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Recently, the media has been highlighting the increasing presence of older women on screen. However, it is important to examine whether this is the case and how exactly older women are being portrayed. This research examined the representations of older women in Hollywood romantic comedies released from 2000 to 2021. To assess diversity and stereotypes, forty-four popular films were analysed. Here we identified, in twenty of the forty-four films, one or more characters aged 60 and over. Results indicate that, while the number of older female characters was high compared to other studies, their diversity was rather limited. Most characters were in their early sixties, white, middle-class, able-bodied, and heterosexual. Characters from ethnic minorities, sexual minorities and with disabilities were almost absent. Stereotypes, such as the Golden Ager and the Shrew, were frequently used. This confirms the dominant discourse on older women, which leads to negative attitudes towards ageing.

Objectives To validate a rapid serological test (RST) for SARS-CoV-2 antibodies used in seroprevalence studies in healthcare providers, including primary healthcare providers (PHCPs) in Belgium.Design A phase III validation study of the RST (OrientGene) within a prospective cohort study.Setting Primary care in Belgium.Participants Any general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages patients were eligible in the seroprevalence study. For the validation study, all participants who tested positive (376) on the RST at the first testing timepoint (T1) and a random sample of those who tested negative (790) and unclear (24) were included.Intervention At T2, 4 weeks later, PHCPs performed the RST with fingerprick blood (index test) immediately after providing a serum sample to be analysed for the presence of SARS-CoV-2 immunoglobulin G antibodies using a two-out-of-three assay (reference test).Primary and secondary outcome measures The RST accuracy was estimated using inverse probability weighting to correct for missing reference test data, and considering unclear RST results as negative for the sensitivity and positive for the specificity. Using these conservative estimates, the true seroprevalence was estimated both for T2 and RST-based prevalence values found in a cohort study with PHCPs in Belgium.Results 1073 paired tests (403 positive on the reference test) were included. A sensitivity of 73% (a specificity of 92%) was found considering unclear RST results as negative (positive). For an RST-based prevalence at T1 (13.9), T2 (24.9) and T7 (70.21), the true prevalence was estimated to be 9.1%, 25.9% and 95.7%, respectively.Conclusion The RST sensitivity (73%) and specificity (92%) make an RST-based seroprevalence below (above) 23% overestimate (underestimate) the true seroprevalence.Trial registration number NCT04779424.

Human myxovirus resistance 2 (MX2) can restrict HIV-1 and herpesviruses at a post-entry step through a process requiring an interaction between MX2 and the viral capsids. The involvement of other host cell factors, however, remains poorly understood. Here, we mapped the proximity interactome of MX2, revealing strong enrichment of phenylalanine-glycine (FG)-rich proteins related to the nuclear pore complex as well as proteins that are part of cytoplasmic ribonucleoprotein granules. MX2 interacted with these proteins to form multiprotein cytoplasmic biomolecular condensates that were essential for its anti-HIV-1 and anti-herpes simplex virus 1 (HSV-1) activity. MX2 condensate formation required the disordered N-terminal region and MX2 dimerization. Incoming HIV-1 and HSV-1 capsids associated with MX2 at these dynamic cytoplasmic biomolecular condensates, preventing nuclear entry of their viral genomes. Thus, MX2 forms cytoplasmic condensates that likely act as nuclear pore decoys, trapping capsids and inducing premature viral genome release to interfere with nuclear targeting of HIV-1 and HSV-1. [Display omitted] • Interferon-induced antiviral protein MX2 forms cytoplasmic condensates with FG Nups • MX2's N-terminal domain and dimerization are required for condensate formation • Restriction of HIV-1 and HSV-1 by MX2 requires condensate formation • MX2 condensates trap HIV-1 capsids and cause premature release of HSV-1 genomes MX2 restricts HIV-1 and herpes simplex virus 1 (HSV-1) through a poorly understood mechanism. Moschonas et al. reveal that MX2 assembles FG nucleoporins into cytoplasmic biomolecular condensates that interact with incoming capsids to trap them or induce premature viral genome release. MX2's N-terminal domain controls condensate formation, which is essential for HIV-1 and HSV-1 restriction. [ABSTRACT FROM AUTHOR]

Abstract Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, only very limited unbiased comprehensive approaches to map its interactome have been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting that HOTAIR has functions independent of its (post-)transcriptional mode-of-action.

