Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases.

Cerebrospinal fluid (CSF) biomarkers reflect brain pathophysiology and are used extensively in translational research as well as in clinical practice for diagnosis of neurological diseases, e.g., Alzheimer's disease (AD). However, CSF biomarker concentrations may be influenced by non-disease related inter-individual variability. Here we use a data-driven approach to demonstrate the existence of inter-individual variability in mean standardized CSF protein levels. We show that these non-disease related differences cause many commonly reported CSF biomarkers to be highly correlated, thereby producing misleading results if not accounted for. To adjust for this inter-individual variability, we identified and evaluated high-performing reference proteins which improved the diagnostic accuracy of key CSF AD biomarkers. Our reference protein method attenuates the risk for false positive findings, and improves the sensitivity and specificity of CSF biomarkers, with broad implications for both research and clinical practice.

Testing Psychological Inoculation to Reduce Reactance to Vaccine-Related Communication.

Research has found that vaccine-promoting messages can elicit state reactance (i.e., negative emotions in response to a perceived threat to behavioral freedom), especially among individuals with high trait reactance (i.e., proneness to experiencing reactance). This can result in a lower willingness to accept vaccines. We investigated whether inoculation against reactance - that is, forewarning individuals about potentially experiencing reactance - can reduce the effects of trait reactance on vaccination willingness. Participants (N = 710) recruited through Facebook were randomly allocated to be either inoculated or not. They were then shown a message promoting a fictitious vaccine, which included either a low, medium, or high threat to freedom. Contrary to research on other health topics, inoculation was ineffective at reducing state reactance toward the vaccination message. Inoculation also did not mitigate the effects of trait reactance on vaccination willingness, and was even counterproductive in some cases. High-reactant individuals were less willing to get vaccinated than low-reactant ones, especially at high freedom threat. Conversely, high freedom threat resulted in increased vaccination willingness among low-reactant individuals. Further research is needed to understand why inoculation against reactance produces different results with vaccination, and to develop communication strategies that mitigate reactance to vaccination campaigns without compromising the positive effects of vaccine recommendations for low-reactant individuals.

Nanometa Live: a user-friendly application for real-time metagenomic data analysis and pathogen identification.

SUMMARY: Nanometa Live presents a user-friendly interface designed for real-time metagenomic data analysis and pathogen identification utilizing Oxford Nanopore Technologies' MinION and Flongle flow cells. It offers an efficient workflow and graphical interface for the visualization and interpretation of metagenomic data as it is being generated. Key features include automated BLAST validation, streamlined handling of custom Kraken2 databases, and a simplified graphical user interface for enhanced user experience. Nanometa Live is particularly notable for its capability to run without constant internet or server access once installed, setting it apart from similar tools. It provides a comprehensive view of taxonomic composition and facilitates the detection of user-defined pathogens or other species of interest, catering to both researchers and clinicians. AVAILABILITY AND IMPLEMENTATION: Nanometa Live has been implemented as a local web application using the Dash framework with Snakemake handling the data processing. The source code is freely accessible on the GitHub repository at https://github.com/FOI-Bioinformatics/nanometa_live and it is easily installable using Bioconda. It includes containerization support via Docker and Singularity, ensuring ease of use, reproducibility, and portability.

Plasma Biomarker Strategy for Selecting Patients With Alzheimer Disease for Antiamyloid Immunotherapies.

