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STUDY QUESTION Can recurrent embryo developmental problems after ICSI be overcome by assisted oocyte activation (AOA)? SUMMARY ANSWER AOA did not improve blastocyst formation in our patient cohort with recurrent embryo developmental problems after ICSI. WHAT IS KNOWN ALREADY The use of AOA to artificially induce calcium (Ca2+) rises by using Ca2+ ionophores (mainly calcimycin and ionomycin) has been reported as very effective in overcoming fertilization failure after ICSI, especially in patients whose Ca2+ dynamics during fertilization are deficient. However, there is only scarce and contradictory literature on the use of AOA to overcome embryo developmental problems after ICSI, and it is not clear whether abnormal Ca2+ patterns during fertilization disturb human preimplantation embryo development. Moreover, poor embryo development after ICSI has also been linked to genetic defects in the subcortical maternal complex (SCMC) genes. STUDY DESIGN, SIZE, DURATION This prospective cohort single-center study compared ICSI-AOA cycles and previous ICSI cycles in couples with normal fertilization rates (≥60%) but impaired embryonic development (≤15% blastocyst formation) in at least two previous ICSI cycles. In total, 42 couples with embryo developmental problems were included in this study from January 2018 to January 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Of the 42 couples included, 17 underwent an ICSI-AOA cycle consisting of CaCl2 injection and double ionomycin exposure. Fertilization, blastocyst development, pregnancy, and live birth rates after ICSI-AOA were compared to previous ICSI cycles. In addition, the calcium pattern induced by the male patient’s sperm was investigated by mouse oocyte calcium analysis. Furthermore, all 42 couples underwent genetic screening. Female patients were screened for SCMC genes (TLE6, PADI6, NLRP2, NLRP5, NLRP7, and KHDC3L) and male patients were screened for the sperm–oocyte-activating factor PLCZ1. MAIN RESULTS AND THE ROLE OF CHANCE We compared 17 AOA cycles to 44 previous ICSI cycles from the same patient cohort. After AOA, a total fertilization rate of 68.95% (131/190), a blastocyst development rate of 13.74% (18/131), a pregnancy rate of 29.41% (5/17), and a live birth rate of 23.53% (4/17) were achieved, which was not different from the previous ICSI cycles (76.25% (321/421, P-value = 0.06); 9.35% (30/321, P-value = 0.18), 25.00% (11/44, P-value = 0.75), and 15.91% (7/44, P-value = 0.48), respectively). Calcium analysis showed that patient’s sperm induced calcium patterns similar to control sperm samples displaying normal embryo developmental potential. Genetic screening revealed 10 unique heterozygous variants (in NLRP2, NLRP5, NLRP7, TLE6, and PADI6) of uncertain significance (VUS) in 14 females. Variant NLRP5 c.623-12_623-11insTTC (p.?) was identified in two unrelated individuals and variant NLRP2 c.1572T>C (p.Asp524=) was identified in four females. Interestingly, we identified a previously reported homozygous mutation PLCZ1, c.1499C>T (p.Ser500Leu), in a male patient displaying impaired embryonic development, but not showing typical fertilization failure. LIMITATIONS, REASONS FOR CAUTION Our strict inclusion criteria, requiring at least two ICSI cycles with impaired embryo development, reduced cycle-to-cycle variability, while the requirement of a lower blastocyst development not influenced by a poor fertilization excluded couples who otherwise would be selective cases for AOA; however, these criteria limited the sample size of this study. Targeted genetic screening might be too restricted to identify a genetic cause underlying the phenotype of poor embryo development for all patients. Moreover, causality of the identified VUS should be further determined. WIDER IMPLICATIONS OF THE FINDINGS Strong evidence for AOA overcoming impaired embryonic development is still lacking in the literature. Thus far, only one article has reported a beneficial effect of AOA (using calcimycin) compared to previous ICSI cycles in this patient population, whilst two more recent sibling-oocyte control studies (one using calcimycin and the other ionomycin) and our research (using ionomycin) could not corroborate these findings. Although no major abnormalities have been found in children born after AOA, this technique should be reserved for couples with a clear Ca2+-release deficiency. Finally, genetic screening by whole-exome sequencing may reveal novel genes and variants linked to embryo developmental problems and allow the design of more personalized treatment options, such as wild-type complementary RNA or recombinant protein injection. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Flemish Fund for Scientific Research (grant FWO.OPR.2015.0032.01 to B.H. and grant no. 1298722N to A.B.). A.C.B., D.B., A.B., V.T., R.P., F.M., I.D.C., L.L., D.S., P.D.S., P.C., and F.V.M. have nothing to disclose. B.H. reports a research grant from the Flemish Fund for Scientific Research and reports being a board member of the Belgian Society for Reproductive Medicine and the Belgian Ethical Committee on embryo research. TRIAL REGISTRATION NUMBER NCT03354013