Fatty acids (FA) in follicular fluid (FF) are present in an esterified form [triglycerides, cholesterol esters and phospholipids] or as non-esterified FA, which partly originate from blood. However, a comprehensive comparison of blood vs. FF FA in various lipid classes is missing. The aim of this study was to determine the distribution of the FA composition in each lipid class of serum and FF, and to investigate their mutual correlations. A total of 74 patients undergoing assisted reproductive technology treatment were involved in the study. Both in serum as well as FF, saturated FA and mono-unsaturated FA were predominant in non-esterified FA and triglycerides fractions while poly-unsaturated FA were mainly present in phospholipids and cholesterol esters fractions, although phospholipids also contained high proportions of saturated FA. Irrespective of the lipid class, the FA proportions differed between serum and FF (P < 0.05). Despite these differences, most of the FA in triglycerides, phospholipids and cholesterol esters of FF were well correlated with their proportions in serum. Nevertheless, only weak to moderate associations (r < 0.60) were observed for the majority of the FA in the non-esterified FA fraction. Differences in FA product/precursor-ratios were found between serum and FF, such as higher C20:4n-6 to C18:2n-6 and C20:5n-3 to C18:3n-3 in FF. FA metabolism (e.g. desaturation and elongation) takes place in cells of the intrafollicular micro-environment. Moreover, good correlations between esterified FA in serum and FF suggest esterified FA in blood could be representative of esterified FA in FF.

During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

Background Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs. Most antidepressants are prescribed by general practitioners (GPs) but it remains unclear why they do not discontinue long-term use. Aim To explore GPs’ views and experiences of discontinuing long-term antidepressants, barriers and facilitators of discontinuation and required support. Design and setting Qualitative study in Belgian GPs. Method 20 semi-structured face-to-face interviews with GPs. Interviews were analysed thematically. Results The first theme, ‘Success stories’ describes three strong motivators to discontinue antidepressants: patient health issues, patient requests and a new positive life event. Second, not all GPs consider long-term antidepressant use a ‘problem’ as they perceive antidepressants as effective and safe. GPs’ main concern is the risk of relapse. Third, GPs foresee that discontinuation of antidepressants is not an easy and straightforward process. GPs weigh up whether they have the necessary skills and whether it is worth the effort to start this process. Conclusion Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs, especially in the absence of a facilitating life-event or patient demand. The absence of a compelling need for discontinuation and fear of relapse of symptoms in a stable patient are important barriers for GPs when considering discontinuation. In order to increase GPs’ motivation to discontinue long-term antidepressants, more emphasis on the futility of the actual effect and on potential harms related to long-term use is needed.KEY POINTS Current awareness: Long-term antidepressant use, much longer than recommended by guidelines, can harm patients and generate unnecessary costs. Main statements: • Discontinuation of long-term antidepressants is a difficult and uncertain process for GPs. • More emphasis on the futility of the actual effect of antidepressants and on potential harms related to long-term use is needed.

Introduction Overdiagnosis is the diagnosis of a disease that would never have caused any symptom or problem. It is a harmful side effect of screening and may lead to unnecessary treatment, costs and emotional drawbacks. Doctors and other healthcare professionals (HCPs) have the opportunity to mitigate these consequences, not only by informing their patients or the public but also by adjusting screening methods or even by refraining from screening. However, it is unclear to what extent HCPs are fully aware of overdiagnosis and whether it affects their screening decisions. With this systematic review, we aim to synthesise all available research about what HCPs know and think about overdiagnosis, how it affects their position on screening policy and whether they think patients and the public should be informed about it.Methods and analysis We will systematically search several databases (MEDLINE, Embase, Web of Science, Scopus, CINAHL and PsycArticles) for studies that directly examine HCPs' knowledge and subjective perceptions of overdiagnosis due to health screening, both qualitatively and quantitatively. We will optimise our search by scanning reference and citation lists, contacting experts in the field and hand searching abstracts from the annual conference on 'Preventing Overdiagnosis'. After selection and quality appraisal, we will analyse qualitative and quantitative findings separately in a segregated design for mixed-method reviews. The data will be examined and presented descriptively. If the retrieved studies allow it, we will review them from a constructivist perspective through a critical interpretive synthesis.Ethics and dissemination For this type of research, no ethical approval is required. Findings from this systematic review will be published in a peer-reviewed journal and presented at the annual congress of 'Preventing Overdiagnosis'. In addition, the results will serve as guidance for further research on this topic.PROSPERO registration number CRD42021244513.

