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Objective: Esketamine (Vesierra) is a molecule, used alone or in combination, to induce and maintain general anaesthesia and to relieve pain in emergency medicine. The aim of this study is to evaluate the long-term physicochemical stability of a 1 mg/mL solution of esketamine diluted in 0.9% sodium chloride (NaCl) and stored in polypropylene syringes at 5±3°C during 65 days (64+1 day at 22±3°C) and 72 hours at 22±3°C (room temperature), in order to centralise preparation under aseptic conditions in hospital pharmacy., Methods: Ten syringes were prepared under aseptic conditions. Five syringes were stored at 22±3°C for 3 days, and the five others were stored at 5±3°C for 64 days (+ 1 day at room temperature). The stability was periodically investigated. Particle appearance or colour changes were checked by visual inspection. A research of crystals was performed under the microscope. pH was followed to assess its stability. The turbidity of the solutions was estimated by a measure of optical densities at 350, 410 and 550 nm. The molecule concentrations were measured by ultra-high performance liquid chromatography (UHPLC) coupled with a photodiode array detection (PDA), using a newly developed method., Results: Based on microscopic examination, no crystals were observed, during the observation period. pH and absorbances at 350, 410 and 550 nm were also stable. Macroscopically, there was no change in colour and appearance of opacity, turbidity or precipitation. Statistical analysis indicates that 1 mg/mL esketamine solutions were chemically stable under these conditions, given that less than 5% of the solutions have lost more than 10% of their initial content during the study based on the prediction interval., Conclusions: One mg/mL solutions of esketamine hydrochloride are physically and chemically stable after production, for at least 72 hours at 22±3°C and 64 days at 5±3°C (+ 1 day at room temperature)., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chemotherapy doses are usually prescribed on the basis of body surface area but dose banding is emerging as an efficient alternative. Dose banding presents the possibility of in-advance preparation in a Centralized Intravenous Admixture Service., Aim of the Study: To evaluate the long-term stability of 5-fluorouracil at banded doses (700 mg and 800 mg) in polyolefin bags., Materials and Methods: Ten polyolefin bags were prepared under aseptic conditions and stored at 23 ± 2°C for 24 days. Five of them were composed of 14 mL 5-fluorocuracil (700 g) in 100 mL 0.9% sodium chloride solution and the five other of 16 mL 5-fluorouracil (800 mg) in 100 mL 0.9% sodium chloride solution. At defined times, physical stability parameters were assessed: optical densities, pH measurements, visual and microscopical inspections. Solutions concentrations were measured using high-performance liquid chromatography coupled with a photodiode array detector., Results: No change was observed on pH and optical density measurements during the study period. Visual and microscopical inspections remained free of colour change, precipitate, microagregate or crystal. The concentrations of 5-Fluorouracil in 800 mg bags remained stable for 24 days while the concentration in 700 mg bags showed a stability of at least 17 days., Conclusion: Five-fluorouracil at banded doses of 700 and 800 mg in polyolefin bags is physicochemically stable for at least 17 days at 23 ± 2°C. These results support the possibility of in advance centralised preparation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Our previous study showed major changes in biomarkers on quitting compared to the smoking state. They reflected a decrease in inflammation, endothelial activation, and oxidative stress, as well as an improved lipid profile. Nicotine replacement therapy (NRT) is effective to increase the rate of successful quitting, but healthcare professionals may have concerns to prescribe this first-line smoking cessation treatment because its effect on inflammation and related processes is controversial., Aims and Methods: The present study assessed the influence of NRT on biomarkers of inflammation, endothelial function, oxidative stress, and lipids, in people who quit smoking. Sixty-five subjects who daily smoke cigarettes were recruited and followed on quitting. Thirty-five quit using NRT and thirty quit without NRT. Biomarkers of inflammation, endothelial function, oxidative stress, and lipids were quantified at baseline when actively smoking and after cessation in the presence of NRT or not., Results: Changes in biomarkers on quitting did not differ according to the treatment used. No difference was