Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics

Aim Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. Methods With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. Results Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. Conclusion Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials.</div

Essential competencies in prescribing : A first european cross-sectional study among 895 final-year medical students

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed

Harmonizing and improving European education in prescribing: An overview of digital educational resources used in clinical pharmacology and therapeutics

Aim: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required. Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose. Methods: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled. Results: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum. A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%). Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes. Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt). A narrative overview of the largest, free and most novel resources is given. Conclusion: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools. Learning objectives are based largely on knowledge rather than skills or attitudes. This may be improved by including more real-life clinical case scenarios. Moreover, the majority of resources are neither free nor open. Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Purpose Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. Methods CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Results Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Conclusion Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system

Is Implant Coating With Tyrosol- and Antibiotic-loaded Hydrogel Effective in Reducing Cutibacterium (Propionibacterium) acnes Biofilm Formation? A Preliminary In Vitro Study

Studies have suggested that Cutibacterium acnes (formerly known as Propionibacterium) is the most frequently isolated pathogen after shoulder arthroplasty. To address the burden of periprosthetic joint infections associated with this pathogen, new prevention methods are needed. Tyrosol has a promising record of effectiveness in the field of biofilm-associated infections; however, to our knowledge, it has not been tested against C. acnes thus far. QUESTIONS/PURPOSES: In this in vitro study, we asked: (1) Is tyrosol effective in inhibiting and eradicating C. acnes planktonic growth? (2) Is there synergy between tyrosol and rifampicin? (3) Is supplementation of hydrogel with tyrosol at the minimum inhibitory and subinhibitory concentrations efficacious in reducing free-floating C. acnes growth? (4) Is implant hydrogel coating (either alone or combined with tyrosol, rifampicin, or vancomycin) beneficial in reducing C. acnes biofilm formation? (5) Is the administration of soluble tyrosol an effective measure against C. acnes biofilm formation? METHODS: We assessed C. acnes planktonic growth and eradication by inspecting visually the results of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. We also evaluated macroscopically the presence of synergy among tyrosol and rifampicin by means of the MIC checkerboard testing. Thereafter, we addressed colorimetrically the efficacy of tyrosol-loaded Defensive Antibacterial Coating (DAC\uae) hydrogel against the C. acnes free-floating form by means of the XTT cell proliferation reduction assay. Then, we explored photometrically the effect of hydrogel and soluble tyrosol at reducing C. acnes biofilm formation on titanium alloy disks that simulated orthopaedic implants by using the minimum biofilm inhibition concentration assay. In particular, 16 disks were sequentially allocated to each of the following testing conditions: (1) hydrogel alone; (2) tyrosol-loaded hydrogel; (3) rifampicin-supplemented hydrogel; (4) vancomycin-loaded hydrogel; and (5) soluble tyrosol. Subsequently, implants were sonicated and cell viability was evaluated in terms of the XTT assay. RESULTS: Tyrosol was effective in inhibiting C. acnes planktonic (free-floating) growth demonstrating MIC values of 63 mM (9 mg/mL) and MBC values of 250 mM (35 mg/mL). Concerning synergy assessment, the checkerboard testing revealed additivity among tyrosol and rifampicin with a fractional inhibitory concentration index of 0.56. In addition, a hydrogel coating with tyrosol at the MIC showed no difference in the inhibition of free-floating C. Acnes form over control (median absorbance [MA] for tyrosol-supplemented hydrogel versus control groups were 0.21 [interquartile range {IQR}, 0.19-0.24] versus 0.26 [IQR, 0.23-0.31], p = 0.066). Furthermore, loaded hydrogel with tyrosol at 597 mg/mL (1 M) was no more effective than control in reducing C. acnes biofilm formation (MAs for tyrosol versus control were 0.12 [IQR, 0.11-0.13] versus 0.14 [IQR, 0.12-0.16], respectively; p = 0.076). This was also the case when we considered hydrogel in conjunction with vancomycin and rifampicin (MAs for vancomycin at 2% and 5% and rifampicin at 1% versus biofilm control were 0.139 [IQR, 0.133-0.143] and 0.141 [IQR, 0.133-0.143] and 0.135 [IQR, 0.128-0.146] versus 0.142 [IQR, 0.136-0.144], correspondingly). In contrast, soluble tyrosol at 597 mg/mL (1 M) inhibited biofilm formation compared to control (MAs for tyrosol and control groups were 0.11 [IQR, 0.09-0.13] versus 0.13 [IQR, 0.12-0.14], p = 0.007). CONCLUSIONS: Although the implant coating with hydrogel (either pure or supplemented with antimicrobial agents) did not diminish C. acnes biofilm development in vitro, soluble tyrosol at 597 mg/mL (1 M) exceeded the meaningful biofilm inhibition threshold of 80%. CLINICAL RELEVANCE: The results of the current preclinical investigation did not support the use of a fast, bioresorbable hydrogel as a coating method against C. acnes biofilms. Instead, direct local administration of soluble tyrosol at high concentrations should be further tested in future animal studies

