Search

Background Exercise referral schemes (ERS) are an effective strategy for increasing physical activity (PA) in older adults. Behavioural self-management strategies (SMS) may augment the maintenance of PA and associated benefits in this population, resulting in preservation of the functional capacity and prevention of disability over the long-term. Aim The primary aim was to investigate the long-term (22-months) effects of ERS enhanced with SMS on functional capacity assessed by the Short Physical Performance Battery (SPPB) compared to ERS (primary comparison) and a control condition (CTRL). Secondarily, between-group effects after 4 and 16 months on the SPPB and self-reported disability outcomes were investigated. Methods 1360 physically inactive community-dwelling older adults ≥65 years from four European countries were randomized into (i) 16 weeks ERS enhanced with SMS (ERS-SMS), (ii) ERS alone and (iii) CTRL. In addition to SPPB, self-reported function and disability were assessed by the short-form late life function and disability index and with a six-item activity of daily living questionnaire. Results No long-term effects were found for the SPPB-score in ERS-SMS vs ERS (0.21 point, 95% CI [−0.04, 0.46]). Significant group × time effects were observed for the SPPB-score after 4 months in favour of ERS-SMS over CTRL (0.51 point, 95% CI [0.29, 0.73]) and ERS (0.46 point, 95% CI [0.24, 0.68]). Conclusion The study did demonstrate differences, in favour of ERS + SMS, but on SPPB these were small, and not sustained over time. The additional effect of SMS was inconsistent and uncertain. [ABSTRACT FROM AUTHOR]

We aimed to synthesise information related to the incidence of depression and depressive symptoms (DDS) in a community‐dwelling older adult population at a global level. In this systematic review, we included articles with a cohort study design that evaluated the incidence of depression or depressive symptoms in older adults aged 60 years or more in a community‐dwelling environment. Six databases were used: Web of Science, PubMed, Scopus, LILACS, SciELO, and Cochrane, and the entire selection process was independently performed by peers. We divided the included articles into subgroups according to the DDS assessment instrument: (i) Geriatric Depression Scale; (ii) Center for Epidemiologic Studies Depression Scale; (iii) miscellaneous scales; and (iv) diagnostic interviews. Each cumulative incidence value obtained per item was adjusted for a 1‐year follow‐up period, which generated an annual cumulative incidence (AcI). From 46 articles, 42 used scales to evaluate the depressive variable, with an AcI estimate of around 4.5%. The articles that assessed depression categorically observed a variation in AcI between 0.2% and 7.0%. Among all the materials included, the group that used the Geriatric Depression Scale observed the lowest and the highest AcI, 1.3% and 26.6% respectively. Most of the productions were from countries in the Asian continent (52.2%), followed by Europe (30.4%), the Americas (13%), and Oceania (4.4%). Despite the variation of AcI, we found a frequent occurrence of DDS in older adults in the community‐dwelling environment, which highlights the need for preventive actions and better‐targeted early care, especially in terms of primary health care. [ABSTRACT FROM AUTHOR]

Multimorbidity, the concurrence of several chronic conditions, is a rising concern that increases the years lived with disability and poses a burden on healthcare systems. Little is known on how it interacts with socioeconomic deprivation, previously associated with poor health-related outcomes. We aimed to characterize the association between multimorbidity and these outcomes and how this relationship may change with socioeconomic development of regions. 55,915 individuals interviewed in 2017 were drawn from the Survey of Health, Ageing and Retirement in Europe, a population-based study. A Latent Class Analysis was conducted to fit multimorbidity patterns based on 16 self-reported conditions. Physical limitation, quality-of-life and healthcare utilization outcomes were regressed on those patterns adjusting for additional covariates. Those analyses were then extended to assess whether such associations varied with the region socioeconomic status. We identified six different patterns, labelled according to their more predominant chronic conditions. After the "healthy" class, the "metabolic" and the "osteoarticular" classes had the best outcomes involving limitations and the lowest healthcare utilization. The "neuro-affective-ulcer" and the "several conditions" classes yielded the highest probabilities of physical limitation, whereas the "cardiovascular" group had the highest probability of hospitalization. The association of multimorbidity over physical limitations appeared to be stronger when living in a deprived region, especially for metabolic and osteoarticular conditions, whereas no major effect differences were found for healthcare use. Multimorbidity groups do differentiate in terms of limitation and healthcare utilization. Such differences are exacerbated with socioeconomic inequities between regions even within Europe. [ABSTRACT FROM AUTHOR]

Purpose: A poor appetite affects up to 27% of community-dwelling older adults in Europe and is an early predictor of malnutrition. Little is known about the factors associated with poor appetite. The present study, therefore, aims to characterise older adults with poor appetite. Methods: As part of the European JPI project APPETITE, data from 850 participants, aged ≥ 70 years of the Longitudinal Ageing Study Amsterdam (LASA) from 2015/16 were analysed. Appetite during the last week was assessed with a five-point scale and dichotomised into "normal" and "poor". Binary logistic regression was used to examine associations between 25 characteristics from 5 domains—physiological, emotional, cognitive, social, and lifestyle—and appetite. First, domain-specific models were calculated using stepwise backward selection. Second, all variables contributing to poor appetite were combined in a multi-domain model. Results: The prevalence of self-reported poor appetite was 15.6%. Fourteen parameters from all five single-domain models contributed to poor appetite and were entered into the multi-domain model. Here, female sex (total prevalence: 56.1%, odds ratio: 1.95 [95% confidence interval 1.10–3.44]), self-reported chewing problems (2.4%, 5.69 [1.88–17.20]), any unintended weight loss in the last 6 months (6.7%, 3.07 [1.36–6.94]), polypharmacy defined as ≥ 5 medications in the past 2 weeks (38.4%, 1.87 [1.04–3.39]), and depressive symptoms (Centre for Epidemiologic Studies Depression Scale without appetite item) (1.12 [1.04–1.21]) were associated with an increased likelihood of having poor appetite. Conclusion: According to this analysis, older people with the characteristics described above are more likely to have a poor appetite. [ABSTRACT FROM AUTHOR]

Objectives: Multinational prevalence data on sarcopenia among generally healthy older adults is limited. The aim of the study was to assess prevalence of sarcopenia in the DO-HEALTH European trial based on twelve current sarcopenia definitions. Setting and Participants: This is an analysis of the DO-HEALTH study including 1495 of 2157 community-dwelling participants age 70+ years from Germany, France, Portugal, and Switzerland with complete measurements of the sarcopenia toolbox including muscle mass by DXA, grip strength, and gait speed. Measurements: The twelve sarcopenia definitions applied were Asian Working Group on Sarcopenia (AWGS1), AWGS2, Baumgartner, Delmonico, European Working Group on Sarcopenia in Older People (EWGSOP1), EWGSOP2, EWGSOP2-lower extremities, Foundation for the National Institutes of Health (FNIH1), FNIH2, International Working Group on Sarcopenia in Older People (IWGS), Morley, and Sarcopenia Definitions and Outcomes Consortium (SDOC). Results: Mean age was 74.9 years (SD 4.4); 63.3% were women. Sarcopenia prevalence ranged between 0.7% using the EWGSOP2 or AWGS2 definition, up to 16.8% using the Delmonico definition. Overall, most sarcopenia definitions, including Delmonico (16.8%), Baumgartner (12.8%), FNIH1(10.5%), IWGS (3.6%), EWGSOP1 (3.4%), SDOC (2.0%), Morley (1.3%), and AWGS1 (1.1%) tended to be higher than the prevalence based on EWGSOP2 (0.7%). In contrast, the definitions AWGS2 (0.7%), EWGSOP2-LE (1.1%), FNIH2 (1.0%) — all based on muscle mass and muscle strength — showed similar lower prevalence as EWGSOP2 (0.7%). Moreover, most sarcopenia definitions did not overlap on identifying sarcopenia on an individual participant-level. Conclusion: In this multinational European trial of community-dwelling older adults we found major discordances of sarcopenia prevalence both on a population- and on a participant- level between various sarcopenia definitions. Our findings suggest that the concept of sarcopenia may need to be rethought to reliably and validly identify people with impaired muscle health. [ABSTRACT FROM AUTHOR]

Copyright of Revista Portuguesa de Enfermagem de Reabilitação is the property of Associacao Portuguesa dos Enfermeiros de Reabilitacao (APER) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Tricuspid valve transcatheter edge-to-edge repair has emerged as a valuable treatment option for patients with severe tricuspid regurgitation (TR)., Objectives: This study aims to investigate the safety and effectiveness of the PASCAL transcatheter valve repair system in treating severe TR in a real-world patient population., Methods: The PASTE (PASCAL for Tricuspid Regurgitation-a European registry) study is an investigator-initiated, multicenter, retrospective, and prospective observational cohort analysis conducted across 16 European heart valve centers including consecutive patients treated with the PASCAL transcatheter valve repair system from February 2019 to November 2023. Echocardiographic assessments were performed at baseline, discharge, and follow-up, and were subjected to centralized analysis., Results: The study included 1,059 high-risk patients (mean age 79 ± 9 years; 53% female; TRI-SCORE risk 23% ± 18%; 87% NYHA functional class III/IV) with multiple comorbidities. Severe or higher graded TR was observed in 96% of patients. Intraprocedural success according to Tricuspid Valve Academic Research Consortium criteria was achieved in 85%, and TR reduced to ≤moderate in 87%. Independent predictors for a postprocedure residual TR of >moderate were coaptation gaps ≥8 mm (OR: 1.67; 95% CI: 1.03-2.72; P = 0.038), tenting height ≥10 mm (OR: 2.18; CI: 1.30-3.65; P = 0.003), the presence of a transvalvular lead (OR: 1.91; 95% CI: 1.19-3.05; P = 0.007), right ventricular dilatation >42 mm (OR: 3.35; 95% CI: 1.37-9.1; P = 0.009) and massive/torrential TR at baseline (OR: 4.59; 95% CI: 2.35-8.96; P < 0.001). At 1 year, 83% of patients showed ≤moderate TR. Significant clinical improvements included enhanced NYHA functional class (66% class I/II vs 17% at baseline; P < 0.001). Patients treated with the first-generation PASCAL system (n = 570) and with the new PASCAL Precision system (n = 489) had similar clinical profiles and TR severity at baseline. However, the Precision cohort showed greater TR reduction to trace/mild (63% vs 49%; P < 0.001), shorter procedure times (median 93 minutes [Q1-Q3: 69-130 minutes] vs 120 minutes [Q1-Q3: 82-165 minutes]; P < 0.001), and higher clinical success rates according to the Tricuspid Valve Academic Research Consortium at 30 days and 1 year (87% vs 81% [P = 0.021] and 56% vs 50% [P = 0.044], respectively). Higher center experience (≥21 patients/year) resulted in higher intraprocedural and clinical success., Conclusions: The PASCAL system effectively treats severe TR in high-risk patients, offering sustained TR reduction and significant clinical improvements at 1-year follow-up. (PASCAL for Tricuspid Regurgitation-a European registry [PASTE]; NCT05328284)., Competing Interests: Funding Support and Author Disclosures Dr Wild has received speaker fees from Abbott Vascular and Edwards Lifesciences; and has received honoraria for consultancy from IPPMed. Dr Stolz has received speaker honoraria from Edwards Lifesciences. Dr Praz has received travel expenses from Abbott Vascular, Polares Medical, and Edwards Lifesciences. Dr Lüdike has received speaker fees from Edwards Lifesciences. Dr Rassaf has received speaker fees from AstraZeneca, Daiichi-Sankyo, Bayer, Novartis, and Abiomed outside the submitted work. Dr Lurz has received grants from Abbott Vascular, Edwards Lifesciences, and ReCor Medical. Dr Stocker has received speaker honoraria from Edwards Lifesciences; and has served as a consultant for Occlutech International. Dr Kalbacher has received personal fees from Abbott Vascular, Edwards Lifesciences, Medtronic Inc, and Pi-Cardia Ltd. Dr Westermann has received honoraria from Abiomed, Medtronic, and Edwards Lifesciences. Dr Hausleiter has received research support and speaker honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. All rights reserved.)