found when comparing participants who were exposed to NRT and those who were not., Conclusions: These results may indicate that NRT has no effect on inflammation, endothelial function, oxidative stress, and lipids, when used as a medication aid for quitting smoking., Implications: This study provides new evidence to support the safety profile of NRT products regarding the biomarkers of endothelial function, oxidative stress, inflammation, and lipids., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Tobacco use is known to be involved in the development of cardiovascular diseases, which leads to premature mortality. Endothelial dysfunction, the first step in this process, was shown induced by smoking. It is reported that quitting smoking could reduce the risk of diseases, but the implied mechanisms are still unclear. This study aimed to evaluate the biological markers of endothelial function in smokers when actively smoking and after cessation., Methods: Quantification of several biomarkers reflecting inflammation, endothelium activation, oxidative stress, and lipids was performed in 65 smokers when actively smoking and after cessation (median abstinence duration of 70 days)., Results: A possible decrease of inflammation was observed through the concentration reduction of a proinflammatory cytokine (interleukine-6) on quitting. A decrease of endothelium activation was visible by the reduced level of the soluble intercellular adhesion molecule. Two antioxidants, uric acid and vitamin C, were found at higher concentration than before the cessation, potentially reflecting the decrease of oxidative stress on quitting. Lipid profile was improved post-quit since HDL level was increased and LDL level was decreased. All these effects were visible at short term with abstinence duration less than 70 days. No sex-specific difference was observed and no additional changes were observed for longer abstinence duration., Conclusion: These observations suggest that some adverse effects of smoking on endothelial function could be reversible on quitting smoking. It could encourage smokers to enter a cessation program to reduce the risk for cardiovascular diseases development., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Objectives: Anatabine and anabasine are two tobacco alkaloids used to differentiate between tobacco users and abstainers, including users of nicotine replacement therapy. Cutoff values (>2 ng/mL for both alkaloids) have not been revised since their implementation in 2002. These values may be too high, leading to increased likelihood of misclassification between smokers and abstainers. This results in major consequences, especially adverse outcomes of transplantation when smokers were incorrectly identified as being abstinent. This study proposes that a lower threshold for anatabine and anabasine will better distinguish tobacco users from non-users and thereby improve patients' care., Design and Methods: A new and more sensitive analytical method by liquid chromatography-mass detection was developed to allow the quantification of low concentrations. Anatabine and anabasine were measured in urine samples of 116 self-reported daily smokers and 47 long-term non-smokers (confirmed by the analysis of nicotine and its metabolites). The best compromise between sensitivity and specificity allowed us to determine new cutoff values., Results: The thresholds >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine were associated with a sensitivity of 97% (anatabine) and 89% (anabasine) and a specificity of 98% for both alkaloids. These cutoff values greatly increased the sensitivity given that it dropped to 75% (anatabine) and 47% (anabasine) when using the reference value (>2 ng/mL)., Conclusions: The cutoff values >0.097 ng/mL for anatabine and >0.236 ng/mL for anabasine appear to better differentiate tobacco users from abstainers than the current reference threshold (>2 ng/mL for both alkaloids). It may considerably impact patients' care, especially in transplantation settings in which smoking abstinence is essential to avoid adverse outcomes of transplantation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Gemcitabine is an analogue of cytidine arabinoside, used alone or in combination chemotherapy to treat various type of cancer. The dose-banding of gemcitabine provides the opportunity to anticipate the preparation of this anticancer drug on condition of carrying out stability studies. The aim of this study is to develop and validate a stability-indicating ultra-high-performance Liquid Chromatography (UHPLC) method for measuring the concentration of gemcitabine and to evaluate its stability at standardised rounded doses in polyolefin bags. The