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This is a systematic literature review on the impact of pharmacists in rheumatology, conducted using the PubMed®, CINAHL®, Cochrane Library®, and Web of science® databases and using the PRISMA 2020 checklist. This review was conducted from 2000 to June 2024. A quality analysis was performed. The selection of articles, as well as all analyses, including quality analyses, were conducted by a pair of pharmacists with experience in rheumatology, and included 24 articles. This study highlights the growth of clinical pharmacy activities in rheumatology and the positive influence of clinical pharmacists on patient care. The implementation of such initiatives has the potential to improve medication adherence, reduce medication-related risks, and optimize associated healthcare costs. All these pharmaceutical interventions aim to make the patient care journey smoother and safer. Additionally, the diversity of available pharmaceutical services caters to the varied needs of rheumatology. Furthermore, outpatient clinical pharmacy is also explored in this field and garners interest from patients. The vast majority of studies demonstrate significant improvement in patient care with promising performance outcomes when pharmacists are involved. This review highlights the diverse range of interventions by clinical pharmacists in rheumatology, which is very promising. However, to better assess the benefits of clinical pharmacists, this activity needs further development and evaluation through controlled and randomized clinical research programs. [ABSTRACT FROM AUTHOR]

Aims: The global older population is growing rapidly, and the rise in polypharmacy has increased potentially inappropriate medication (PIM) encounters. PIMs pose health risks, but detecting them automatically in large medical databases is complex. This review aimed to uncover PIM prevalence in individuals aged 65 years or older using health databases and emphasized the risk of underestimating PIM prevalence due to underutilization of detection tools. Methods: This study conducted a broad search on the Medline database to identify articles about the prevalence of PIMs in older adults using various databases. Articles published between January 2010 and June 2023 were included, and specific criteria were applied for study selection. Two literature reviews conducted before our study period were integrated to obtain a perspective from the 1990s to the present day. The selected papers were analysed for variables including database type, screening method, adaptations and PIM prevalence. The study categorized databases and original screening tools for clarity, examined adaptations and assessed concordance among different screening methods. Results: This study encompassed 48 manuscripts, covering 58 sample evaluations. The mean prevalence of PIMs within the general population aged over 65 years was 27.8%. Relevant heterogeneity emerged in both the utilized databases and the detection methods. Adaptation of original screening tools was observed in 86.2% (50/58) of cases. Half of the original screening tools used for assessing PIMs belonged to the simple category. About a third of the studies employed less than half of the original criteria after adaptation. Only three studies used over 75% of the original criteria and more than 50 criteria. Conclusions: This extensive review highlights PIM prevalence among the older adults, emphasizing method intricacies and the potential for underestimation due to data limitations and algorithm adjustments. The findings call for enhanced methodologies, transparent algorithms and a deeper understanding of intricate rules' impact on public health implications. [ABSTRACT FROM AUTHOR]

The evolving landscape of opioid prescription practices necessitates a comprehensive understanding of emerging patterns, particularly among new opioid users discharged from emergency departments. This study delves into the intricate realm of opioid utilization by elucidating the prevalence of their prescriptions. A retrospective analysis of electronic health records was conducted, including a cohort of 71 patients who received opioid prescriptions upon discharge from emergency departments from 1 January 2022 to 30 June 2022. Demographic characteristics and prescription details were systematically examined. This study illuminates tramadol's prominence, with 84% of prescriptions and a Defined Daily Dose (DDD) morphine equivalent of 60 mg, as the primary choice as a new opioid, a finding that draws attention due to the closely aligned dosages with morphine equivalents. This discovery prompts a critical reassessment of tramadol's therapeutic role, considering its multifaceted nature encompassing serotonergic effects and heightened fall risks. This study advocates for a nuanced and vigilant approach to tramadol prescription, cognizant of its potential risks and therapeutic implications, and highlights the imperative of optimizing data quality and traceability within electronic health records to enhance patient care and facilitate future research endeavors. [ABSTRACT FROM AUTHOR]

Introduction: Clinical pharmacist (CP) intervention improves drug prescription by identifying potentially inappropriate prescriptions (PIPs). Geriatric perioperative care units (UPOGs) provide enhanced care for patients with hip fracture, including drug prescription. However, it is not known whether adding a CP intervention in a UPOG decreases the number of PIPs. This study aimed to evaluate the effect of a CP intervention, combining an implicit and an explicit method, on the number of PIPs in a UPOG. Methods: This single centre before-after-control-impact study recruited patients aged over 75 years admitted to a UPOG for a hip fracture. The "control group" ("before period") received usual care including two medication reconciliations, one at admission and one at discharge. The "intervention group" ("after period") received usual care and a CP intervention including two medication reconciliations, a medication review with two tools, STOPP/START and Medication Appropriateness Index, and a meeting between a CP and geriatricians. PIPs were assessed in both groups by STOPP/START and Medication Appropriateness Index and compared from hospital admission to discharge. Results: A total of 209 patients were included, 150 in the control group and 59 in the intervention group (mean age: 87.2 ± 5.9 years). The number of PIPs decreased in both groups from hospital admission to discharge (p < 0.001). The number of PIPs, potentially inappropriate medications, and potential prescribing omissions decreased more in the intervention group than in the control group (adjusted intervention effect: −2.46 (95% CI: −2.63; −2.24); −1.13 (95% CI: −1.27; −0.98); and −1.35 (95% CI: −1.52; −1.18), respectively, p < 0.001 for all). Discussion/Conclusion: A CP intervention with an explicit and implicit method improved prescriptions in a UPOG. Further randomized studies are necessary to evaluate the effect of a CP intervention on adverse drug events, health costs, and mortality. [ABSTRACT FROM AUTHOR]