Importance: Antiamyloid immunotherapies against Alzheimer disease (AD) are emerging. Scalable, cost-effective tools will be needed to identify amyloid ß (Aß)-positive patients without an advanced stage of tau pathology who are most likely to benefit from these therapies. Blood-based biomarkers might reduce the need to use cerebrospinal fluid (CSF) or positron emission tomography (PET) for this. Objective: To evaluate plasma biomarkers for identifying Aß positivity and stage of tau accumulation. Design, Setting, and Participants: The cohort study (BioFINDER-2) was a prospective memory-clinic and population-based study. Participants with cognitive concerns were recruited from 2017 to 2022 and divided into a training set (80% of the data) and test set (20%). Exposure: Baseline values for plasma phosphorylated tau 181 (p-tau181), p-tau217, p-tau231, N-terminal tau, glial fibrillary acidic protein, and neurofilament light chain. Main Outcomes and Measures: Performance to classify participants by Aß status (defined by Aß-PET or CSF Aß42/40) and tau status (tau PET). Number of hypothetically saved PET scans in a plasma biomarker-guided workflow. Results: Of a total 912 participants, there were 499 males (54.7%) and 413 females (45.3%), and the mean (SD) age was 71.1 (8.49) years. Among the biomarkers, plasma p-tau217 was most strongly associated with Aß positivity (test-set area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI, 0.90-0.97). A 2-cut-point procedure was evaluated, where only participants with ambiguous plasma p-tau217 values (17.1% of the participants in the test set) underwent CSF or PET to assign definitive Aß status. This procedure had an overall sensitivity of 0.94 (95% CI, 0.90-0.98) and a specificity of 0.86 (95% CI, 0.77-0.95). Next, plasma biomarkers were used to differentiate low-intermediate vs high tau-PET load among Aß-positive participants. Plasma p-tau217 again performed best, with the test AUC = 0.92 (95% CI, 0.86-0.97), without significant improvement when adding any of the other plasma biomarkers. At a false-negative rate less than 10%, the use of plasma p-tau217 could avoid 56.9% of tau-PET scans needed to identify high tau PET among Aß-positive participants. The results were validated in an independent cohort (n = 118). Conclusions and Relevance: This study found that algorithms using plasma p-tau217 can accurately identify most Aß-positive individuals, including those likely to have a high tau load who would require confirmatory tau-PET imaging. Plasma p-tau217 measurements may substantially reduce the number of invasive and costly confirmatory tests required to identify individuals who would likely benefit from antiamyloid therapies.

Trait reactance as psychological motivation to reject vaccination: Two longitudinal studies and one experimental study.

Anti-science attitudes can be resilient to scientific evidence if they are rooted in psychological motives. One such motive is trait reactance, which refers to the need to react with opposition when one's freedom of choice has been threatened. In three studies, we investigated trait reactance as a psychological motivation to reject vaccination. In the longitudinal studies (n = 199; 293), we examined if trait reactance measured before the COVID-19 pandemic was related to people's willingness to get vaccinated against COVID-19 up to 2 years later during the pandemic. In the experimental study (n = 398), we tested whether trait reactance makes anti-vaccination attitudes more resistant to information and whether this resistance can be mitigated by framing the information to minimize the risk of triggering state reactance. The longitudinal studies showed that higher trait reactance before the COVID-19 pandemic was related to lower willingness to get vaccinated against COVID-19. Our experimental study indicated that highly reactant individuals' willingness to vaccinate was unaffected by the amount and framing of the information provided. Trait reactance has a strong and durable impact on vaccination willingness. This highlights the importance of considering the role of trait reactance in people's vaccination-related decision-making.

Healthcare professionals' attitudes to mandatory COVID-19 vaccination: Cross-sectional survey data from four European countries.

Mandatory vaccinations are widely debated since they restrict individuals' autonomy in their health decisions. As healthcare professionals (HCPs) are a common target group of vaccine mandates, and also form a link between vaccination policies and the public, understanding their attitudes toward vaccine mandates is important. The present study investigated physicians' attitudes to COVID-19 vaccine mandates in four European countries: Finland, France, Germany, and Portugal. An electronic survey assessing attitudes to COVID-19 vaccine mandates and general vaccination attitudes (e.g. perceived vaccine safety, trust in health authorities, and openness to patients) was sent to physicians in the spring of 2022. A total of 2796 physicians responded. Across all countries, 78% of the physicians were in favor of COVID-19 vaccine mandates for HCPs, 49% favored COVID-19 vaccine mandates for the public, and 67% endorsed COVID-19 health passes. Notable differences were observed between countries, with attitudes to mandates found to be more positive in countries where the mandate, or similar mandates, were in effect. The associations between attitudes to mandates and general vaccination attitudes were mostly small to neglectable and differed between countries. Nevertheless, physicians with more positive mandate attitudes perceived vaccines as more beneficial (in Finland and France) and had greater trust in medical authorities (in France and Germany). The present study contributes to the body of research within social and behavioral sciences that support evidence-based vaccination policymaking.

