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Byline: S. Assen (1,6), F. Bosma (3,6), L. M. E. Staals (2), B. J. Kullberg (1,6), W. J. G. Melchers (3,6), M. Lammens (4,5), F. H. M. Kornips (7), P. E. Vos (5), B. G. Fikkers (2) Author Affiliation: (1) University Medical Center St. Radboud, Dept. of General Internal Medicine, 9101, 6500, HB Nijmegen, The Netherlands (2) Dept. of Intensive Care Medicine, University Medical Center St. Radboud, Nijmegen, The Netherlands (3) Dept. of Clinical Microbiology, University Medical Center St. Radboud, Nijmegen, The Netherlands (4) Dept. of Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands (5) Dept. of Neurology, University Medical Center St. Radboud, Nijmegen, The Netherlands (6) Nijmegen University, Center for Infectious Diseases, Nijmegen, The Netherlands (7) Maxima Medical Center, Department of Neurology, Veldhoven, The Netherlands Article History: Registration Date: 01/01/2004 Received Date: 17/04/2003 Accepted Date: 16/01/2004

Importance: Euthanasia or assisted suicide (EAS) in patients suffering from a psychiatric disorder (PD) is a controversial topic worldwide. In the Netherlands, this practice is regulated by law. All cases of EAS have to be reported and are assessed by the Regional Euthanasia Review Committees (RTEs), who publish a selection of all cases on their website., Objective: To provide insight into the Dutch practice of EAS in patients suffering from a psychiatric disorder., Design Setting and Participants: We performed a retrospective case review study in which all published cases of EAS in patients suffering from a PD between 2017 and 2022 were analyzed., Interventions or Exposures: Not applicable., Main Outcomes and Measures: Characteristics of patients who died by EAS because of suffering from a PD, characteristics of the reporting physician and consultant(s) and the RTEs assessment of published cases., Results: Of the 72 cases studied, the majority of patients were female (n=48, 67%), suffered from 3 or more conditions (n=38, 53%) and died by euthanasia instead of assistance in suicide (n=56, 78%). In 63% of cases (n=45), the life termination was performed by a physician from the Euthanasia Expertise center (EE). The RTEs' judgement that the case did not meet the due care criteria (n=11) was in all cases related to issues regarding the (advice of the) independent physician or psychiatric expert., Conclusion and Relevance: This qualitative study shows that the RTEs attach great importance to a careful evaluation procedure of physicians handling EAS requests and to the physician demonstrating ability to reflect on his views, especially when the independent consultant evaluates the case different than the physician. Training for physicians and more transparency in the assessment of EAS requests in patients with a PD may lower the threshold for physicians to handle requests of these patients themselves., Trial Registration: Not applicable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bosma, Mink, van Delden, van der Heide, van de Vathorst and van Thiel.)

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients., Methods: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes., Results: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048)., Conclusion: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number ( n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM ( n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM ( n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment., Importance: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures., Competing Interests: The authors declare no conflict of interest.

Purpose: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy., Methods: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated., Results: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles., Conclusion: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Introduction: Metastatic urothelial carcinoma (mUC) is a lethal disease with limited treatment options. We aimed to compare the treatment patterns and outcomes of patients with mUC who were treated before and after the introduction of immune checkpoint inhibitors (ICIs) at a tertiary hospital in Barcelona., Methods: Single-center retrospective study from 2004 to 2021. Access to ICIs began in December 2014. We analyzed differences in clinical characteristics and survival outcomes, such as overall survival (OS), progression-free survival (PFS), and restricted mean survival time (RMST)., Results: A total of 206 patients were included. The median follow-up was 48.6 months. Ninety and 116 patients were treated during the pre-ICIs and the post-ICIs eras, respectively. We found high treatment attrition rates, with no differences in the number of patients who received second-line (48%) and third-line (26%) therapies between the two eras. In the second-line, ICIs became the predominant therapy (58%), leading to a 30% reduction in the utilisation of platinum-based ChT and non-platinum ChT. Innovative approaches including ICIs in the first-line treatment (18%) and targeted therapies in the third-line setting (34%) were observed. We found no differences in the median OS, 2-year OS, or 24-month RMST between the two periods., Conclusion: ICIs have emerged as a transformative treatment option, reshaping the treatment landscape. Nevertheless, substantial attrition rates from first-line to subsequent lines of systemic therapies might impede the potential impact of ICIs on long-term survival outcomes across the entire population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: In the Netherlands, assisting in suicide is allowed for physicians and regulated by the Termination of Life on Request and Assisted Suicide (review procedures) Act. However, some people decide to end their lives outside the medical domain, without a physician's help. Two approaches for such self-directed dying are voluntary stopping eating and drinking (VSED) and independently taking lethal medication attended by a confidant (ILMC). The frequency of deaths by either of these methods in the Netherlands was examined in 2007. Since then, there have been societal, political and healthcare developments which may have had an influence on the frequency of self-directed dying. The primary objective of this study is to estimate how many people in the Netherlands currently die by VSED or ILMC. Secondary objectives include providing insight in the characteristics and quality of dying of people who choose for self-directed dying., Methods and Analysis: This cross-sectional study consists of an online questionnaire study (January to February 2024) among a randomly drawn sample (n=37 500) from a representative panel of the Dutch adult population in which participants are asked about potential experiences of close relatives choosing for VSED or ILMC. A two-stage screening procedure will be used to determine whether the respondents' experiences represent a death by VSED or ILMC. Additional interviews (n=40) will be held with questionnaire respondents indicating their willingness to participate (May to September 2024). Quantitative data will be analysed using SPSS software, and qualitative data will be thematically analysed using NVivo software., Ethics and Dissemination: The study obtained approval from the Medical Research Ethics Committee of the Erasmus Medical Center, under number MEC-2023-0689. Informed consent will be sought from study participants in line with General Data Protection Regulation legislation. Results of the study will be disseminated through publications in scientific journals and conference presentations., Trial Registration Number: NCT06186791., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We explored characteristics of people with an accumulation of health problems related to old age requesting euthanasia or physician-assisted suicide (EAS) and identified characteristics associated with granting EAS requests. Methods: We conducted a cross-sectional questionnaire study among Dutch physicians on characteristics of these people requesting EAS ( n = 123). Associations between characteristics and granting a request were assessed using logistic regression analyses. Results: People requesting EAS were predominantly >80 years old (82.4%), female (70.0%), widow/widower (71.7%), (partially) care-dependent (76.7%), and had a life expectancy >12 months (68.6%). The most prevalent health problems were osteoarthritis (70.4%) and impaired vision and hearing (53.0% and 40.9%). The most cited reasons to request EAS were physical deterioration (68.6%) and dependence (61.2%). 44.7% of requests were granted. Granting a request was positively associated with care dependence, disability/immobility, impaired vision, osteoporosis, loss of control, suffering without prospect of improvement and a treatment relationship with the physician >12 months. Conclusion: Enhanced understanding of people with an accumulation of health problems related to old age requesting EAS can contribute to the ongoing debate on the permissibility of EAS in people without life-threatening conditions., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Kraak-Steenken, Renckens, Pasman, Bosma, van der Heide and Onwuteaka-Philipsen.)