Background: Seasonal influenza vaccination coverage data for adults with chronic medical conditions are very scarce. We aimed to investigate the influenza vaccination rates and explore the common social determinants associated with vaccination in Europe across two influenza seasons., Methods: This cross-sectional study used data from the European SHARE survey for the 2019-2020 and 2021-2022 influenza seasons. Participants over 50 diagnosed with diabetes were included, and weighted influenza vaccination rates for both seasons were calculated. Multivariable analyses were used to examine the relationships between vaccination coverage and demographic, physical, social, and healthcare factors over the two seasons., Results: The weighted seasonal influenza vaccination coverage rate was significantly higher in the 2021-2022 season (54 %) than in the 2019-2020 season (46 %) among people over 50 with diabetes. Factors simultaneously and positively associated with influenza vaccination in both seasons included being aged 65 or older; residing in Western, Northern, or Southern Europe; satisfaction with basic health insurance; having supplementary health insurance; and frequent medical consultations., Conclusions: Despite the increase, the average European influenza vaccination level remains below the EU target of 75 %. This study fills an important data gap for the ECDC by providing information on influenza vaccination coverage rates among people over 50 with diabetes. The findings highlight the crucial role of a robust social and healthcare system in promoting vaccination. To improve vaccination rates, the ECDC-funded VENICE network should enhance vaccination knowledge, address socioeconomic disparities by strengthening local programs and funding, and collaborate with various stakeholders to develop regional strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Our study explores the utilization of objective tools for preoperative assessment of elderly patients by Emergency General Surgeons (EGS)., Methods: A descriptive cross-sectional survey was conducted via the European Society for Trauma and Emergency Surgery (ESTES) Research Committee. EGS were invited through the ESTES members' mailing list and social media platforms. The survey included two sections: (1) clinical scenarios involving elderly patients with varying chronic conditions, and (2) participant characteristics. Data collection lasted 12 weeks, with reminders sent every 4 weeks. Statistical analyses were performed using Microsoft Excel and EasyMedStat., Results: One hundred and seven surgeons responded to the survey. Median respondent age was 41 years, with a male prevalence (72.9%). Most participants were from Europe (85%). Key-findings included that 62.6% reported using one or more risk assessment tools (RATs), while 35.5% used one or more frailty scores. Additionally, 4.7% were unaware of any RATs, and 35.5% were unaware of any frailty scores. Decision-making strategies leveraging personal experience with minimal impact from RATs predominated., Conclusions: Preoperative risk assessment tool and frailty score use for elderly patients requiring emergency surgery remains limited among ESTES surgeons. Our study highlights the need for focused education and tool workflow integration to improve risk stratification, decision-making and outcomes. Institutional approaches coupled with targeted educational interventions using implementation science principles are recommended to bridge this knowledge-to-action gap. Future research should focus on developing comprehensive, user-friendly tools and evaluating their impact on patient-centered outcomes., Competing Interests: Declarations. Competing interests: Gary Alan Bass is the ESTES Chair of Research and is a Section Editor for EJTES. All other authors declare no competing interests. Lewis J. Kaplan is a past-President of the Society of Critical Care Medicine (2020-2021), is an Associate Editor for Critical Care Explorations, and serves on the editorial board of Critical Care Medicine. As an employee of the Veterans Health Administration, Dr. Kaplan’s opinions do not reflect the opinions or policies of the Veterans Health Administration or the United States Federal government., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: In 2023, the European Society of Intensive Care Medicine (ESICM) recommended updated criteria for acute respiratory distress syndrome (ARDS). In 2024, Matthay et al. updated the global ARDS definition in AJRCCM, titled "A New Global Definition of Acute Respiratory Distress Syndrome." However, the impact of this new definition on ARDS treatments is currently unknown., Objective: This study aims to determine the effect of the new ARDS definition on patients with hypoxemic respiratory failure and study the heterogeneity of patients in the new definition to guide treatment., Methods: Clinical consultation data from the Medical Information Mart for Intensive Care IV database were extracted using Structured Query Language based on the PostgreSQL tool (version 10.0). Data were analyzed using Python (version 3.9) and the deep learning framework Pytorch. Kaplan-Meier survival analysis was used to compare survival between the old and new definitions. A hierarchical clustering approach was applied to identify potential ARDS clinical subtypes., Results: The new definition diagnosed ARDS earlier and included individuals with lower mortality rates compared with the Berlin definition. Patients meeting the new definition but not the Berlin criteria exhibited a favorable response to non-invasive ventilation strategies (p = 0.009). The XGBoost classifier, trained to predict subphenotypes, achieved an AUC of 0.88 ± 0.02 on the training set. Additionally, mortality was significantly associated with patients with hypoxemia compared with survivors, particularly regarding respiratory parameters. Easily accessible metrics, such as respiratory rate and urea nitrogen (BUN), can help diagnose ARDS in high-risk populations in resource-limited settings., Conclusions: The new ARDS definition offers advantages in earlier detection, more accurate grading, and more precise diagnosis in resource-limited settings compared with the Berlin definition. This study also established a robust prediction model for early ARDS identification, improving the patient prognosis and reducing the mortality rate., Competing Interests: Declarations. Ethics approval and consent to participate: The Medical Information Mart for Intensive Care IV (MIMIC-IV) database (v2.2) provides publicly available data for this study, which means that obtaining informed consent from participants or ethical approval from an institutional review board is not necessary. Ethical approval for the use of the MIMIC-IV database was obtained from the Institutional Review Board and the Massachusetts Institute of Technology. It is important to note that MIMIC-IV does not contain personally identifiable health information, thereby qualifying for a waiver of informed consent. The Medical Ethics Committee of the Second Affiliated Hospital of Fujian Medical University (Approval No. IRB2024-050) approved the research. Consent for publication: Informed consent was obtained from all subjects involved in the study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: The aetiology of pancreatic cancer is complex, and there is limited research on its incidence. We aimed to investigate the incidence trends of pancreatic cancer in 43 countries and predict trends up to 2030., Methods: The annual incidence of pancreatic cancer was obtained from the Cancer Incidence in Five Continents database, which comprises 108 cancer registries from 43 countries. Based on available data, we calculated age-standardized incidence rates (ASRs) per 100 000 people for 1988-2012. A Bayesian age-period-cohort model was used to predict the number of new cases and incidence rates up to 2030., Results: From 1988 to 2012, the global incidence rate of pancreatic cancer showed a continuously increasing trend, with the ASR increasing from 5.89 in 1988 to 6.78 in 2012, representing an overall average annual percentage change of 8.45%. This increasing trend is expected to persist in most selected countries, whereas a few countries are projected to exhibit a declining trend by 2030., Conclusion: It appears that the future global incidence of pancreatic cancer is on the rise, but the rate of increase varies among different countries, with some showing a declining trend., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Despite the high global prevalence, burden, and direct and indicated costs, migraines are often under-diagnosed and undertreated. Understanding the prevalence of migraine and unmet needs is crucial for improving diagnosis and treatment across Europe (EU) countries; however, real-world studies are limited., Methods: This retrospective cross-sectional survey utilized weighted patient-reported data from the 2020 National Health and Wellness Survey (NHWS) in five EU (5EU) countries (France, Germany, United Kingdom [UK], Italy, and Spain). The survey included adults aged ≥ 18 years who self-reported experiencing migraines in the past 12 months and had a physician's diagnosis. The survey assessed migraine prevalence by age and sex. Other measures included migraine characteristics, disability assessment, migraine frequency (monthly migraine days [MMDs] and monthly headache days [MHDs], menstrually-related migraine, treatment patterns, and provider characteristics., Results: The study included 7,311 respondents with diagnosed migraines, representing an estimated 30.5 million adults with a weighted prevalence of 11.5% in the 5EU. Spain had the highest prevalence (14.0%), followed by Italy, France, UK, and Germany. Migraine prevalence was highest in the age group of 30-39 years, and females had nearly twice the prevalence compared to males. About 56% of respondents reported disability due to migraines, with highest percentage reported in Germany (66.0%). About 46% of female respondents reported experiencing menstrually-related migraines. One-fourth of the study respondents reported > 4 MMDs and 56.2% reported > 4 MHD. Current treatment patterns revealed that 79.7% of respondents were receiving some form of migraine treatment, with non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, and triptans being the most commonly reported prescription medications. Primary care physicians (PCPs) were the most common providers diagnosing migraines, followed by neurologists., Conclusions: In the 5EU, one-fourth of diagnosed respondents reported > 4 MMDs, and 56.2% reported > 4 MHDs. Nearly half of females experienced menstrually-related migraines. Although most patients reported taking medication for migraine, severe disability and medication overuse were observed. PCPs were the main treatment providers, highlighting the need for improved expertise and referrals to specialists. Further research is required for a better understanding of the disparities between migraine frequency and treatment approaches., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol and questionnaire for the NHWS were reviewed by the Pearl Institutional Review Board and were granted an exemption from review. Potential respondents were invited to complete the survey via an email invitation. Respondents who clicked the email link from their invitation were then directed to an informed consent statement and, if they provided consent, were provided screening questions to assess eligibility. Consent for publication: Not applicable. Competing interests: JB, ARM, AJ, and KHB are employees of Pfizer, Inc. SD and NS are employees of Oracle Life Sciences, which was a paid consultant to Pfizer to conduct the study and to develop the manuscript. ARM was an employee of Oracle Life Sciences at the time of this study. AG reports financial support for ad boards, consulting and speaker honoraria from: Grünenthal, Mundipharma, Abbvie/Allergan, Lilly, Teva, Amgen, Novartis, Hormosan, Stada, Lundbeck, Pfizer, Hexal, Esanumperfood, Medscape, streamed up, Ärztekammer Nordrhein, Ärztekammer Westfalen Lippe, DGS, Regionalbeauftragte der DMKG. GC has received honoraria for participation in clinical trials and contribution to advisory boards or presentations from TEVA, Biohaven, Eli Lilly, Abbvie, and Pfizer. He serves as an Associate Editor for Cephalalgia, BMC Neurology – Pain section, Frontiers in Neurology – Neurotechnology section, Frontiers in Human Neuroscience – Brain Imaging and Stimulation section, and on the Advisory Board of The Journal of Headache and Pain., (© 2024. The Author(s).)

