Toxic and drug-induced peripheral neuropathies: updates on causes, mechanisms and management.

PURPOSE OF REVIEW: This review discusses publications highlighting current research on toxic, chemotherapy-induced peripheral neuropathies (CIPNs), and drug-induced peripheral neuropathies (DIPNs). RECENT FINDINGS: The emphasis in clinical studies is on the early detection and grading of peripheral neuropathies, whereas recent studies in animal models have given insights into molecular mechanisms, with the discovery of novel neuronal, axonal, and Schwann cell targets. Some substances trigger inflammatory changes in the peripheral nerves. Pharmacogenetic techniques are underway to identify genes that may help to predict individuals at higher risk of developing DIPNs. Several papers have been published on chemoprotectants; however, to date, this approach has not been shown effective in clinical trials. SUMMARY: Both length and nonlength-dependent neuropathies are encountered, including small-fiber involvement. The introduction of new diagnostic techniques, such as excitability studies, skin laser Doppler flowmetry, and pharmacogenetics, holds promise for early detection and to elucidate underlying mechanisms. New approaches to improve functions and quality of life in CIPN patients are discussed. Apart from developing less neurotoxic anticancer therapies, there is still hope to identify chemoprotective agents (erythropoietin and substances involved in the endocannabinoid system are promising) able to prevent or correct painful CIPNs

Fractures After Denosumab Discontinuation: A Retrospective Study of 797 Cases.

A rebound of osteoclast activity during the 2 years after a treatment or prevention of osteoporosis with denosumab (Dmab) leads to an increased risk of vertebral fractures (VFs). We attempted to identify the risk factors for these VF and to examine the protective role of bisphosphonates. For that, 22 specialists in Switzerland provided data of unselected patients, treated with denosumab for osteoporosis or breast cancer without metastases under aromatase inhibitors, who have received at least two injections of Dmab, with at least 1 year of follow-up after discontinuation. The questionnaire covered separately the periods before, during, and after Dmab treatment, and registered clinical, radiological, and lab data. For the analysis of the risk factors, the main outcomes were the time to the first VF after the treatment, the presence of multiple VFs (MVFs), and the number of VFs. The incidence of VF was 16.4% before, 2.2% during, and 10.3% after the treatment with Dmab. The risk of VF after Dmab discontinuation was associated with an increased risk of non-vertebral fractures. The pretreatment predictors of the post-treatment fracture risk were a parental hip fracture and previous VFs. Further risk factors appeared later, such as low total hip bone mineral density (BMD) during and after denosumab, increased bone resorption markers, and the loss of total hip BMD after the denosumab. Treatment with bisphosphonates, especially after Dmab, had a protective effect. Bisphosphonates given before Dmab did not further decrease the risk of VF in cases who got bisphosphonates after Dmab. This study shows that the risk of VF is poorly predictable before the prescription of denosumab. But during and after the treatment, bone resorption markers and BMD have a significant predictive value. Bisphosphonates after the treatment with denosumab are protective against VFs. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

The effects of morphine on dyspnea and ventilatory function in elderly patients with advanced cancer: A randomized double-blind controlled trial

Background: Dyspnea represents a very frequent and distressing symptom in patients with advanced cancer. This study was undertaken to assess the efficacy of morphine on dyspnea and its safety for ventilatory function in elderly advanced cancer patients. Patients and methods: Nine elderly patients with dyspnea due to lung involvement were randomized to receive either morphine subcutaneously (5 mg in seven opioid-naïve patients and 3.75 mg in two patients on top of their regular oral dose of 7.5 mg q4h) or placebo on day 1. On day 2, they were crossed over to receive the alternate treatment. Dyspnea was assessed every fifteen minutes using a visual analogue scale (VAS: 0-100 mm) and the ordinal scale developed by Borg (0-10 points). Pain, somnolence and anxiety were assessed using VAS. Respiratory effort, respiratory rate and oxygen saturation were also measured repeatly. Results: Mean changes in dyspnea 45 minutes after injection were −25 ± 10 mm and −1.2 ± 1.2 points for morphine, versus 0.6 ± 7.7 mm (P < 0.01) and −0.1 ± 0.3 points (P = 0.03) for placebo on VAS and Borg scale, respectively. No relevant changes were observed in somnolence, pain, anxiety, respiratory effort and rate, and oxygen saturation. Conclusions: Morphine appears effective for cancer dyspnea, and it does not compromise respiratory function at the dose level use

Vents contraires. Le Parti socialiste suisse face aux crises économiques et à l'essor du néolibéralisme (1973-1995)

Le 12 février 1984, c’est dans une ambiance survoltée, après 11 heures de débat, que les délégué·es au congrès du Parti socialiste suisse (PSS) décident que leurs représentant·es continueront de siéger au Conseil fédéral. Ce choix constitue une défaite pour l’aile gauche du PSS, car celle-ci réclamait un retour à l’opposition après que la candidate socialiste pour l’élection au gouvernement a été évincée par la majorité de droite. Cet épisode illustre parfaitement les difficultés rencontrées à partir du milieu des années 1970 par la principale force politique de gauche du pays. Sur fond de crises économiques à répétition et d’essor des politiques néolibérales sur le plan international, le PSS se heurte à des adversaires de moins en moins enclins au compromis. Ce climat politique plus dur remet en cause la conquête graduelle des progrès sociaux visée par le parti dans la période d’après-guerre. Le présent ouvrage examine les débats et tensions traversés par le PSS et comment ce dernier a bravé de nombreux vents contraires entre 1973 et 1995. L’auteur y montre que les dirigeant·es socialistes ont dû user d’un art de la synthèse permanent pour que tiennent ensemble des sensibilités politiques divergentes, entre partisan·es d’une adaptation accrue à la mondialisation libérale et défenseur·es d’un État social fort et interventionniste. À travers l’étude d’un parti gouvernemental, ce texte invite à une plongée dans plus de deux décennies de politique fédérale, en revisitant les enjeux qui ont marqué la Suisse contemporaine, du système de retraites à la construction européenne en passant par l’empreinte des mouvements sociaux sur la vie politique