ABSTRACT The VALHUDES framework (NCT03064087) was established to evaluate the clinical accuracy of HPV testing on self-samples compared with HPV testing on matched clinician-taken cervical samples. Women referred to colposcopy due to previous cervical abnormalities were recruited at five Belgian colposcopy centers. A total of 486 pairs of matched cervical samples and vaginal self-samples were included in the analysis (228 collected with Evalyn Brush and 258 with Qvintip). The dry vaginal brushes were transferred into 20 mL ThinPrep PreservCyt solution. All specimens were tested with the Abbott RealTime High Risk HPV assay (Abbott RT). Testing on vaginal and cervical specimens was considered the index and comparator tests, respectively, and colposcopy and histology as the reference standard. The clinical sensitivity for CIN2+ of Abbott RT (cutoff ≤32 cycle number [CN]) on vaginal self-samples (Evalyn Brush and Qvintip combined) was 8% lower than on the cervical clinician-collected samples (ratio = 0.92 [95% CI, 0.87 to 0.98]), while the specificity was similar (ratio = 1.04 [95% CI, 0.97 to 1.12]). Sensitivity (ratio = 0.95 [95% CI, 0.89 to 1.02]) and specificity (ratio = 1.11 [95% CI, 0.995 to 1.23]) on Evalyn Brush samples was similar to cervical, while on Qvintip samples, the sensitivity was 12% lower than cervical samples (ratio = 0.88 [95% CI, 0.78 to 0.998]) with similar specificity (0.99 [95% CI, 0.90 to 1.10]). Exploratory cutoff optimization (cutoff ≤35 CN) resulted in an improvement of the relative sensitivity (self-sampling versus clinician sampling: ratio = 0.96 [95% CI, 0.91 to 1.02]) but yielded a loss in relative specificity (ratio = 0.92 [0.85 to 1.00]). The clinical accuracy of Abbott RT differed from the self-sampling device. However, after cutoff optimization, the sensitivity on self-samples taken with either of two vaginal brushes became similar to clinician-collected samples. IMPORTANCE Self-samples are becoming a crucial part of HPV-based cervical cancer screening programs to reach nonattendee women and increase screening coverage. Therefore, the VALHUDES framework was established to validate and evaluate HPV tests and devices on self-samples. Here, in the present manuscript, we evaluated the accuracy of the RealTime High Risk HPV assay (Abbott RT) on two different vaginal devices to detect cervical intraepithelial neoplasia grade two or higher (CIN2+). The study results demonstrated that the Abbott RT assay is similarly accurate on vaginal self-samples as on matched clinician-taken cervical samples after adjusting cutoff values. Moreover, we observed that some vaginal devices perform better than others in CIN2+ detection. We also underline the necessity of standardization and validation of general workflow and sample handling procedures for vaginal self-samples.

BackgroundThe COVID-19 pandemic brought global disruption to health, society and economy, including to the conduct of clinical research. In the European Union (EU), the legal and ethical framework for research is complex and divergent. Many challenges exist in relation to the interplay of the various applicable rules, particularly with respect to compliance with the General Data Protection Regulation (GDPR). This study aimed to gain insights into the experience of key clinical research stakeholders [investigators, ethics committees (ECs), and data protection officers (DPOs)/legal experts working with clinical research sponsors] across the EU and the UK on the main challenges related to data protection in clinical research before and during the pandemic.Materials and methodsThe study consisted of an online survey and follow-up semi-structured interviews. Data collection occurred between April and December 2021. Survey data was analyzed descriptively, and the interviews underwent a framework analysis.Results and conclusionIn total, 191 respondents filled in the survey, of whom fourteen participated in the follow-up interviews. Out of the targeted 28 countries (EU and UK), 25 were represented in the survey. The majority of stakeholders were based in Western Europe. This study empirically elucidated numerous key legal and ethical issues related to GDPR compliance in the context of (cross-border) clinical research. It showed that the lack of legal harmonization remains the biggest challenge in the field, and that it is present not only at the level of the interplay of key EU legislative acts and national implementation of the GDPR, but also when it comes to interpretation at local, regional and institutional levels. Moreover, the role of ECs in data protection was further explored and possible ways forward for its normative delineation were discussed. According to the participants, the pandemic did not bring additional legal challenges. Although practical challenges (for instance, mainly related to the provision of information to patients) were high due to the globally enacted crisis measures, the key problematic issues on (cross-border) health research, interpretations of the legal texts and compliance strategies remained largely the same.