Background/Objectives: The global population is undergoing a significant demographic shift characterised by an increasing proportion of older individuals. Healthy aging has become a priority for personal well-being and sustainable healthcare systems, with nutrition playing a pivotal role. However, the rise in non-communicable diseases (NCDs), malnutrition, and a shift in eating behaviour underscore the need for tailored, effective nutrition communication strategies. This research is intended to provide the basic data needed to support the development of tailored nutritional communication strategies and practices. Methods: To investigate these aspects, a cross-national survey about nutrition and nutrition communication was conducted within the framework of the Innovative Training Network SmartAge, focusing on older adults aged 60 years and above in Germany, Switzerland, Spain, and France (each 25%; N = 1000 persons). This paper specifically focuses on the development, methodology, and discussion of the survey and aims to investigate the characteristics of the sample in relation to their dietary patterns and food choices within the European context. Results: The analysis identified significant associations between various plant- and animal-based food items and the variables gender, age group, and country. Spanish participants showed a dietary pattern towards the Mediterranean Diet, while German participants showed tendencies towards the Western Diet. Furthermore, the findings revealed that protein-rich foods such as meat, fish, nuts and seeds, legumes, and (whole) grains were infrequently consumed, particularly among German and Swiss participants. Conclusions: This study highlights the need to promote adequate protein intake among older adults, emphasising diverse sources like legumes, nuts and seeds, (whole) grains, and lean meats to support healthy aging. For the development of future nutrition communication strategies, the influence of the specific social, cultural, and traditional factors needs to be considered.

Introduction: Current care plans for stroke survivors typically focus on acute management, resulting in many stroke survivors being discharged to their communities without adequate follow-up, despite their often experiencing significant post-stroke complications, such as post-stroke spasticity (PSS). While studies have explored the incidence and prevalence of PSS, little is known about how early PSS develops and how many stroke survivors develop 'problematic' PSS that would benefit from pharmacological treatment., Methods and Analysis: EPITOME is a prospective, international, observational, epidemiological study of participants (aged 18-90 years) who develop paresis within days 3-14 of a first-ever stroke that occurred within the past 4 weeks. Participants at sites across seven different countries are monitored remotely at 2 weeks and 1, 2, 3, 6, 9 and 12 months post-stroke to detect the possible onset of PSS using the Post-stroke Spasticity Monitoring Questionnaire (PSMQ). If the PSMQ indicates the possible presence of PSS, participants undergo a full in-clinic assessment to confirm the presence of PSS. For participants with confirmed PSS, the severity and distribution of spasticity is documented, and the investigator assesses whether the participant has spasticity that could benefit from pharmacological therapy. Participants without clinically confirmed PSS return to remote monitoring., Ethics and Dissemination: Ethics approval was obtained in all seven participating countries. Results will be published at international meetings and in an international peer-reviewed journal. Lay summaries will be prepared to accompany the primary paper and will also be provided to study participants., Trial Registration Number: ClinicalTrials.gov NCT06055725., Competing Interests: Competing interests: RDZ, LSB, SB, SG, DHH, RP and AP are investigators in the EPITOME study and either they or their institutions receive payment for participation from Ipsen. In addition, RDZ reports research funding from Ipsen and AbbVie, consulting fees from Ipsen, royalties from Demos Medical for the Textbook of Stroke Recovery and Rehabilitation, and participation in a data safety monitoring board for SPR Therapeutics. SG reports research funding from Bundesministerium fur Bildung und Forschung (BMBF), Disabled Facilities Grants (DFG), Universitätsmedizin Mainz, Abbott, Boston Scientific, Böhringer Foundation, Magventure, Precisis, Innovationsfond GBA and lecture fees from Abbott, AbbVie, Bial, BVDN, Ipsen, and UCB. SS is a patient representative of Different Strokes and has no financial disclosures to report. SM, SP and PM are employed by Ipsen. AP reports consultancy for Ipsen, Merz and AbbVie., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: Lifetime treatment of aortic valve disease is a matter of increasing debate. Although the risks of a second aortic valve intervention are recognized, little attention has been given to the challenges of a third., Objectives: This study delves into the clinical characteristics, indications, and outcomes of patients undergoing 3 aortic valve interventions., Methods: The THIRD (THree aortIc Reinterventions for valve Disease) registry is a retrospective multicenter, international study of patients who underwent a third procedure on the aortic valve, either surgically or transcatheter-based. Patients undergoing 2 aortic procedures during the same hospital admission were excluded. Baseline characteristics, timing, and mode of bioprosthetic failure, sequence of the procedures, and clinical outcomes were adjudicated according to the Valve Academic Research Consortium criteria., Results: A total of 51 patients from 11 centers were enrolled in this study. Median follow-up time was 565 (314-1,560) days. Eighteen patients (35%) underwent surgical aortic valve replacement (SAVR), and 33 of 51 patients (65%) underwent transcatheter aortic valve replacement (TAVR) as the third intervention. Mean age was 69 ± 14 years, 20 of 51 patients (39%) were female. STS score was 5.0% (Q1-Q3: 3.3%-7.0%). In all TAVR cases, the indication for the first intervention was severe aortic stenosis, as was the indication in 31 of 45 (69%) of SAVR cases (33% bicuspid). The most prevalent procedure sequence was SAVR-SAVR-TAVR (19/51, 37%), followed by SAVR-SAVR-SAVR (10/51, 20%) and SAVR-TAVR-TAVR (10/51, 20%). TAVR-TAVR-TAVR was performed in 4 of 51 cases (8%). The primary indications for a third intervention included structural valve deterioration (SVD) (39/51, 76%), non-SVD (8/51, 16%), and endocarditis (2/51, 4%). Excluding patients with a mechanical prosthesis, predictors of SAVR as third intervention included a lower STS score (OR: 0.58; 95% CI: 0.34-0.98; P = 0.04) and the presence of moderate or severe prosthesis-patient mismatch (OR: 44.8; 95% CI: 2.41-122.00; P = 0.01). Thirty-day device success was 85% for TAVR and 94% for SAVR., Conclusions: In the THIRD registry, SVD emerged as the predominant indication for a third aortic valve procedure. The most frequent procedure sequence was SAVR-SAVR-TAVR, whereas TAVR-TAVR-TAVR was less common. Although the short-term outcomes in our selected cohort were favorable, further investigation is needed., Competing Interests: Funding Support and Author Disclosures Dr Tarantini has received honoraria for lectures/consulting from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, GADA. Dr Tang is a physician proctor, consultant, and advisory board member for Medtronic; is a consultant and advisory board member for Abbott Structural Heart; is an advisory board member for Boston Scientific and JenaValve; and has received speaker honoraria from Siemens Healthineers. Dr Kim has received personal fees from Abbott, Boston Scientific, Edwards Lifesciences, HI-D Imaging, Meril Life Sciences, and Shockwave Medical. Dr Pilgrim has received research, travel or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and has received speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Greenbaum has received institutional research support from Abbott Vascular, Ancora Heart, Edwards Lifesciences, Gore Medical, JenaValve, Medtronic, Polares Medical, Transmural Systems, and 4C Medical; has received consulting fees from Abbott Vascular, Edwards Lifesciences, and Medtronic; and has an equity interest in Transmural Systems. Dr Webb is a consultant for Edwards Lifesciences; and has received research funding from Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Makkar is a consultant for and received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. Dr Franco is a proctor for Abbott Vascular and Edwards Lifesciences. Dr De Backer has received institutional research grants and consulting fees from Boston Scientific. Dr Fovino received consulting fees from Edwards Lifesciences and research grant from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Deaths of despair are a key contributor to stagnating life expectancy in the USA, especially among those without a university-level education, but these findings have not been compared internationally., Methods: Mortality and person-year population exposure data were collected in 14 Organisation for Economic Co-operation and Development member countries and stratified by age, sex, educational attainment and cause of death. The sample included 1.4 billion person-year observations from persons aged ≥25 years between 2013 and 2019. Country-specific and sex-specific contributions of deaths of despair to: (a) the life expectancy gap at age 25 and (b) rate differences in age-standardised mortality rates between high and low educational attainment groups were calculated., Results: Eliminating deaths of despair could reduce the life expectancy gap in the USA by 1.1 years for men and 0.6 years for women was second only to Korea, where it would reduce the gap by 3.4 years for men and 2.2 years for women. In Italy, Spain and Türkiye, eliminating deaths of despair would improve life expectancy gains by less than 0.1 years for women and 0.3 years for men, closing the educational gap by <1%. Findings were robust to controls for differences in population structures., Conclusions: Deaths of despair are a major determinant of educational inequalities in longevity in Korea and the USA, while having limited impact in Southern European countries, indicating substantial international variation and scope for improvement in high burden high-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Background: Heart failure (HF) often occurs in patients with atrial fibrillation (AF), with a major impact on prognosis. Few data are available on the effect of integrated treatment strategies to improve prognosis in patients with AF. We aimed to evaluate the association between HF (according to left ventricular ejection fraction [LVEF]), HF optimal medical therapy and adherence to the Atrial Fibrillation Better Care pathway, and major outcomes in patients with AF., Methods and Results: From the ESC-EHRA EORP-AF (European Society of Cardiology-European Heart Rhythm Association EURObservational Research Programme in Atrial Fibrillation) General Long-Term Registry, we evaluated patients with HF, categorized according to LVEF (HF with reduced ejection fraction, HF with mildly reduced ejection fraction, HF with preserved ejection fraction). Optimal medical therapy for HF was guidelines-defined. The primary end point was the composite of all-cause death and major adverse cardiovascular events. From the original cohort, 9373 (84.5%) patients were included in this analysis (median age, 71 [interquartile range, 62-77] years; 39.9% women). Compared with no HF, all HF categories were associated with an increased risk of the primary composite outcome, with highest figures observed for HF with reduced ejection fraction (hazard ratio [HR], 2.36 [95% CI, 2.00-2.78]). The risk was reduced in patients with AF and HF adherent to optimal medical therapy (HR, 0.83 [95% CI, 0.70-0.98]), as well as in those adherents to the Atrial Fibrillation Better Care pathway (HR, 0.65 [95% CI, 0.48-0.88]). The effect of Atrial Fibrillation Better Care pathway was consistent across the spectrum of LVEF., Conclusions: Patients with AF and HF have a high risk of major adverse events, and this risk is inversely associated with LVEF. Atrial Fibrillation Better Care pathway adherent management is associated with improved clinical outcomes in patients with HF, across the spectrum of LVEF.

