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Objectives: The aim of this study was to evaluate the toxicity of a new lipid complex formulation of amphotericin B (LC-AmB) produced by a simple process. Methods: Toxicity was evaluated after daily administration for 21 consecutive days in female CD1 mice. Doses of LC-AmB up to 20 mg/kg were used, and compared with Fungizone at 0.5 mg/kg and Abelcet at 10 mg/kg. Acute toxicity after a single bolus injection was also determined, as well as the haemolytic activity and toxicity to mouse macrophages in vitro. Results: LC-AmB reduced both the haemolytic activity of amphotericin B and its toxicity towards mouse peritoneal macrophages. Its acute toxicity (LD50 > 200 mg/kg in CD1 mice) was similar to that in the literature for the least toxic lipid formulations of amphotericin B. The relative liver weight increased slightly in mice treated daily with a dose of 20 mg/kg LC-AmB, as did the kidney weight in this group and the group treated with Fungizone. There was also a dose-dependent decrease in the haematocrit with all formulations. All treatments caused significant increases in transaminase levels. Total hepatic CYP 450 was slightly but not significantly increased in the groups treated with 20 mg/kg LC-AmB, Abelcet and Fungizone. However, expression of some isoforms of CYP 450 was reduced, the most marked being the hepatic CYP 3A1 after treatment with 20 mg/kg LC-AmB, Abelcet and Fungizone. The effects on hepatic function are probably related to accumulation in organs rich in phagocytic cells. Conclusion: LC-AmB did not induce any new toxicity compared with Abelcet and Fungizone. [ABSTRACT FROM AUTHOR]

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared., Methods: Between 2017 and 2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared., Results: The median OS and RFS were 71.3 months [63-71.5] and 26.8 months [20-35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10-0.90], p = 0.032) and ASA score>2 (HR = 2.32 [1.32- 4.06], p = 0.003) and number of resection (HR = 1.21 [1.06-1.39], p = 0.006) as a risk factors of RFS. Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11 (35.5 %) vs 6 (14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively., Conclusions: OS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient., Competing Interests: Declaration of competing interest Anne-Cécile Ezanno, Sihame Chkair, Jean-Louis Quesada, Julio Abba, Brice Malgras, Bertrand Trilling, Pierre-Yves Sage, Sophie Bouvet, Alison Foote, Adeline Aime, Marc Pocard, Catherine Arvieux and Fatah Tidadini have no conflict of interest to declare. Olivier Glehen is a consultant for Gamida., (© 2023 Published by Elsevier Ltd.)

Background: Chronic obstructive pulmonary disease (COPD) is an irreversible chronic respiratory disease which outcome depends on medication adherence. Pharmacists may increase this adherence by advising patients on inhaler devices proper use. This paper presents the protocol for a randomized controlled trial, which assesses impact of pharmaceutical consultations on COPD exacerbations, medical care, adherence to inhaler devices and quality of life., Methods: This trial will include 226 COPD patients treated with inhaler devices: 94 in a control group, 66 receiving a pharmaceutical consultation at hospital and 66 receiving up to 12 pharmaceutical consultations corresponding to dispensing at their community pharmacy. The aim of these interventions is to inform patients about COPD medication, train them in the use of inhaler devices and improve adherence. Patients included by hospital pharmacist will be randomly assigned to the control and hospital experimental groups. Community pharmacists (CP) will include patients in the experimental community group. CPs will follow-up all study patients for 12 months. Primary outcome is the mean number of COPD exacerbations. Secondary outcomes include number of medical consultations, emergency visits and hospitalizations, patients' adherence devices and quality of life., Discussion: This is the first French trial which assesses both hospital and community pharmaceutical interventions on COPD patients. Study limitations include recruitment and CP adherence to follow-up. Indeed, the success of this trial depends on the willingness of CPs to collect the data. This work is the first step towards building a network of CPs trained for clinical research., Trial Registration: Clinicaltrials.gov, NCT03704545. Registered on October 12th, 2018. https://clinicaltrials.gov/ct2/show/NCT03704545?cond=COPD&cntry=FR&city=nimes&draw=2&rank=1., Competing Interests: 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., (© 2024 Published by Elsevier Inc.)

Phagosome maturation is critical for immune defense, defining whether ingested material is destroyed or converted into antigens. Sec22b regulates phagosome maturation, yet how has remained unclear. Here we show Sec22b tethers endoplasmic reticulum-phagosome membrane contact sites (MCS) independently of the known tether STIM1. Sec22b knockdown increases calcium signaling, phagolysosome fusion and antigen degradation and alters phagosomal phospholipids PI(3)P, PS and PI(4)P. Levels of PI(4)P, a lysosome docking lipid, are rescued by Sec22b re-expression and by expression of the artificial tether MAPPER but not the MCS-disrupting mutant Sec22b-P33. Moreover, Sec22b co-precipitates with the PS/PI(4)P exchange protein ORP8. Wild-type, but not mutant ORP8 rescues phagosomal PI(4)P and reduces antigen degradation. Sec22b, MAPPER and ORP8 but not P33 or mutant-ORP8 restores phagolysosome fusion in knockdown cells. These findings clarify an alternative mechanism through which Sec22b controls phagosome maturation and beg a reassessment of the relative contribution of Sec22b-mediated fusion versus tethering to phagosome biology., (© 2023. Springer Nature Limited.)