Background Early distinction between mild and serious infections (SI) is challenging in children in ambulatory care. Clinical prediction models (CPMs), developed to aid physicians in clinical decision-making, require broad external validation before clinical use. We aimed to externally validate four CPMs, developed in emergency departments, in ambulatory care. Methods We applied the CPMs in a prospective cohort of acutely ill children presenting to general practices, outpatient paediatric practices or emergency departments in Flanders, Belgium. For two multinomial regression models, Feverkidstool and Craig model, discriminative ability and calibration were assessed, and a model update was performed by re-estimation of coefficients with correction for overfitting. For two risk scores, the SBI score and PAWS, the diagnostic test accuracy was assessed. Results A total of 8211 children were included, comprising 498 SI and 276 serious bacterial infections (SBI). Feverkidstool had a C-statistic of 0.80 (95% confidence interval 0.77–0.84) with good calibration for pneumonia and 0.74 (0.70–0.79) with poor calibration for other SBI. The Craig model had a C-statistic of 0.80 (0.77–0.83) for pneumonia, 0.75 (0.70–0.80) for complicated urinary tract infections and 0.63 (0.39–0.88) for bacteraemia, with poor calibration. The model update resulted in improved C-statistics for all outcomes and good overall calibration for Feverkidstool and the Craig model. SBI score and PAWS performed extremely weak with sensitivities of 0.12 (0.09–0.15) and 0.32 (0.28–0.37). Conclusions Feverkidstool and the Craig model show good discriminative ability for predicting SBI and a potential for early recognition of SBI, confirming good external validity in a low prevalence setting of SBI. The SBI score and PAWS showed poor diagnostic performance. Trial registration ClinicalTrials.gov, NCT02024282. Registered on 31 December 2013.

BACKGROUND: Stroke is a major concern in transcatheter aortic valve replacement (TAVR). The introduction of a cerebral protection devices may counteract the evolution towards minimally invasive TAVR. At this time, there is insufficient data to support the routine use of these devices. METHODS: We aimed to evaluate the outcome of the routine use of the Sentinel Cerebral protection system® (CPS) in patients undergoing TAVR, after completing a CT-based screening process for feasibility of Sentinel implantation. We report our initial experience with the routine implementation of the Sentinel CPS in all anatomically suitable patients undergoing TAVR. We retrospectively compared the procedural characteristics and outcomes between all TAVR patients treated with (n = 78) and without (n = 79) intended Sentinel. RESULTS: The Sentinel CPS could successfully be deployed in 99% of intended cases after CT feasibility screening. TAVR procedures with Sentinel CPS were not longer than procedures without Sentinel use (89 ± 20 versus 120 ± 50 min, p = 0.007). Sentinel CPS use was not associated with an increased risk of procedural complications. Stroke was observed in none (0%) of the Sentinel CPS patients, and in 6.3% of the non-Sentinel CPS patients (p = 0.05). The finding of stroke was associated with a high risk of early postprocedural mortality: 60% of stroke patients died within 3 months. CONCLUSION: Routine use of the Sentinel CPS in CT-screened TAVR patients is feasible with high procedural success, without significant adverse events and without counteracting the evolution towards minimally invasive TAVR. Clinically relevant stroke was observed in none of the Sentinel CPS patients.

ObjectivesTo estimate the prevalence, incidence and longevity of antibodies against SARS-CoV-2 among primary healthcare providers (PHCPs).DesignProspective cohort study with 12 months of follow-up.SettingPrimary care in Belgium.ParticipantsAny general practitioner (GP) working in primary care in Belgium and any other PHCP from the same GP practice who physically manages (examines, tests, treats) patients were eligible. A convenience sample of 3648 eligible PHCPs from 2001 GP practices registered for this study (3044 and 604 to start in December 2020 and January 2021, respectively). 3390 PHCPs (92,9%) participated in their first testing time point (2820 and 565, respectively) and 2557 PHCPs (70,1%) in the last testing time point (December 2021).InterventionsParticipants were asked to perform a rapid serological test targeting IgM and IgG against the receptor binding domain of SARS-CoV-2 and to complete an online questionnaire at each of maximum eight testing time points.Primary and secondary outcome measuresThe prevalence, incidence and longevity of antibodies against SARS-CoV-2 both after natural infection and after vaccination.ResultsAmong all participants, 67% were women and 77% GPs. Median age was 43 years. The seroprevalence in December 2020 (before vaccination availability) was 15.1% (95% CI 13.5% to 16.6%), increased to 84.2% (95% CI 82.9% to 85.5%) in March 2021 (after vaccination availability) and reached 93.9% (95% CI 92.9% to 94.9%) in December 2021 (during booster vaccination availability and fourth (delta variant dominant) COVID-19 wave). Among not (yet) vaccinated participants the first monthly incidence of antibodies against SARS-CoV-2 was estimated to be 2.91% (95% CI 1.80% to 4.01%). The longevity of antibodies is higher in PHCPs with self-reported COVID-19 infection.ConclusionsThis study confirms that occupational health measures provided sufficient protection when managing patients. High uptake of vaccination resulted in high seroprevalence of SARS-CoV-2 antibodies in PHCPs in Belgium. Longevity of antibodies was supported by booster vaccination and virus circulation.Trial registration numberNCT04779424.

Background Oseltamivir is usually not often prescribed (or reimbursed) for non-high-risk patients consulting for influenza-like-illness (ILI) in primary care in Europe. We aimed to evaluate the cost-effectiveness of adding oseltamivir to usual primary care in adults/adolescents (13 years +) and children with ILI during seasonal influenza epidemics, using data collected in an open-label, multi-season, randomised controlled trial of oseltamivir in 15 European countries. Methods Direct and indirect cost estimates were based on patient reported resource use and official country-specific unit costs. Health-Related Quality of Life was assessed by EQ-5D questionnaires. Costs and quality adjusted life-years (QALY) were bootstrapped (N = 10,000) to estimate incremental cost-effectiveness ratios (ICER), from both the healthcare payers’ and the societal perspectives, with uncertainty expressed through probabilistic sensitivity analysis and expected value for perfect information (EVPI) analysis. Additionally, scenario (self-reported spending), comorbidities subgroup and country-specific analyses were performed. Results The healthcare payers’ expected ICERs of oseltamivir were €22,459 per QALY gained in adults/adolescents and €13,001 in children. From the societal perspective, oseltamivir was cost-saving in adults/adolescents, but the ICER is €8,344 in children. Large uncertainties were observed in subgroups with comorbidities, especially for children. The expected ICERs and extent of decision uncertainty varied between countries (EVPI ranged €1–€35 per patient). Conclusion Adding oseltamivir to primary usual care in Europe is likely to be cost-effective for treating adults/adolescents and children with ILI from the healthcare payers’ perspective (if willingness-to-pay per QALY gained > €22,459) and cost-saving in adults/adolescents from a societal perspective.