The volume of distribution at steady state (Vss) in neonates is still often estimated through isometric scaling from adult values, disregarding developmental changes beyond body weight. This study aimed to compare the accuracy of two physiologically based pharmacokinetic (PBPK) Vss prediction methods in neonates (Poulin & Theil with Berezhkovskiy correction (P&T+) and Rodgers & Rowland (R&R)) with isometrical scaling. PBPK models were developed for 24 drugs using in-vitro and in-silico data. Simulations were done in Simcyp (V22) using predefined populations. Clinical data from 86 studies in neonates (including preterms) were used for comparison, and accuracy was assessed using (absolute) average fold errors ((A)AFEs). Isometric scaling resulted in underestimated Vss values in neonates (AFE: 0.61), and both PBPK methods reduced the magnitude of underprediction (AFE: 0.82–0.83). The P&T+ method demonstrated superior overall accuracy compared to isometric scaling (AAFE of 1.68 and 1.77, respectively), while the R&R method exhibited lower overall accuracy (AAFE: 2.03). Drug characteristics (LogP and ionization type) and inclusion of preterm neonates did not significantly impact the magnitude of error associated with isometric scaling or PBPK modeling. These results highlight both the limitations and the applicability of PBPK methods for the prediction of Vss in the absence of clinical data.

Abstract Background Interventions to reach women who do not participate regularly in screening may reduce the risk of cervical cancer. Self-collection of a vaginal specimen has been shown to increase participation. The relative clinical accuracy of human papillomavirus (HPV) testing on first-void urine (with Colli-Pee) and on vaginal self-samples versus on cervical clinician-collected samples is being investigated in the VALHUDES trial. The current study assesses attitudes and experiences regarding self-sampling among women enrolled in VALHUDES. Methods Questionnaires from 515 women (age 25–64 years [N = 498]; 95%) declared that instructions for self-collection were clear, that collection was easy, and that they were confident about having performed the procedure correctly, for both urine and vaginal collection. However, a proportion of women found self-sampling unpleasant (9.5% [49/515] for urine collection; 18.6% [96/515] and 15.5% [80/515] for vaginal sampling with cotton swabs or plastic brushes, respectively). For their next screening round, 57% would prefer self-sampling whereas 41% opted for collection by a clinician. Among women preferring self-sampling, 53% would choose for urine collection, 38% for vaginal self-collection and 9% had no preference. Age did not modify preferences. Conclusion We conclude that both urine and vaginal self-sampling are well accepted by women, with a preference for urine sampling. Although the large majority of women are confident in their ability to perform self-sampling, four to five over ten women preferred specimen collection by a clinician. Trial registration The study VALHUDES was registered in ClinicalTrials.gov (identifier: NCT03064087 ).

Abstract Background The landscape of clinical research has evolved over the past decade. With technological advances, the practice of using electronic informed consent (eIC) has emerged. However, a number of challenges hinder the successful and widespread deployment of eIC in clinical research. Therefore, we aimed to investigate the views of various stakeholders on the potential advantages and challenges of eIC. Methods Semi-structured interviews were conducted with 39 participants from 5 stakeholder groups from across 11 European countries. The stakeholder groups included physicians, patient organization representatives, regulator representatives, ethics committee members, and pharmaceutical industry representatives, and all were involved in clinical research. Interviews were analyzed using the framework method. Results Interviewees identified that a powerful feature of eIC is its personalized approach as it may increase participant empowerment. However, they identified several ethical and practical challenges, such as ensuring research participants are not overloaded with information and offering the same options to research participants who would prefer a paper-based informed consent rather than eIC. According to the interviewees, eIC has the potential to establish efficient long-term interactions between the research participants and the research team in order to keep the participants informed during and after the study. Interviewees emphasized that a personal interaction with the research team is of utmost importance and this cannot be replaced by an electronic platform. In addition, interviewees across the stakeholder groups supported the idea of having a harmonized eIC approach across the European Member States. Conclusions Interviewees reported a range of design and implementation challenges which needs to be overcome to foster innovation in informing research participants and obtaining their consent electronically. It was considered important that the implementation of eIC runs alongside the face-to-face contact between research participants and the research team. Moreover, interviewees expect that eIC could offer the opportunity to enable a personalized approach and to strengthen continuous communication over time. If successfully implemented, eIC may facilitate the engagement of research participants in clinical research.