Background: There is a need to develop an awareness raising tool for GPs to reach out their patients in order to increase blood donation. The main objective was to create and validate a tool to raise awareness about blood donation that meets acceptability and preference criteria and is applicable in general practice., Material and Methods: This cross-sectional study was conducted in three phases. 1. Tool creation: A stakeholder meeting co-developed three potential tools to raise awareness about blood donation: a consulting room poster, a waiting room poster and a lapel badge for the doctor. Three GPs pilot-tested each tool for one day during their regular consultations. Then, once the pilot was completed each GP assessed acceptability and preference using a semi-structured interview, and patients were also interviewed. 2. Consensual tool selection: An appropriate tool was selected based on pilot data using nominal group technique and expert review. 3. The tool was validated for its acceptability in practice via a quantitative questionnaire distributed electronically to GPs., Results: The consensual tool selected by the nominal group was a combination of elements from all three tools trialled in the pilot, reported to be non-intrusive and convenient for both GPs and patients. Patient responses indicated a high level of acceptability and indicated a strong preference for self-generated discussion of the topic with their GP. In the validation step, 217 responses to the quantitative questionnaire were received: 74.5% of responses fulfilled the acceptability criteria for using this combined tool in general practice. Furthermore, 93.1% of GPs indicated they would use the tool in the proposed format for the purpose of raising awareness., Discussion: The validation of our blood donation awareness tool for use in general practice justifies its evaluation on a larger scale as part of a wider blood donation awareness campaign., 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 © 2022. Published by Elsevier Masson SAS.)

Introduction and Hypothesis: The main objective of the study was to evaluate the rates of de novo stress urinary (SUI) and postoperative dyspareunia after both sacrocolpopexy/hysteropexy (SCP) and vaginal mesh surgery., Methods: A prospective, multicenter, randomized, open-label study with two parallel groups treated by either SCP or Uphold Lite vaginal mesh was carried out. Study participants were ≥ 50 and < 80 years old patients with Pelvic Organ Prolapse Quantification (POP-Q) stage ≥2 who were considered eligible for reconstructive surgery and who were sexually active with no dyspareunia and free from bothersome SUI at presentation. Women were assessed before surgery and at 4-8 weeks and 11-13 months after using validated measures including POP-Q, Pelvic Floor Disability Index (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, IUGA-Revised (PISQ-IR), and Patient Global Impression of Improvement (PGI-I). Data were also collected for health economics evaluation., Results: Of the required sample of 156 women, 42 women (19 SCP and 23 vaginal mesh) were only recruited owing to the discontinuation of vaginal mesh worldwide. The median follow-up was 376 days. The rates of bothersome de novo SUI were similar in the SCP and Uphold vaginal mesh groups (15.79 vs 15.00%, OR 0.95 [95% CI 0.22-4.14]). Among 30 sexually active patients at follow-up, the rates of women reporting de novo dyspareunia "usually or always" were 6.7% after SCP vs 13.3% after vaginal mesh (p = 1). Health economics evaluation showed a cost saving of 280€ in favor of the Uphold vaginal mesh technique, but no significant difference in the total cost (2,934.97€ for SCP vs 3,053.26€ for Uphold vaginal mesh)., Conclusions: Bothersome de novo SUI and de novo dyspareunia occurred in approximately 15% and 23% of our study cohorts, with no significant difference between sacrocolpopexy/hysteropexy and anterior/apical vaginal mesh surgery. However, these results should be interpreted with caution owing to the small sample size., (© 2022. The International Urogynecological Association.)

Objectives: Interventional radiology procedures expose individuals to ionizing radiation. However, existing dosimetry methods do not provide the dose effectively absorbed to the skin, and do not consider the patient's individual response to irradiation. To resolve this lack of dosimetry data, we developed a new external irradiation biodosimetry device, DosiKit, based on the dose-dependent relationship between irradiation dose and radiation-induced H2AX protein phosphorylation in hair follicles. This new biological method was tested in Clermont-Ferrand University Hospital to evaluate the assay performances in the medical field and to estimate DosiKit sensitivity threshold., Methods: DosiKit was tested over 95 patients treated with neuroradiological interventions. For each intervention, lithium fluoride thermoluminescent dosimeters (TLD) were used to measure total dose received at each hair collection point (lateral and occipital skull areas), and conventional indirect dosimetry parameters were collected with a Dosimetry Archiving and Communication System (DACS)., Results: Quantitative measurement of radiation-induced H2AX protein phosphorylation was performed on 174 hair samples before and after the radiation exposure and 105 samples showed a notable induction of gammaH2AX protein after the radiological procedure. According to a statistical analysis, the threshold sensitivity of the DosiKit immunoassay was estimated around 700 mGy., Conclusions: With this study, we showed that DosiKit provides a useful way for mapping the actually absorbed doses, allowing to identify patients overexposed in interventional radiology procedures, and thus for anticipating risk of developing dermatitis., Key Points: • DosiKit is a new external irradiation biodosimetry device, based on the dose-dependent relationship between irradiation dose and radiation-induced H2AX protein phosphorylation in hair follicles. • DosiKit was tested over 95 patients treated with neuroradiological interventions. • The threshold sensitivity of the DosiKit immunoassay was estimated around 700 mGy and DosiKit provides a useful way for mapping the actually absorbed doses., (© 2021. European Society of Radiology.)