Is sonication superior to dithiothreitol in diagnosis of periprosthetic joint infections? A meta-analysis

Purpose: Even though effective techniques in diagnosis of periprosthetic joint infections (PJIs) have been developed, the optimal modality has yet to be determined. The present meta-analysis aimed to compare the diagnostic accuracy of dithiothreitol (DTT) and sonication against the Musculoskeletal Infection Society criteria in patients undergoing revision joint surgery. Methods: We searched the PubMed, Scopus, and Central Cochrane register of controlled trials as well as gray literature until the 9th of November, 2021. We included articles considering the comparative diagnostic accuracy of sonication and DTT in adult patients having revision hip and knee arthroplasty for septic or aseptic reasons. We calculated pooled sensitivity, specificity, and diagnostic accuracy of the above diagnostic techniques against the Musculoskeletal Infection Society (MSIS) criteria and created receiver operating characteristics (ROC) curves to enable comparisons between each other. The quality of included papers was evaluated utilizing QUADAS-2 and QUADAS-C tools. Results: Data from five comparative studies totaling 726 implants were pooled together. The diagnostic accuracy of DTT and sonication were 86.7% (95% CI 82.7 to 90.1) and 83.9% (95% CI 79.7 to 87.5), respectively. Pooled sensitivity and specificity showed no statistically significant differences between DTT and sonication (0.7 [95% CI 0.62 to 0.77] vs 0.72 [95% CI 0.65 to 0.78], p = 0.14; and 0.99 [95% CI 0.97 to 1] vs 0.97 [95% CI 0.93 to 0.99], p = 5.5, respectively). Conclusions: This meta-analysis did not identify any clinically meaningful difference between the diagnostic potential of sonication and the chemical-based biofilm dislodgment methods. This finding remained robust after adjusting for the administration of antibiotics prophylaxis, implementation of the polymerase chain reaction of sonicated fluid, and study quality. © 2022, The Author(s) under exclusive licence to SICOT aisbl

Comparative pharmacodynamic interaction analysis between ciprofloxacin, moxifloxacin and levofloxacin and antifungal agents against Candida albicans and Aspergillus fumigatus

Objectives: Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Ciprofloxacin, a carboxyfluoroquinolone, was previously observed to demonstrate the pharmacodynamic interactions with antifungal agents by altering their growth inhibitory activity against Candida albicans and Aspergillus fumigatus. However, little is known about the interaction between other extended-spectrum fluoroquinolones, such as levofloxacin and moxifloxacin, and antifungal agents against C. albicans and A. fumigatus. Methods: Using a microdilution chequerboard technique, we employed isobolographic analysis adapted to incorporate a non-active agent in order to analyse the potential in vitro interaction between ciprofloxacin, levofloxacin or moxifloxacin and the following representative antifungal agents: amphotericin B, fluconazole or voriconazole and caspofungin. Results: Synergistic interactions [interaction indices (Iis) 0.69-0.83, P &lt; 0.05] were observed between amphotericin B (0.07-0.31 mg/L) and either ciprofloxacin (0.19-7.65 mg/L) or levofloxacin (0.41-32.88 mg/L) against C. albicans and A. fumigatus. Synergy (Iis 0.56-0.87, P &lt; 0.05) also was found between voriconazole (0.09-0.14 mg/L) and ciprofloxacin (0.22-11.41 mg/L) as well as between caspofungin (8.94-22.07 mg/L) and levofloxacin (0.14-5.17 mg/L) against A. fumigatus. Some antagonistic (Iis 1.16-1.29, P &lt; 0.05) interactions were observed between fluoroquinolones and fluconazole against C. albicans. In general, ciprofloxacin enhanced the activity of antifungal agents more than moxifloxacin and levofloxacin against both C. albicans and A. fumigatus. Conclusions: The knowledge of the pharmacodynamic interactions between fluoroquinolones and antifungal agents may guide selection and potentially improve the outcome of immunosuppressed patients with concurrent bacterial and fungal infections