With the ongoing emergence of SARS-CoV-2 variants, there is a need for standard approaches to characterize the risk of vaccine breakthrough. We aimed to estimate the association between variant and vaccination status in case-only surveillance data. Included cases were symptomatic adult laboratory-confirmed COVID-19 cases, with onset between January 2021 and April 2022, reported by five European countries (Estonia, Ireland, Luxembourg, Poland, and Slovakia) to The European Surveillance System. Associations between variant and vaccination status were estimated using conditional logistic regression, within strata of country and calendar date, and adjusting for age and sex. We included 80,143 cases including 20,244 Alpha (B.1.1.7), 152 Beta (B.1.351), 39,900 Delta (B.1.617.2), 361 Gamma (P.1), 10,014 Omicron BA.1, and 9,472 Omicron BA.2. Partially vaccinated cases were more likely than unvaccinated cases to be Beta than Alpha (adjusted odds ratio [aOR] 2.48, 95% CI 1.29-4.74), and Delta than Alpha (aOR 1.75, 1.31-2.34). Fully vaccinated cases were relative to unvaccinated cases more frequently Beta than Alpha (aOR 4.61, 1.89-11.21), Delta than Alpha (aOR 2.30, 1.55-3.39), and Omicron BA.1 than Delta (aOR 1.91, 1.60-2.28). We found signals of increased breakthrough infections for Delta and Beta relative to Alpha, and Omicron BA.1 relative to Delta.

The broad spectrum of clinical manifestations caused by peripheral arterial disease [PAD] and the morphologic heterogeneity of associated atherosclerotic lesions present a considerable management challenge. Endovascular interventions are recognized an effective treatment for PAD. Within this revascularization strategy the role of atherectomy debulking modalities continue to evolve. Accordingly, the study herein assessed the efficacy and safety of a novel, solid state, Nd: YAG pulsed-wave [355 nm wavelength] laser atherectomy in the treatment of symptomatic infra-inguinal PAD. The EX-PAD-01 study, a prospective, single-arm, open label trial enrolled 50 patients (38 males, 12 females; mean age 64 years] with symptomatic peripheral arterial disease, who underwent percutaneous revascularization with a novel, solid state, pulsed-wave [355 nm wavelength] laser atherectomy followed with adjunct treatment. The Ankle-brachial index [ABI], Rutherford classification for chronic limb ischemia and the walking impairment questionnaire [WIQ] were used for assessment of the index clinical condition of the enrolled patients, for post procedure evaluation and during follow-up. Accordingly, the patients were followed for 12-months with repeated direct physician contact visits. Fifty-three atherosclerotic stenoses (51 femoropopliteal, 2 tibial) with a mean length of 7.4 cm. (ranged 1cm to 25cm) were treated. There were 79% occlusions, and 61% containing moderate-to-severe calcifications. The pre-procedure stenosis was 95.3 ± 10.3%, the Rutherford classification for chronic limb ischemia [CLI] was 2.90 ± 0.54 ranging between 2-4 and the WIQ 34.6 ± 8.62. Technical success was achieved in 52 of the 53 (98%) target lesions. Following laser debulking the baseline stenosis was reduced from 95.3 ± 10.3% to 61.3 ± 25.5% [ [p < 0.0001] and with adjunct balloon/stenting to final of 14.0 ± 14.0% [p < 0.0001]. Embolic protection devices were utilized in 6 [12%] patients. At 30-day post procedure evaluation the ABI increased from baseline of 0.57 ± 0.14 to 0.94 ± 0.14 [p < 0.0001] and no major adverse effects or device adverse effects were detected. At 6 months follow -up the ABI was 0.84 ± 0.20% (p < 0.0001 vs. initial) and at 1 year follow-up 0.79 ± 0.16 (P = 0.0001 vs. initial) without major adverse events. Out of 46 [92%] patients who reached the 12 months follow-up mark, 2 [4.3%] experienced clinically driven target lesion revascularization. Sustained clinical benefit for up to 12 months post procedure was demonstrated through documentation of statistically significant decrease of Rutherford CLI class as well as concomitant improvement in WIQ score and an increase of ABI value. The primary patency rate, as defined by peak systolic velocity ratio (PSVR) of < 2.5m/second was 95.7% (22 of 23) and 81.8% (18 of 22) at 6 months and 12 months, respectively. In an early European clinical experience with a series of 50 patients with symptomatic peripheral arterial disease, the novel Nd: YAG solid state, pulsed- wave 355nm cardiovascular laser atherectomy device provided effective and safe revascularization treatment. Follow-up at 6 and 12 months, respectively, substantiate the efficacy, safety profile and clinical merits of this novel laser. Thus, this device is useful in the management of select patients with symptomatic infra-inguinal atherosclerotic lesions.Clinical Trial Registration: Clinical trials.gov number: NTC02556255., Competing Interests: Declarations. Compliance with Ethical Standards: All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the Upper-Silesian Medical Centre of the Silesian Medical University, Katowice, Poland, and by the Bioethics Committee of University Hospital of Lord’s Transfiguration of Poznan University of Medical Sciences, Poznan, Poland. Informed consent: Informed consent was obtained from all individual participants included in the study. Patients signed informed consent regarding publishing their data and photographs., (© 2024. The Author(s).)

Aims/purpose: This study aims to assess whether changes in intraocular pressure (IOP) occur after a blood draw and quantify these changes' magnitude in a group of patients over 60 years old., Methods: We analysed data from the right eye of 54 subjects, with a mean ( ± SD) age of 68 ± 4 years. The measurements were conducted in the morning while fasting. First of all, subjects rested in a seated position for 5 minutes to equalise baseline conditions. IOP was then measured using the iCare rebound tonometer (IC100, iCare Oy, Finland) and the mean value obtained from 6 measurements was recorded. After 10 minutes, subjects underwent the blood draw. Five minutes after the blood draw, the subject sat back in the chair for the second IOP measurement, conducting the same procedures for both measurements. Pre- and post-drawing IOP values were compared with Wilcoxon signed rang test, for related samples., Results: The analysis showed that IOP decreased after extraction, with a mean ( ± SD) of 14.09 ± 3.18 mmHg pre-extraction and a mean ( ± SD) of 13.33 ± 2.90 mmHg post-extraction. Grouping the sample into age groups, no statistically significant differences were found in the 60-64 age group (n = 11; p = 0.35) and the 75-79 age group (n = 5; p = 0.68). A trend towards significance was found in the 70-74 age group (n = 18; p = 0.06) and statistically significant differences in the 65-69 age group (n = 20; p = 0.04). Grouping the sample according to their IOP values (using to the sample IOP median) no statistical differences were found when IOP values were between 8 and 15 mmHg (n = 38; p = 0.57) and statistically significant differences were found in the group with IOP between 16 and 28 mmHg (n = 16; p = 0.001)., Conclusions: It was found that IOP decrease after a blood draw, tending to decrease more in subjects aged 65 to 74 years and remains unchanged in the other age groups. Additionally, higher baseline IOP levels lead to greater changes post-extraction. These results may be related to reflex effects of the autonomic nervous system, activating a vagal reflex, which may induce a decrease in IOP. Future studies are required to analyse the various influencing factors., (© 2025 The Authors Acta Ophthalmologica © 2025 Acta Ophthalmologica Scandinavica Foundation.)

Background: Drug-drug interactions (DDIs), highly prevalent amongst the elderly, can lead to avoidable medication-related harm. Cardiovascular and central nervous system (CNS) drugs are commonly implicated. To date, there is no consensus on how to measure DDIs, making comparisons across countries challenging., Objective: To (i) establish a common data model (CDM) to measure DDI prevalence in the older (aged ≥ 70 years) community-dwelling population of three European countries and (ii) compare and describe cardiovascular and CNS DDI prevalence rates across these countries., Methods: This cross-country study will apply a harmonised method of DDI identification and analysis using the WHO ATC classification system and national pharmacy claims data from three European countries (Ireland, Italy, Spain). Patients aged ≥ 70 years dispensed ≥ 2 medications during 2016 will be identified from each country's national database. 'Severe' cardiovascular and CNS DDIs (i.e., may result in a life-threatening event/permanent detrimental effect) will be identified using the British National Formulary and Stockley's Drug Interactions. Two separate lists of 'severe' DDIs, per medications reimbursed, will be applied to each database: (i) DDIs relevant to each individual country and (ii) DDIs relevant to all three countries. DDIs will be defined as co-dispensed (same day) and concomitantly (±7 days) dispensed., Results: Descriptive statistics, including DDI prevalence and 95% confidence intervals, will be reported for each country. Prevalence will be pooled and compared across countries using random effects models and meta-regression, where feasible., Conclusion: The EuroDDI study will develop a harmonised method to measure and compare DDI prevalence across health-related databases in Europe., (© 2025 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Previous reports have indicated that during the era of combination antiretroviral therapy, the major causes of morbidity and mortality in people living with HIV (PLWH) were not solely linked to HIV-related opportunistic infections but also to cancers that were difficult to manage due to HIV-related immunodeficiency. We investigated whether PLWH who underwent autologous hematopoietic stem cell transplantation (ASCT) for lymphomas experienced significant morbidity over the past thirty years following HIV infection. We conducted a retrospective follow-up study of 49 PLWH over a 10-year period following ASCT. We collected survival data, examined the occurrence of long-term events, assessed CD4 + T-cell immune recovery, and analysed the correlation between immune recovery and the events experienced by these patients. The data confirmed the significant long-term effectiveness of ASCT, with an overall survival rate of 78% at 10 years post-ASCT. Opportunistic infections, which occurred soon after ASCT and were associated with lower CD4 + T-cell counts, were successfully managed. However, lymphoma relapse, secondary malignancies, cardiovascular disease, and bone disease, which developed years after ASCT, were major causes of morbidity and mortality in this population. Our findings highlight the need for the development and validation of specific tests to predict risk and guide effective interventions for metabolic diseases, secondary malignancies, and lymphoma relapses in PLWH treated with ASCT for lymphoma., (© 2025 Wiley Periodicals LLC.)