The electroreduction of SF 6 is shown at ambient temperature in acetonitrile using an array of platinum microelectrodes to improve the electrical detection. Its half reduction potential occurs at -2.17 V vs Fc + /Fc. The exact number of electrons for the full consumption of sulfur hexafluoride was determined and this gas further quantitatively transformed into environmentally benign fluoride anion and sulfur by electrochemical reduction., (Copyright © 2020, Bouvet et al.; licensee Beilstein-Institut.)

Objectives : Adverse drug events (ADE) are a common cause of morbidity and mortality in elderly patients. In this study, we assessed the impact of multidisciplinary medication review (MMR) for nursing home residents on patient safety and costs incurred by the hospital and the national health service. Methods : Medical files of residents were retrospectively assessed for medications prescribed in the previous six months. A pharmacist reviewed the prescriptions and suggested modifications to the patient's medical team. Patients were followed for six months. Trivalle's ADE geriatric risk score was calculated before and after MMR, as were number of potentially inappropriate medications, and economic impact from the perspective of the health care system and the nursing home. Results : Forty-nine patients were recruited. ADE score dropped one risk level (median score of 4 before versus 1 after, p < 0.0001). The number of patients taking at least one potentially inappropriate medication decreased from 30.6% before to 6.1% after MMR (p = 0.005). A mean saving of €232 per patient was made from the nursing home perspective following MMR (p = 0.008). Conclusion : The MMR reduced the iatrogenic drug risk for elderly residents and costs from the nursing home perspective, particularly drug expenditure.

Background: Good management of disposable and reusable supplies may improve surgical efficiency in the operating room (OR) and also corresponds to the best eco-responsible approach. The purpose of this study was to assess the impact of a clinical pharmacist's intervention in the OR on the non-compliant use of medical devices. We also assessed the economic impact of the pharmaceutical intervention., Materials and Methods: We conducted a monocentric prospective study in the OR of a University hospital over one year. Three surgical specialties: urologic, digestive and gynecologic were audited after a preparatory phase to optimize usage of medical devices used for surgeries. The supply costs concerning the three specialties were compared before and after the pharmacist intervention., Results: One hundred and fifty surgical procedures were audited in digestive (33.3%, n = 50), gynecologic (32%, n = 48) and urologic (34.7%, n = 52) surgeries. With the pharmacist in OR, 51 procedures (34% CI95%[26.4%; 41.6%]) with a non-compliance concerning at least one medical device were found compared to the 50% rate without the pharmacist reported previously (P < .0001). Eighteen percent of surgical procedures had at least one circulator retrieval for the reason "incomplete case cart despite device listed on the case cart list" versus 29.1% before pharmacist intervention (P = .0028). A €33 014 saving associated with the presence of the pharmacist in OR was observed., Conclusions: This prospective interventional study showed that the intervention of a pharmacist specialized in the medical device field could significantly reduce non-compliances in medical device use and reduce costs in OR., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression., Methods: Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects., Results: In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, p = 0.71). Multivariate analysis showed poorer social functioning in patients (24.3% vs. 16.3%, p = 0.0209), more dyspnea (22% vs. 12.4%, p = 0.0078), and yet less current pain (23% vs 33%, p = 0.0151)., Conclusions: Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients < 75 years at diagnosis. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction., Trial Registration: clinicaltrials.gov, NCT02854982 . Registered 4 August 2016, retrospectively registered.

Purpose: The present study aimed at assessing the efficiency of ropivacaine on post-operative pain for extraction of third molars., Methods: In a single centre, prospective, parallel, double blind randomised trial, patients scheduled for removal of all four third molars, ASA I-III patients<65 year-old patients were included. After intubation under general anesthesia (using intravenous remifentanil and propofol), for each of the third molars, 2mL of ropivacaine (7.5mg/mL) or placebo (0.9% saline solution) was injected into the vestibular capsule (total: 8mL) before extraction. At the end of surgery, similar analgesia was injected for both groups (intravenous paracetamol 1g and ketoprofene 100mg). The primary outcome was postoperative pain assessed by Visual Analog Scale (VAS). Postoperative consumption of analgesics (morphine titration in post-operative care unit when VAS>3/10, followed by oral tramadol 50mg after discharge), patient satisfaction, chronic pain (1-3 month), time in PACU and total hospitalization time were also recorded., Results: A total of 50 patients were analysed in each group with similar characteristics (ropivacaine vs. control, for age (years) 18 [17-21] vs. 18 [17-21], for sex (female) 33 (66%) vs. 25 (50%), and BMI (kg/m 2 ): 20 [19-23] vs. 21 [19-23]). Area Under the Curve for VAS pain (0 to 4h) was lower for Ropivacaine group: 0.43 [0.19-0.66] vs. 0.63 [0.43-0.87], P=0.005. Use of morphine in PACU (8 vs. 18, P=0.02) and median length of stay in ambulatory setting (5 vs. 6h, P=0.03) were reduced in Ropivacaine vs. Placebo group. At days 1 and 4, VAS of pain was higher in Ropivacaine group (respectively 4 vs. 2, P=0.006 and 3 vs. 2, P=0.05). At month 1 and 3, pain and DN4 score were similar between groups, with a median VAS pain score at 0 for both groups (P=0.42). No difference was observed for patient satisfaction and adverse events., Conclusions: Ropivacaine provides an immediate efficient pain relief after extraction of third molars without benefit after discharge., Clinicaltrial Registration: NCT01541059., (Copyright © 2019. Published by Elsevier Masson SAS.)