UHPLC with photodiode array (PDA) detector method was developed and validated (linearity, precision, accuracy, limits of detection and quantification, robustness and degradation test). Thirty polyolefin bags of gemcitabine (1600 mg/292 ml (n = 10), 1800 mg/297 ml (n = 10) and 2000 mg/303 ml (n = 10)) were prepared under aseptic conditions and stored at 5 ± 3 °C and 23 ± 2 °C for 49 days. Physical stability tests were periodically performed: visual and microscopic inspection and optical densities. The chemical stability was evaluated through pH monitoring and chromatographic assays. The results confirm the stability of Gemcitabine at selected standardised rounded doses of 1600 mg, 1800 mg and 2000 mg in NaCl 0.9% polyolefin bags for at least 49 days at 5 ± 3 °C and 23 ± 2 °C, allowing in-advance preparation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes., Methods: The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection., Results: During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures., Conclusions: The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Smoking is a well-established risk factor for strokes, leading to a high incidence of cognitive deficits. Since the impact of cognitive impairment on the effectiveness of interventions for smoking cessation is not yet known, we considered important to assess it., Methods: We compared, from April 2012 to November 2015, the success rate of quitting smoking in two groups of acutely hospitalised adult smokers. The first group consisted of stroke patients (SP, n = 54) with lesions confirmed by cerebral imaging. The second used as a control group (NSP, n = 38), included patients hospitalised for any reason other than stroke and characterised by normal global cognition. All participants were assessed twice, in acute phase (T0) and 3 months later (T1), using exhaled carbon monoxide (CO) and several questionnaires., Results: At T1, we observed in SP group an inverse correlation between the Montreal Cognitive Assessment (MoCA) and CO (r = -0.33, p = 0.015). Amongst patients who continued smoking, a higher increase in CO between T0 and T1 was observed in SP group (average 20 ± 15, p < 0.001) than NSP (average 9 ± 13, p = 0.002)., Conclusions: The inverse correlation between CO and cognitive parameters at T1 in SP group suggests an increased susceptibility to tobacco dependency in case of residual cognitive impairment. The global cognitive assessment should thus be taken into consideration when providing assistance with quitting smoking, especially in case of stroke patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Death rattle, which could often be associated with a pulmonary fluid overload, occurs in 25% to 90% of dying patients. The co-administration of scopolamine (anticholinergic drug) and bumetanide (loop diuretic) could be considered in order to avoid unnecessary fluid overload at end-stage of life. The objective of this study was to investigate the physical and chemical stabilities of the admixture bumetanide and scopolamine in order to prepare them in advance by a centralized intravenous additive service in-hospital pharmacy. The stability of the lowest (LOW) concentration was evaluated on five polypropylene syringes containing the admixture bumetanide (Burinex, 2 mg/4 mL) and scopolamine (0.25 mg/mL) at 41.67 µg/mL and 5.21 µg/mL. The highest (HIGH) concentration with 125 µg/mL of bumetanide and 31.25 µg/mL of scopolamine was evaluated on five polypropylene syringes. All syringes were stored for 18 days at 5°C ± 3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or color change. The pH and absorbance at 3 wavelengths (350 nm, 410 nm, and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection, using a newly developed method. During the 18 days of test, there was no change in color or appearance of opacity, turbidity, or precipitation, and the pH remained stable. Mean concentrations of bumetanide and scopolamine at LOW and HIGH concentrations after 18 days remained statistically unchanged. The lower limits of the 95% confidence intervals of both molecules at LOW and HIGH concentrations remained higher than a 90% threshold of concentration, indicating the mixture was chemically stable. Degradation rates of bumetanide and scopolamine content at LOW and HIGH concentrations should not exceed a maximum of 0.70% every 10 days. This study was the first to show that the admixture of bumetanide and scopolamine is physically and chemically stable at two concentrations used in a palliative-care unit. This combination available in ready-to-use polypropylene syringes presents numerous advantages for patient's comfort and safety., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)