Background: This study investigated the impact of posaconazole (POSA) prophylaxis in COVID-19 patients with acute respiratory failure receiving systemic corticosteroids on the risk for the development of COVID-19-associated pulmonary aspergillosis (CAPA)., Methods: The primary aim of this prospective, multicentre, case-control study was to assess whether application of POSA prophylaxis in mechanically ventilated COVID-19 patients reduces the risk for CAPA development. All consecutive patients from centre 1 (cases) who received POSA prophylaxis as standard-of-care were matched to one subject from centre 2 and centre 3 who did not receive any antifungal prophylaxis, using propensity score matching for the following variables: (i) age, (ii) sex, (iii) treatment with tocilizumab and (iv) time at risk., Results: Eighty-three consecutive patients receiving POSA prophylaxis were identified at centre 1 and matched to 166 controls. In the matched cohort, incidence rates of CAPA were 1.69 (centre 1), 0.84 (centre 2) and 7.18 (centre 3) events per 1000 ICU days. In multivariable logistic regression analysis, the presence of an EORTC/MSGERC risk factor at ICU admission (OR 4.35) and centre 3 versus centre 1 (OR 6.07; 95% CI 1.76-20.91; p = 0.004) were associated with an increased risk of CAPA. No increased risk of CAPA was registered for centre 2 versus centre 1., Conclusions: The impact of POSA prophylaxis depends on the baseline CAPA incidence rate, which varies widely between centres. Future trials should therefore investigate targeted antifungal prophylaxis (e.g., stratified for high-prevalence centres or high-risk patients) in COVID-19 patients., Trial Registration: NCT05065658., (© 2025 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Rationale & Objective: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend, and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival., Study Design: Observational prospective cohort study., Setting & Participants: Adult hemodialysis patients treated in 500 hemodialysis facilities participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) between 1999 and 2015 in the United States, Japan, and 4 European countries: Germany, Italy, Spain, and the United Kingdom., Predictors: Four practice measures at each facility: the percentages of patients with Kt/V≥1.2, interdialytic weight gain [IDWG]<5.7%, phosphorus<6mg/dL, and using arteriovenous fistulas (AVFs)., Outcome: Patient survival., Analytical Approach: Mediation analyses, adjusted for case mix, were conducted using 3-year study phase as the exposure and facility practice measures as potential mediators., Results: In Europe, we observed a 13% improvement in overall case-mix adjusted survival per decade. Trends in facility practice measures, especially Kt/V and phosphorus, explained 10% improvement in case-mix survival per decade, representing 77% (10% explained of 13% improvement) of the observed improvement. In Japan, 73% of the observed 12%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially Kt/V and IDWG. In the United States, 56% of the observed 47%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially AVF use and phosphorus control., Limitations: Unmeasured changes in the characteristics of the patient population over this period may confound the observed associations., Conclusions: The improvements in adjusted hemodialysis patient survival in Europe, Japan, and the United States from 1999 to 2015 can be largely explained by improvements in specific facility practices. Future changes in patient survival may be responsive to further evolution in the implementation of common clinical practices., Plain-Language Summary: Case-mix adjusted survival of patients treated with hemodialysis has improved over the last 2 decades in the United States, Japan, and Europe. Some of this improvement can be explained by region-specific changes in 4 dialysis practices, namely increases in the proportions of patients achieving (1) Kt/V≥1.2, (2) serum phosphorus levels<6mg/dL, (3) interdialytic weight gain<5.7% of body weight, and/or (4) use of arteriovenous fistulas as vascular access, with the magnitude varying according to region-specific trends in these practices. These findings suggest that further improvement in these practice measures may be attended by further reductions in mortality among patients treated with maintenance hemodialysis., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

This study investigates the impact of the overall intensity and changes in grandparental caregiving on loneliness in grandparents in European countries. Data from waves 5 to 8 of the Survey on Health, Ageing, and Retirement in Europe (SHARE) were used (N individuals = 30,896 and N observations = 48,562). We included grandparents (aged 50 years and over) with at least one grandchild at the beginning of the study. The analyses reveal that any intensity of grandparental care decreases the risk of loneliness. When looking at changes in grandparental care the results show that stable caregiving roles appeared to reduce loneliness, while starting to provide grandparental care makes grandparents more vulnerable to loneliness. In conclusion, our findings underscore that consistent grandparental care is important for grandparents in mitigating loneliness, highlighting the importance of sustained caregiving roles over fluctuations in caregiving intensity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Complete mesocolic excision (CME) is an oncologically driven technique for treating right colon cancer. While laparoscopic CME is technically demanding and has been associated with more complications, the robotic approach might reduce morbidity. The aim of this study was to assess the safety of stepwise implementation of robotic CME., Method: A multicentre retrospective analysis of prospectively collected data on robotic right colectomy was performed at five European tertiary centres. Patients were classified for type of surgery: R-RHC (standard right colectomy), R-impCME (learning cases towards robotic CME defined as R-RHC with one but not all the hallmarks of CME) or R-CME (robotic CME). Primary outcomes were overall and severe 30-day complication rates before and after propensity score matching (PSM) analysis., Results: Five hundred and fifty-one consecutive patients undergoing robotic surgery for (pre)malignant lesions of the right colon between 2010 and 2020 were included: R-RHC (n = 101), R-impCME (n = 135) and R-CME (n = 315). Baseline characteristics differed for American Society of Anesthesiologists score (p = 0.0012) and preoperative diagnosis of adenocarcinoma (p < 0.001). Procedure time increased by surgical complexity (p < 0.001). Vascular event rates did not differ, with no superior mesenteric vein injuries. Conversion, complication and anastomotic leak rates, time to flatus/soft diet and length of stay (LOS) did not differ. While R-RHC was performed for a lower rate of malignancies (p < 0.001), lymph node yield was significantly higher in R-CME (p < 0.001). After PSM, analyses on 186 patients documented no differences in overall and severe 30-day complication rate, conversion rate, LOS or 30-day mortality., Conclusion: R-CME can be implemented without increasing the overall or 30-day severe complication rate., (© 2025 The Association of Coloproctology of Great Britain and Ireland.)

Background: While medication errors (MEs) have been studied in the European Medicines Agency's EudraVigilance, extensive characterisation and signal detection based on sexes and age groups have not been attempted., Objectives: The aim of this study was to characterise all ME-related individual case safety reports in EudraVigilance and explore notable signals of disproportionate reporting (SDRs) among sexes and age groups for the 30 most frequently reported drugs., Methods: Individual case safety reports were used from EudraVigilance reported between 2002 and 2021. An ME was defined as any Preferred Term from the narrow Standardised Medical Dictionary for Regulatory Activities ® Query. Signals of disproportionate reporting were selected based on a lower boundary of the 95% confidence interval ≥ 1 of the reporting odds ratio, and at least 3 individual case safety reports. Analysed subgroups were female individuals, male individuals, and age groups 0-1 month, 2 months to 2 years, 3-11 years, 12-17 years, 18-64 years, 65-85 years, and >85 years. Heatmaps were utilised as a visual aid to identify striking SDRs., Results: Of the 9,662,345 EudraVigilance reports, 267,262 (2.8%) contained at least one ME, with a total of 300,324 MEs, for 429,554 drugs. The most reported ME was "Inappropriate schedule of product administration" (52,646; 17.5%), followed by "Incorrect dose administered" (32,379; 10.8%) and "Wrong technique in product usage process" (26,831; 8.9%). Individual case safety reports with MEs were most frequently related to female individuals (148,009; 55.4%), most often submitted by healthcare professionals (155,711; 58.3%), originated predominantly from the USA (98,716; 36.9%), followed by France (26,678; 10.0%), and showed a median reported age of 50 years (interquartile range: 26-68). Most ME individual case safety reports (158,991; 59.5%) were associated with a serious health outcome. A total of 847 SDRs were identified, based on the entire EudraVigilance database; for subgroups, the number of SDRs ranged from 84 for the age group 0-1 month to 749 for female individuals. Signals of disproportionate reporting for female individuals and male individuals were very similar. Most MEs were reported for the vaccine against human papillomavirus (Anatomical Therapeutic Chemical [ATC]: J07BM01; 11,086 MEs, 57% being "inappropriate schedule of product administration"), with reporting odds ratios that range from 1.5 to 47.0 among age groups. The SDR for the live-attenuated vaccine against herpes zoster (ATC: J07BK02) had a reporting odds ratio that ranged from 26.6 to 78.1 among all subgroups. Signals of disproportionate reporting for oxycodone (ATC: N02AA05; 847 cases of "Accidental overdose", 35%), risperidone (ATC: N05AX08; 469 cases "Inappropriate schedule of product administration", 22.3%) and rivaroxaban (ATC: B01AF01; 1,377 cases of "Incorrect dose administered", 34.6%) stood out with higher magnitude SDRs for the age group 2 months to 2 years, with an reporting odds ratio range between 8.2 and 10.7, while for the entire EudraVigilance the reporting odds ratio ranged between 1.3 and 1.6 for the same drugs., Conclusions: This exploratory research provides an overview of characterised ME individual case safety reports and SDRs from the EudraVigilance database. Most conspicuous SDRs were identified in specific age groups. Signals of disproportionate reporting, not described in the literature, were found for vaccines, oxycodone, rivaroxaban and risperidone, and may prompt further examination by stakeholders. Top-reported MEs ("Inappropriate schedule of product administration", "Incorrect dose administered" and "Wrong technique in product usage process") emerged as a general priority focus to perform a further root-cause analysis involving healthcare providers, manufacturers and regulatory bodies, to improve the understanding and prevention of MEs., Competing Interests: Declarations. Funding: This work has received support from the European Health Data & Evidence Network (EHDEN) project. EHDEN has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 806968. Conflicts of Interest/Competing Interests: The research group from the Department of Medical Informatics received unconditional research grants from Chiesi, UCB, Amgen, Johnson and Johnson, and the European Medicines Agency, none of which relates to the content of this article. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: An agreement has been made with the EMA not to transfer or dispose of the ICSR data set Level 2A for which access is provided under the condition of the Confidentiality Undertaking to any third party. It is agreed not to permit any third party to access, study, analyse, refer to or otherwise use the data or permit any party to reproduce any ICSR data. A publicly available version of this database is available here: https://www.adrreports.eu/en/index.html . Further inquiries can be directed to the corresponding author. Code Availability: Not applicable. Authors’ Contributions: VP: conceptualisation, formal analysis, visualisation, writing (original draft), writing (review and editing), methodology, visualisation. JK: software, writing (review and editing). EV: software, writing (review and editing). MdW: software, writing (review and editing). PR: supervision, writing (review and editing). KV: conceptualisation, supervision, writing (review and editing). All authors read and approved the final version. , (© 2024. The Author(s).)

Background: Cancer is a leading cause of death in Europe and prevention measures, like screening, are therefore becoming increasingly important. Although European countries provide universal health coverage, including cancer screenings, many people also have private health insurance., Aim: The aim of this study is to analyse the relationship between Voluntary private health insurance (VPHI) and cancer screening, specifically breast and colorectal cancer screening., Method: Using data from SHARE, the Survey of Health, Ageing and Retirement in Europe, different logistic and multilevel regressions were estimated., Results: The major finding shows a positive correlation between people being screened for cancer and having VPHI., Conclusions: Three conclusions can be drawn: advantageous selection may exist in private health insurance; spillover effects may exist from the public sector into the private sector, which in turn may result in a lower insurance premium; and there may be a perpetuation of inequalities in health service utilisation. Several policy implications can be drawn from this result, but the most relevant concerns narrowing the inequities that could potentially arise between those who have private health insurance and those who do not., (© 2024 John Wiley & Sons Ltd.)