Background: The majority of GIST are driven by constitutively activated KIT/PDGFRA kinases and are susceptible to treatment with tyrosine kinase inhibitors. During treatment, most of these tumors will develop secondary mutations in KIT or PDGFRA inducing drug resistance, so there is an unmet need for novel therapies. We tested the efficacy of IDRX-42, a novel selective KIT inhibitor with high activity towards the most relevant KIT mutations, in 4 GIST xenograft models. Methods: NMRI nu/nu mice were transplanted with patient-derived GIST xenograft models UZLX-GIST9 (KIT:p.P577del;W557LfsX5;D820G), UZLX-GIST2B (KIT:p.A502_Y503dup), UZLX-GIST25 (KIT:p.K642E) and the cell-line derived model GIST882 (KIT:p.K642E). Mice were treated daily with vehicle (control), imatinib (100mg/kg), sunitinib (20mg/kg), avapritinib (5mg/kg), or IDRX-42 (10mg/kg, 25mg/kg). Efficacy was assessed by tumor volume evolution, histopathology, grading of histological response and immunohistochemistry. The Kruskal-Wallis and Wilcoxon Matched Pairs tests were used for statistical analysis, with p

Supplementary Figure from Validation of BD Onclarity HPV Assay on Vaginal Self-Samples versus Cervical Samples Using the VALHUDES Protocol

Background:In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples.Methods:Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31–49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation.Results:The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90–1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02–1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94–1.06) and 1.15 (95% CI, 1.05–1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79–1.04) and 1.03 (95% CI, 0.95–1.13), respectively for Qvintip.Conclusions:Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples.Impact:VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening.

Background Acute infections are a common reason for children to consult primary care. Serious infections are rare but differentiating them from self-limiting illnesses remains challenging. This can lead to inappropriate antibiotic prescribing. Point-of-care C-reactive protein testing is used to guide antibiotic prescribing in adults. However, in children its use remains unclear. The purpose of this study was to assess point-of-care CRP test levels with respect to patients’ characteristics, care setting, preliminary diagnosis, and management. Methods A prospective observational study was performed in children with an acute infection presenting to ambulatory care in Belgium. Results In this study 8280 cases were analysed, of which 6552 had a point-of-care CRP value available. A total of 276 physicians participated. The median patient age was 1.98 years (IQR 0.97 to 4.17), 37% of children presented to a general practitioner, 33% to a paediatric out-patient clinic, and 30% to the emergency department. A total of 131 different preliminary diagnoses were found, with acute upper airway infection as the most frequent. In 6% (n = 513) patients were diagnosed with a serious infection. The most common serious infection was pneumonia. Antibiotics were prescribed in 28% (n = 2030) of all episodes. The median CRP over all infectious episodes was 10 mg/L (IQR Conclusion A low POC CRP as a standalone tool did not seem to be sufficient to rule out serious infections, but its potential in assessing serious infections could increase when integrated in a clinical decision rule. Trial registration ClinicalTrials.gov Identifier: NCT02024282 (registered on 31/12/2013).

Cystic fibrosis (CF) has been linked to altered drug disposition in various studies. However, the magnitude of these changes, influencing factors, and underlying mechanisms remain a matter of debate. The primary aim of this work was therefore to quantify changes in drug disposition (top-down) and the pathophysiological parameters known to affect pharmacokinetics (PKs; bottom-up). This was done through meta-analyses and meta-regressions in addition to theoretical PK simulations. Volumes of distribution and clearances were found to be elevated in people living with CF. These increases were larger in studies which included patients with pulmonary exacerbations. Differences in clearance were smaller in more recent studies and when results were normalized to body surface area or lean body mass instead of body weight. For the physiological parameters investigated, measured glomerular filtration rate and serum cytokine concentrations were found to be elevated in people living with CF, whereas serum albumin and creatinine levels were decreased. Possible pathophysiological mechanisms for these alterations relate to renal hyperfiltration, increases in free fraction, and inflammation. No differences were detected for cardiac output, body fat, fat free mass, hematocrit, creatinine clearance, and the activity of drug metabolizing enzymes. These findings imply that, in general, lower total plasma concentrations of drugs can be expected in people living with CF, especially when pulmonary exacerbations are present. Given the potential effect of CF on plasma protein binding and the variability in outcome observed between studies, the clinical relevance of adapting existing dosage regimens should be evaluated on a case-by-case basis.

To provide longitudinal data on the evolution of lipid levels and the intake of lipid-lowering therapies in patients with stable coronary artery disease.Single-centre retrospective study with inclusion of 350 patients with a first coronary artery event in 2014 or earlier and outpatient cardiac clinic follow-up in 2015 and 2019. Lipid levels were collected within a time frame of 3 months of their visits.This retrospective study protocol (2020.086) was approved by the ethical committee and by the Data Privacy Officer of AZ Maria Middelares Ghent. For this type of study, formal consent is not required, following local law and regulations.Average LDL levels were 82 (±26) mg/dl in 2015 and 70 (±24) mg/dl in 2019 (This study shows significant intensification of lipid-lowering therapy use during follow-up, and a significant lipid level lowering after 5-year follow-up, in an outpatient cardiac clinic follow-up. Further improvement in lipid control is still desirable, especially after the European Society of Cardiology recommend stricter lipid levels in the 2021 Prevention Guidelines.