Background: The dimensions of the prostatic gland in castrated adult dogs, as assessed by ultrasonography, is currently not yet reported in veterinary literature. The current study was aimed at reporting the prostatic dimensions in castrated dogs and investigate the relationship between the dogs' body weight and prostate size. A second aim of the study was to investigate whether there was a relationship between the dogs' age and prostate dimensions. A prospective, single-centre, observational study was conducted and 72 privately owned, adult, male castrated dogs with a range of breeds and ages met the final inclusion criteria. The subjects were divided into three categories based on body weight., Results: A Kruskal-Wallis test found prostatic length and prostatic depth in the longitudinal orientation to be significantly different among the 3 categories (P < 0.005), with an increase in both prostatic length and prostatic depth with increasing body weight. Linear regression of the data set provided comprehensive formulas calculating prostatic length and depth based on the body weight of the dog (r 2 of 0.69 and 0.53 for prostatic length and depth respectively). Kendall's Tau rank test showed no correlation between dogs' age and prostate dimensions (P > 0.100)., Conclusions: The current study is the first to provide a comprehensive, weight-based reference for the canine prostate gland of castrated dogs when assessed on ultrasonography., (© 2022. The Author(s).)

Objectives: General practitioners (GPs) and sexual health centres (SHCs) are the main providers of HIV testing and diagnose two-thirds of HIV infections in the Netherlands. We compared regional HIV testing and positivity by GPs versus SHCs to gain insight into strategies to improve HIV testing, to enable timely detection of HIV infections., Methods: Laboratory data (2011-2018) on HIV testing by GPs and SHCs in five Dutch regions with varying levels of urbanisation were evaluated. Regional HIV testing rates per 10 000 residents ≥15 years (mean over period and annual) were compared between providers using negative binomial generalised additive models and additionally stratified by sex and age (15-29 years, 30-44 years, 45-59 years, ≥60 years). χ 2 tests were used to compare positivity percentage between the two groups of providers., Results: In the study period, 505 167 HIV tests (GP 36%, SHC 64%) were performed. The highest HIV testing rates were observed in highly urbanised regions, with large regional variations. The HIV testing rates ranged from 28 to 178 per 10 000 residents by GPs and from 30 to 378 per 10 000 by SHCs. Testing rates by GPs were lower than by SHCs in three regions and comparable in two. In all regions, men were tested less by GPs than by SHCs; for women, this varied by region. Among those aged 15-29 years old, GPs' testing rates were lower than SHCs', while this was reversed in older age categories in four out of five regions. The overall mean HIV positivity was 0.4%. In contrast to other regions, positivity in Amsterdam was significantly higher among individuals tested by GPs than by SHCs., Conclusions: This retrospective observational study shows that besides SHCs, who perform opt-out testing for key groups, GPs play a prominent role in HIV testing, especially in non-key populations, such as women and older individuals. Large regional variation exists, requiring region-specific interventions to improve GPs' HIV testing practices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

TBE is an emerging infectious disease in the Netherlands since July 2016, and risk areas have not been defined yet. Until October 2020 twelve autochthonous cases of TBE have been identified. In six of these cases transmission of TBE virus likely occurred in the Twente region, which therefore is the region with the highest case number and risk of contracting the disease. Here we summarize the Twente cases so far and discuss if the Twente region should be considered a risk-area using criteria of traditional TBE endemic countries, and the public health measures that may accompany such designation., (Copyright © 2022. Published by Elsevier GmbH.)