Background: Anti-glycoprotein 2 (anti-GP2) IgA and antineutrophil-cytoplasmic antibodies to proteinase 3 (PR3-ANCA) have been reported as predictive markers of cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC), but their prevalence in CCA patients without PSC remains unclear., Methods: This study involved Asian discovery (n = 118) and European validation (n = 38) cohorts of CCA patients without PSC, alongside 49 Asian and 82 European pancreatic ductal adenocarcinoma (PDAC) patients, 21 with benign pancreatic neoplasms (BPN) and 45 with hepatocellular carcinoma (HCC), and 157 healthy controls (HC) from Asia and Europe. We analyzed the prevalence of PR3-ANCA, IgA and IgG against GP2 1 and GP2 4 , and the CA19-9 levels., Results: Anti-GP2 1 IgA was the most prevalent in both CCA cohorts (discovery: 55.1 %; validation: 42.1 %) and significantly higher than in other groups except PDAC (all p < 0.05). It demonstrated the best diagnostic performance in distinguishing CCA from disease controls and HC, outperforming tumor markers. No significant correlation was found between anti-GP2 1 IgA levels and CA19-9 levels., Conclusion: Our findings show that anti-GP2 1 IgA revealing the loss of mucosal tolerance is a potential novel diagnostic biomarker for CCA., Competing Interests: Declaration of competing interest Dirk Roggenbuck has ownership of Medipan and GA Generic Assays corporation stocks and profits earned from the stocks. The other authors declare that they have no conflicts of interest., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Even though antithrombotic therapy (ATT) probably has little or even negative effect on the well-being of patients with cancer near the end of life, it is often continued until death, possibly leading to excess bleeding complications, increased disease burden, reduced quality of life and higher healthcare costs., Aim: To explore and describe European practice patterns and perspectives of healthcare professionals from different disciplines and specialties on ATT in the end-of-life care (EOLC) of patients with cancer., Methods: We performed a two-week international cross-sectional survey study using flash-mob research methodology. Eligible were healthcare professionals from different institutions across Europe, who prescribed ATT and/or dealt with EOLC of patients with cancer. The survey comprised three parts, including a series of choice sets (hypothetical scenarios involving a set of characteristics changing in level [e.g., high vs. low thrombotic risk]) on ATT management in EOLC. The discrete choice experiment analysis was conducted using multinomial logistic regression., Results: Out of 467 pre-registrants, 208 participated in the survey from 4 to 18 July 2023. The majority (53 %) considered a patient with cancer as in EOLC when life expectancy is below 3 months. Respondents reported seeing or treating 20 patients with cancer on ATT in EOLC per year (IQR 10-50). The median estimated frequency of considering ATT deprescription per healthcare professional was 10 times per year (IQR 4-10), while the frequency of actual deprescription was 5 times per year (IQR 2-10). Twenty percent of respondents had never deprescribed ATT in the context of EOLC. Across the eight choice sets, five respondents (2.7 %) found deprescribing inappropriate in any scenario. Deprescribing was more often considered in patients with poor ECOG-performance status, high bleeding risk and low-molecular-weight heparin use as opposed to oral ATT. Haemato-oncology and cardiovascular medicine specialists were more inclined to deprescribe antiplatelet therapy than other specialties., Conclusion: Our study describes medical decision-making regarding ATT in EOLC of patients with cancer. Healthcare professionals' perspectives and practice patterns vary, and some preferences appear associated with the therapists' professional focus and region of practice., Competing Interests: Declaration of competing interest LB reports personal fees from Merck Sharp & Dohme, LEO-Pharma, Bristol-Myers Squibb-Pfizer, and a grant for research from Merck Sharp & Dohme, outside the submitted work. AAH has received research grants from The Danish Heart Foundation and The Novo Nordisk Foundation, has received personal consulting fees from Bayer and has been on the speaker bureaus for Bayer, LEO-Pharma, and Bristol Myers Squibb, all of which are unrelated to this work. MJHAK reports grants from Sobi, The Netherlands Organisation for Health Research and Development, and the Dutch Thrombosis Association, and speaker fees from Roche, Sobi, and Bristol Myers Squibb, all grants and fees were unrelated to this work and paid to her institution. MP reports grants or contracts from the National Institute for Health Research to the Medical Research Council, Marie Curie to Yorkshire Cancer Research, National Health & Medical Research Council to the UKRI Arts & Humanities Research Council, and AstraZeneca to Research England, along with support for attending meetings and/or travel from the All-Ireland Institute of Hospice and Palliative Care. FAK reports grants or contracts from Bayer, Bristol Myers Squibb, British Society of Cardiovascular Imaging, Merck Sharp & Dohme, LEO-Pharma, Actelion, Varm-X, The Netherlands Organisation for Health Research and Development, the Dutch Thrombosis Association, the Dutch Heart Foundation, and the Horizon Europe Program, all unrelated to this work and paid to his institution. SVK reports research funding (grants) and consultation fees via his institution from Bayer AG, Boston Scientific, Inari Medical and Penumbra Inc.; and personal lecture & consultation honoraria/fees from Bayer AG, Boston Scientific, Daiichi-Sankyo and Penumbra Inc. All other authors declared no potential conflicts of interest with respect to the research., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Transcatheter aortic valve replacement (TAVR) is an established treatment option for many patients with severe symptomatic aortic stenosis; however, debris dislodged during the procedure can cause embolic stroke. The Sentinel cerebral embolic protection (CEP) device is approved for capture and removal of embolic material during TAVR but its efficacy has been debated., Objective: To explore regional differences in the association of CEP utilization with stroke outcomes in patients undergoing TAVR., Design, Setting, and Participants: This post hoc analysis of a prospective, postmarket, randomized clinical trial evaluating TAVR performed with or without the CEP took place at 51 hospitals in the US, Europe, and Australia from February 2020 to January 2022. Patients with symptomatic aortic stenosis treated with transfemoral TAVR were included. Randomization was stratified according to center, operative risk, and intended TAVR valve type. Patients were excluded if the left common carotid or brachiocephalic artery had greater than 70% stenosis or if the anatomy precluded placement of the CEP device. Data for this post hoc study were analyzed from August to October 2024., Intervention: TAVR with or without CEP., Main Outcomes and Measures: The primary end point was the rate of all stroke events at hospital discharge or 72 hours post-TAVR, whichever came first. Neurological examinations were performed at baseline and postprocedure to identify stroke, disabling stroke, and other neurological outcomes., Results: The Stroke Protection With Sentinel During Transcatheter Aortic Valve Replacement (PROTECTED TAVR) trial enrolled and randomized 3000 patients (1803 [60.1%] male; mean [SD] age, 78.9 [7.8] years): 1833 in the US cohort (TAVR alone: 919, TAVR with CEP: 914) and 1167 patients in the outside the US (OUS) cohort (TAVR alone: 580, TAVR with CEP: 587). Patients in the US cohort were younger, more predominantly male, had a lower prevalence of atrial fibrillation, and had a higher prevalence of bicuspid aortic valve, diabetes, and peripheral vascular disease compared with the OUS cohort. In the main trial, the incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group, and there was no interaction by geographic region. In this post hoc analysis, patients treated with CEP in the US cohort exhibited a 50% relative risk reduction for overall stroke and a 73% relative risk reduction for disabling stroke compared to TAVR alone; a treatment effect on stroke risk reduction was not observed in the OUS cohort., Conclusion and Relevance: The PROTECTED TAVR trial could not show that the use of CEP had a significant effect on the incidence of periprocedural stroke during TAVR. Although there was no significant interaction by geographic region, this exploratory post hoc analysis suggests a trend toward greater stroke reduction in the US cohort but not in the OUS cohort. These findings are hypothesis generating, and further research is needed to determine if regional differences in patient characteristics or procedural practices affect CEP efficacy., Trial Registration: ClinicalTrials.gov Identifier: NCT04149535.

Aim: To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD)., Materials and Methods: We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks. Of the 2381 participants, 1048 (44.0%) had a DD of less than 8 years and 1333 (56.0%) had a DD of 8 years or longer. We further analysed the subgroups of participants having a DD of less than 4 years (N = 450), 4-8 years (N = 598), 8-12 years (N = 627) and 12 years or longer (N = 706)., Results: Mean ± standard deviation age was 60.2 ± 9.0 years in participants with a DD less than 8 years and 64.2 ± 8.8 years in those with a DD of 8 years or longer. At 24 weeks of Gla-300 therapy, HbA1c improved with a least-squares (LS) mean change from baseline of -1.88% (95% confidence interval [CI], -1.95 to -1.80) and -1.71% (95% CI, -1.77 to -1.65), respectively, resulting in a LS mean difference between groups of 0.17% (95% CI, 0.07 to 0.26; P = .0005). In the subgroup analysis, LS mean HbA1c reduction from baseline to week 24 was highest in participants with a DD of less than 4 years and lowest in participants with a DD of 12 years or longer. Overall, incidences of symptomatic and severe hypoglycaemia were low, irrespective of DD, without body weight changes., Conclusions: Gla-300 was effective and safe in insulin-naïve individuals with T2D, regardless of DD. Improvement in HbA1c was greater when Gla-300 was initiated in participants with a DD of less than 4 years, although the difference between the groups was modest., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Purpose: There is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty., Methods: Secondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0-2 (non-frail), 3-6 (frail) and 7-14 (most-frail). Data were analyzed using descriptive statistics., Results: Overall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %)., Conclusions: One in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm., Competing Interests: Declaration of competing interest A.J.C. has received grant or consulting funds from the Medical Research Future Fund, Dementia Australia Research Foundation and the Pharmaceutical Society of Australia. All these funds were paid to the administering University. A.J.C. is also a national board director for the Pharmaceutical Society of Australia. S.H. belongs to an endowed chair funded by donations from Hakue technology, PROUMED, Japan Bio Products, Towa Pharmaceutical, Yellow Eight and Sugi Holdings and received research funding from SOMPO Care Inc. outside of this work. N.M.V. has received grant or consulting funds from UCB Biopharma, Nestlé and Vegenat. R.V. was previously on the board of Resthaven and the board governance committee. Visvanathan is co-founder and chair of the clinical advisory group for a wearable sensor technology start-up HealthVibes.ai. J.S.B. has received grant or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Australian Commission on Safety and Quality in Health Care, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations. All these funds were paid to the administering University. All other authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome-wide association study (GWAS)., Methods: We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole-genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity., Results: The GWAS identified five non-coding variants on chromosome 20 with a p-value <5.0 × 10 -8 . For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions., Conclusions: Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients., Significance Statement: This genome-wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

