[First French-speaking days of users of decision support system in clinical pharmacy: Feedback and perspectives]. / Premières journées francophones des utilisateurs de système d'aide à la décision en pharmacie clinique : retour d'expériences et perspectives.

Clinical decision support systems (CDSS) are tools that have been used for several years by clinical pharmacy teams to support pharmaceutical analysis, with a perspective of contributing to the quality of care in collaboration with the other health care team members. These tools require both technical, logistical and human resources. The growing use of these systems in different establishments in France and in Europe gave birth to the idea of meeting to share our experiences. The days organized in Lille in September 2021 aimed at proposing a time of exchange and reflection on the use of these CDSS in clinical pharmacy. A first session was devoted to feedback from each establishment. These tools are essentially used to optimize pharmaceutical analysis and to secure patient medication management. This session outlined the clear advantages and common limitations of these CDSS. Two research projects were also presented to put the use of these tools into perspective. The second session of these days, in the form of workshops, addressed 4 themes that surround the implementation of CDSS: their usability, the legal aspect, the creation of rules and their possible valorization. Common problems were raised, the resolution of which requires close collaboration. This is a first step proposing a beginning of harmonization and sharing that should be deepened in order not to lose the dynamics created between the different centers. This event ended with the proposal to set up two working groups around these systems: the creation and structuring of rules for the detection of risk situations and the common valorization of the work.

Comparison of the validity, perceived usefulness, and usability of I-MeDeSA and TEMAS, two tools to evaluate alert system usability.

OBJECTIVE: Two tools are currently available in the literature to evaluate the usability of medication alert systems, the instrument for evaluating human factors principles in medication-related decision support alerts (I-MeDeSA) and the tool for evaluating medication alerting systems (TEMAS). This study aimed to compare their convergent validity, perceived usability, usefulness, strengths, and weaknesses, as well as users' preferences. METHOD: To evaluate convergent validity, two experts mapped TEMAS' items against I-MeDeSA's items with respect to the usability dimensions they target. To assess perceived usability, usefulness, strengths, and weaknesses of both tools, staff with expertise in their medication alerting system were asked to use French versions of the TEMAS and I-MeDeSA. After the use of each tool, participants were asked to complete the System Usability Scale (SUS) and answer questions about the understandability and usefulness of each tool. Finally, participants were asked to name their preferred tool. Numeric scores were statistically compared. Free-text responses were analyzed using an inductive approach. RESULTS: Forty-five participants from 10 hospitals took part in the study. In terms of convergent validity, I-MeDeSA focuses more on the usability of the graphical user interface while TEMAS considers a wider range of usability principles. Both tools have a fair level of perceived usability (I-MeDeSA' SUS score = 61.85 and TEMAS' SUS score = 62.87), but results highlight that revisions are necessary to both tools to improve their usability. Participants found TEMAS more useful than I-MeDeSA (t = -3.63, p =.005) and had a clear preference for TEMAS to identify problems in formative evaluation (39 of 45; 0.867, p <.001) and to compare the usability of alert systems during the procurement process (36 of 45; 0.8, p <.001). CONCLUSIONS: The TEMAS is perceived as more useful and is preferred by participants. The I-MeDeSA seems more relevant for quick evaluations that focus on the graphical user interface. The TEMAS seems to be more suitable for in-depth usability evaluations of alert systems. Even if both tools are perceived to be equally usable, they suffer from wording, instructional, and organizational problems that hinder their use. The results of this study will be used to improve the design of I-MeDeSA and TEMAS.

Encrusted Urinary Tract Infections Due to Corynebacteria Species.

INTRODUCTION: Encrusted pyelitis and cystitis are peculiar disorders characterized by the calcification of the vesical, the pyelic, and/or the ureteral walls. These calcifications are composed of struvite and calcium carbonate‒apatite due to the presence of Corynebacterium urealyticum. METHODS: We have identified the clinical features and outcomes of 17 patients with encrusted pyelitis (n = 15) or encrusted cystitis (n = 2). Diagnosis was based on computed tomography scan and sonography including thickening and calcified lesions of the urinary tract. RESULTS: The main clinical presentation was suggestive of subacute urinary tract infection with fever and urologic symptoms, mostly gross hematuria. Biologic features were characterized by the presence of struvite crystals and alkaline urine. Acute kidney injury was reported in 70.6% of cases. Predisposing factors were mostly due to urologic background (82.4%) with a history of urologic procedure (71%) and prior exposure to antibiotics (59%). All patients received appropriate antibiotherapy and 15 were treated with topical urinary acidification. A significant reduction of encrusted calcifications was observed in 88% of cases. Renal function improved in 71% of the patients. Nevertheless, poor tolerance of the treatment and side effects were common, affecting 71% of patients, with Gram-negative bacilli urinary tract infections (53%) being the most frequent. At last follow-up, 4 patients (23.5%) progressed to end-stage renal disease and only 1 had a clinical relapse. CONCLUSIONS: Encrusted urinary tract infections are rare, characterized by a severe renal and overall prognosis in the absence of appropriate treatment. Topical urinary acidification and appropriate antibiotherapy are efficient but may be burdened by significant adverse events.