Research in medical imaging is hampered by a lack of programming languages that support productive, flexible programming as well as high performance. In search for higher quality imaging, researchers can ideally experiment with novel algorithms using rapid-prototyping languages such as Python. However, to speed up image reconstruction, computational resources such as those of graphics processing units (GPUs) need to be used efficiently. Doing so requires re-programming the algorithms in lower-level programming languages such as CUDA C/C++ or rephrasing them in terms of existing implementations of established algorithms in libraries. The former has a detrimental impact on research productivity and requires system-level programming expertise, and the latter puts severe constraints on the flexibility to research novel algorithms. Here, we investigate the use of the Julia scientific programming language in the domain of PET image reconstruction as a means to obtain both high performance (portability) on GPUs and high programmer productivity and flexibility, all at once, without requiring expert GPU programming knowledge. Using rapid-prototyping features of Julia, we developed basic and performance-optimized GPU implementations of baseline maximum likelihood expectation maximization (MLEM) positron emission tomography (PET) image reconstruction algorithms, as well as multiple existing algorithmic extensions. Thus, we mimic the effort that researchers would have to invest to evaluate the quality and performance potential of algorithms. We evaluate the obtained performance and compare it to state-of-the-art existing implementations. We also analyse and compare the required programming effort. With the Julia implementations, performance in line with existing GPU implementations written in the low-level, unproductive programming language CUDA C is achieved, while requiring much less programming effort, even less than what is needed for much less performant CPU implementations in C++. Switching to Julia as the programming language of choice can therefore boost the productivity of research into medical imaging and deliver excellent performance at a low cost in terms of programming effort.

STUDY QUESTION Can spindle transfer (ST) overcome inferior embryonic development of in vitro matured ovarian tissue oocytes (OTO-IVM) originating from testosterone-treated transgender men? SUMMARY ANSWER ST shows some potential to overcome the embryo developmental arrest observed in OTO-IVM oocytes from transgender men. WHAT IS KNOWN ALREADY OTO-IVM is being applied as a complementary approach to increase the number of oocytes/embryos available for fertility preservation during ovarian tissue cryopreservation in cancer patients. OTO-IVM has also been proposed for transgender men, although the potential of their oocytes remains poorly investigated. Currently, only one study has examined the ability of OTO-IVM oocytes originating from transgender men to support embryo development, and that study has shown that they exhibit poor potential. STUDY DESIGN, SIZE, DURATION Both ovaries from 18 transgender men undergoing oophorectomy were collected for the purposes of this study, from November 2020 to September 2022. The patients did not wish to cryopreserve their tissue for fertility preservation and donated their ovaries for research. All patients were having testosterone treatment at the time of oophorectomy and some of them were also having menses inhibition treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS Sibling ovaries were collected in either cold or warm medium, to identify the most optimal collection temperature. Cumulus oocyte complexes (COCs) from each condition were isolated from the ovarian tissue and matured in vitro for 48 h. The quality of OTO-IVM oocytes was assessed by calcium pattern releasing ability, embryo developmental competence following ICSI, and staining for mitochondrial membrane potential. In vitro matured metaphase I (MI) oocytes, germinal vesicle (GV) oocytes, and in vivo matured oocytes with aggregates of smooth endoplasmic reticulum (SERa) were donated from ovarian stimulated women undergoing infertility treatment and these served as Control oocytes for the study groups. ST was applied to overcome poor oocyte quality. Specifically, enucleated mature Control oocytes served as cytoplasmic recipients of the OTO-IVM spindles from the transgender men. Embryos derived from the different groups were scored and analysed by shallow whole genome sequencing for copy number variations (CNVs). MAIN RESULTS AND THE ROLE OF CHANCE In total, 331 COCs were collected in the cold condition (OTO-Cold) and 282 were collected in the warm condition (OTO-Warm) from transgender men. The maturation rate was close to 54% for OTO-Cold and 57% for OTO-Warm oocytes. Control oocytes showed a calcium releasing ability of 2.30 AU (n = 39), significantly higher than OTO-Cold (1.47 AU, P = 0.046) oocytes (n = 33) and OTO-Warm (1.03 AU, P = 0.036) oocytes (n = 31); both values of calcium release were similar between the two collection temperatures. Mitochondrial membrane potential did not reveal major differences between Control, OTO-Warm, and OTO-Cold oocytes (P = 0.417). Following ICSI, 59/70 (84.2%) of Control oocytes were fertilized, which was significantly higher compared to 19/47 (40.4%) of OTO-Cold (P LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Due to the limited access to human oocytes and ovarian tissue, our results should be interpreted with some caution, as only a limited number of human oocytes and embryos could be investigated. WIDER IMPLICATIONS OF THE FINDINGS The results of this study, clearly indicate that OTO-IVM oocytes originating from transgender patients are of inferior quality, which questions their use for fertility preservation. The poor quality is likely to be related to cytoplasmic factors, supported by the increased blastocyst numbers following application of ST. Future research on OTO-IVM from transgender men should focus on the cytoplasmic content of oocytes or supplementation of media with factors that promote cytoplasmic maturation. A more detailed study on the effect of the length of testosterone treatment is also currently missing for more concrete guidelines and guidance on the fertility options of transgender men. Furthermore, our study suggests a potentially beneficial role of experimental ST in overcoming poor embryo development related to cytoplasmic quality. STUDY FUNDING/COMPETING INTEREST(S) A.C. is a holder of FWO grants (1S80220N and 1S80222N). A.B. is a holder of an FWO grant (1298722N). B.H. and A.V.S. have been awarded with a special BOF (Bijzonder Onderzoeksfonds), GOA (Geconcerteerde onderzoeksacties) and 2018000504 (GOA030-18 BOF) funding. B.H. has additional grants from FWO-Vlaanderen (Flemish Fund for Scientific Research, G051516N and G1507816N) and Ghent University Special Research Fund (Bijzonder Onderzoeksfonds, BOF funding (BOF/STA/202109/005)), and has been receiving unrestricted educational funding from Ferring Pharmaceuticals (Aalst, Belgium). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Background Electronic informed consent (eIC) may offer various advantages compared to paper-based informed consent. However, the regulatory and legal landscape related to eIC provides a diffuse image. By drawing from the perspectives of key stakeholders in the field, this study aims to inform the creation of a European guidance framework on eIC in clinical research. Methods Focus group discussions and semi-structured interviews were conducted with 20 participants from six stakeholder groups. The stakeholder groups included representatives of ethics committees, data infrastructure organizations, patient organizations, and the pharmaceutical industry as well as investigators and regulators. All were involved in or knowledgeable about clinical research and were active in one of the European Union Member States or at a pan-European or global level. The framework method was used for data analysis. Results Stakeholders underwrote the need for a multi-stakeholder guidance framework addressing practical elements related to eIC. According to the stakeholders, a European guidance framework should describe consistent requirements and procedures for implementing eIC on a pan-European level. Generally, stakeholders agreed with the definitions of eIC issued by the European Medicines Agency and the US Food and Drug Administration. Nevertheless, it was raised that, in a European guidance framework, it should be emphasized that eIC aims to support rather than replace the personal interaction between research participants and the research team. In addition, it was believed that a European guidance framework should include details on the legality of eIC across European Union Member States and the responsibilities of an ethics committee in the eIC assessment process. Although stakeholders supported the idea to include detailed information on the type of eIC-related materials to be submitted to an ethics committee, opinions varied on this regard. Conclusion The creation of a European guidance framework is a much needed factor to advance eIC implementation in clinical research. By collecting the views of multiple stakeholder groups, this study advances recommendations that may facilitate the development of such a framework. Particular consideration should go to harmonizing requirements and providing practical details related to eIC implementation on a European Union-wide level.