Among halogenated aromatics, iodoarenes are unique in their ability to produce the bench-stable halogen(III) form. Earlier, such iodine(III) centers were shown to enable C-H functionalization ortho to iodine via halogen-centered rearrangement. The broader implications of this phenomenon are explored by testing the extent of an unusual iodane-directed para C-H benzylation, as well as by developing an efficient C-H coupling with sulfonyl-substituted allylic silanes. Through the combination of the one-shot nature of the coupling event and the iodine retention, multisubstituted arenes can be prepared by sequentially engaging up to three aromatic C-H sites. This type of iodine-based iterative synthesis will serve as a tool for the formation of value-added aromatic cores., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

DosiKit is a field radiation biodosimetry immunoassay for fast triage of individuals exposed to external total-body or partial-body irradiation (TBI or PBI). Assay proof-of-concept based on γ-H2AX analysis of human blood samples has been previously described as a promising tool for rapid assessment of TBI. Here, we report on the performance of the assay for PBI based on an analysis of hair follicles irradiated with a 137 Cs gamma-ray source, at doses ranging from 0 to 20 Gy and dose rates ranging from ∼0.8 to ∼3 Gy/min. First, we show that the DosiKit protocol allows extraction and analysis of hair follicle proteins. Next, we show that irradiated hair follicles trigger a DNA damage response by inducing dose-dependent γ-H2AX expression. Since γ-H2AX expression strongly decreases 2 to 4 h postirradiation, due to DNA repair, we hypothesized that an antibody targeting the S*/T*Q domains, phosphorylated by ATM for DNA repair activation (pSQTQ), would extend the postirradiation dosimetry time window. DosiKit analysis of pSQTQ in ex vivo irradiated cynomolgus monkey skin explants shows that these sequences are phosphorylated in a dose-dependent manner up to 8 h postirradiation, and that statistically different ranges of external radiation exposure can be distinguished (0-2 Gy, 5-10 Gy, 20 Gy). Since the DosiKit protocol is intended to be used on both blood and hair samples, we also show that SQTQ sequences are phosphorylated dose-dependently in human blood, allowing samples to be classified into three radiation dose ranges (0-0.1 Gy, 0.5-3 Gy and 5-8 Gy). In conclusion, radiation biodosimetry can be performed on both blood and hair samples up to 8 h after exposure using the DosiKit protocol, allowing the concomitant characterization of TBI and PBI for fast and efficient radiological crisis management.

As early as 1991 Ochiai et al. reported that an acid-activated form of phenyliodine diacetate, PhI(OAc) 2 , undergoes a reaction with propargyl-silanes, germanes and stannanes to give the ortho-propargyl iodobenzene. This formal C-H alkylation was proposed to take place through an unusual (even to date) iodonio-based [3,3] rearrangement of an intermediate allenylsilane. Although this mechanistic principle has been invoked in related iodane-directed C-H coupling reaction, some underlying principles have remained unaddressed, and the reaction rarely employed. Herein, DFT evidence for a mechanism best described as iodine-guided electrophilic aromatic substitution is presented. Using a newly optimized reaction protocol that significantly reduces the undesired reduction process, the potency of the method is showcased through the synthesis of >40 structurally diverse ortho-iodo propargyl (or allenyl) arenes., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

