Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

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To overcome the intermittency in energy generation from renewable sources such as solar and wind, the implementation of electrical energy storage systems, such as redox flow batteries (RFBs) have received great attention. Research for the development and use of organic species, such as quinones, has grown, since such species are abundant, can be extracted from natural sources, are chemically versatile and have a low cost. Quinones are redox active molecules with good electrochemical reversibility, easy synthetic modulation. It is extremely important to understand the chemical factors that interfere with its reduction potentials, and the formation of intra-and intermolecular bonds is a possible tool for the rational control of this property. When studying it, hydrogen bonding is a notorious possibility for modulating the electrochemical profile of quinones, obtaining more positive reduction potential values due to the increase in electrophilicity in its core. In this work, the formation of hydrogen bonds was explored as a tool for modulating the reduction potential in substituted naphthoquinones. The computational investigation demonstrated an efficient modulation of the reduction potential of both mono- and disubstituted derivatives with mercaptoethanol, leading to a weakening of the hydrogen bonds as the alkyl chain becomes longer. Nitrogenous derivative 82 showed no significant effect on the formation of intramolecular hydrogen bonding, due to the conjugation between the π electrons of the quinone nucleus and the pair of electrons of the nitrogen atom, disfavoring the interaction. However, experimentally, only compound 74 showed efficiency in modulating its redox potential, conjecturing that only one interaction per bond is taking place, as a terminal hydroxyl is blocked by the supporting electrolyte. In addition to demonstrating the modulation of the reduction potential of 74, such interaction justifies the effect not observed for the monosubstituted derivatives.A fim de contornar a intermitência na geração de energia a partir de fontes renováveis como a solar e a eólica, a implementação de sistemas de armazenamento de energia elétrica, como as baterias de fluxo redox (RFBs, do inglês redox flow batteries) têm recebido grande atenção. Pesquisas para o desenvolvimento e utilização de espécies orgânicas, como as quinonas, têm crescido, visto que tais compostos são abundantes, podem ser extraídas de fontes naturais, são quimicamente versáteis e apresentam custo reduzido. Quinonas são moléculas redox ativas com boa reversibilidade eletroquímica e fácil modulação sintética. É de suma importância a compreensão dos fatores químicos que interferem em seus potenciais de redução, sendo a formação de ligações intra- e intermoleculares uma possível ferramenta para o controle racional dessa propriedade. Ao estudá-la, a ligação de hidrogênio é uma notória possibilidade para modulação do perfil eletroquímico de quinonas, obtendo valores de potenciais de redução mais positivos decorrentes do aumento da eletrofilicidade em seu núcleo. Neste trabalho, a formação de ligações de hidrogênio foi explorada como ferramenta para a modulação do potencial de redução em naftoquinonas substituídas. A investigação computacional demonstrou uma eficiente modulação no potencial de redução de derivados tanto mono- quanto dissubstituídos com mercaptoetanol, levando à um enfraquecimento das ligações de hidrogênio a medida que a cadeia alquílica se torna mais longa. O derivado nitrogenado 82 não possui efeito significativo em relação a formação da ligação de hidrogênio intramolecular, isso devido à conjugação entre os elétrons π do núcleo quinônico e o par de elétrons do átomo de nitrogênio, desfavorecendo a interação. Entretanto, experimentalmente, apenas o composto 74 mostrou eficiência na modulação de seu potencial redox, conjecturando que apenas uma interação por ligação esteja ocorrendo, pois uma hidroxila terminal é bloqueada pelo eletrólito de suporte. Além de demonstrar a modulação no potencial de redução de 74, tal interação justifica o efeito não observado para os derivados monossubstituídos.Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Synthetic naphthoquinone derivatives as anticancer agents in ovarian cancer: cytotoxicity assay and investigation of possible biological mechanisms action

In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their in vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3–5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4, bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3–5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK

Recent progress in L-H transition studies at JET: Tritium, Helium, Hydrogen and Deuterium

We present an overview of results from a series of L-II transition experiments undertaken at JET since the installation of the ITER-like-wall (JET-ILW), with beryllium wall tiles and a tungsten divertor. Tritium, helium and deuterium plasmas have been investigated. Initial results in tritium show ohmic L-H transitions at low density and the power threshold for the L-H transition (P-LH) is lower in tritium plasmas than in deuterium ones at low densities, while we still lack contrasted data to provide a scaling at high densities. In helium plasmas there is a notable shift of the density at which the power threshold is minimum ((n) over bar (e,min)) to higher values relative to deuterium and hydrogen references. Above (n) over bar (e,min) (He) the L-H power threshold at high densities is similar for D and He plasmas. Transport modelling in slab geometry shows that in helium neoclassical transport competes with interchange-driven transport, unlike in hydrogen isotopes. Measurements of the radial electric field in deuterium plasmas show that E-r shear is not a good indicator of proximity to the L-H transition. Transport analysis of ion heat flux in deuterium plasmas show a non-linearity as density is decreased below (n) over bar (e,min). Lastly, a regression of the JET-ILW deuterium data is compared to the 2008 ITPA scaling law