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.

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. 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. Synergistic interactions [interaction indices (Iis) 0.69–0.83, P < 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 < 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 < 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. 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.

Background: Several pharmacological interventions are used for the management of adhesive capsulitis of the shoulder, although the optimal treatment has yet to be defined. Purpose: To conduct a network meta-analysis to compare the effects of different pharmacological interventions for adhesive capsulitis, administered either alone or after distension of the shoulder capsule. Study Design: Network meta-analysis. Methods: The authors searched Scopus, PubMed, and the Cochrane Central Register of Controlled Trials up to April 22, 2018, for completed studies. They enrolled trials that assessed the results of different pharmacological treatments for the primary management of adhesive capsulitis. The primary outcome was pain relief as measured by self-administered questionnaires. The secondary outcome included the assessment of composite instruments that evaluated, at a minimum, pain and function. The authors clinically interpreted the results after back-transforming the standardized mean differences into mean differences in simple instruments and assessed the quality of the source studies using the Cochrane “risk of bias” tool. Results: The authors considered 30 trials with a total of 2010 participants in this systematic review. For pain relief, there was a significant difference in favor of intra-articular corticosteroids and distension of the shoulder capsule with steroids as compared with control in the short term (mean difference in visual analog scale (VAS): –1.4 [95% CI, −2.5 to −0.4] and −1.7 [95% CI, −3.2 to −0.1], respectively). Furthermore, rotator-interval injections were found to be superior to placebo (mean difference in VAS: –7.2; 95% CI, −10.1 to −4.4), although the intervention was considered in only 1 trial. Finally, there was a statistically significant difference in favor of multiple-site corticosteroid injections compared to placebo in both the short- (mean difference in Shoulder Pain and Disability Index [SPADI]: −86.7; 95% CI, −133.6 to −40) and intermediate-term assessment (mean difference in SPADI: −102.9; 95% CI, −163.9 to −41.8). Conclusion: Intra-articular corticosteroid intervention, administered either alone or after distension of the shoulder capsule, provided clinically meaningful improvements in the short term. Likewise, rotator-interval corticosteroid injections yielded promising results in terms of pain relief. However, these short-term benefits of steroids dissipated over time. Multiple-site corticosteroid injections showed clinical advantage over placebo for short- and intermediate-term composite outcome assessments.

Patients suffering from invasive mycoses often receive concomitant antifungal therapy and antibacterial agents. Assessment of pharmacodynamic interactions between antifungal and antibacterial agents is complicated by the absence of a common antifungal end point for both agents. Ciprofloxacin has no intrinsic antifungal activity but may interact with antifungal agents, since it inhibits DNA gyrase (topoisomerase II), which is abundant in fungi. We therefore employed isobolographic analysis adapted to incorporate a nonactive agent in order to analyze the potential in vitro interaction between the fluoroquinolone ciprofloxacin and several representative antifungal agents against Candida albicans and Aspergillus fumigatus strains by using a microdilution checkerboard technique. In agreement with earlier in vitro studies, conventional fractional inhibitory concentration index analysis was unable to detect interactions between ciprofloxacin and antifungal agents. However, isobolographic analysis revealed significant pharmacodynamic interactions between antifungal agents and ciprofloxacin against C. albicans and A. fumigatus strains. Amphotericin B demonstrated concentration-dependent interactions for both species, with synergy (interaction indices, 0.14 to 0.81) observed at ciprofloxacin concentrations of <10.64 μg/ml. Synergy (interaction indices, 0.10 to 0.86) was also found for voriconazole and caspofungin against A. fumigatus . Isobolographic analysis may help to elucidate the pharmacodynamic interactions between antifungal and non-antifungal agents and to develop better management strategies against invasive candidiasis and aspergillosis.