Abstract Background Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood. Methods This work was conducted to analyze the implication of Rac3 in the aggressiveness of two breast cancer cell lines, MDA-MB-231 and MCF-7: both express Rac3, but MDA-MB-231 expresses more activated RhoA. The effect of Rac3 in cancer cells was also compared with its effect on the non-tumorigenic mammary epithelial cells MCF-10A. We analyzed the consequences of Rac3 depletion by anti-Rac3 siRNA. Results Firstly, we analyzed the effects of Rac3 depletion on the breast cancer cells’ aggressiveness. In the invasive MDA-MB-231 cells, Rac3 inhibition caused a marked reduction of both invasion (40%) and cell adhesion to collagen (84%), accompanied by an increase in TNF-induced apoptosis (72%). This indicates that Rac3 is involved in the cancer cells’ aggressiveness. Secondly, we investigated the effects of Rac3 inhibition on the expression and activation of related signaling molecules, including NF-κB and ERK. Cytokine secretion profiles were also analyzed. In the non-invasive MCF-7 line; Rac3 did not influence any of the parameters of aggressiveness. Conclusions This discrepancy between the effects of Rac3 knockdown in the two cell lines could be explained as follows: in the MDA-MB-231 line, the Rac3-dependent aggressiveness of the cancer cells is due to the Rac3/ERK-2/NF-κB signaling pathway, which is responsible for MMP-9, interleukin-6, -8 and GRO secretion, as well as the resistance to TNF-induced apoptosis, whereas in the MCF-7 line, this pathway is not functional because of the low expression of NF-κB subunits in these cells. Rac3 may be a potent target for inhibiting aggressive breast cancer.

Abstract Background Infiltration by macrophages (Mφ) indicates a poor prognosis in breast cancers, in particular by inducing angiogenesis. Our study aimed 1) to investigate the mechanism by which cooperation between Mφ and aggressive breast cancer cells (MDA-MB-231) induces angiogenesis; 2) to examine the effect of tetrathiomolybdate (TM) on this angiogenic activity. Methods Mφ coincubated with MDA-MB-231 were used as a model to mimic the inflammatory microenvironment. Angiogenesis induced by the culture media was tested in the chick chorioallantoic membrane (CAM). Mφ phenotype was evaluated by 1) expression of the M1 marker CD80, and secretion of interleukin 10 (IL-10), an M2 marker; 2) capacity to secrete Tumour Necrosis Factor α (TNFα) when stimulated by lipopolysaccharide/interferon γ (LPS/IFNγ); 3) ability to induce MDA-MB-231 apoptosis. To explore the molecular mechanisms involved, cytokine profiles of conditioned media from MDA-MB-231, Mφ and the coculture were characterised by an antibody cytokine array. All experiments were carried out both in presence and in absence of TM. Results Incubation of Mφ with MDA-MB-231 induced a pro-angiogenic effect in the CAM. It emerged that the angiogenic activity of the coculture is due to the capacity of Mφ to switch from M1 Mφ towards M2, probably due to an increase in Macrophage Colony Stimulating Factor. This M1-M2 switch was shown by a decreased expression of CD80 upon LPS/IFNγ stimulation, an increased secretion of IL-10, a decreased secretion of TNFα in response to LPS/IFNγ and an inability to potentiate apoptosis. At the molecular level, the angiogenic activity of the coculture medium can be explained by the secretion of CXC chemokines/ELR+ and CC chemokines. Although TM did not modify either the M2 phenotype in the coculture or the profile of the secreted chemokines, it did decrease the angiogenic activity of the coculture medium, suggesting that TM inhibited angiogenic activity by interfering with the endothelial cell signalling induced by these chemokines. Conclusions Cooperation between Mφ and MDA-MB-231 transformed M1 Mφ to an angiogenic, M2 phenotype, attested by secretion of CXC chemokines/ELR+ and CC chemokines. TM inhibited this coculture-induced increase in angiogenic activity, without affecting either Mφ phenotype or cytokine secretion profiles.

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. [ABSTRACT FROM AUTHOR]