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BACKGROUND Frailty is the loss of ability to withstand a physiological stressor and is associated with multiple adverse outcomes in older people. Trials to prevent or ameliorate frailty are in their infancy. A range of different outcome measures have been proposed, but current measures require either large sample sizes, long follow-up, or do not directly measure the construct of frailty. METHODS We propose a composite outcome for frailty prevention trials, comprising progression to the frail state, death, or being too unwell to continue in a trial. To determine likely event rates, we used data from the English Longitudinal Study for Ageing, collected 4 years apart. We calculated transition rates between non-frail, prefrail, frail or loss to follow up due to death or illness. We used Markov state transition models to interpolate one- and two-year transition rates and performed sample size calculations for a range of differences in transition rates using simple and composite outcomes. RESULTS The frailty category was calculable for 4650 individuals at baseline (2226 non-frail, 1907 prefrail, 517 frail); at follow up, 1282 were non-frail, 1108 were prefrail, 318 were frail and 1936 had dropped out or were unable to complete all tests for frailty. Transition probabilities for those prefrail at baseline, measured at wave 4 were respectively 0.176, 0.286, 0.096 and 0.442 to non-frail, prefrail, frail and dead/dropped out. Interpolated transition probabilities were 0.159, 0.494, 0.113 and 0.234 at two years, and 0.108, 0.688, 0.087 and 0.117 at one year. Required sample sizes for a two-year outcome in a two-arm trial were between 1040 and 7242 for transition from prefrailty to frailty alone, 246 to 1630 for transition to the composite measure, and 76 to 354 using the composite measure with an ordinal logistic regression approach. CONCLUSION Use of a composite outcome for frailty trials offers reduced sample sizes and could ameliorate the effect of high loss to follow up inherent in such trials due to death and illness.BACKGROUND We aimed to describe primary care management at the time of a suicide attempt (SA) and after the SA. METHODS An observational (cross-sectional) study was conducted among 166 sentinel GPs within France (a non-gatekeeping country) between 2013 and 2017 for all GP's patients who attempted suicide. MEASUREMENTS frequency of patients 1) managed by the GP at the time of the SA, 2) addressed to an emergency department (ED), 3) without care at the time of the SA, and 4) managed by the GP after the SA and factors associated with GP management at the time of and after the SA. RESULTS Three hundred twenty-one SAs were reported, of which N = 95 (29.6%) were managed by the GP at the time of the SA, N = (70.5%) were referred to an ED, and N = (27.4%) remained at home. Forty-eight (14.9%) patients did not receive any care at the time of the SA and 178 (55.4%) were managed directly by an ED. GPs were more likely to be involved in management of the patient at the time of the SA if they were younger (39.2% for patients less then  34 years old; 22.9% for those 35 to 54 years old, and 30.3% for those more than 55 years old p = 0.02) or the SA involved a firearm or self-cutting (51.9%) versus those involving drugs (23.7%); p = 0.006). After the SA, GPs managed 174 patients (54.2%), more often (60%) when they provided care at home at the time of the SA, p = 0.04; 1.87 [1.07; 3.35]. No other factor was associated with management by GPs after the SA. CONCLUSIONS The study faced limitations data were not available for patients managed solely by specialists during their SA and results may not be generalisable to countries with a stronger gatekeeping system. We concluded that GPs are involved in the management of patients at the time of a SA for a third of patients. EDs are the major provider of care at that time. Half patients consulted GPs after the SA and connections between GPs and ED upon discharge should be improved.BACKGROUND Rapid neuromuscular block reversal at the end of major abdominal surgery is recommended to avoid any postoperative residual block. To date, no study has evaluated sugammadex performance after rocuronium administration in patients undergoing liver transplantation. This is a randomized controlled trial with the primary objective of assessing the neuromuscular transmission recovery time obtained with sugammadex versus neostigmine after rocuronium induced neuromuscular blockade in patients undergoing orthotopic liver transplantation. METHODS The TOF-Watch SX®, calibrated and linked to a portable computer equipped with TOF-Watch SX Monitor Software®, was used to monitor and record intraoperative neuromuscular block maintained with a continuous infusion of rocuronium. selleck chemicals Anaesthetic management was standardized as per our institution's internal protocol. At the end of surgery, neuromuscular moderate block reversal was obtained by administration of 2 mg/kg of sugammadex or 50 mcg/kg of neostigmine (plus 10 mcg/kg of atropine). RESULTS Data from 41 patients undergoing liver transplantation were analysed. In this population, recovery from neuromuscular block was faster following sugammadex administration than neostigmine administration, with mean times±SD of 9.4 ± 4.6 min and 34.6 ± 24.9 min, respectively (p  less then  0.0001). CONCLUSION Sugammadex is able to reverse neuromuscular block maintained by rocuronium continuous infusion in patients undergoing liver transplantation. The mean reversal time obtained with sugammadex was significantly faster than that for neostigmine. It is important to note that the sugammadex recovery time in this population was found to be considerably longer than in other surgical settings, and should be considered in clinical practice. TRIAL REGISTRATION ClinicalTrials.govNCT02697929 (registered 3rd March 2016).BACKGROUND Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. METHODS Fifteen osteoarthritis patients undergoing total knee replacement due to chronic knee pain and 15 patients without pain undergoing other surgeries with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia. CSF were added to cultured T98G cells in the presence of lipopolysaccharide.

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