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

Supplemental material, sj-pdf-2-jhi-10.1177_1460458220980039 for Patients’ moral attitudes toward electronic health records: Survey study with vignettes and statements by Tania Moerenhout, Ignaas Devisch, Laetitia Cooreman, Jodie Bernaerdt, An De Sutter and Veerle Provoost in Health Informatics Journal

Additional File 6: Table S3: Summary of studies reporting on the association stress and BV

The presence of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) patients suffering from chronic lung infections contributes to the failure of antimicrobial therapy. Conventionally, the minimal inhibitory concentration (MIC) is determined to assess the antimicrobial susceptibility of a pathogen, however this parameter fails to predict success in treating biofilm-associated infections. In the present study we developed a high throughput method to determine the antimicrobial con-centration required to prevent P. aeruginosa biofilm formation, using a synthetic cystic fibrosis sputum medium (SCFM2). Biofilms were grown in SCFM2 for 24 h in the presence of antibiotics (tobramycin, ciprofloxacin or colistin), whereafter biofilms were disrupted and a resazurin staining was used to quantify the number of surviving metabolically active cells. In parallel, the content of all wells was plated to determine the number of colony forming units (CFU). Biofilm preventing concentrations (BPCs) were compared to MICs and minimal bactericidal concentrations (MBCs) determined according to EUCAST guidelines. Correlations between the resazurin-derived fluorescence and CFU counts were assessed with Kendall's Tau Rank tests. A significant correlation between fluorescence and CFU counts was observed for 9 out of 10 strains investigated, suggesting the fluorometric assay is a reliable alternative to plating for most P. aeruginosa isolates to determine biofilm susceptibility in relevant conditions. For all isolates a clear difference between MICs and BPCs of all three antibiotics was observed, with the BPCs being consistently higher than the MICs. Additionally, the extent of this difference appeared to be antibiotic -dependent. Our findings suggest that this high throughput assay could be a valuable addition to evaluate the antimicrobial susceptibility in P. aeruginosa biofilms in the context of CF.

Supplemental material, sj-pdf-2-jhi-10.1177_1460458220980039 for Patients’ moral attitudes toward electronic health records: Survey study with vignettes and statements by Tania Moerenhout, Ignaas Devisch, Laetitia Cooreman, Jodie Bernaerdt, An De Sutter and Veerle Provoost in Health Informatics Journal

Additional File 1: Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist

Additional File 4: Table S1: Characteristics of included studies

Additional File 3: Search Strategy

Man-at-the-end (MATE) attackers have full control over the system on which the attacked software runs, and try to break the confidentiality or integrity of assets embedded in the software. Both companies and malware authors want to prevent such attacks. This has driven an arms race between attackers and defenders, resulting in a plethora of different protection and analysis methods. However, it remains difficult to measure the strength of protections because MATE attackers can reach their goals in many different ways and a universally accepted evaluation methodology does not exist. This survey systematically reviews the evaluation methodologies of papers on obfuscation, a major class of protections against MATE attacks. For 572 papers, we collected 113 aspects of their evaluation methodologies, ranging from sample set types and sizes, over sample treatment, to performed measurements. We provide detailed insights into how the academic state of the art evaluates both the protections and analyses thereon. In summary, there is a clear need for better evaluation methodologies. We identify nine challenges for software protection evaluations, which represent threats to the validity, reproducibility, and interpretation of research results in the context of MATE attacks.

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.