Background: The COVID-19 pandemic underscored the issue of vaccine hesitancy, leading researchers to study the determinants of people's willingness to receive the COVID-19 vaccine. This study is the first to comprehensively investigate the role of preventive practices at both the individual and contextual level, drawing on the theoretical concept of "cultural health capital"., Methods: Utilizing data from the Survey of Health, Ageing, and Retirement (SHARE), covering information from 18,454 individuals aged 50 years and above residing in 25 European countries, we examined the influence of past engagement in preventive practices and the prevalence of such practices within a country on the likelihood of COVID-19 vaccine uptake. Our analysis included (i) previous vaccination behaviors, (ii) other healthcare-related behaviors, and (iii) lifestyle factors at both the individual and contextual levels. Leveraging the longitudinal design of the SHARE, we accounted for the temporal ordering of the relationships., Results: At the individual level, almost all preventive behaviors were significantly related to people's willingness to receive the COVID-19 vaccine. Individuals who (i) had received an influenza vaccination prior to the COVID-19 outbreak and during childhood, (ii) had regularly participated in dental and blood pressure check-ups throughout their lives, and (iii) did not engage in lifestyle-related risk behaviors, were more likely to accept the COVID-19 vaccine. Notably, alcohol use was not significantly associated. At the contextual level, only the vaccination coverage rate for influenza was found to be robustly related, indicating that individuals were more inclined to receive the COVID-19 vaccine in countries with higher influenza vaccination rates prior to the pandemic., Conclusion: Active participation in preventive practices and effective implementation of vaccination campaigns can contribute to the development of (institutional) cultural health capital, which ultimately promotes a greater willingness to get vaccinated against COVID-19., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Katrijn Delaruelle reports financial support was provided by EU Framework Programme for Research and Innovation Societal Challenges. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Rare cancers correspond to approximately 200 clinical entities, which can be grouped into 12 families. Updated data are available for childhood and haematological cancers, ie, for only two of the 12 families of rare cancer. We provide incidence and survival for the remaining ten families of rare adult solid cancers (RAC), across 29 EU Member States and over time. We also evaluate the association between resources invested in health and survival from RACs., Methods: We used the EUROCARE-6 database, which includes data from 108 cancer registries from 29 countries. We calculated incidence rates (IR) and 5-year relative survival (RS) for cases diagnosed during 2006-2013. We calculated 5-year RS in the follow-up period 2010-2014 using the period approach (last follow-up: December 31, 2014). We estimated changes in 5-year RS and IR over the period 2000-2013. We used a forest plot to report the differences in RS among countries with the highest and lowest health spending., Results: RACs are heterogeneous in terms of incidence, survival, sex, and age distribution. Several RACs (eg, those of the hypopharynx, small intestine, and trachea) still have a 5-year RS < 30 %, which is not improving. Survival differs among European countries and is higher in countries with the greatest investments in health. The incidence of smoking-related RACs is decreasing but rising in HPV-related RACs., Conclusion: Investments in health and healthcare networks at national and European level can help increase the survival of RACs, especially those requiring centralisation of care (eg, bone sarcomas, penile cancer). These investments are critical considering that survival from RACs is not significantly improving. Our results unmask the heterogeneity of RACs, which needs to be considered in clinical trial design. Finally, our findings support the importance of prevention strategies for known risk factors such as smoking., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Excessively prescribed opioids promote chronic drug abuse and worsen a highly prevalent public health problem in the era of the opioid epidemic. This study aimed to (a) determine general analgesic prescription patterns after surgery for vestibular schwannoma (VS) with a focus on opioid prescription rates, (b) identify risk factors for receiving narcotics for postoperative pain management, and (c) highlight the feasibility of opioid-free analgesic treatment strategies., Study Design: Retrospective chart review., Setting: Tertiary referral center., Patients: A total of 105 adult inpatients who underwent VS surgery., Interventions: Analgesic prescription patterns were evaluated, and factors associated with opioid prescriptions were identified., Main Outcome Measure: Number of prescribed analgesics., Results: Metamizole (=dipyrone) and acetaminophen (=paracetamol) were the most frequently prescribed non-opioid drugs. Sixty-three (60%) patients received an opioid with a median intake of 23.2 ± 24 mg of oral morphine equivalents. Only 10 (9.5%) individuals received opioids for longer than postoperative day 1. Subjects with small tumors undergoing middle cranial fossa tumor removal (p = 0.007) were more likely to receive opioid drugs. In contrast, patients undergoing retrosigmoid craniotomy required fewer opioids for pain control (p = 0.004). Furthermore, individuals receiving opioids were prone to obtain higher dosages of acetaminophen (odds ratio 1.054, 95% confidence interval 1.01-1.10, p = 0.022)., Conclusions: Opioids for acute postoperative analgesia after VS surgery may be necessary in many patients. However, middle- and long-term pain control can be accomplished using non-opioid treatment regimens, resulting in a reduction in opioid prescriptions and the accompanying negative effects on individual and public health., Competing Interests: Conflict of interest: C.A. receives research funding from MED-EL. L.D.L. receives research funding from Decibel Therapeutics/Regeneron Pharmaceuticals and Amgen and has worked as an independent consultant for Gerson Lehrman Group and Conclave Capital. L.D.L. is supported by a Career Development Award from the American Society of Gene & Cell Therapy and the Children's Tumor Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the American Society of Gene & Cell Therapy. The financial support of the Austrian Federal Ministry for Labour and Economy and the National Foundation for Research, Technology and Development and the Christian Doppler Research Association is gratefully acknowledged., (Copyright © 2024, Otology & Neurotology, Inc.)

Objectives: To understand country-level differences in the population's health and well-being in Europe in the aftermath of the COVID-19 pandemic, while also investigating the internal relationships among health and well-being outcomes., Study Design: Cross-sectional study., Methods: We collected representative panel-based samples of 1000 adult respondents per country across 14 Western European countries in early 2023. The survey used standardised instruments to assess health and well-being, including EQ-5D-5L, GHQ-12, PHQ-9, general satisfaction, the Brief Resilience Scale and the ULS-6 (Loneliness) Scale. Summary statistics of the aggregate scores for each country were calculated and ranked. Multidimensional unfolding was used to visualize the rank relationships across countries and the indices, whereby a closer distance between a country and an index indicated a higher/better rank. Additionally, two key objective country-level indices (GDP growth rate and excess mortality rates) were integrated into the analysis., Results: Austria was found to report better status on most of the indices, while Sweden and the UK ranked consistently worse than the other countries. The loneliness, EQ-VAS and satisfaction scores were plotted further from the mental well-being scores and EQ-5D utility scores. Countries that did well in controlling excess mortality and maintaining economic growth tended to exhibit lower performance in self-reported well-being., Conclusion: This study presents the variability in health and well-being across 14 West-European countries. Discrepancies between countries in self-reported outcomes reveal the complex interrelationship among different aspects of well-being. The study also highlights the complexities and challenges in optimising policies to maximize the overall well-being of society., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Objective: The COVID-19 pandemic had a major impact on medical care. This study evaluated the influence of the pandemic on blood pressure (BP) control and hypertension phenotypes as assessed by office and 24-hour ambulatory BP monitoring (ABPM)., Design and Methods: Data were collected from 33 centers including Excellence Centers of the European Society of Hypertension. Two groups of patients with treated hypertension were compared. Pandemic group: including participants who had ABPM twice - at visit 2 during the COVID-19 pandemic and visit 1 performed 9-15 months prior to visit 2. Pre-pandemic group: had ABPM at two visits, performed before the pandemic within 9-15 months interval. We determined the following hypertension phenotypes: masked hypertension, white coat hypertension, sustained controlled hypertension (SCH) and sustained uncontrolled hypertension (SUCH). We analyzed the prevalence of phenotypes and their changes between visits., Results: Data of 1419 patients, 616 (43 %) in the pandemic group and 803 (57 %) in the pre-pandemic group, were analyzed. At baseline (visit 1), the prevalence of hypertension phenotypes did not differ between groups. In the pandemic group, the change in hypertension phenotypes between two visits was not significant (p = 0.08). In contrast, in the pre-pandemic group, the prevalence of SCH increased during follow-up (28.8 % vs 38.4 %, p < 0.01) while the prevalence of SUCH decreased (34.2 % vs 27.8 %, p < 0.01). In multivariable adjusted analysis, the only factor influencing negative changes of hypertension phenotypes was the COVID-19 pandemic period., Conclusion: These results indicate a negative impact of the COVID-19 pandemic on BP control assessed by hypertension phenotypes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The challenge of selecting thyroid nodules for fine needle aspiration (FNA) cytology has led to the development of the Thyroid Imaging Reporting and Data System, primarily in 2 formats: European Thyroid Imaging Reporting and Data System (EU-TIRADS) and American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). Clinical observations suggest imperfect risk assessment for TIRADS 3 nodules ≥20 mm. This study aimed to evaluate the efficacy of TIRADS systems in distinguishing benign from malignant nodules in this subgroup., Methods: From May 2023 to March 2024, 1094 patients with thyroid nodules were referred for ultrasound at a University Hospital. Data on clinical, ultrasound, cytological, and histopathological parameters were collected. Nodules ≥20 mm were categorized by EU-TIRADS and ACR-TIRADS, and their predictive performance for malignancy was assessed through postthyroidectomy histopathology or FNA cytology (Bethesda classification)., Results: Two hundred sixty-seven patients (mean age 60.3 ± 14.3 years; 46 men, 221 women) with 308 nodules were analyzed. Twenty-two malignancies and 286 benign nodules were recorded. Recalculating European Thyroid Imaging Reporting and Data System 3 performance using 25-mm and 30-mm thresholds (ACR-modified EU-TIRADS) avoided 24% and 41% of FNAs, respectively, while ACR-TIRADS would prevent 26.6% (P > .05). Two malignancies were missed., Conclusion: EU-TIRADS and ACR-TIRADS show similar efficacy when using a 25 mm FNA threshold. Raising the cutoff for FNA in European Thyroid Imaging Reporting and Data System 3 nodules could reduce unnecessary procedures but may increase the risk of missed malignancies, impacting patient outcomes., Competing Interests: Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain., Methods: A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline). Proportional hazards models were fitted in 245,699 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to identify robust environmental predictors. Polygenic risk scores (PRS) of 5 proxies of adiposity [BMI, WHR, and three body shape phenotypes (PCs)] were computed using genetic weights from an independent cohort (UK Biobank). Environmental and genetic models were validated in 29,953 EPIC participants., Findings: Environmental models presented a remarkable predictive ability (AUC BMI : 0.69, 95% CI: 0.68-0.70; AUC WHR : 0.75, 95% CI: 0.74-0.77). The genetic geographic distribution for WHR and PC1 (overall adiposity) showed higher predisposition in North than South Europe. Predictive ability of PRSs was null (AUC: ∼0.52) and did not improve when combined with environmental models. However, PRSs of BMI and PC1 showed some prediction ability for BMI gain from self-reported BMI at 20 years old to baseline observation (early adulthood) (AUC: 0.60-0.62)., Interpretation: Our study indicates that environmental models to discriminate European individuals at higher risk of adiposity gain can be integrated in standard prevention protocols. PRSs may play a robust role in predicting adiposity gain at early rather than mid-late adulthood suggesting a more important role of genetic factors in this life period., Funding: French National Cancer Institute (INCA&#95;N°2019-176) 1220, German Research Foundation (BA 5459/2-1), Instituto de Salud Carlos III (Miguel Servet Program CP21/00058)., Competing Interests: Declaration of interests L.M. discloses that an immediate family member holds stocks in Novo Nordisk. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The worldwide prevalence of diabetes is increasing, particularly among older adults. Understanding the association between muscle strength and mortality in this population is crucial for developing targeted exercise recommendations., Objectives: To assess the prospective association of muscle strength with mortality in older adults with diabetes., Methods: From the Survey of Health, Ageing and Retirement in Europe (SHARE) study, spanning 28 countries, we included 16 149 diabetic adults aged 50 years and older (mean age 68.2 [standard deviation, SD, 9.2] years). Participants fulfilled two criteria: (1) diabetes diagnosis (ever) and (2) current use of diabetes medication. Muscle strength was assessed using handgrip dynamometry (unit: kg). Using time-varying Cox regression with restricted cubic splines, we determined the prospective association of muscle strength with all-cause and cause-specific mortality, controlling for various confounders., Results: Over a mean follow-up of 5.9 years (SD 3.8), 2754 participants died (17%). Using the median level of muscle strength as reference (30 kg), lower and higher levels were associated in a curvilinear fashion with higher and lower all-cause mortality risk, respectively. The 10th percentile of muscle strength (17 kg) showed a hazard ratio (HR) of 1.65 (95% confidence interval (CI) 1.53-1.79). The 90th percentile (47 kg) of muscle strength showed a HR of 0.55 (95% CI 0.49-0.63). A somewhat similar pattern, with varying strength of associations, was seen for mortality due to cardiovascular disease (CVD), respiratory disease, severe infectious disease, digestive system disease and cancer., Conclusion: Muscle strength is gradually and inversely associated with all-cause and cause-specific mortality risk in older adults with diabetes. As muscle strength is highly adaptable to resistance training at all ages, the present findings highlight the importance of improving muscle strength in older adults with diabetes., (© 2024 John Wiley & Sons Ltd.)

