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Rational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2-round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti-infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country-specific lists and could be used for the training and assessment of CPT.

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Antimicrobial resistance is a global health threat resulting in increased morbidity and mortality. This retrospective study aimed to estimate antimicrobial susceptibility and multidrug resistance prevalence of clinical isolates in a regional hospital in Northern Greece during the last 6 years by analyzing the annual reports of the Laboratory of Microbiology. A total of 12,274 strains of certain bacteria were isolated from both hospitalized and ambulatory patients from biological products, mainly urine (range 63-78% during the study period). E. coli was the most frequent pathogen found (37.4%). A significant increase in the number of the main pathogens causing hospital-acquired infections (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecium) was found in the time period of 2021-2023 compared to 2018-2020 (p < 0.0001). In total, 1767 multidrug-resistant bacterial strains were isolated, most of them belonging to Acinetobacter baumannii (36.4%) and Klebsiella pneumoniae (39.6%), and were located in the intensive care unit (ICU) (59.8%). Extensively drug resistance (XDR) and pan drug resistance (PDR) were significantly higher in 2021-2023 than in 2018-2020 (XDR: 641/1087 in 2021-2023 vs. 374/680 in 2018-2020 and PDR: 134/1087 in 2021-2023 vs. 25/680 in 2018-2020, p < 0.0001), resulting in an urgent need to establish certain strategies in order to eliminate this threatening condition.

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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease, associated with obesity, type 2 diabetes mellitus and dyslipidemia, which can lead to liver cirrhosis and hepatocellular carcinoma in some patients. Apart from lifestyle modifications, which are the cornerstone for its management, several drugs are under evaluation, including glucagon-like peptide-1 receptor agonists (GLP-R1RAs). In this review, we summarized major clinical data concerning the effects of GLP-1RAs on NAFLD, trying to highlight existing knowledge and to elucidate areas of uncertainty, thus providing clues to potential clinical implications and research. AREAS COVERED: Selected clinical studies on GLP-R1As in NAFLD are presented in this narrative review. EXPERT OPINION: There is evidence that treatment with GLP-R1As in NAFLD has beneficial effects on NAFLD, i.e. improvement in liver function tests and histological improvement in hepatic steatosis and inflammation, but not fibrosis. Further research is required toward the early use of GLP-R1Αs, i.e. in NAFLD patients without fibrosis to evaluate whether they may prevent the progression to fibrosis, or in patients with advanced disease in combination with other medications, which may have additive or even synergistic effects on NAFLD.

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The musculoskeletal system involves multiple tissues which are constantly exposed to being exposed to various biological and mechanical stimuli. As such, isolating and studying a particular system from a complex human clinical environment is not always a realistic expectation. On top of that, recruitment limitations, in addition to the nature of orthopaedic interventions and their associated cost, sometimes preclude consideration of human trials to answer a clinical question. Therefore, in this mini review, we sought to rationalize the rapid evolution of biomedical research at a basic scientific level and explain why the perception of orthopaedic conditions has fundamentally changed over the last decades. In more detail, we highlight that the number of orthopaedic in vitro publications has soared since 1990. Last but not least, we elaborated on the minimum requirements for conducting a scientifically sound infection-related laboratory experiment to offer valuable information to clinical practitioners. We also explained the rationale behind implementing molecular biology techniques, ex vivo experiments, and artificial intelligence in this type of laboratory research.

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BACKGROUND: Lifetime elongation of the silicone voice rubber prostheses by inhibition of biofilm formation is a primary objective in voice restoration of laryngectomized patients. This systematic review sought to explore the existing strategies in this direction. MATERIALS: We conducted a systematic search of both in vitro and in vivo literature published in PubMed, Scopus, and Cochrane Central Register of Controlled Trials, until December 31, 2022, for published and unpublished trials assessing the strategies for inhibiting biofilm formation on silicone rubber voice prostheses, and appraised quality assessment with the modified Consolidated Standards of Reporting Trials tool. We analyzed the infection prevention capacity of the included antibacterial and antifungal agents. RESULTS: The qualitative synthesis showed that both surface modification methods and prophylactic treatment of silicone rubber voice prostheses present adequate antibiofilm activity. Of note, the majority of the suggested prosthetic surfaces were not chronically exposed to both human fluids and biofilm-forming microorganisms. CONCLUSION: Various experimental methods provide promising antibiofilm activity and, thus, possible lifespan elongation of silicone rubber voice prostheses.