Endorsement of alternative medicine and vaccine hesitancy among physicians: A cross-sectional study in four European countries.

Vaccine hesitancy has become a threat to public health, especially as it is a phenomenon that has also been observed among healthcare professionals. In this study, we analyzed the relationship between endorsement of complementary and alternative medicine (CAM) and vaccination attitudes and behaviors among healthcare professionals, using a cross-sectional sample of physicians with vaccination responsibilities from four European countries: Germany, Finland, Portugal, and France (total N = 2,787). Our results suggest that, in all the participating countries, CAM endorsement is associated with lower frequency of vaccine recommendation, lower self-vaccination rates, and being more open to patients delaying vaccination, with these relationships being mediated by distrust in vaccines. A latent profile analysis revealed that a profile characterized by higher-than-average CAM endorsement and lower-than-average confidence and recommendation of vaccines occurs, to some degree, among 19% of the total sample, although these percentages varied from one country to another: 23.72% in Germany, 17.83% in France, 9.77% in Finland, and 5.86% in Portugal. These results constitute a call to consider health care professionals' attitudes toward CAM as a factor that could hinder the implementation of immunization campaigns.

International adaptation and validation of the Pro-VC-Be: measuring the psychosocial determinants of vaccine confidence in healthcare professionals in European countries.

BACKGROUND: Healthcare professionals (HCPs) play an important role in vaccination; those with low confidence in vaccines are less likely to recommend them to their patients and to be vaccinated themselves. The study's purpose was to adapt and validate long- and short-form versions of the International Professionals' Vaccine Confidence and Behaviors (I-Pro-VC-Be) questionnaire to measure psychosocial determinants of HCPs' vaccine confidence and their associations with vaccination behaviors in European countries. RESEARCH DESIGN AND METHODS: After the original French-language Pro-VC-Be was culturally adapted and translated, HCPs involved in vaccination (mainly GPs and pediatricians) across Germany, Finland, France, and Portugal completed a cross-sectional online survey in 2022. A 10-factor multigroup confirmatory factor analysis (MG-CFA) of the long-form (10 factors comprising 34 items) tested for measurement invariance across countries. Modified multiple Poisson regressions tested the criterion validity of both versions. RESULTS: 2,748 HCPs participated. The 10-factor structure fit was acceptable to good everywhere. The final MG-CFA model confirmed strong factorial invariance and showed very good fit. The long- and short-form I-Pro-VC-Be had good criterion validity with vaccination behaviors. CONCLUSION: This study validates the I-Pro-VC-Be among HCPs in four European countries; including long- and short-form tools for use in research and public health.

The kinetics of SARS-CoV-2 viremia in COVID-19 patients receiving remdesivir.

Detection of SARS-CoV-2 RNA in serum, viremia, has been linked to disease severity and outcome. The kinetics of viremia in patients receiving remdesivir has not been thoroughly studied and could help predict treatment response and outcome. We investigated the kinetics of SARS-CoV-2 viremia and factors associated with baseline viremia, viral clearance and 30-day mortality in patients receiving remdesivir. An observational study including 378 hospitalised patients (median age 67 years, 67% male) sampled with serum SARS-CoV-2 RT-PCR within ± 24 h of initiation of remdesivir treatment. Baseline viremia was present in 206 (54%) patients with a median Ct value of 35.3 (IQR = 33.3-37.1). In patients with baseline viremia, the estimated probability of viral clearance was 72% by day 5. Ct values decreased significantly during remdesivir treatment for viremic patients, indicating an increase in viral load. In total, 44 patients (12%) died within 30 days, and mortality was significantly associated with viremia at baseline (OR = 2.45, p = 0.01) and lack of viral clearance by day 5 (OR = 4.8, p = < 0.01). Viral clearance was not associated with any individual risk factor. Viremia appears to be a prognostic marker before and during remedesivir treatment. The resolution of viremia was similar to patients not receiving remdesivir in other studies, and the decrease in Ct values during treatment questions the antiviral capacity of remdesivir in vivo. Prospective studies are warranted to confirm our findings.