Background Bacterial vaginosis (BV) is a condition that, if symptomatic, is characterized by discharge and odor, with high recurrence rates even when treated. This study aims to review what literature exists on the association between BV and the emotional, sexual, and social health of women. Methods MEDLINE, Embase and Web of Science databases were searched from inception until November 2020. Studies reporting an association between women’s emotional, sexual and/or social health and symptomatic BV in a qualitative and/or quantitative manner were included. Selected studies were divided in three categories, i.e. reporting on the emotional, sexual and/or social association. All studies were critically evaluated and discussed. Results Sixteen studies were included. Concerning emotional health, we found eight studies that calculated the association between stress and BV, in four this was statistically significant. Four qualitative studies on emotional health showed that the severity of the symptoms influenced the impact on women’s lives. All studies on sexual health reported that many women experienced an impact on their relationship and sexual intimacy. Results for social life ranged from no association found to most of the study population showing avoidance behavior. Conclusion This review shows that symptomatic BV can be associated with diminished emotional, sexual, and social health, but there is too little evidence to state the extent of this association.

The aim of this study was to provide an up-to-date overview of gender differences or similarities in risk factor control and medical management in the Belgian CHD population. All analyses are based on the ESC EORP EUROASPIRE IV and EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) surveys. Patients between 18 and 80 years old, hospitalised for a first or recurrent coronary event, were included in the survey. Data were available for 10,519 patients, of which 23.9% were women. Women had a worse risk factor profile compared to men. Women were more physical inactive (OR = 1.31, 95% CI = 1.19–1.44), had a higher prevalence of obesity (OR = 1.37, 95% CI = 1.25–1.50) and had a worse LDL-C control (OR = 1.52, 95% CI = 1.36–1.70). Moreover, women were less likely to use ACE-I/ARBs (OR = 0.84, 95% CI = 0.76–0.94) and statins (OR = 0.79, 95% CI = 0.70–0.90). In addition, little gender differences were found in patients’ risk factor awareness, except on cholesterol awareness. Women were more aware about their total cholesterol levels (OR = 1.37, 95% CI = 1.21–1.56). Despite little to no gender differences in the management of CHD patients, women still have a worse risk factor profile, both in Belgian and in other European high-income countries.

Additional File 2: PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only

Additional file 1: Table S1-S7. Comparison of population characteristics, proxy variables, missing data and original and updated coefficients for each model. Table S8-S11. Sensitivity analyses for each model.

The last years have seen an increase in Man-at-the-End (MATE) attacks against software applications, both in number and severity. However, software protection, which aims at mitigating MATE attacks, is dominated by fuzzy concepts and security-through-obscurity. This paper presents a rationale for adopting and standardizing the protection of software as a risk management process according to the NIST SP800-39 approach. We examine the relevant constructs, models, and methods needed for formalizing and automating the activities in this process in the context of MATE software protection. We highlight the open issues that the research community still has to address. We discuss the benefits that such an approach can bring to all stakeholders. In addition, we present a Proof of Concept (PoC) decision support system that instantiates many of the discussed construct, models, and methods and automates many activities in the risk analysis methodology for the protection of software. Despite being a prototype, the PoC's validation with industry experts indicated that several aspects of the proposed risk management process can already be formalized and automated with our existing toolbox and that it can actually assist decision-making in industrially relevant settings., Comment: Preprint submitted to Computers & Security. arXiv admin note: substantial text overlap with arXiv:2011.07269

Aim: To use normalization process theory (NPT) to build a strategy for the implementation of goal-oriented care (GOC) in primary care in Flanders, Belgium. Background: GOC is a possible approach to more coordinated and integrated care and tailors care to patients’ personal life goals. The concept has gained interest among policy makers and researchers, but the main drivers for successful implementation are the primary healthcare professionals (PHCPs) who need to see added value of GOC in order to embed it into their daily practice. NPT, developed to understand the processes of implementing new ways of organizing care, offers a useful lens to understand adoption of GOC in primary care practice. Method: PHCPs (n = 131) who participated in a 2-hour community meeting on GOC were asked to complete the Normalization MeAsure Development survey. This 23-item survey is based on NPT and describes participants’ views about how an intervention would impact their work, their expectations about it, and whether it could become a routine part of their work. Findings: The NPT constructs coherence (sense-making work) and cognitive participation (relational work) showed positive tendency toward implementation of GOC. The participants had an initial understanding on GOC and there was much interest in supporting and start working with this approach. The other constructs collective action (operational work) and reflexive monitoring (appraisal work) will need further efforts to trigger implementation. A common ground is needed to integrate GOC as a common practice which can be achieved by intensive interprofessional collaboration.

This is just the introduction of the thesis - Cosmology, the activity of describing the universe’s overall structure and origins, is understood today as the preserve of physics. Physical cosmology is an area of research that has seen such rapid progress in the last decades that it is regarded as the next chapter in physicists’ ambition toward unlocking the secrets of the cosmos and delivering a singular and final account of reality. This thesis argues, however, that rather than a story of linear scientific progress, the becoming scientific of our modern cosmology may be read as the expression of a crisis in fundamental physics, and a sign that its turn towards unity and finality of explanation may be reaching its end, what I call the “end of the universe.” Weaving together the scientific literature, recent historical studies, and philosophical reflection, combined with ethnographic fieldwork and interviews from a sustained engagement with cosmological researchers, I seek to think from this crisis in order to characterise the meaning and purpose of cosmology otherwise. Drawing on the work of William James, Étienne Souriau, Isabelle Stengers, and Alfred North Whitehead, among others, the thesis adopts an empiricist sensibility that explores how the problem of cosmology might be expanded away from a problem of physics to occupy a broader “cosmology of problems.” In this expanded cosmology, exemplified by attending to physicists’ dark matter problem, problems are real, immanent forces that work to form inquirers and the worlds they inhabit. It is this approach – one that seeks to understand how problems come (in)to matter for the peoples, practices, and worlds that belong to them – that I conclude holds promise in the development of a “pluralistic” cosmology. A cosmology that admits a plurality of divergent knowledges and practices into its explanations, ensuring that physicists’ “end of the universe” need not imply the end of their world.