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Early failure of silicone voice prostheses resulting from fungal colonization and biofilm formation poses a major concern in modern ear nose throat surgery. Therefore, developing new infection prevention techniques to prolong those implants' survivorship is crucial. We designed an in vitro laboratory study to include nanomaterial-enhanced polymer coating with a plasma spraying technique against Candida albicans growth to address this issue. The anti-biofilm effects of high- and low-dose Al2O3 nanowire and TiO2 nanoparticle coatings were studied either alone or in conjunction with each other using checkerboard testing. It was demonstrated that both nanomaterials were capable of preventing fungal biofilm formation regardless of the anti-fungal agent concentration (median absorbance for high-dose Al2O3-enhanced polymer coating was 0.176 [IQR = 0.207] versus control absorbance of 0.805 [IQR = 0.381], p = 0.003 [98% biofilm reduction]; median absorbance for high-dose TiO2-enhanced polymer coating was 0.186 [IQR = 0.024] versus control absorbance of 0.766 [IQR = 0.458], p < 0.001 [93% biofilm reduction]). Furthermore, synergy was revealed when the Bliss model was applied. According to the findings of this work, it seems that simultaneous consideration of Al2O3 and TiO2 could further increase the existing antibiofilm potential of these nanomaterials and decrease the likelihood of localized toxicity.

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The aim of this work was to study age, sex, and BMI (Body Mass Index)-related differences in the development of anti-SARS-CoV-2-Spike IgG antibodies, after vaccination with the BNT162b2 COVID-19 vaccine, in health care workers of a General Hospital in a city in Northern Greece. Blood sampling was drawn two to four weeks following the second dose of the vaccine, and six months after the first blood sample collection. Measurement of serum IgG antibodies against the spike domain of SARS-CoV-2 was performed using the SARS-CoV-2 IgG II Quant assay. All participants had sufficient serum IgG titers in the first measurement. Women developed higher IgG titers than men. The IgG titers were inversely related to age in both sexes; there was also a small, insignificant tendency to be inversely related to BMI. Six months after the first measurement, the IgG titers decreased dramatically to values less than 5% of the initial. This decrease was observed in both men and women and was inversely related to age. Multivariate regression analysis showed that age and sex explained with statistical significance 9% of the variance in SARS-CoV-2 IgG titers in our study population; the role of BMI was limited and insignificant.

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PURPOSE: Periprosthetic joint infections induced by methicillin-resistant Staphylococcus aureus (MRSA) pose a major socioeconomic burden. Given the fact that MRSA carriers are at high risk for developing periprosthetic infections regardless of the administration of eradication treatment pre-operatively, the need for developing new prevention modalities is high. METHODS: The antibacterial and antibiofilm properties of vancomycin, Al2O3 nanowires, and TiO2 nanoparticles were evaluated in vitro using MIC and MBIC assays. MRSA biofilms were grown on titanium disks simulating orthopedic implants, and the infection prevention potential of vancomycin-, Al2O3 nanowire-, and TiO2 nanoparticle-supplemented Resomer® coating was evaluated against biofilm controls using the XTT reduction proliferation assay. RESULTS: Among the tested modalities, high- and low-dose vancomycin-loaded Resomer® coating yielded the most satisfactory metalwork protection against MRSA (median absorbance was 0.1705; [IQR = 0.1745] vs control absorbance 0.42 [IQR = 0.07]; p = 0.016; biofilm reduction was 100%; and 0.209 [IQR = 0.1295] vs control 0.42 [IQR = 0.07]; p < 0.001; biofilm reduction was 84%, respectively). On the other hand, polymer coating alone did not provide clinically meaningful biofilm growth prevention (median absorbance was 0.2585 [IQR = 0.1235] vs control 0.395 [IQR = 0.218]; p < 0.001; biofilm reduction was 62%). CONCLUSIONS: We advocate that apart from the well-established preventative measures for MRSA carriers, loading implants with bioresorbable Resomer® vancomycin-supplemented coating may decrease the incidence of early post-op surgical site infections with titanium implants. Of note, the payoff between localized toxicity and antibiofilm efficacy should be considered when loading polymers with highly concentrated antimicrobial agents.