DosiKit is a new field-radiation biodosimetry immunoassay for rapid triage of individuals exposed to external total-body irradiation. Here, we report on the validation of this immunoassay in human blood cell extracts 0.5 h after in vitro exposure to 137 Cs gamma rays, using γ-H2AX analysis. First, calibration curves were established for five donors at doses ranging from 0 to 10 Gy and dose rates ranging from ∼0.8 to ∼3 Gy/min. The calibration curves, together with a γ-H2AX peptide scale, enabled the definition of inter-experimental correction factors. Using previously calculated correction factors, blind dose estimations were performed at 0.5 h postirradiation, and DosiKit performance was compared against concomitant dicentric chromosome assay (DCA), the current gold standard for external irradiation biodosimetry. A prototype was then assembled and field tested. We show that, despite significant inter-individual variations, DosiKit can estimate total-body irradiation doses from 0.5 to 10 Gy with a strong linear dose-dependent signal and can be used to classify potentially exposed individuals into three dose ranges: below 2 Gy, between 2 and 5 Gy and above 5 Gy. The entire protocol can be performed in 45 min, from sampling to dose estimation, with a new patient triaged every 10 min. While DCA enables precise measurement of doses below 5 Gy, it is a long and difficult method. In contrast, DosiKit is a quick test that can be performed directly in the field by operational staff with minimal training, and is relevant for early field triage and identification of individuals most likely to experience acute radiation syndrome. These findings suggest that DosiKit and DCA are complementary and should be combined for triage in a mass scale event. While the proof-of-concept reported here validates the use of DosiKit at 0.5 h postirradiation, further studies are needed to calibrate and evaluate the performance of the DosiKit assay at longer times after irradiation.

So far, the context of care supply does not meet all the needs of patients, especially those with chronic diseases. In epileptology in particular, the impact of the disease on patients' quality of life is serious enough that a lack of or insufficient care is added to critical risks, to those with existing multiple disabilities or the lack of specialised patient follow-up., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Clinical pharmaceutical care has long played an important role in the improvement of healthcare safety. Pharmaceutical care is a collaborative care approach, implicating all the actors of the medication circuit in order to prevent and correct drug-related problems that can lead to adverse drug events. The collaborative pharmaceutical care performed during patients' hospitalization requires two mutually reinforcing activities: medication reconciliation and medication review. Until now, the impact of the association of these two activities has not been clearly studied., Methods: This is a multicentric stepped wedge randomized study involving six care units from six French University Hospitals (each unit corresponding to a cluster) over seven consecutive 14-day periods. Each hospital unit will start with a control period and switch to an experimental period after a randomized number of 14-day periods. Patients aged at least 65 years hospitalized in one of the participating care units and having given their consent to be called for a 30-day and 90-day follow-up can be enrolled. For each 14-day period, 15 patients will be recruited in each care unit to obtain a total of 630 patients enrolled in all centers. Patients with a hospital stay of more than 21 days will be excluded. During the control period, there will be no clinical pharmacist in the care unit, whereas during the experimental period a clinical pharmacist will perform medication reconciliation and review with the healthcare team. The primary outcome will assess the impact of collaborative pharmaceutical care on preventable medication error rate. The secondary outcomes will evaluate the clinical impact of the strategy, the acceptance rate of pharmaceutical interventions, the induced and avoided costs of the strategy (cost-consequence analysis), and the healthcare team's satisfaction., Discussion: This study will assess the impact of collaborative pharmaceutical care associating medication reconciliation and review at patient admission to hospital in terms of preventable medication error rate and costs. This activity will prevent and correct medication errors arising earlier in the hospitalization., Trial Registration: ClinicalTrials.gov, NCT02598115 . Registered on 4 November 2015.

The lack of time to devote to care is a frequent complaint of nurses and nursing assistants. The results of a study show that an improvement in the nutritional status of nursing home residents could help to improve their quality of life and to optimise the working time of the nursing teams, thanks to the reduction of pressure ulcers, diarrhoea, falls, fractures and infections., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Antigen cross-presentation by dendritic cells (DC) stimulates cytotoxic T cell activation to promote immunity to intracellular pathogens, viruses and cancer. Phagocytosed antigens generate potent T cell responses, but the signalling and trafficking pathways regulating their cross-presentation are unclear. Here, we show that ablation of the store-operated-Ca 2+ -entry regulator STIM1 in mouse myeloid cells impairs cross-presentation and DC migration in vivo and in vitro. Stim1 ablation reduces Ca 2+ signals, cross-presentation, and chemotaxis in mouse bone-marrow-derived DCs without altering cell differentiation, maturation or phagocytic capacity. Phagosomal pH homoeostasis and ROS production are unaffected by STIM1 deficiency, but phagosomal proteolysis and leucyl aminopeptidase activity, IRAP recruitment, as well as fusion of phagosomes with endosomes and lysosomes are all impaired. These data suggest that STIM1-dependent Ca 2+ signalling promotes the delivery of endolysosomal enzymes to phagosomes to enable efficient cross-presentation.

Maternal mortality and severe maternal morbidity are devastating for women, their families, and care providers. International efforts have been made to develop and to implement data collection, management, and surveillance systems that capture pregnancy-related information that can be assessed and used to improve health and system outcomes. At present, Canada does not have a national enquiry process to review maternal deaths, severe morbidity, and near misses, and has not set targets for maternal mortality reduction. Maternal mortality rates are critical measures of maternal health and provide important information for analysis of trends and priorities among and within countries. Information about near misses as well as maternal morbidity is crucial to truly understand and to prevent maternal mortality. Canadian experts must work together with governments, provinces, and territories to determine key indicators, measurement, and meaningful data analysis strategies. These data and their comparisons will form the foundation of evidence to guide programs, policies, priorities, and interventions that will ultimately improve the health of mothers and their children., (Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. All rights reserved.)