[Complex management of type 2 heparin-induced thrombocytopenia in patients with major bleeding tendency: two case report]. / Prise en charge de la thrombopénie induite par l'héparine immuno-allergique de type 2 au travers de deux cas cliniques chez des patients à risque hémorragique majeur.

Type 2 heparin-induced thrombocytopenia (HIT 2) is a rare pro-thrombotic disorder occurring in patients treated with heparin. It is defined as a clinical-biological syndrome associating the sudden onset of a thrombocytopenia, characterized by a drop of more than 50% of the initial platelet count, and thrombosis. We report two cases of HIT 2 occurring in patients with major bleeding tendency. The first HIT occurred in a patient whose management, in accordance with current guidelines, made it possible to control the thrombocytopenia and the anticoagulation despite the complexity of adapting and monitoring treatments in the context of recent cerebral hemorrhage. The second refers to an autoimmune HIT, which occurred in a patient whose management required the use of alternative therapies to the standard treatments suggested for HIT 2, to correct the severe refractory thrombocytopenia.

Drug-drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors.

The HMG-CoA reductase inhibitors are a class of drugs also known as statins. These drugs are effective and widely prescribed for the treatment of hypercholesterolemia and prevention of cardiovascular morbidity and mortality. Seven statins are currently available: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. Although these drugs are generally well tolerated, skeletal muscle abnormalities from myalgia to severe lethal rhabdomyolysis can occur. Factors that increase statin concentrations such as drug-drug interactions can increase the risk of these adverse events. Drug-drug interactions are dependent on statins' pharmacokinetic profile: simvastatin, lovastatin and atorvastatin are metabolized through cytochrome P450 (CYP) 3A, while the metabolism of the other statins is independent of this CYP. All statins are substrate of organic anion transporter polypeptide 1B1, an uptake transporter expressed in hepatocyte membrane that may also explain some drug-drug interactions. Many HIV-infected patients have dyslipidemia and comorbidities that may require statin treatment. HIV-protease inhibitors (HIV PIs) are part of recommended antiretroviral treatment in combination with two reverse transcriptase inhibitors. All HIV PIs except nelfinavir are coadministered with a low dose of ritonavir, a potent CYP3A inhibitor to improve their pharmacokinetic properties. Cobicistat is a new potent CYP3A inhibitor that is combined with elvitegravir and will be combined with HIV-PIs in the future. The HCV-PIs boceprevir and telaprevir are both, to different extents, inhibitors of CYP3A. This review summarizes the pharmacokinetic properties of statins and PIs with emphasis on their metabolic pathways explaining clinically important drug-drug interactions. Simvastatin and lovastatin metabolized through CYP3A have the highest potency for drug-drug interaction with potent CYP3A inhibitors such as ritonavir- or cobicistat-boosted HIV-PI or the hepatitis C virus (HCV) PI, telaprevir or boceprevir, and therefore their coadministration is contraindicated. Atorvastatin is also a CYP3A substrate, but less potent drug-drug interactions have been reported with CYP3A inhibitors. Non-CYP3A-dependent statin concentrations are also affected although to a lesser extent when coadministered with HIV or HCV PIs, mainly through interaction with OATP1B1, and treatment should start with the lowest available statin dose. Effectiveness and occurrence of adverse effects should be monitored at regular time intervals.

Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells.

WISP-2/CCN5 is an estrogen-regulated member of the "connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed" (CCN) family of the cell growth and differentiation regulators. The WISP-2/CCN5 mRNA transcript is undetectable in normal human mammary cells, as well as in highly aggressive breast cancer cell lines, in contrast with its higher level in the breast cancer cell lines characterized by a more differentiated phenotype. We report here that knockdown of WISP-2/CCN5 by RNA interference in estrogen receptor alpha (ERalpha)-positive MCF-7 breast cancer cells induced an estradiol-independent growth linked to a loss of ERalpha expression and promoted epithelial-to-mesenchymal transdifferentiation. In contrast, forced expression of WISP-2/CCN5 directed MCF-7 cells toward a more differentiated phenotype. When introduced into the poorly differentiated, estrogen-independent, and invasive MDA-MB-231 breast cancer cells, WISP-2/CCN5 was able to reduce their proliferative and invasive phenotypes. In a series of ERalpha-positive tumor biopsies, we found a positive correlation between the expression of WISP-2/CCN5 and ID2, a transcriptional regulator of differentiation in normal and transformed breast cells. We propose that WISP-2/CCN5 is an important regulator involved in the maintenance of a differentiated phenotype in breast tumor epithelial cells and may play a role in tumor cell invasion and metastasis.