Background: Countries are struggling to provide affordable access to medicines while supporting the market entry of innovative, expensive products. This Perspective aims to discuss challenges and avenues for balancing health care system objectives of access, affordability and innovation related to medicines in Belgium (and in other countries).Methods: This Perspective focuses on the R&D, regulatory approval and market access phases, with particular attention to oncology medicines, precision medicines, orphan medicines, advanced therapies, repurposed medicines, generics and biosimilars. The authors conducted a narrative review of the peer-reviewed literature, of the grey literature (such as policy documents and reports of consultancy agencies), and of their own research.Results: Health care stakeholders need to consider various initiatives for balancing innovation with access to medicines, which relate to clinical and non-clinical outcomes (e.g. supporting the conduct of pragmatic clinical trials, treatment optimisation and patient preference studies, optimising the use of real-world evidence in market access decision making), value assessment (e.g. increasing the transparency of the reimbursement system and criteria, tailoring the design of managed entry agreements to specific types of uncertainty), affordability (e.g. harnessing the role of generics and biosimilars in encouraging price competition, maximising opportunities for personalising and repurposing medicines) and access mechanisms (e.g. promoting collaboration and early dialogue between stakeholders including patients).Conclusion: Although there is no silver bullet that can balance valuable innovation with affordable access to medicines, (Belgian) policy and decision makers should continue to explore initiatives that exploit the potential of both the on-patent and off-patent pharmaceutical markets.

BackgroundOwing to the infectious nature of COVID-19, alternative solutions, such as electronic informed consent (eIC), needed to be implemented to inform research participants about study-related information and to obtain their consent. This study aimed to investigate stakeholders’ experiences with alternative consenting methods as well as their views on any regulatory or legal guidelines for eIC implementation in clinical research. Results may serve as the cornerstone to rethink the informed consent process in clinical research.Materials and methodsThis study consisted of an online survey among three stakeholder groups across European Union (EU) Member States and the United Kingdom. The stakeholder groups included (i) investigators, (ii) data protection officers (DPOs) or legal experts working in the pharmaceutical industry, academia, and academic biobanks, and (iii) ethics committee (EC) members. Data collection occurred between April and December 2021. The data collected were analyzed using descriptive and inferential statistics.ResultsThe online survey was completed by 191 respondents, of whom 52% were investigators. Respondents were active in 24 out of the 27 EU Member States and the United Kingdom. The majority of each stakeholder group considered validated electronic methods moderately or extremely useful to re-consent previously enrolled research participants upon study amendments or to obtain consent from COVID-19 patients. Nevertheless, this exploratory survey identified that only 13% of DPOs/legal experts, 26% of investigators, and 41% of EC members had experience with eIC. In addition, results suggest that the legal acceptance of eIC across EU Member States and the United Kingdom is variable and that a definition of eIC, issued by national law or policy, is rarely available. The results also showed that the COVID-19 pandemic brought additional challenges to inform participants and to obtain their consent; for example, related to travel restrictions.ConclusionA number of alternative consenting methods were recommended, for example by the European Medicines Agency, to ensure clinical study continuation during the COVID-19 pandemic. Although stakeholders support the use of eIC in clinical research, it seems that the experience with eIC is low. To harmonize eIC practices as much as possible, further investments in multi-stakeholder, multi-national guidance are needed.

Background: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. Methods: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. Trial registration: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

Abstract This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p

Objective This study aimed to provide recommendations for a personalized electronic informed consent interface that is adapted to research participants’ needs and could enable a longitudinal interaction between the participants and the research team. Methods The co-creation process consisted of three co-creation workshops, one focus group discussion, and four semi-structured interviews. In total, 24 participants, who had taken part in four disparate clinical studies in Belgium, were involved. Descriptive statistics and qualitative content analysis were applied to analyze the survey data and audio recordings. Results Varying perceptions on the type and amount of information described in an informed consent form were reported. Other findings were related to the structure and presentation of information, setting preferences for data sharing, and electronically signing new informed consent versions. Regarding the long-term interaction, most of the participants wanted to receive progress updates, including the results, of the study in which they had taken part. They proposed to receive a notification, preferably via email, in case new information is made available on the electronic informed consent interface. Conclusions To optimally support the design of an electronic informed consent interface, it is key to understand the research participants’ needs. Study findings suggest that an electronic informed consent interface may be a promising technological application to interactively provide study-related information and to keep participants informed during and after the clinical study.

