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Several studies in rabbits demonstrated the efficacy and safety of topical losartan, an angiotensin II receptor blockers (ARB) that modulates the TGF-β intracellular signaling pathways by inhibiting the activation of Extracellular Signal-regulated Kinase (ERK), in preventing or treating stromal fibrosis after a range of injuries such as Descemetorhexis, alkali burns, incisions, and photorefractive keratectomy (PRK). Several case reports have shown that topical losartan treatment is also efficacious and safe in humans to prevent or treat stromal fibrosis after many different injuries or diseases. Topical losartan penetrates the full thickness of the cornea and, therefore, can treat both anterior and posterior stromal fibrosis. These rabbit studies have demonstrated that there can be epithelial and stromal toxicity to losartan at dosages greater than 0.8 mg/ml and that higher dosages will not accelerate the return to transparency of fibrotic corneas. In corneas with an epithelial defect, it is likely safer to use 0.2 mg/ml losartan six times a day until the epithelium closes to further decrease the risk of epithelial toxicity before going to the 0.8 mg/ml six times a day dosage. Future clinical studies will explore additional questions, such as whether four times a day dosing is less effective than six times a day dosing in the treatment of stromal fibrosis. [ABSTRACT FROM AUTHOR]

Randomized clinical trials designed to assess analgesic agents and/or techniques used for postoperative pain control have several limitations, which are addressed in this article. Efficacy of analgesics cannot be limited to the evaluation of pain intensity or the amount of opioid rescue medication, but it also means to evaluate parameters such as the delay and duration of the effect, the number of patients with satisfactory pain control, and side effects. Because combination of analgesics is the standard of care in clinical practice, its value also needs to be documented. Eventually, analgesic treatments have to be considered in the settings of postoperative supportive care and enhanced recovery programmes after surgery. [ABSTRACT FROM AUTHOR]

Highlights • We examine the impact of tick-size reductions on market quality in three currency futures. • The bid-ask spreads drop significantly for the EUR, JPY, and MXN contracts. • We find significant improvement in market quality for the Mexican peso contracts. • The overall improvement for the EUR and JPY contracts is less significant. Abstract The Chicago Mercantile Exchange (CME) recently reduced the tick sizes of three foreign currency futures contracts: the Mexican peso, the Japanese yen, and the euro. We examine the impact of tick-size reductions on market quality in these three futures contracts. We find significant evidence of increased market quality for the Mexican peso contracts, but less significant evidence for the other two contracts. [ABSTRACT FROM AUTHOR]

the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H 2 O) 2 ]·H 2 O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl 2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction. [Display omitted] • The Zn-α-methyldopa complex (ZnMD) has been synthesized and characterized. Compared to MD. • It showed similar moderate spontaneous interaction with BSA. • It improved the antihypertensive action. • It is significantly more effective in the prevention of cardiac hypertrophy and fibrosis. • It negatively regulates ROS production more effectively than MD alone. [ABSTRACT FROM AUTHOR]

Context Before updating the French guidelines on postoperative pain treatment in 2015, the Pain Committee of the French Society of Anaesthesiology and Intensive Care (SFAR) conducted a survey on the medical use of ketamine in France. Methods An online questionnaire was nationally distributed to members of SFAR, the French Pain Society (SFETD) and the French Society of Emergency Medicine (SFMU). The questionnaire included questions on demographic data, the type of patients for whom ketamine was prescribed, the doses used, the side effects and safety measures associated with the administration of ketamine. Results A total of 1388 questionnaires were analysed. Ninety-two percent of the responders declared that they used ketamine. Ketamine was widely used as anti-hyperalgesic medication but the modalities of administration and the doses varied greatly and were not in accordance with the guidelines. Despite the lack of evidence and guidelines, ketamine has also been used to treat acute and chronic pain. Doses, duration and localization of the patients during administration have varied greatly. Psychedelic effects and hallucinations are the most feared side effects. In terms of monitoring during ketamine infusion, 15% of physicians declared that no monitoring was necessary while 59%, 55%, 59% and 77% monitored heart rate, SpO 2 , blood pressure and level of consciousness, respectively. Conclusion Anaesthesiologists have integrated the benefit of ketamine in preventing hyperalgesia but there is no consensus on doses and duration. For other indications (acute and chronic pain treatment), toxicity and the absence of significant benefit call for guidelines from scientific societies. [ABSTRACT FROM AUTHOR]

Background: Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented.Methods: We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method.Results: We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 μg kg-1 or with continuous administration alone.Conclusions: Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia.Protocol Registration: CRD42017071583. [ABSTRACT FROM AUTHOR]

The French Society of Anaesthesia and Intensive Care Medicine (SFAR) published experts' guidelines on the care of postoperative pain. This was an update of the 2008 guidelines. Fourteen experts analysed the literature (PubMed™, Cochrane™) on questions that had not been treated in the previous guidelines, or to modify the guidelines following new data in the published literature. The used method is invariably the GRADE© method, which guarantees a rigorous work. Seventeen recommendations were formalised on the assessment of perioperative pain, and most particularly in non-communicating patients, on opioid and non-opioid analgesics and on anti-hyperalgesic drugs, such as ketamine and gabapentinoids, as well as on local and regional anaesthesia. The concept of vulnerability and therefore the identification of the most fragile patients in terms of analgesics requirements were specified. Because of the absence of sufficient data or new information, no recommendation was made about analgesia monitoring, the procedures for the surveillance of patients in conventional care structures, or perinervous or epidural catheterism. [ABSTRACT FROM AUTHOR]

Multimodal analgesia, including a regional technique using perineural catheters (PNCs), is recommended for the treatment of moderate-to-severe acute postoperative pain. Perineural catheters are at risk of bacterial colonisation. In this study, we compared the cutaneous antiseptic efficacy of 2% alcoholic chlorhexidine and povidone-iodine-alcohol for preventing the bacterial colonisation of PNCs in orthopaedic surgery. We performed a randomised, controlled trial, comparing two cutaneous antisepsis strategies, one based on 2% alcoholic chlorhexidine and the other on povidone-iodine-5% alcohol, for placed PNCs before orthopaedic surgery. The primary endpoint was the incidence of catheter bacterial colonisation (threshold > 1000 colony-forming units/ml). The secondary endpoints were the incidence of catheter-related infections and the adverse effects of the antiseptic solutions. From November 2016 to May 2018, we included 113 patients in this study. The use of alcoholic chlorhexidine was associated with a lower incidence of catheter colonisation (15.5% (n = 9) versus 32.7% (n = 18); OR: 0.28 [0.09-0.77], p = 0.01). No catheter-related infections or adverse effects of antiseptic solutions were observed in either group. The risk factors associated with colonisation were a duration of catheter use ≥ 3 days (p = 0.04) and obesity (p = 0.005). The most frequently identified bacterium was Staphylococcus epidermidis. Skin disinfection with 2% alcoholic chlorhexidine decreases bacterial colonisation rates for placed perineural catheters. [ABSTRACT FROM AUTHOR]