Fluoroalkyl amino reagents 1a and 2a have been developed from commercially available trifluoromethyl trifluorovinyl ether via a hydroamination reaction with diethylamine or dimethylamine. These reagents can be activated by treatment with a Lewis acid and subsequently used as a mono- or dielectrophile for the introduction of the fluoro(trifluoromethoxy)methyl group, either in Vilsmeier-type acylations of aromatic substrates or in the synthesis of fluorinated pyrazoles from CH-acidic substrates and of bis-fluorinated pyrazoles, all being important building blocks for medicinal and agricultural chemistry.

Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis. Our data showed for the first time that calcium supplementation of BCP microparticles had anti-inflammatory properties compared to BCP alone that induced an inflammatory response in blood cells. Our results strongly suggest that the anti-inflammatory property of calcium supplemented-BCP results from its down-modulating effect on P2X7R gene expression and its capacity to inhibit ATP/P2X7R interactions, decreasing the NLRP3 inflammasome activation. Considering that monocytes have a vast regenerative potential, and since the excessive inflammation often observed after bone substitutes implantation limits their performance, our results might have great implications in terms of understanding the mechanisms leading to an efficient bone reconstruction., Statement of Significance: Although scaffolds and biomaterials unavoidably come into direct contact with blood during bone defect filling, whole blood-biomaterials interactions have been poorly explored. By studying in 3D the interactions between biphasic calcium phosphate (BCP) in microparticulate form and blood, we showed for the first time that calcium supplementation of BCP microparticles (BCP/Ca) has anti-inflammatory properties compared to BCP-induced inflammation in whole blood cells and provided information related to the molecular mechanisms involved. The present study also showed that BCP, as well as BCP/Ca particles stimulate monocyte proliferation. As monocytes represent a powerful target for regenerative therapies and as an excessive inflammation limits the performance of biomaterials in bone tissue engineering, our results might have great implications to improve bone reconstruction., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Sore throat is a common complaint after surgery. It affects patient satisfaction and can affect activity after discharge. The supraglottic airway device (SAD) offers an alternative to traditional tracheal intubation with potential benefit in preventing sore throat., Objective: The aim of this study was to compare the incidence of sore throat following three different SADs, the laryngeal mask airway Unique (LMA-U) and the more recent LMA Supreme (LMA-S) and the I-gel., Design: A randomised single-blind controlled three parallel-group trial., Setting: University Hospital of Nîmes, Division of Anaesthesia Intensive Care Pain and Emergency, Nîmes, France, from April 2009 to September 2012., Patients: A total of 546 patients scheduled to undergo elective surgery of less than 2 h under general anaesthesia were randomly allocated to receive the LMA-U, the LMA-S or the I-gel., Interventions: Anaesthesia was induced with propofol and sufentanil and maintained with propofol or with sevoflurane in air-oxygen. After airway device insertion, intra-cuff pressure was adjusted to less than 60 mmHg (LMA-U, LMA-S) and pressure-controlled ventilation initiated., Main Outcomes: The primary study endpoint was to compare incidence of sore throat 24 h postoperatively (H+24) following placement of the LMA-U, LMA-S and the I-gel. Secondary endpoints were clinical performance (airway leak pressure, dynamic airway compliance, complications during maintenance), ease of use (device insertion time, success on first attempt, ease of insertion and removal) and other adverse events (neck or jaw pain, dysphonia, dysphagia, nausea and vomiting)., Results: The authors analysed 177, 174 and 173 patients who received LMA-U, the LMA-S and the I-gel, respectively. The primary endpoint was assessed in 436 patients. In total, 104 patients (23.9%) patients reported a H+24 sore throat, with no difference between groups (P = 0.34). H+24 dysphagia with liquids was higher (P = 0.0065) with the LMA-S (12.1%) compared with LMA-U (5.3%) and I-gel (2.9%). Airway leak pressure (cmH2O) was lower (P < 0.0001) with LMA-U [21 (18 to 27)] compared with I-gel [26 (20 to 30)] and LMA-S [25 (21 to 30)]. Device insertion time (sec) was shorter (P < 0.0167) with the I-gel [30 (20 to 40)] compared with the LMA-U [34 (23 to 48)] and LMA-S [32 (22 to 50)]., Conclusion: The incidence of postoperative sore throat was not significantly different between the three SADs studied.

We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation of new amides.