BackgroundRapid technological advancements are reshaping the conduct of clinical research. Electronic informed consent (eIC) is one of these novel advancements, allowing to interactively convey research-related information to participants and obtain their consent. The COVID-19 pandemic highlighted the importance of establishing a digital, long-distance relationship between research participants and researchers. However, the regulatory landscape in the European Union (EU) is diverse, posing a legal challenge to implement eIC in clinical research. Therefore, this study takes the necessary steps forward by providing an overview of the current regulatory framework in the EU, relevant to eIC.MethodsWe reviewed and analyzed the key EU regulations, such as the EU General Data Protection Regulation (GDPR) and the Clinical Trials Regulation (CTR). We investigated the legality of eIC in several EU Member States, Switzerland, and the United Kingdom. To this end, we contacted the medicines agencies of various countries to clarify the national requirements related to the implementation and use of eIC in clinical research. Our research was complemented by comparing the legal acceptance of eIC between the EU and the United States.ResultsIn the EU, a distinction must be made between eIC for participation in clinical research and eIC for processing the participants’ personal data, complying respectively with requirements laid down by the CTR and the GDPR. On a national level, countries were classified into three groups: (1) countries accepting and regulating the use of eIC, (2) countries accepting the use of eIC without explicitly regulating it, and (3) countries not accepting the use of eIC. As a result, the regulation of eIC through laws and guidelines shows a large variety among EU Member States, while in the United States, it is harmonized through the Code of Federal Regulations.ConclusionVarious requirements must be considered when implementing eIC in clinical research. Nevertheless, requirements across the EU Member States may differ significantly, whereas, in the United States, efforts have already been made to achieve a harmonized approach.

Objective To estimate the rate and type of downstream activities (DAs) after laboratory testing in primary care, with a specific focus on check-up laboratory panels, and to explore the effect of a clinical decision support system (CDSS) for laboratory ordering on these DAs.Design Cluster randomised clinical trial.Setting 72 primary care practices in Belgium, with 272 general practitioners (GPs), randomly assigned to the intervention arm or the control arm.Participants The study included 10 270 lab panels from 9683 primary care patients (women 55.1%, mean age 56.5). All adult patients who consulted one of the participating GPs during the trial period and needed a laboratory exam were eligible for participation.Interventions GPs in the intervention group used a CDSS integrated into their online laboratory ordering system, while GPs in the control arm used their lab ordering system as usual. The trial duration was 6 months, with another 6 months follow-up.Main outcome measures This publication reports on the exploratory outcome of DAs after an initial laboratory exam and the effect of the CDSS on these DAs.Results 19.7% of all laboratory panels resulted in further diagnostic procedures (95% CI 18.9% to 20.5%) and 19% (95% CI 18.2% to 19.7%) in treatment changes. Check-up laboratory exams showed similar rates of DAs, with 17.5% (95% CI 13.8% to 21.2%) diagnostic DAs and 18.9% (95% CI 13.9% to 23.9%) treatment changes. Using the CDSS resulted in a significant reduction in downstream referrals (−2.4%; 95% CI −4.2% to −0.6%; p=0008), imaging and endoscopies (−0.9%; 95% CI −1.6% to −0.1%; p=0026) and treatment changes (−5.4%; 95% CI −9.5% to −1.2%; p=0.01).Conclusion This is the largest study so far to examine DAs after laboratory testing. It shows that almost one in three laboratory exams leads to further DAs, even in check-up panels. Using a CDSS for laboratory orders may reduce the rate of some DAs.Trial registration number NCT02950142.

