Plos One
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Activation of the muscarinic M1 receptor is a promising approach to improve cognitive deficits associated with cholinergic dysfunction in Alzheimer's disease, dementia with Lewy bodies, and schizophrenia. TAK-071 is an M1-selective positive allosteric modulator that improves cognitive deficits induced by scopolamine, a non-selective muscarinic receptor antagonist, with reduced side effects on gastrointestinal function in rats. In this study, we explored changes in quantitative electroencephalography (qEEG) power bands, with or without scopolamine challenge, as a non-invasive translational biomarker for the effect of TAK-071 in cynomolgus monkeys. ⋯ The effects of TAK-071 on scopolamine (25 μg/kg, s.c.)-induced qEEG spectral changes were examined using an acetylcholinesterase inhibitor donepezil and a muscarinic M1/M4 receptor agonist xanomeline as comparative cholinomimetics. TAK-071 (0.3-3 mg/kg, oral administration [p.o.]), donepezil (3 mg/kg, p.o.), and xanomeline (1 mg/kg, s.c.) suppressed the scopolamine-induced increases in alpha, theta, and delta power bands. These results suggest that changes in specific qEEG power bands, in particular theta and delta power bands in the context of scopolamine challenge, could be used as translational biomarkers for the evaluation of TAK-071 in clinical studies.
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Meta Analysis
Anticoagulant therapy for acute venous thrombo-embolism in cancer patients: A systematic review and network meta-analysis.
Low-molecular-weight heparin (LMWH) is usually recommended for the treatment of cancer-associated thrombosis (CAT) but this treatment requires burdensome daily injections. We did a systematic review to compare the efficacy and safety of direct oral anticoagulants (DOAC), vitamin K antagonists (VKA) and LMWH in patients with CAT. ⋯ DOAC are effective to prevent VTE recurrence in patients with CAT but are associated with an increased risk of bleeding compared to LMWH. The choice of anticoagulant should be personalised, taking into account the patient's bleeding risk, including cancer site, and patient's values and preferences.
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Multicenter Study Clinical Trial
Prevalence and predictors of peripherally inserted central catheter-associated bloodstream infections in adults: A multicenter cohort study.
To evaluate the prevalence and predictors of peripherally inserted central catheter-associated bloodstream infection (PBSI) and PBSI-related death in hospitalized adult patients. ⋯ Our results indicated that risk factors associated with PBSI included the number of catheter lumens, the use of PICCs for chemotherapy, and the hospital length of stay. Furthermore, PBSI-related death was common in patients undergoing chemotherapy, diabetics, and elderly patients.
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Multicenter Study
Drug tolerability and reasons for discontinuation of seven biologics in elderly patients with rheumatoid arthritis -The ANSWER cohort study.
The aim of this study is to evaluate the retention rates and reasons for discontinuation for seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of elderly patients (65 years of age or older) with rheumatoid arthritis (RA). ⋯ ABT showed lowest discontinuation rate by lack of effectiveness and by toxic adverse events, which lead to highest overall retention rates (excluding non-toxic reasons and remission) among seven bDMARDs in adjusted model of elderly RA patients.
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Multicenter Study Observational Study
Prevalence of hypothermia on admission to recovery room remains high despite a large use of forced-air warming devices: Findings of a non-randomized observational multicenter and pragmatic study on perioperative hypothermia prevalence in France.
Despite the availability of effective warming systems, the prevalence of hypothermia remains high in patients undergoing surgery. Occurrence of perioperative hypothermia may influence the rate of postoperative complications. Recommendations for the prevention of inadvertent perioperative hypothermia have been developed and are effective to reduce the frequency of perioperative hypothermia when professionals comply with. French Society of Anesthesiology (SFAR) decided to promote guidelines for the prevention of inadvertent hypothermia, and to conduct beforehand a pragmatic assessment of the prevalence of hypothermia in France. The hypothesis was that the rate of hypothermic patients (Tc<36°C) admitted to the RR remains high (around 50%), and that was the consequence of a warming device underutilization and/or was related to the type of health facilities. ⋯ The prevalence of hypothermia among patients admitted to the RR remains high. Our results suggest that only the combination of pre-warming and intraoperative warming significantly decreases it.