Additional File 4: Table S3: Characteristics of excluded studies

BACKGROUND: Nursing home residents (NHR) and staff have been disproportionally affected by the COVID-19 pandemic and were therefore prioritised in the COVID-19 vaccination strategy. However, frail older adults, like NHR, are known to have decreased antibody responses upon vaccination targeting other viral antigens. OBJECTIVES: As real-world data on vaccine responsiveness, we assessed the prevalence of SARS-CoV-2 antibodies among Belgian NHR and staff during the primary COVID-19 vaccination campaign. METHODS: In total, we tested 1629 NHR and 1356 staff across 69 Belgian NHs for the presence of SARS-CoV-2 IgM/IgG antibodies using rapid tests. We collected socio-demographic and COVID-19-related medical data through questionnaires. Sampling occurred between 1 February and 24 March 2021, in a randomly sampled population that received none, one or two BNT162b2 vaccine doses. RESULTS: We found that during the primary vaccination campaign with 59% of the study population fully vaccinated, 74% had SARS-CoV-2 antibodies. Among fully vaccinated individuals only, fewer residents tested positive for SARS-CoV-2 antibodies (77%) than staff (98%), suggesting an impaired vaccine-induced antibody response in the elderly, with lowest seroprevalences observed among infection naïve residents. COVID-19 vaccination status and previous SARS-CoV-2 infection were predictors for SARS-CoV-2 seropositivity. Alternatively, age ≥ 80 years old, the presence of comorbidities and high care dependency predicted SARS-CoV-2 seronegativity in NHR. CONCLUSION: These findings highlight the need for further monitoring of SARS-CoV-2 immunity upon vaccination in the elderly population, as their impaired humoral responses could imply insufficient protection against COVID-19. TRIAL REGISTRATION: This study was retrospectively registered on ClinicalTrials.gov (NCT04738695). ispartof: EUROPEAN JOURNAL OF GENERAL PRACTICE vol:29 issue:2 ispartof: location:England status: published

Background Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both pp Conclusions Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration CAPACITY-COVID (NCT04325412)

Study Objectives International guidelines recommend using benzodiazepine receptor agonists (BZRA) for maximally four weeks. Nevertheless, long-term use for chronic insomnia disorder remains a common practice. This study aimed to test the effectiveness of blended care for discontinuing long-term BZRA use in general practice. Methods A pragmatic cluster randomized controlled superiority trial compared blended care to usual care through urine toxicology screening. In the intervention, care by the general practitioner (GP) was complemented by an interactive e-learning program, based on cognitive behavioral therapy for insomnia. Adults using BZRA daily for minimally 6 months were eligible. Participants were clustered at the level of the GP surgery for allocation (1:1). Effectiveness was measured as the proportion of patients who had discontinued at one-year follow-up. Data analysis followed intention-to-treat principles. Results In total, 916 patients in 86 clusters, represented by 99 GPs, were randomized. Primary outcome data was obtained from 727 patients (79%). At one-year follow-up, 82 patients (18%) in blended care, compared to 91 patients (20%) in usual care, had discontinued. There was no statistically significant effect for the intervention (OR: 0.924; 95% CI: 0.60; 1.43). No adverse events were reported to the research team. Conclusions The findings did not support the superiority of blended care over usual care. Both strategies showed clinical effectiveness, with an average of 19% of patients having discontinued at one-year follow-up. Further research is important to study the effect of structurally implementing digital interventions in general practice. Clinical trial Big Bird trial; KCE-17016. This trial is registered at clinicaltrials.gov (NCT03937180).

Background The development of technological applications in clinical research, such as electronic informed consent (eIC), is on the rise. The involvement of end users throughout the design process of eIC is of utmost importance to improve the current informed consent process. Methods Using a provocative design, we conducted interviews with 30 clinical research participants. Provotypes were used as a starting base to discuss various aspects relevant to eIC. By providing a medium to encourage divergent thinking, participants’ views and concerns were solicited. Thematic analysis was undertaken using NVivo. Results The majority of participants placed trust in the principal investigator or the hospital to perform the role of eIC hosting party. Differing opinions were reported on the amount of information required related to stakeholders’ access to an eIC system, and thus, to participants’ personal data, to enable trust in an eIC system. Nevertheless, this study indicates a general willingness of participants to share personal data with physicians and pharmaceutical companies on an international level, and to receive requests for new research studies via an eIC system. Participants suggested to tailor an eIC system based upon their preferences, for example, regarding whom they want to share their personal data with. Moreover, they expressed a desire to choose how they can contact the research team, and to indicate which study-related information they would like to receive electronically. In addition, positive opinions were voiced on the integration of a test to assess participants’ understanding before providing their eIC. Conclusions Following a research through design approach, insights have been generated which inform the design of eIC. Provotypes were designed to help participants think beyond what is familiar to them. Study findings revealed that not all situations were perceived as provocative, because of participants’ motivation to advance scientific research and the trust they place in the research team. Nevertheless, the use of provocative design resulted in additional insights, generated by clinical research participants, which could be considered in the further design of eIC.