Background: Cachexia is a poor prognostic factor in many advanced cancers. Cachexia diagnostic criteria of the European Palliative Care Research Collaboration (EPCRC) may underestimate cachexia in Asians; therefore, new criteria have been proposed by the Asian Working Group for Cachexia (AWGC). We compared both criteria to determine differences in diagnostic rates and their association with lung cancer prognosis., Patients and Methods: This single-center, retrospective cohort study considered lung cancer outpatients receiving chemotherapy. Survival was analyzed using Kaplan-Meier curves and log-rank tests. The association between cachexia diagnosis and prognosis was examined for each set of criteria using a Cox proportional hazards model. C-statistic analysis was performed to compare the discriminative power for prognosis., Results: Among the 106 participants analyzed (median age, 75 [71-79] years; 75 males [70.8%]; 91 [85.9%] with performance status [PS] 0-1), 58 (54.7%) and 77 (72.6%) cachexia cases were diagnosed using the EPCRC and AWGC criteria, respectively. The latter encompassed all but one patient diagnosed using the EPCRC criteria. Patients with cachexia had a significantly poorer prognosis according to both criteria (EPCRC, p = 0.002; AWGC, p = 0.001). Both criteria had almost equal discriminative power for prognosis (EPCRC, C-statistic = 0.658; AWGC, C-statistic = 0.658). CRP in the AWGC criteria was most strongly related to prognosis., Conclusions: Cachexia was an independent poor prognostic factor in lung cancer patients receiving chemotherapy under the AWGC and EPCRC criteria, both of which had similar prognostic discriminatory power. Among CRP, anorexia, and grip strength, elevated CRP may be the most prognostically relevant parameter in the AWGC criteria., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background: Globally, loneliness is a growing public health concern associated with poor mental and physical health among older adults. Therefore, we performed a meta-analysis to explore the prevalence of loneliness and associated risk factors among older adults across six continents., Methods: Web of Science, PubMed, Embase, CINAHL, Cochrane Library, and references lists were comprehensively searched until April 2024. Data analysis was performed using Logit Transformation model in R-Software for pooled prevalence and DerSimonian-Lard random-effects model in Comprehensive Meta-Analysis for associated factors of loneliness. Heterogeneity was quantified by I 2 and τ 2 statistics. The funnel plot and Egger's regression test assessed publication bias., Results: A total of 70 studies with 462,083 older adults were included. The pooled prevalence of loneliness was 26 % (95 %CI, 23 %-30 %) with 38 % for North America, 34 % for Africa, 32 % for Asia and South America, 23 % for Europe, and 13 % for Oceania. Cognitive impairment (2.98; 95 %CI, 1.30-6.81), poor health (2.35; 95 %CI, 1.59-3.45), female (1.92; 95 %CI, 1.53-2.41), depression (1.74; 95 %CI, 1.40-2.16), widowed (1.67; 95 %CI, 1.13-2.48), single (1.51; 95 %CI, 1.06-2.17), institutionalization (2.95; 95 %CI, 1.48-5.88), rural residency (1.18; 95 %CI, 1.04-1.34) were associated with increased risk of loneliness. Being married (0.51; 95 %CI, 0.31-0.82), male (0.55; 95 %CI, 0.43-0.70), and non-institutionalization (0.34; 95 %CI, 0.17-0.68) were associated with lower risk of loneliness., Conclusion: Approximately, three among ten older adults aged ≥ 60 years are lonely worldwide. Early detection, prevention, and management of loneliness among older adults should consider diverse needs using gender-specific approaches., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is a curative treatment option. We investigated survival outcomes based on recipient-donor sex constellation (RDSC) following LT., Methods: We performed a European Liver Transplant Registry analysis, including patients from 1988 to December 2022. The cohort was split into four RDSC groups: female donor female recipient (FDFR), female donor male recipient (FDMR), male donor female recipient (MDFR) and male donor male recipient (MDMR). Survival analysis, including death with recurrence, was performed., Results: In 7601 LT for HCC with an overall median follow-up of 22.6 months (5.8, 60.7), death was registered in 25.1% and, as primary cause of death, HCC tumour recurrence in 26.0%. There was no statistically significant difference on crude survival estimates among the different RDSC groups (log-rank p = 0.66) with 10-year overall survival (OS) of 54.5% in FDFR, 54.6% in FDMR, 59.1% in MDFR and 56.9% in MDMR. On multivariable analysis, RDSC showed a significant effect on OS (FDFR as reference): MDFR (aHR 0.72, p = 0.023). No significant difference was found for FDMR (aHR 0.98, p = 0.821) and MDMR (aHR 0.90, p= 0.288). Regarding overall registered causes of death, differences between RDSC groups were found in rejection (p = 0.017) and cardiovascular (p = 0.046) associated deaths., Conclusions: In female recipients undergoing LT for HCC, male donor grafts were associated with a 28% reduction of mortality compared to female donor grafts., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Background & Aims: Conventional endoscopic mucosal resection (C-EMR) is established as the primary treatment modality for superficial nonampullary duodenal epithelial tumors (SNADETs), but recently underwater endoscopic mucosal resection (U-EMR) has emerged as a potential alternative. The majority of previous studies focused on Asian populations and small lesions (≤20 mm). We aimed to compare the efficacy and outcomes of U-EMR vs C-EMR for SNADETs in a Western setting., Methods: This was a retrospective multinational study from 10 European centers that performed both C-EMR and U-EMR between January 2013 and July 2023. The main outcomes were the technical success, procedure-related adverse events (AEs), and the residual/recurrent adenoma (RRA) rate, evaluated on a per-lesion basis. We assessed the association between the type of endoscopic mucosal resection and the occurrence of AEs or RRAs using mixed-effects logistic regression models (propensity scores). Sensitivity analyses were performed for lesions ≤20 mm or >20 mm., Results: A total of 290 SNADETs submitted to endoscopic resection during the study period met the inclusion criteria and were analyzed (C-EMR: n = 201, 69.3%; U-EMR: n = 89, 30.7%). The overall technical success rate was 95.5% and comparable between groups. In logistic regression models, compared with U-EMR, C-EMR was associated with a significantly higher frequency of overall delayed AEs (odds ratio [OR], 4.95; 95% CI, 2.87-8.53), postprocedural bleeding (OR, 7.92; 95% CI, 3.95-15.89), and RRAs (OR, 3.66; 95% CI, 2.49-5.37). Sensitivity analyses confirmed these results when solely considering either small (≤20 mm) or large (>20 mm) lesions., Conclusions: Compared with C-EMR, U-EMR was associated with a lower rate of overall AEs and RRAs, regardless of lesion size. Our results confirm the possible role of U-EMR as an effective and safe technique in the management of SNADETs., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as early as possible to obtain >50% low-density-lipoprotein cholesterol (LDL-c) reduction and an LDL-c < 1.4 mmol/l., Methods: A multinational European survey study of ACS patients between 2021-2022 and acquired data on LLT and lipid levels on admission and during 1-year posthospitalization. We compared plasma lipid changes and adherence to post-ACS lipid targets across two in-hospital LLT groups: high-intensity statin (HIS) monotherapy (mono-HIS) and a combination of HIS and ezetimibe (combo-HIS)., Results: Of 286 patients, 268 (94%) received in-hospital HIS and were included in the final analysis. Patients (median age: 61.1 years) had a median baseline LDL-c of 3.3 mmol/l. Mono-HIS was the predominant in-hospital LLT (72.4%). In-hospital combo-HIS was administered in 27.6% of the cases. Patients from high-income countries ( n  = 141) were more likely to receive in-hospital combo-HIS than patients from middle-income countries [ n  = 127; 38.3% vs. 15.7% patients, P  < 0.001). One-year post-ACS, 50 (26.5%) patients from the mono-HIS group received ezetimibe. The target of LDL-c ≤ 55 mg/dl was reached in 85 patients (31.7%), without significant difference between study groups [mono-HIS: 56 (28.9%) and combo-HIS: 29 (39.2%) patients, P  = 0.10]. The target of >50% reduction was achieved more frequently among the combo-HIS group than in the mono-HIS group (50.0% vs. 29.9%, respectively, P  = 0.002)., Conclusion: LDL-c targets were achieved in less than half of the patients post-ACS, regardless of the LLT regimen. Combo-HIS was initiated in-hospital post-ACS in only 28% and was associated with greater LDL-c reduction compared to a staged approach of mono-HIS with up-titration at follow-up., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10-20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671-5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10 -4 ), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m 2 . Pathway and correlation analyses revealed that miR-4533 targets SIPA1L2 in the Rap1 signalling pathway, and SIPA1L2 was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with SIPA1L2 in GBC development need to be further investigated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Common recreational drugs and new psychoactive substances pose challenges to public health. This study investigated the feasibility of merging cases of recreational drug poisoning reported to European poison centres., Methods: Four European poison centres (Freiburg, Germany; the Netherlands; Sweden and Switzerland) collaborated in a retrospective, observational study. We collected aggregated data on poisonings with 11 common recreational drugs and case-by-case data on poisonings with new psychoactive substances in 2021 by using anonymized data from electronic case reports., Results: In 2021, 2.0% of the poison centre calls involved poisonings with recreational drugs. The poison centres were contacted about 3,705 patients, involving 4,380 drug exposures, of which 3,708 were common recreational drugs, and 672 were new psychoactive substances. Per million inhabitants, the poisoning rate with common recreational drugs varied between 48 (Freiburg) and 145 (Sweden). Poisonings with amfetamine (22%), cocaine (20%), all delta-9-tetra-hydrocannabinol-containing preparations (20%), and 3,4-methylenedioxymetamfetamine (13%) exposures were most frequent. The poisoning rate per million inhabitants with new psychoactive substances varied between two (Switzerland) and 29 (Netherlands). Cathinones (43%), designer benzodiazepines (28%), and phenethylamines (13%) were the most commonly involved new psychoactive substance classes. Symptoms following cathinone poisoning were tachycardia (35%) and hypertension (13%), while following designer benzodiazepines, somnolence was most prominent (38%). The majority of users of new psychoactive substances were male (67%), 55% were between 18 and 30 years, and 8% involved minors (<18 years)., Discussion: This study showed the feasibility of merging data on recreational drug poisoning collected by poison centres in four countries. Despite underestimating the overall incidence of drug-related health incidents, poison centre data offers national coverage, unlike other data sources, such as drug-related emergency department visits., Conclusion: This multi-centre, multi-national study reported a substantial annual number of recreational drug poisonings, with a variable proportion of new psychoactive substances. It shows that poison centre data offers detailed insights into exposures to common recreational drugs and new psychoactive substances, user characteristics, and symptoms. It can be used for comprehensive monitoring of drug-related health incidents on a multi-national level.