Training family physicians and residents in family medicine in shared decision making to improve clinical decisions regarding the use of antibiotics for acute respiratory infections: protocol for a clustered randomized controlled trial.

BACKGROUND: To explore ways to reduce the overuse of antibiotics for acute respiratory infections (ARIs), we conducted a pilot clustered randomized controlled trial (RCT) to evaluate DECISION+, a training program in shared decision making (SDM) for family physicians (FPs). This pilot project demonstrated the feasibility of conducting a large clustered RCT and showed that DECISION+ reduced the proportion of patients who decided to use antibiotics immediately after consulting their physician. Consequently, the objective of this study is to evaluate, in patients consulting for ARIs, if exposure of physicians to a modified version of DECISION+, DECISION+2, would reduce the proportion of patients who decide to use antibiotics immediately after consulting their physician. METHODS/DESIGN: The study is a multi-center, two-arm, parallel clustered RCT. The 12 family practice teaching units (FPTUs) in the network of the Department of Family Medicine and Emergency Medicine of Université Laval will be randomized to a DECISION+2 intervention group (experimental group) or to a no-intervention control group. These FPTUs will recruit patients consulting family physicians and residents in family medicine enrolled in the study. There will be two data collection periods: pre-intervention (baseline) including 175 patients with ARIs in each study arm, and post-intervention including 175 patients with ARIs in each study arm (total n = 700). The primary outcome will be the proportion of patients reporting a decision to use antibiotics immediately after consulting their physician. Secondary outcome measures include: 1) physicians and patients' decisional conflict; 2) the agreement between the parties' decisional conflict scores; and 3) perception of patients and physicians that SDM occurred. Also in patients, at 2 weeks follow-up, adherence to the decision, consultation for the same reason, decisional regret, and quality of life will be assessed. Finally, in both patients and physicians, intention to engage in SDM in future clinical encounters will be assessed. Intention-to-treat analyses will be applied and account for the nested design of the trial will be taken into consideration. DISCUSSION: DECISION+2 has the potential to reduce antibiotics use for ARIs by priming physicians and patients to share decisional process and empowering patients to make informed, value-based decisions.

AMPK activation with AICAR provokes an acute fall in plasma [K+].

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K(+) homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg x kg bolus then 4 mg x kg(-1) x min(-1) infusion. Plasma [K(+)] and [glucose] both dropped at 1 h of AICAR infusion and [K(+)] dropped to 3.3 +/- 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K(+) excretion. AICAR lowered [K(+)] whether plasma [K(+)] was chronically elevated or lowered. The K(+) infusion rate needed to maintain baseline plasma [K(+)] reached 15.7 +/- 1.3 micromol K(+) x kg(-1) x min(-1) between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K(+)] was not different from controls (4.2 +/- 0.1 mM), but the fall in plasma [K(+)] in response to AICAR (0.25 g/kg) was blunted: [K(+)] fell to 3.6 +/- 0.1 in controls and to 3.9 +/- 0.1 mM in Tg-KD1, suggesting that ECF K(+) redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K(+)] and suggest a novel mechanism for redistributing K(+) from ECF to ICF.

The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases alpha and beta in skeletal muscle.

The AMP-activated protein kinase (AMPK) pathway participates in the metabolic effects of contraction on muscle glucose uptake. We have shown that contraction increases both GLUT4 translocation to the cell surface and p38 mitogen-activated protein kinase (p38 MAPK) activity. The latter pathway may be involved in the activation of GLUT4. Here we investigated whether the AMPK activator AICAR increases glucose uptake by inducing translocation of GLUT4 and/or by activating the p38 MAPK pathway. AICAR infusion into glucose-clamped rats increased muscle glucose uptake and GLUT4 translocation from an intracellular fraction to the plasma membrane but not to T-tubules. AICAR also caused recruitment of the transferrin receptor to the plasma membrane and increased [125I]-transferrin uptake in isolated muscle. AICAR treatment in vivo or in vitro activated both p38 MAPKalpha and beta (1.6- to 2.8-fold) in EDL muscles with a time course identical to that of stimulation of AMPK and glucose transport. The p38 MAPK inhibitor SB203580 abrogated the stimulatory effect of AICAR on glucose uptake. These results suggest that AICAR increases muscle glucose uptake by two mechanisms: 1) inducing selective recruitment of GLUT4 to the plasma membrane, and 2) activating p38 MAPKalpha and beta, which may be involved in the activation of GLUT4.