Aims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low... Show moreAims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement.Methods and results An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination).Conclusion Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk. Show less
Background Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international... Show moreBackground Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international guidelines. We performed a nationwide study into the application of predictive mutation testing in GIST patients and its impact on targeted treatment decisions in clinical practice. Methods Real-world clinical and pathology information was obtained from GIST patients with initial diagnosis in 2017-2018 through database linkage between the Netherlands Cancer Registry and the nationwide Dutch Pathology Registry. Results Predictive mutation analysis was performed in 89% of the patients with high risk or metastatic disease. Molecular testing rates were higher for patients treated in expertise centers (96%) compared to non-expertise centers (75%, P < 0.01). Imatinib therapy was applied in 81% of the patients with high risk or metastatic disease without patient's refusal or adverse characteristics, e.g., comorbidities or resistance mutations. Mutation analysis that was performed in 97% of these imatinib-treated cases, did not guarantee mutation-tailored treatment: 2% of these patients had the PDGFRA p.D842V resistance mutation and 7% initiated imatinib therapy at the normal instead of high dose despite of having a KIT exon 9 mutation. Conclusion In conclusion, nationwide real-world data show that over 81% of the eligible high risk or metastatic disease patients receive targeted therapy, which was tailored to the mutation status as recommended in guidelines in 88% of cases. Therefore, still 27% of these GIST patients misses out on mutation-tailored treatment. The reasons for suboptimal uptake of testing and treatment require further study. Show less
Gadjradj, P.S.; Jalimsing, M.; Jalimsing, S.; Voigt, I. 2021
Background and Objective According to the International Committee of Medical Journal Editors (ICMJE), authorship should be offered based on fulfilling four criteria. Honorary authorship (HA) is a... Show moreBackground and Objective According to the International Committee of Medical Journal Editors (ICMJE), authorship should be offered based on fulfilling four criteria. Honorary authorship (HA) is a term used for authors enlisted who did not fulfill these criteria. The objective of this study was to determine the proportion of HA in the field of oral and maxillofacial surgery. Material and Methods In 2020, a twenty-two question survey was sent to corresponding authors of four high-impact journals in the field of oral and maxillofacial surgery. The survey covered (1) demographics, (2) awareness of authorship guidelines and decision-making of authorship, and (3) honorary authorship. Results The response rate was 24.8%. Of the respondents, 81.1% was aware of the issue of guidelines on authorship, while 56.3% was aware of the issue of HA. Yet, 15.5% of the respondents felt that one or more of their co-authors did not deserve authorship based on the ICMJE-guidelines. Conclusion Based on the estimated proportions of HA, attempts should be made by universities, medical journals and individual researchers to further reduce authorship misuse. Show less
Baumgartner, H.; Backer, J. de; Babu-Narayan, S.V.; Budts, W.; Chessa, M.; Diller, G.P.; ... ; Zeppenfeld, K. 2021
Elevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia... Show moreElevated low-density lipoprotein cholesterol (LDL-C) is a principally modifiable cause of atherosclerotic cardiovascular disease; accordingly, recent European and US multisociety dyslipidaemia guidelines emphasise the importance of lowering LDL-C to reduce cardiovascular risk. This review provides perspectives on established and emerging agents that reduce LDL-C to help providers synthesize the abundance of new evidence related to prevention of cardiovascular disease. We provide hypothetical cases of patients with different cardiovascular risk factors and medical histories to illustrate application of current lipid-lowering guidelines in various clinical settings. As a core focus of preventive therapy, both European and US lipid management guidelines emphasise the importance of identifying patients at very high cardiovascular risk and treating to achieve LDL-C levels as low as possible, with European guidelines setting a goal of <1.4 mmol/L (<55 mg/dL) in patients with very high-risk cardiovascular disease. The proprotein convertase subtilisin/kexin type 9 inhibitors are now included in the guidelines and may fulfil an important unmet need for very high-risk patients who are not able to achieve LDL-C goals with conventional agents. The recently approved bempedoic acid and other promising agents under development will add to the armamentarium of lipid-lowering drugs available for clinicians to help patients meet their treatment goals. Show less
Scope: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized... Show moreScope: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19).Methods: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology.Questions addressed by the guideline and Recommendations: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Background and aims: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. Aim of... Show moreBackground and aims: Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. Aim of this survey was to evaluate the compliance to ESC/EAS guidelines during the management of ACS patients and the effectiveness of secondary prevention in seven European countries.Methods: By means of an online questionnaire, data on 2775 ACS patients (either acute case or follow-up patients) were collected, including data on lipid profile, medications, follow-up visit planning, screening for familial hypercholesterolemia.Results: Lipid profiles were obtained for 91% of ACS patients