[Less is more, Choosing wisely, Smarter medicine : perspectives and issues]. / Less is more, Choosing wisely, Smarter medicine : enjeux et perspectives.

The « Choosing Wisely ¼ initiative aims to reduce overtreatment by issuing specific lists of recommendations. These campaigns have spread around the world over the last ten years, including in Switzerland, under the brand « Smarter Medicine ¼. The methodology used by different medical societies to issue these recommendations remains heterogeneous and heavily consensus-based and could benefit from a better synergy with the recent development of Evidence-Based Medicine and GRADE. Patient partnership, and reflections regarding economic and sustainability issues represent future avenues to enhance the potential impacts of such campaigns.

Le mouvement « Choosing Wisely ¼ a comme objectif de lutter contre la surmédicalisation via le développement de listes de recommandations. La dernière décennie a vu ce mouvement se diffuser à travers le monde, y compris en Suisse sous le nom de « Smarter Medicine ¼. La méthodologie avec laquelle ces recommandations sont élaborées par les sociétés savantes reste hétérogène et fortement basée sur le consensus, et pourrait bénéficier d'une meilleure synergie avec les développements de l'« Evidence-Based Medicine ¼ et de GRADE. Le partenariat avec les patients et les réflexions quant aux enjeux économiques et de durabilité sont autant de perspectives d'évolution de ces mouvements, afin de renforcer leurs impacts.

Long-Term Dexmedetomidine Use and Safety Profile in Palliative Care: A Case Report.

There is a lack of report of conscious sedation used as a last resort therapy for alleviating severe symptoms. To achieve this goal, dexmedetomidine appears to be a promising option. We report a case of successful two-month long treatment of intravenous (IV) dexmedetomidine added to hydromorphone for intractable cancer pain, restlessness, severe sleep disorder, anxiety, and craving symptoms in a 40-year-old man with active polysubstance use, receiving escalating doses of opioids for intractable abdominal cancer pain together with benzodiazepines. Under dexmedetomidine infusion at 1.2 µg/kg/hour, his symptoms markedly decreased. He could sleep at night and find respite during the day while continuing walking, eating, and other activities. Long-term conscious sedation with IV dexmedetomidine was well tolerated. We did not observe anxiety or agitation rebound during short periods of discontinuation of the infusion. Neither side effects nor tolerance were observed over time. Further research is needed to investigate the indications for conscious sedation and analgesia with dexmedetomidine in palliative patients with a prognosis that is longer than few weeks or uncertain.

Pioglitazone, a PPARγ Agonist, Upregulates the Expression of Caveolin-1 and Catalase, Essential for Thyroid Cell Homeostasis: A Clue to the Pathogenesis of Hashimoto's Thyroiditis.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates the expression of multiple target genes involved in several metabolic pathways as well as in inflammation. The expression and cell localization of caveolin-1 (Cav-1), thyroperoxidase (TPO), and dual oxidase (DUOX), involved in extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT). OBJECTIVES: The objectives of this study were (i) to analyze the PPARγ protein and mRNA expression at the follicular level in HT versus controls in correlation with the one of Cav-1; (ii) to study the effects of Th1 cytokines on PPARγ and catalase expression in human thyrocyte primary cultures; and (iii) to study the effects of pioglitazone, a PPARγ agonist, on thyroxisome components (Cav-1, TPO, DUOX) and on catalase, involved in antioxidant defense. RESULTS: Although the global expression of PPARγ in the whole gland of patients with HT was not modified compared with controls, there was great heterogeneity among glands and among follicles within the same thyroid. Besides normal (type 1) follicles, there were around inflammatory zones, hyperactive (type 2) follicles with high PPARγ and Cav-1 expression, and inactive (type 3) follicles which were unable to form thyroxine and did not express PPARγ or Cav-1. In human thyrocytes in primary culture, Th1 cytokines decreased PPARγ and catalase expression; pioglitazone increased Cav-1, TPO, and catalase expression. CONCLUSION: PPARγ may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPARγ may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for HT, and the use of PPARγ agonists could open a new therapeutic approach.