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The relationship between race and biology is complex. In contemporary medical science, race is a social construct that is measured via self-identification of study participants. But even though race has no biological essence, it is often used as variable in medical guidelines (e.g., treatment recommendations specific for Black people with hypertension). Such recommendations are based on clinical trials in which there was a significant correlation between self-identified race and actual, but often unmeasured, health-related factors such as (pharmaco)genetics, diet, sun exposure, etc. Many teachers are insufficiently aware of this complexity. In their classes, they (unintentionally) portray self-reported race as having a biological essence. This may cause students to see people of shared race as biologically or genetically homogeneous, and believe that race-based recommendations are true for all individuals (rather than reflecting the average of a heterogeneous group). This medicalizes race and reinforces already existing healthcare disparities. Moreover, students may fail to learn that the relation between race and health is easily biased by factors such as socioeconomic status, racism, ancestry, and environment and that this limits the generalizability of race-based recommendations. We observed that the clinical case vignettes that we use in our teaching contain many stereotypes and biases, and do not generally reflect the diversity of actual patients. This guide, written by clinical pharmacology and therapeutics teachers, aims to help our colleagues and teachers in other health professions to reflect on and improve our teaching on race-based medical guidelines and to make our clinical case vignettes more inclusive and diverse.

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The European Open Platform for Prescribing Education (EurOP2E) seeks to improve and harmonize European clinical pharmacology and therapeutics (CPT) education by facilitating international collaboration and sharing problem-based, online, open educational resources. The COVID-19 pandemic forced teachers to switch to virtual modalities, highlighting the need for high-quality online teaching materials. The goal of this study was to establish the online problem-based teaching resources needed to sustain prescribing education during the pandemic and thereafter. A nominal group technique study was conducted with prescribing teachers from 15 European countries. Results were analyzed through thematic analysis. In four meetings, 20 teachers from 15 countries proposed and ranked 35 teaching materials. According to the participants, the most necessary problem-based-online teaching materials related to three overarching themes. Related to learning outcomes for CPT, participants proposed creating prescription scenarios, including materials focusing on background knowledge and resources on personalized medicine and topical/ethical issues such as the prescription's impact on planetary health. Second, related to teaching, they proposed online case discussions, gamification and decision support systems. Finally, in relation to faculty development, they recommend teacher courses, a repository of reusable exam questions and harmonized formularies. Future work will aim to collaboratively produce such materials.

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BACKGROUND AND STUDY AIMS: This cross-sectional study aimed to evaluate the association between hepatic steatosis and fibrosis indices and adherence to the Mediterranean diet (MD), physical activity (PA), and quality of life (QoL) in individuals unaware of the status of their liver. PATIENTS AND METHODS: Participants were asked to complete three questionnaires validated in Greek, namely: (1) the Chronic Liver Disease Questionnaire (CLDQ) for QoL assessment; (2) the semi-quantitative Food Frequency Questionnaire (FFQ), from which the MedDietScore was calculated; and (3) the International Physical Activity Questionnaire (IPAQ) for PA evaluation. Hepatic steatosis was evaluated using the Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), and Lipid Accumulation Product (LAP). Hepatic fibrosis was evaluated using the NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), and AST-to-platelet ratio index (APRI). RESULTS: This study recruited 200 participants (90% men) aged 36 ± 6 years. Hepatic steatosis indices were not associated with MedDietScore and QoL. In terms of PA, univariable analysis showed that higher values of hepatic steatosis indices were associated with less intense activity. This association remained significant only for HSI during multivariable analysis (moderate activity vs. low activity: beta: -2.0, 95% confidence interval (CI): -3.5, -0.37, p = 0.016; and high activity vs. low activity: beta: -3.3, 95% CI: -5.03, -1.60, p < 0.001), after controlling for age, waist circumference, and the presence of metabolic syndrome. When using hepatic fibrosis indices, none of the participants had high probability of advanced hepatic fibrosis or cirrhosis (F3-F4). Consequently, we were unable to extensively evaluate the association between hepatic fibrosis indices and lifestyle characteristics or QoL. CONCLUSION: We showed that HSI, but not other steatosis indices, remained robustly associated with PA after adjusting for potential confounders in a population unaware of the presence of fatty liver.

