltered in the 2 groups.Conclusions: we provide the first direct evidence in CMS patients that exaggerated exercise-induced pulmonary hypertension causes rapid lung fluid accumulation and right ventricular dysfunction. We speculate that in patients with CMS these two phenomena contribute to reduced exercise performances and Figure 1 increased cardiovascular morbidity and mortality that characterise these subjects.

Breakpoints in ventilation, cerebral and muscle oxygenation, and muscle activity during an incremental cycling exercise.

The aim of this study was to locate the breakpoints of cerebral and muscle oxygenation and muscle electrical activity during a ramp exercise in reference to the first and second ventilatory thresholds. Twenty-five cyclists completed a maximal ramp test on an electromagnetically braked cycle-ergometer with a rate of increment of 25 W/min. Expired gazes (breath-by-breath), prefrontal cortex and vastus lateralis (VL) oxygenation [Near-infrared spectroscopy (NIRS)] together with electromyographic (EMG) Root Mean Square (RMS) activity for the VL, rectus femoris (RF), and biceps femoris (BF) muscles were continuously assessed. There was a non-linear increase in both cerebral deoxyhemoglobin (at 56 ± 13% of the exercise) and oxyhemoglobin (56 ± 8% of exercise) concomitantly to the first ventilatory threshold (57 ± 6% of exercise, p > 0.86, Cohen's d < 0.1). Cerebral deoxyhemoglobin further increased (87 ± 10% of exercise) while oxyhemoglobin reached a plateau/decreased (86 ± 8% of exercise) after the second ventilatory threshold (81 ± 6% of exercise, p < 0.05, d > 0.8). We identified one threshold only for muscle parameters with a non-linear decrease in muscle oxyhemoglobin (78 ± 9% of exercise), attenuation in muscle deoxyhemoglobin (80 ± 8% of exercise), and increase in EMG activity of VL (89 ± 5% of exercise), RF (82 ± 14% of exercise), and BF (85 ± 9% of exercise). The thresholds in BF and VL EMG activity occurred after the second ventilatory threshold (p < 0.05, d > 0.6). Our results suggest that the metabolic and ventilatory events characterizing this latter cardiopulmonary threshold may affect both cerebral and muscle oxygenation levels, and in turn, muscle recruitment responses.

Iowa Disaster Recovery Tabletop Exercise - After Action Report / Improvement Plan

On June 24, 2010, the Rebuild Iowa Office (RIO) held a discussion-based tabletop exercise for the purpose of creating a framework to support disaster recovery coordination within the State of Iowa. The purpose of this report is to provide an overview of the tabletop exercise, summarize and analyze exercise results, identify strengths which should be maintained and built upon, identify areas for further improvement, and support development of recommendations and corrective actions.

Development of an erythropoietin prescription simulator to improve abilities for the prescription of erythropoietin stimulating agents: is it feasible?

BACKGROUND: The increasing use of erythropoietins with long half-lives and the tendency to lengthen the administration interval to monthly injections call for raising awareness on the pharmacokinetics and risks of new erythropoietin stimulating agents (ESA). Their pharmacodynamic complexity and individual variability limit the possibility of attaining comprehensive clinical experience. In order to help physicians acquiring prescription abilities, we have built a prescription computer model to be used both as a simulator and education tool. METHODS: The pharmacokinetic computer model was developed using Visual Basic on Excel and tested with 3 different ESA half-lives (24, 48 and 138 hours) and 2 administration intervals (weekly vs. monthly). Two groups of 25 nephrologists were exposed to the six randomised combinations of half-life and administration interval. They were asked to achieve and maintain, as precisely as possible, the haemoglobin target of 11-12 g/dL in a simulated naïve patient. Each simulation was repeated twice, with or without randomly generated bleeding episodes. RESULTS: The simulation using an ESA with a half-life of 138 hours, administered monthly, compared to the other combinations of half-lives and administration intervals, showed an overshooting tendency (percentages of Hb values > 13 g/dL 15.8 ± 18.3 vs. 6.9 ± 12.2; P < 0.01), which was quickly corrected with experience. The prescription ability appeared to be optimal with a 24 hour half-life and weekly administration (ability score indexing values in the target 1.52 ± 0.70 vs. 1.24 ± 0.37; P < 0.05). The monthly prescription interval, as suggested in the literature, was accompanied by less therapeutic adjustments (4.9 ± 2.2 vs. 8.2 ± 4.9; P < 0.001); a direct correlation between haemoglobin variability and number of therapy modifications was found (P < 0.01). CONCLUSIONS: Computer-based simulations can be a useful tool for improving ESA prescription abilities among nephrologists by raising awareness about the pharmacokinetic characteristics of the various ESAs and recognizing the factors that influence haemoglobin variability.