7 research outputs found

    Molecular interactions between zoledronic acid and bone: an in vitro Raman microspectroscopic study

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    Abstract The aim of this study was to investigate molecular interactions between a bisphosphonate (BP), zoledronic acid, and bone tissue by the use of Raman microspectroscopy. In this way, samples of hydroxyapatite (HA), as a bone model, and Wistar rat femurs were soaking in zoledronic acid solutions. Sample surfaces were studied by Environmental Scanning Electron Microscopy and Raman spectroscopy. The amount of zoledronic acid incorporated onto the samples was determined by 31P NMR spectroscopy. After impregnation new Raman bands with frequencies close to characteristic peaks of zoledronic acid (in particular phosphate moieties and imidazole ring of the R2 side-chain) were observed on the both types of samples. Physico-chemical parameters of bone were significantly modified (P<0.0001). The mineral to organic ratio and the carbonate to phosphate ratio were decreased and the crystallinity was increased. Released inorganic phosphate was detected in the solutions by 31P NMR spectroscopy. The Raman shift of the bands corresponding to the phosphate groups and the imidazole ring of the BP highlight their implication in the binding to the mineral. The detection of released inorganic phosphate in solutions, the modifications of the mineral to phosphate ratio and the carbonate to phosphate ratio demonstrate the existence of ionic substitutions in the lattice secondary to BP binding, and especially at CO32- type-B and PO43- sites. The increase of the crystallinity is in favour of a re-organisation of the lattice with a higher symmetry. The use of Raman spectrometry brings new and complementary information on the impact of zoledronic acid on the bone composition at a molecular level

    Elevation of Trimethylamine-N-Oxide in Chronic Kidney Disease: Contribution of Decreased Glomerular Filtration Rate.

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    International audience(1) Background: Gut microbiota-dependent Trimethylamine-N-oxide (TMAO) has been 5 reported to be strongly linked to renal function and to increased cardiovascular events in the 6 general population and in Chronic Kidney Disease (CKD) patients. Considering the lack of data 7 assessing renal handling of TMAO, we conducted this study to explore renal excretion and 8 mechanisms of accumulation of TMAO during CKD. (2) Methods: We prospectively measured 9 glomerular filtration rate (mGFR) with gold standard methods and plasma concentrations of 10 trimethylamine (TMA), TMAO, choline, betaine and carnitine by LC-MS/MS in 124 controls, CKD 11 and hemodialysis (HD) patients. Renal clearance of each metabolite was assessed in a subgroup of 12 32 patients. (3) Results: Plasma TMAO was inversely correlated with mGFR (r 2 =0.388, p<0.001), 13 confirming elevation of TMAO plasma levels in CKD. TMAO clearances were not significantly 14 different from mGFR, with a mean ± SD TMAO fractional excretion of 105 ± 32 %. This suggests a 15 complete renal excretion of TMAO by glomerular filtration with a negligible participation of 16 tubular secretion or reabsorption, during all stages of CKD. Moreover, TMAO was effectively 17 removed within 4 hours of hemodiafiltration, showing a higher fractional reduction value than that 18 of urea (84.9 ± 6.5 % vs 79.2 ± 5.7 %, p = 0.04). (5) Conclusions: This study reports a strong 19 correlation between plasma TMAO levels and mGFR, in CKD, that can be mainly related to a 20 decrease in TMAO glomerular filtration. Clearance data did not support a significant role for 21 tubular secretion in TMAO renal elimination. 2

    Impact of a Pharmacist-included Mobile Geriatrics team intervention on potentially inappropriate drug prescribing: protocol for a prospective feasibility study (PharMoG study)

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    Introduction Research has shown that potentially inappropriate drug prescription (PIDP) is highly prevalent in older people. The presence of PIDPs is associated with adverse health outcomes. This study aims to evaluate the impact of a PHARmacist-included MObile Geriatrics (PharMoG) team intervention on PIDPs in older patients hospitalised in the medical, surgical and emergency departments of a university hospital.Methods and analysis The PharMoG study is a prospective, interventional, single-centre feasibility study describing the impact of a PharMoG team on PIDPs in older hospitalised patients. Pharmacist intervention will be a treatment optimisation (clinical medication review) based on a combination of explicit and implicit criteria to detect PIDPs. The primary outcome is the acceptance rate of the mobile team’s proposed treatment optimisations related to PIDPs, measured at the patient’s discharge from the department. This pharmacist will work in cooperation with the physician of the mobile geriatric team. After the intervention of the mobile geriatric team, the proposals for improving therapy will be sent to the hospital medical team caring for the patient and to the patient’s attending physician. The patient will be followed for 3 months after discharge from the hospital.Ethics and dissemination This study was approved by the South-West and Overseas Territories II Ethics Committee. Oral consent must be obtained prior to participation, either from the patient or from the patient’s representative (trusted person and/or a family member). The results will be presented at national and international conferences and published in peer-reviewed journals.Trial registration number NCT04151797

    Using ELEFIGHT&reg; QR Codes for Quick Access to Information on Influenza Burden and Prevention: A Pilot Study in Lyon University Hospital

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    (1) Background: The Vaccine Coverage Rate of influenza remains low and omnichannel efforts are required to improve it. The objective was to evaluate the feasibility and outcomes of a QR Code nudging system in outpatient departments. (2) Methods: The study was performed in 6 departments ensuring ambulatory activities in a French university Hospital between November and December 2021. By scanning QR codes, users accessed anonymously to the ELEFIGHT&reg; web app, which provides medical information on influenza and invites them to initiate a discussion about influenza prevention with their physicians during the consultation. (3) Results: 351 people made 529 scans with an average reading time of 1 min and 4 s and a conversion rate of 32%, i.e., people willing to engage in a discussion. (4) Conclusions: The study suggests that direct access to medical information through QR codes in hospitals might help nudge people to raise their awareness and trigger their action on influenza prevention

    COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

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    International audienceBackground: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases
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