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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.

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Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder whose current rapidly expanding prevalence is causing it to develop into a major global health concern. NAFLD is closely linked to the modern, unhealthy lifestyle. The Western diet, characterized by excessive energy intake, frequent consumption of red meat, processed meat and foods, soft drinks, and sugar-sweetened beverages (SSBs), irregular meal distribution throughout the day, and unhealthy ways of cooking, predisposes to development of NAFLD. Low levels of physical activity and prolonged sedentary time are additional lifestyle risk factors for NAFLD. Given the present lack of effective pharmacological treatment, lifestyle modifications are regarded as the cornerstone of NAFLD management. Reducing daily calorie intake together with following the Mediterranean diet (MD) is an increasingly accepted approach. Furthermore, increasing the level of physical activity and limiting sedentary behavior are additional measures proposed to improve the outcomes of the disease. Apart from being affected by lifestyle, NAFLD may also affect patients' quality of life (QoL), mostly in the domain of physical function. In this regard, while the early and more benign form of the disease, i.e., simple hepatic steatosis, may not affect QoL, there is evidence, though conflicting, of the impact of nonalcoholic steatohepatitis (NASH) on this index, with, however, most studies showing that QoL is consistently affected in advanced disease, i.e., hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Considering all the above, appropriate management of lifestyle is likely to attenuate the severity of the disease and improve the QoL of NAFLD patients.

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INTRODUCTION: Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education. METHODS AND ANALYSIS: This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision. ETHICS AND DISSEMINATION: The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO-ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.

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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.

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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.

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BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM. METHODS: In this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6-18 months) the addition of a DPP-4i (n = 152) or a GLP-1 RA (n = 37) in patients with T2DM. RESULTS: Regarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p = 0.001), but not in the DPP-4i group (p = 0.25); the difference for group∗time interaction was significant (p = 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group∗time interaction. Indices of fibrosis were not essentially changed within or between groups. CONCLUSIONS: NAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials.

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BACKGROUND: Antibiotic management of low-virulent implant-associated infections induced by Cutibacterium acnes may be compromised by multi-drug resistance development, side effects, and increased cost. Therefore, we sought to assess the effects of shock wave therapy against the above pathogen using an in vitro model of infection. METHODS: We used a total of 120 roughened titanium alloy disks, simulating orthopedic biomaterials, to assess the results of radial extracorporeal shock wave therapy (rESWT) against C. acnes (ATCC 11827) biofilms relative to untreated control. In particular, we considered 1.6 to 2.5 Bar with a frequency ranging from 8-11 Hz and 95 to 143 impulses per disk to investigate the antibacterial effect of rESWT against C. acnes planktonic (free-floating) and biofilm forms. RESULTS: Planktonic bacteria load diminished by 54% compared to untreated control after a 1.8-bar setting with a frequency of 8 Hz and 95 impulses was applied (median absorbance (MA) for intervention vs. control groups was 0.9245 (IQR= 0.888 to 0.104) vs. 0.7705 (IQR = 0.712 to 0.864), respectively, p = 0.001). Likewise, a statistically significant reduction in the amount of biofilm relative to untreated control was documented when the above setting was considered (MA for treatment vs biofilm control groups was 0.244 (IQR= 0.215-0.282) and 0.298 (IQR = 0.247-0.307), respectively, p = 0.033). CONCLUSION: A 50% biofilm eradication was documented following application of low-pressure and low-frequency radial shock waves, so rESWT could be investigated as an adjuvant treatment to antibiotics, but it cannot be recommended as a standalone treatment against device-associated infections induced by C. ances.