BackgroundSeveral changes have led to general practitioners (GPs) working in a more differentiated setting today and being supported by other health professions. As practice changes, primary care specific continuing medical education (CME) may also need to adapt. By comparing different primary care specific CME approaches for GPs across Europe, we aim at identifying challenges and opportunities for future development.MethodsNarrative review assessing, analysing and comparing CME programs for general practitioners across different north-western European countries (UK, Norway, the Netherlands, Belgium (Flanders), Germany, Switzerland, and France). Templates containing detailed items across seven dimensions of country-specific CME were developed and used. These dimensions are role of primary care within the health system, legal regulations regarding CME, published aims of CME, actual content of CME, operationalisation, funding and sponsorship, and evaluation.ResultsGeneral practice specific CME in the countries under consideration are presented and comparatively analysed based on the dimensions defined in advance. This shows that each of the countries examined has different strengths and weaknesses. A clear pioneer cannot be identified. Nevertheless, numerous impulses for optimising future GP training systems can be derived from the examples presented.ConclusionsIndependent of country specific CME programs several fields of potential action were identified: the development of curriculum objectives for GPs, the promotion of innovative teaching and learning formats, the use of synergies in specialist GP training and CME, the creation of accessible yet comprehensive learning platforms, the establishment of clear rules for sponsorship, the development of new financing models, the promotion of fair competition between CME providers, and scientifically based evaluation.

This document provides methodological guidelines for work package 4, which is concerned with analysing media representations of the two critical issues of im/migration and gender. The guidelines apply to the quantitative analysis embedded in Task 4.2 – Representation of Im/migration in 10 countries and Task 4.3 – Representation of gender in 10 countries. The goal of this work package is to provide an in-depth analysis of media narratives, aiming at detecting to what degree platformization has been changing the representation of gender and im/migration in Europe. The specific focus will be on how platformization affects the process of Europeanisation and how Europe is represented through gender and im/migration.

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 POINTSCurrent 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: This study investigates the incidence, clinical characteristics, and treatment response of macular neovascularization (MNV) occurring after retinal pigment epithelium (RPE) and choroid graft translocation surgery (RPE-choroid TS). Methods: Retrospective analysis of 36 eyes of 36 consecutive patients who underwent RPE-choroid TS. Longer term follow-up of graft survival focusing on the occurrence of MNV was performed using multimodal imaging. Results: Indications for RPE-choroid TS included complications of neovascular age-related macular degeneration in 34 patients and drusenoid pigment epithelial detachment in 2 patients. With a mean follow-up of 30 months, 8 patients out of 36 developed signs of MNV. Of these 8 patients, 4 presented with a drop in visual acuity (VA) due to centrally located type 3 MNV. Early diagnosis and treatment prevented significant functional consequences. Four patients developed type 2 MNV at the border of the graft, which did not tend to affect the VA. Conclusion: We report a high incidence of MNV after RPE-choroid TS. Early diagnosis and treatment may preserve function in these patients. The type of MNV and location can be used to guide the management.

Objective Urine self-sampling has gained increasing interest for cervical cancer screening. In contrast to analytical performance, little information is available regarding the clinical accuracy for high-risk Human Papillomavirus (hrHPV) testing on urine. Methods VALHUDES is a diagnostic test accuracy study comparing clinical accuracy to detect high-grade cervical precancer (CIN2+) of HPV testing on self-collected compared to clinician-collected samples ( NCT03064087 ). Disease outcome was assessed by colposcopy and histology. The Abbott RealTime High Risk HPV assay performance was evaluated on Colli-Pee collected first-void urine with cervical outcomes as comparator. Results As no assay cut-off for urine has been clinically validated, we used the predefined cut-off for cervical samples (CN ≤ 32). Using this cut-off, hrHPV testing was similarly sensitive (relative sensitivity 0.95; 95% CI: 0.88–1.01) and specific (relative specificity 1.03; 95% CI: 0.95–1.13) for detection of CIN2+ compared to testing cervical samples. In the subgroup of women of 30 years and older, similar relative sensitivity (0.97; 95% CI: 0.89–1.05) and specificity (1.02; 95% CI: 0.93–1.12) was found. Additionally, an exploratory cut-off (CN ≤ 33.86) was defined which further improved sensitivity and analytical test performance. Conclusion HrHPV-DNA based PCR testing on home-collected first-void urine has similar accuracy for detecting CIN2+ compared to cervical samples taken by a clinician.

Background Primary health care providers (PHCPs) are assumed to be at high risk of a COVID-19 infection, as they are exposed to patients with usually less personal protective equipment (PPE) than other frontline health care workers (HCWs). Nevertheless, current research efforts focussed on the assessment of COVID-19 seroprevalence rates in the general population or hospital HCWs. Objective We aimed to determine the seroprevalence in PHCPs during the second SARS-CoV-2 wave in Flanders (Belgium) and compared it to the seroprevalence in the general population. We also assessed risk factors, availability of PPE and attitudes towards the government guidelines over time. Methods A prospective cohort of PHCPs (n = 698), mainly general practitioners, was asked to complete a questionnaire and self-sample capillary blood by finger-pricking at five distinct points in time (June–December 2020). We analysed the dried blood spots for IgG antibodies using a Luminex multiplex immunoassay. Results The seroprevalence of PHCPs remained stable between June and September (4.6–5.0%), increased significantly from October to December (8.1–13.4%) and was significantly higher than the seroprevalence of the general population. The majority of PHCPs were concerned about becoming infected, had adequate PPE and showed increasing confidence in government guidelines. Conclusions The marked increase in seroprevalence during the second COVID-19 wave shows that PHCPs were more at risk during the second wave compared to the first wave in Flanders. This increase was only slightly higher in PHCPs than in the general population suggesting that the occupational health measures implemented provided sufficient protection when managing patients.