Background: The implementation of primary care for mental health is often insufficient, which leaves its mark on staff. A team-based approach of mental healthcare prevents poor staff morale. A community health centre (CHC), therefore, set up a project promoting interprofessional collaboration with a mental health team (MHT). Objectives: This study aimed to understand how an MHT would influence staff morale in a primary care setting, aiming to formulate some recommendations for future projects. Methods: In 2017, interviews and a focus group discussion were conducted among the staff of a CHC. Using a qualitative approach, we aimed to unravel contextual factors and mechanisms that determine the effect of an MHT on staff morale. Results: The project relieved the burden of the patient encounters and staff members felt more valuable to patients. Underlying mechanisms were recognition, altered attitudes towards patients and role clarity. Facilitating factors were intercultural care mediators and a positive team atmosphere, whereas inhibiting factors were inefficient time management and communicative issues. Conclusion: Our study elucidated mechanisms and the contextual factors by which an MHT in general practice improves staff morale. KEY MESSAGES An MHT improves staff morale in a CHC, through nurturing recognition, through altering staff members' attitudes and through ensuring role clarity. Pitfalls are inefficient time management and poor communication. Policymakers should stimulate interprofessional collaboration in primary mental health.

Introduction: Emotions are theorized to contain the components of affect and action readiness. Affect guides behavior by causing an approach or withdrawal orientation. Action readiness is the individual's degree of willingness to interact with the environment. Emotions contribute to changes in behavior and physiological responses. Aim: The present study applied these notions to sexuality and examined the associations between affect, action readiness, and sexual functioning. Methods: Participants were male patients with urologic condition (N = 70) with and without sexual problems. Main Outcome Measure: Affect and action readiness were jointly assessed using the latent factor of affective polarity of the Positive and Negative Affect Schedule. Trait affective polarity was assessed questioning generally experienced feelings. State affective polarity was assessed after exposure to an erotic stimulus and questioning momentaneously experienced feelings. Sexual functioning was assessed using the International Index of Erectile Functioning questionnaire. Results: A significant increase of approach-oriented action readiness was found after erotic stimulation, relative to trait levels. In addition, significant associations were found between state approach-oriented action readiness and various aspects of sexual functioning. Interventions based on principles of positive psychology might be developed to reinforce action readiness in men with erectile dysfunction. The strength of the current research concerns the introduction of action readiness as a potential psychological factor implied in sexual functioning. Limitations pertain to the use of the algorithm used to calculate state approach-oriented action readiness and the use of the current sample of patients with urological conditions, limiting generalizability of findings. Conclusion: Action readiness was found to correlate positively with all aspects of sexual functioning. Further research into the role of action readiness in sexuality is recommended.Henckens MJMJ, de Vries P, Janssen E, et al. Associations of Affect, Action Readiness, and Sexual Functioning. Sex Med 2020;8:691–698.

Abstract Background Inappropriate laboratory test ordering poses an important burden for healthcare. Clinical decision support systems (CDSS) have been cited as promising tools to improve laboratory test ordering behavior. The objectives of this study were to evaluate the effects of an intervention that integrated a clinical decision support service into a computerized physician order entry (CPOE) on the appropriateness and volume of laboratory test ordering, and on diagnostic error in primary care. Methods This study was a pragmatic, cluster randomized, open-label, controlled clinical trial. Setting Two hundred eighty general practitioners (GPs) from 72 primary care practices in Belgium. Patients Patients aged ≥ 18 years with a laboratory test order for at least one of 17 indications: cardiovascular disease management, hypertension, check-up, chronic kidney disease (CKD), thyroid disease, type 2 diabetes mellitus, fatigue, anemia, liver disease, gout, suspicion of acute coronary syndrome (ACS), suspicion of lung embolism, rheumatoid arthritis, sexually transmitted infections (STI), acute diarrhea, chronic diarrhea, and follow-up of medication. Interventions The CDSS was integrated into a computerized physician order entry (CPOE) in the form of evidence-based order sets that suggested appropriate tests based on the indication provided by the general physician. Measurements The primary outcome of the ELMO study was the proportion of appropriate tests over the total number of ordered tests and inappropriately not-requested tests. Secondary outcomes of the ELMO study included diagnostic error, test volume, and cascade activities. Results CDSS increased the proportion of appropriate tests by 0.21 (95% CI 0.16–0.26, p < 0.0001) for all tests included in the study. GPs in the CDSS arm ordered 7 (7.15 (95% CI 3.37–10.93, p = 0.0002)) tests fewer per panel. CDSS did not increase diagnostic error. The absolute difference in proportions was a decrease of 0.66% (95% CI 1.4% decrease–0.05% increase) in possible diagnostic error. Conclusions A CDSS in the form of order sets, integrated within the CPOE improved appropriateness and decreased volume of laboratory test ordering without increasing diagnostic error. Trial registration ClinicalTrials.gov Identifier: NCT02950142 , registered on October 25, 2016