Background and Objective: Low level laser therapy (LLLT) in both infrared and visible light is a therapeutic tool ever more proposed in clinical practice in different fields. The effect of near infrared LLLT has been described in a growing number of scientific publications related to bone tissue healing, both in vitro and in vivo. More recently, green visible light using potassium-titanyl-phosphate KTiOPO4 (KTP, 532 nm) laser has been proposed in dermatology, urology, oral and maxillofacial surgery but has never been tested on bone tissue. The aim of the present work was to perform a preliminary in vitro study to analyze the effects of KTP laser, on the osteogenic differentiation of bone marrow stromal cells (BMSCs)., Materials and Methods: Using a power meter the first step of this study aimed to evaluate the real power emitted by the KTP laser device and the amount of energy absorbed by culture medium and plastic in order to calculate the appropriate irradiation parameters for cultured cells. Primary bone marrow stromal cells prepared from C57BL/6 mice were cultured and induced to differentiate in the osteogenic lineage in the presence or in the absence of KTP LLLT at a fluence of 4 J/cm(2) three times a week. Specific staining of the cells and the extracellular matrix, microscopic analysis as well as quantitative RT-PCR were used to assess cell proliferation and differentiation., Results: We show here that KTP LLLT enhances the osteogenic differentiation of bone marrow stromal cells and the mineralization of their extracellular matrix., Conclusion: Our results highlight that this LLLT experimental protocol with green light (KTP, 532 nm) at 4 J/cm(2) has a positive effect on the osteogenic differentiation of murine bone marrow stromal cells. These preliminary results could be used as a basis to further investigate the effect of this KTP laser protocol on bone tissue engineering models in vivo and in vitro., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: DESIR is a prospective longitudinal multicentric French cohort of patients with inflammatory back pain suggestive of spondyloarthritis, with a 10-year-follow-up. The purpose is to evaluate the performances of the different sets of classification criteria for axial spondyloarthritis, and to describe the frequency and characteristics of the clinical features of axial spondyloarthritis., Methods: Demographic data and items allowing classification and indices calculation were collected, as well as biologic and imaging data. Baseline data are analyzed. The performance of the several classification criteria sets was evaluated (likelihood ratio) with the physician's diagnosis as external gold standard. For the clinical presentation of axial spondyloarthritis, a descriptive analysis was conducted., Results: Seven hundred and eight patients are included. Ninety-two percent of them satisfy at least one set of classification criteria: mNY 26%, Amor 79%, ESSG 78%, ASAS 70%; physician's confidence level 6.8±2.7. 81 and 83% of patients fulfil modified (including MRI) Amor or ESSG criteria. Axial involvement is present in 100% of the cases. NSAIDs are taken by 90%, with an NSAID sore of 50±46. BASDAI over 40 is noted in 60% and elevated CRP in 30% of the cases. HLA-B27 is present in 58%. According to ASDAS CRP levels, 12.7% are in inactive disease, 63% in high disease activity; mean BASFI was 30. Peripheral involvement is present in 57%, with arthritis in 37% of these. Enthesitis is noted in 49% of the patients, and first symptom in 22.5%; anterior chest wall involvement is noted in 44.6%, and dactylitis in 13%. For extra articular manifestations, psoriasis is recorded in 16%, uveitis in 8.5% and IBD in 5.1%. Smoking is present in 36.3% and hypertension in 5.1% of the cases., Conclusion: These data represent the base of evaluation of the follow-up of this cohort, allowing future specific studies., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Quality of transitions of care is one of the first concerns in patient safety. Redesigning the discharge process to incorporate clinical pharmacy activities could reduce the incidence of postdischarge adverse events by improving medication adherence. The present study investigated the value of pharmacist counseling sessions on primary medication adherence after hospital discharge.This study was conducted in a 1844-bed hospital in France. It was divided in an observational period and an interventional period of 3 months each. In both periods, ward-based clinical pharmacists performed medication reconciliation and inpatient follow-up. In interventional period, initial counseling and discharge counseling sessions were added to pharmaceutical care. The primary medication adherence was assessed by calling community pharmacists 7 days after patient discharge.We compared the measure of adherence between the patients from the observational period (n = 201) and the interventional period (n = 193). The rate of patients who were adherent increased from 51.0% to 66.7% between both periods (P < 0.01). When discharge counseling was performed (n = 78), this rate rose to 79.7% (P < 0.001). The multivariate regression performed on data from both periods showed that age of at least 78 years old, and 3 or less new medications on discharge order were predictive factors of adherence. New medications ordered at discharge represented 42.0% (n = 1018/2426) of all medications on discharge order. The rate of unfilled new medications decreased from 50.2% in the observational period to 32.5% in the interventional period (P < 10). However, patients included in the observational period were not significantly more often readmitted or visited the emergency department than the patients who experienced discharge counseling during the interventional period (45.3% vs. 46.2%; P = 0.89).This study highlights that discharge counseling sessions are essential to improve outpatients' primary medication adherence. We identified predictive factors of primary nonadherence in order to target the most eligible patients for discharge counseling sessions. Moreover, implementation of discharge counseling could be facilitated by using Health Information Technology to adapt human resources and select patients at risk of nonadherence.