Effect of ceftriaxone on the outcome of murine pyelonephritis caused by extended-spectrum-β-lactamase-producing Escherichia coli

Urinary tract infections (UTIs) due to extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae in children are becoming more frequent, and they are commonly treated initially with a second- or third-generation cephalosporin. We developed a murine model of ascending UTI caused by ESBL-producing Escherichia coli. Using this model, we investigated the renal bacterial burden, interleukin-6 (IL-6) expression, and histopathological alterations caused by ESBL- and non-ESBL-producing bacteria after 1, 2, or 6 days with or without ceftriaxone therapy. The renal bacterial burden, IL-6 concentration, and histological inflammatory lesions were not significantly different between mice infected with ESBL- and non-ESBL-producing bacteria without treatment at any of the time points examined. Following ceftriaxone administration, the bacterial burden was eliminated in the kidneys of mice infected with ESBL- and non-ESBL-producing bacteria on the 6th postinfection day. The histological analysis demonstrated that among mice treated with ceftriaxone, those infected with ESBL-producing bacteria had more profound renal alterations than those infected with non-ESBL-producing bacteria on the 6th day (P &amp;lt; 0.001). In comparison, microbiological outcomes did not differ significantly between mice infected with ESBL- and non-ESBL-producing bacteria at any of the time points examined. The effectiveness of ceftriaxone in mice with UTIs due to ESBL-producing E. coli may have therapeutic implications; it is, however, hampered by limited activity on the histopathological lesions, a finding that needs further investigation. Copyright © 2014 American Society for Microbiology. All Rights Reserved

Non-selective β-blockers decrease thrombotic events in patients with heart failure

Background: β-blockers are often prescribed to patients with heart failure (HF) without distinctions between types of β-blockers, although non-selective β-blockers may have a better effect on arterial thrombosis. The 2002 COMET study showed superiority of carvedilol (non-selective β-blocker) over metoprolol (selective β-blocker) on mortality and cardiovascular events in patients with HF, but this study was criticised for inappropriate formulation of metoprolol. Laboratory findings suggest a reduced prothrombotic response upon sympathetic activation by non-selective β-blockers. Objectives: To compare the incidence of thromboembolic events (acute coronary syndrome (ACS), stroke, or pulmonary embolism) between patients using selective and nonselective β-blockers. Methods: Data were obtained from the PHARMO Record Linkage System, a population-based registry of pharmacy records linked with hospital discharge records in The Netherlands. We identified a cohort of 24,398 patients admitted for HF in the period 1998-2007. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: The median follow up was 2.1 years (interquartile range: 0.8-4.0). In a 3-month time window after discharge, 6,864 patients were prescribed a selective and 2,356 patients a non-selective β-blocker. The incidence of thrombotic events during follow up was 3.3% for non-selective β-blockers and 4.6% for selective β-blockers, resulting in a crude HR of 0.69 (95%CI: 0.59-0.79). After adjustment for confounders, including age, sex, history of ACS, and other drug use, the difference remained significant (HR 0.75, 95%CI: 0.65-0.87). Conclusions: Non-selective β-blockers were associated with a lower risk of thromboembolic events compared to selective β-blockers in patients with HF. The hypothesis that non-selective β-blockers reduce the prothrombotic state in these patients should be explored further