Introduction: A lot of attention has been given to the quest of parents, children and donors to find donor siblings (= half siblings who share the same donor gametes but who are born in different families). However, literature is scarce about the use of the same sperm donor for subsequent children in the same family. Methods: This study included 68 lesbian and heterosexual (aspiring) parents, recruited at the Department of Reproductive Medicine of Ghent University Hospital (Belgium). The in-depth semi-structured couple interviews were performed between October 2012 and October 2013. Data were analyzed through step-by-step inductive thematic analysis. Results: The couples showed a clear preference to use the same sperm donor for their children. The most common reasons for this preference were related to the family or sibling relationships and medical reasons. Uncertainty about the availability of the same donor over time seeped through in their stories. Most lesbian aspiring parents decided that both partners should have a genetic link with at least one child. Conclusion: The use of the same sperm donor for subsequent conceptions appeared quasi unambiguously in the interviews of the lesbian and heterosexual (aspiring) parents in our study.

BackgroundThe healthcare system is faced by an ageing population, increase in chronic conditions and multimorbidity. Multimorbid patients are faced with multiple parallel care processes leading to a risk of fragmented care. These problems relate to the disease-oriented paradigm. In this paradigm the treatment goals can be in contrast with what patients value. The concept of goal-oriented care is proposed as an alternative way of providing care as meeting patients' goals could have potential benefits. Though, there is a need to translate this concept into tangible knowledge so providers can better understand and use the concept in clinical practice. The aim of this study is to address this need by means of a concept analysis.MethodThis concept analysis using the method of Walker and Avant is based on a literature search in PubMed, Embase, Cochrane Library, PsychInfo, CINAHL, OTSeeker and Web of Science. The method provides eight iterative steps: select a concept, determine purpose, determine defining attributes, identify model case, identify additional case, identify antecedents and consequences and define empirical referents.ResultsThe analysis of 37 articles revealed that goal-oriented care is a dynamic and iterative process of three stages: goal-elicitation, goal-setting, and goal-evaluation. The process is underpinned by the patient's context and values. Provider and patient preparedness are required to provide goal-oriented care. Goal-oriented care has the potential to improve patients' experiences and providers' well-being, to reduce costs, and improve the overall population health. The challenge is to identify empirical referents to evaluate the process of goal-oriented care.ConclusionA common understanding of goal-oriented care is presented. Further research should focus on how and what goals are set by the patient, how this knowledge could be translated into a tangible workflow and should support the development of a strategy to evaluate the goal-oriented process of care.

ABSTRACT In the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, testing for SARS-CoV-2-specific antibodies is paramount for monitoring immune responses in postauthorization vaccination and seroepidemiological studies. However, large-scale and iterative serological testing by venipuncture in older persons can be challenging. Capillary blood sampling using a finger prick and collection on protein saver cards, i.e., dried blood spots (DBSs), has already proven to be a promising alternative. However, elderly persons have reduced cutaneous microvasculature, which may affect DBS-based antibody testing. Therefore, we aimed to evaluate the performance of DBS tests for the detection of SARS-CoV-2 antibodies among nursing homes residents. We collected paired venous blood and DBS samples on two types of protein saver cards (Whatman and EUROIMMUN) from nursing home residents, as well as from staff members as a reference population. Venous blood samples were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Abbott chemiluminescent microparticle immunoassay (CMIA). DBS samples were analyzed by the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2 IgG antibodies. We performed a statistical assessment to optimize the ELISA cutoff value for the DBS testing using Youden's J index. A total of 273 paired DBS-serum samples were analyzed, of which 129 were positive, as assessed by the reference test. The sensitivities and specificities of DBS testing ranged from 95.0% to 97.1% and from 97.1% to 98.8%, respectively, depending on the population (residents or staff members) and the DBS card type. Therefore, we found that DBS sampling is a valid alternative to venipuncture for the detection of SARS-CoV-2 antibodies among elderly subjects. IMPORTANCE Since the implementation of newly developed SARS-CoV-2 vaccines in the general population, serological tests are of increasing importance. Because DBS samples can be obtained with a finger prick and can be shipped and stored at room temperature, they are optimal for use in large-scale SARS-CoV-2 serosurveillance or postauthorization vaccination studies, even in an elderly study population.