in the acute phase, mostly within the first day of hospitalization (73%). During hospitalization, 93% of the patients received a lipid-lowering treatment; at discharge, only 66% of the patients received a high intensity statin therapy. At the first follow-up, most of the patients (77.6%) had LDL-C 70 mg/dL; among them, 41% had no change in their lipid-lowering therapies. Similar data were obtained during the second follow-up visit. The analysis of a subgroup of patients with at least 2 follow-up visits and known LDL-C levels showed that the percentage of patients at goal increased from 9% to 32%, and patients with LDL-C <100 mg/dL raised from 23% to 72%. Among acute cases, 44 were admitted with a diagnosis of familial hypercholesterolemia (FH); only 18% of the remaining patients were screened for FH.Conclusions: Contemporary lipid management of very high CV risk patients is sub-optimal despite available treatments. Greater efforts are warranted to optimize cardiovascular prevention.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Post-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath... Show morePost-acute coronary syndrome (ACS) patients are at very high risk for recurrent events and mortality, despite the availability of effective pharmacological approaches. In 2018, the ACS EuroPath Survey, performed in collaboration with 555 European cardiologists, identified a sub-optimal LDL-C management in post-ACS patients.Based on these premises, the ACS EuroPath II project led to the development of a self-assessment tool to improve lipid management in these very high risk patients, taking into consideration the new 2019 ESC/EAS guidelines. This tool is built in 3 sections. The first is a questionnaire to assess the lipid management practice from the acute phase up to 12 months of follow-up. The main topics covered in this section relate to 1) acute phase (lipid management of ACS patients during hospitalization; 2) discharge (lipid management at discharge, with focus on follow-up plan); 3) follow-up (lipid management at the time of first and subsequent follow-ups); 4) referral pathway for definitive lipid management care of post-ACS patients; 5) evaluation of the achieved goal at 6 months to 1 year and key implications. The second section is a brief report to position the results against other European Union clinical practice and European guidelines. The last section allows the physician to evaluate and consider the implementation of one or more strategies, successfully developed in leading European centers, in order to optimize their own clinical practice.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Show less
Willmann, R.; Lee, J.; Turner, C.; Nagaraju, K.; Aartsma-Rus, A.; Wells, D.J.; ... ; Luca, A. de 2020
Clinical trials for rare neuromuscular diseases imply, among other investments, a high emotional burden for the whole disease community. Translation of data from preclinical studies to justify any... Show moreClinical trials for rare neuromuscular diseases imply, among other investments, a high emotional burden for the whole disease community. Translation of data from preclinical studies to justify any clinical trial must be carefully pondered in order to minimize the risk of clinical trial withdrawal or failure. A rigorous distinction between proofof-concept and preclinical efficacy studies using animal models is key to support the rationale of a clinical trial involving patients. This Review evaluates the experience accumulated by the TREAT-NMD Advisory Committee for Therapeutics, which provides detailed constructive feedback on clinical proposals for neuromuscular diseases submitted by researchers in both academia and industry, and emphasizes that a timely critical review of preclinical efficacy data from animal models, including biomarkers for specific diseases, combined with adherence to existing guidelines and standard protocols, can significantly help to de-risk clinical programs and prevent disappointments and costly engagement. Show less
Investigations and treatment options of recurrent pregnancy loss (RPL) differ internationally. This manuscript reviews the similarities and differences between international guidelines. The... Show moreInvestigations and treatment options of recurrent pregnancy loss (RPL) differ internationally. This manuscript reviews the similarities and differences between international guidelines. The European Society of Human Reproduction and Embryology (ESHRE) guideline (2017), the American Society for Reproductive Medicine (ASRM) Committee Opinion (2013) and the Royal College of Obstetricians and Gynaecologists (RCOG) guideline (2011) were appraised using the AGREE II criteria. The guidelines were checked for definitions, risk factors, investigations and therapeutic options. The guidelines agreed on acquired thrombophilia analysis. All guidelines agreed on a regimen for the treatment of antiphospholipid antibody syndrome consisting of aspirin and heparin, but only the ESHRE guideline specified the order of starting these medications. Treatment of thrombophilia and uterine anomalies was advised against; all guidelines recommended supportive care for unexplained RPL. The guidelines did not agree on the definition of RPL and differed in investigations regarding lifestyle, karyotype analysis of parents and/or pregnancy tissue, and the diagnostic tool for uterine anomalies. All three guidelines indicate an association between lifestyle and RPL; the ESHRE recommends health behaviour changes. Couples suffering from RPL should be informed about possible investigations and treatment options, and whether those are evidence-based. It is important for clinicians to realize that the guidelines differ internationally. Show less
Broeck, T. van den; Bergh, R.C.N. van den; Arfi, N.; Gross, T.; Moris, L.; Briers, E.; ... ; Mottet, N. 2019
Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the... Show moreFibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients' advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally. Show less