Background: Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available., Patients and Methods: Eighty-four women with severe PPH unresponsive to uterotonics were randomized to receive one early single rhuFVIIa infusion (n = 42) or standard care (no rhuFVIIa; n = 42). The primary efficacy outcome measure was the reduction of the need for specific second-line therapies, such as interventional hemostatic procedures, for blood loss and transfusions. The primary safety outcome measure was the number of deaths and thrombotic events during the 5 days following rhuFVIIa infusion., Results: rhuFVIIa was associated with a reduction in the number of patients who needed second-line therapies compared with controls (standard care). Specifically, 39/42 (93%) patients in the standard care arm received second-line therapies and 22/42 (52%) patients in the rhuFVIIa arm (absolute difference, 41%; range, 18-63%; relative risk RR, 0.56 [0.42-0.76]). The delivery mode (vaginal or Cesarean section) did not affect the primary outcome. No death occurred. Two venous thrombotic events were recorded in the rhuFVIIa arm: one ovarian vein thrombosis and one deep vein thrombosis with a non-severe pulmonary embolism., Conclusion: This open RCT in women with severe PPH refractory to uterotonics shows that rhuFVIIa reduces the need for specific second-line therapies in about one in three patients, with the occurrence of non-fatal venous thrombotic events in one in 20 patients., (© 2015 International Society on Thrombosis and Haemostasis.)

Nannochloropsis has emerged as a promising alga for biodiesel production. However, the genus consists of 6 species and hundreds of strains making strain selection a challenge. Furthermore, oil productivity is instrumental to economic viability of any algal strain for industrial production, which is dependent on growth rate and oil content. In most cases, these two parameters have been studied independently. Thus, the goal of this study is to provide a combined method for evaluating strain performance in specially designed photobioreactors together with an in-depth lipidomic analyses. The nine strains of Nannochloropsis tested showed considerable variations in productivity and lipidomics highlighting the importance of strain selection. Finally, Nannochloropsis gaditana CCMP527 and Nannochloropsis salina CCMP537 emerged as the two most promising strains, with an oil content of 37 and 27 dry wt% after 11-day nitrogen starvation, respectively, resulting in TAG productivity of 13×10(-3) and 18×10(-3) kg m(-3) d(-1), respectively., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Many activities contribute to reduce drug-related problems. Among them, the medication reconciliation (MR) is used to compare the best possible medication history (BPMH) and the current admission medication order (AMO) to identify and solve unintended medication discrepancies (UMD). This study aims to assess the impact of the implementation of admission MR by clinical pharmacists on UMD., Method: This prospective study was carried out in two units of general medicine and infectious and tropical diseases in a 1844-bed French hospital. A retroactive MR performed in an observational period was compared to a proactive MR realized in an interventional period. We used a logistic regression to identify risk factors of UMD., Results: During both periods, 394 patients were enrolled and 2,725 medications were analyzed in the BPMH. Proactive MR reduced the percentage of patients with at least one UMD compared with retroactive process (respectively 2.1% vs. 45.8%, p<0.001). Patients with at least one UMD during both periods were older compared to patients without UMD (79 vs. 72, p<0.005) and had more medications at admission (7 vs. 6, p<0.0001). UMD occur 38 times more often when there is no clinical pharmacist intervention. Among the 226 UMD detected in both periods, 42% would have required monitoring or intervention to preclude harm, and 10% had potential harm to the patient and 2% were life threatening., Conclusion: Proactive MR performed by clinical pharmacists is an acute process of detection and correction of UMD, but it requires a lot of human resources., (Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

A combination of autologous bone marrow stromal cells (BMSCs) and biomaterials is a strategy largely developed in bone tissue engineering, and subcutaneous implantation in rodents or large animals is often a first step to evaluate the potential of new biomaterials. This study aimed at investigating the influence of the immune status of the recipient animal on BMSCs-induced bone formation. BMSCs prepared from C57BL/6 mice, composed of a mixture of mesenchymal stromal and monocytic cells, were combined with a biomaterial that consisted of biphasic calcium phosphate (BCP) particles and plasma clot. This composite was implanted subcutaneously either in syngenic C57BL/6 immune-competent mice or in T-lymphocyte-deficient Nude (Nude) mice. Using histology, immunohistochemistry, and histomorphometry, we show here that this BMSC/BCP/plasma clot composite implanted in Nude mice induces the formation of mature lamellar bone associated to hematopoietic areas and numerous vessels. Comparatively, implantation in C57BL/6 results in the formation of woven bone without hematopoietic tissue, a lower number of new vessels, and numerous multinucleated giant cells (MNGCs). In situ hybridization, which enabled to follow the fate of the BMSCs, revealed that BMSCs implanted in Nude mice survived longer than BMSCs implanted in C57BL/6 mice. Quantitative expression analysis of 280 genes in the implants indicated that the differences between C57BL/6 and Nude implants corresponded almost exclusively to genes related to the immune response. Gene expression profile in C57BL/6 implants was consistent with a mild chronic inflammation reaction characterized by Th1, Th2, and cytotoxic T-lymphocyte activation. In the implants retrieved from T-deficient Nude mice, Mmp14, Il6st, and Tgfbr3 genes were over-expressed, suggesting their putative role in bone regeneration and hematopoiesis. In conclusion, we show here that the T-mediated inflammatory microenvironment is detrimental to BMSCs-induced bone formation and shortens the survival of implanted cells. Conversely, the lack of T-lymphocyte reaction in T-deficient animals is beneficial to BMSCs-induced mature bone formation. This should be taken into account when evaluating cell/biomaterial composites in these models.