Spillover effects of the COVID-19 pandemic on attitudes to influenza and childhood vaccines.

The current study sought to determine whether public perceptions of other vaccines and diseases than COVID-19 have been impacted by the COVID-19 pandemic. We longitudinally examined whether there had been a change from before the COVID-19 pandemic to during the pandemic in: (a) influenza vaccination behaviour and intentions; (b) the perceived benefit of childhood vaccines and influenza vaccines; (c) the perceived safety of childhood vaccines and influenza vaccines; (d) the perceived severity of measles and influenza; and (e) trust in healthcare professionals in two samples of Finnish adults (N = 205 in Study 1 and N = 197 in Study 2). The findings showed that during the pandemic, more people than before had received or wanted to receive the influenza vaccine. The respondents also believed that influenza was more dangerous during the pandemic and that vaccinations were safer and more beneficial. On the other hand, for childhood vaccines only perceived safety increased. Finally, in one of the studies, people had more confidence in medical professionals during the pandemic than they had before. Together, these findings imply a spillover of the COVID-19 pandemic on how people view other vaccines and illnesses.

Outcome of COVID-19 in allogeneic stem cell transplant recipients: Results from the EPICOVIDEHA registry.

Background: The outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT. Methods: This multicenter retrospective study promoted by the European Hematology Association - Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022. Results: The median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53). Conclusions: Mortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Tailoring interventions to suit self-reported format preference does not decrease vaccine hesitancy.

Individually tailored vaccine hesitancy interventions are considered auspicious for decreasing vaccine hesitancy. In two studies, we measured self-reported format preference for statistical vs. anecdotal information in vaccine hesitant individuals, and experimentally manipulated the format in which COVID-19 and influenza vaccine hesitancy interventions were presented (statistical vs. anecdotal). Regardless of whether people received interventions that were in line with their format preference, the interventions did not influence their vaccine attitudes or vaccination intentions. Instead, a stronger preference for anecdotal information was associated with perceiving the material in both the statistical and the anecdotal interventions as more frustrating, less relevant, and less helpful. However, even if the participants reacted negatively to both intervention formats, the reactions to the statistical interventions were consistently less negative. These results suggest that tailoring COVID-19 and influenza vaccine hesitancy interventions to suit people's format preference, might not be a viable tool for decreasing vaccine hesitancy. The results further imply that using statistics-only interventions with people who hold anti-vaccination attitudes may be a less risky choice than using only anecdotal testimonies.

Genomic characterization of Francisella tularensis and other diverse Francisella species from complex samples.

Francisella tularensis, the bacterium that causes the zoonosis tularemia, and its genetic near neighbor species, can be difficult or impossible to cultivate from complex samples. Thus, there is a lack of genomic information for these species that has, among other things, limited the development of robust detection assays for F. tularensis that are both specific and sensitive. The objective of this study was to develop and validate approaches to capture, enrich, sequence, and analyze Francisella DNA present in DNA extracts generated from complex samples. RNA capture probes were designed based upon the known pan genome of F. tularensis and other diverse species in the family Francisellaceae. Probes that targeted genomic regions also present in non-Francisellaceae species were excluded, and probes specific to particular Francisella species or phylogenetic clades were identified. The capture-enrichment system was then applied to diverse, complex DNA extracts containing low-level Francisella DNA, including human clinical tularemia samples, environmental samples (i.e., animal tissue and air filters), and whole ticks/tick cell lines, which was followed by sequencing of the enriched samples. Analysis of the resulting data facilitated rigorous and unambiguous confirmation of the detection of F. tularensis or other Francisella species in complex samples, identification of mixtures of different Francisella species in the same sample, analysis of gene content (e.g., known virulence and antimicrobial resistance loci), and high-resolution whole genome-based genotyping. The benefits of this capture-enrichment system include: even very low target DNA can be amplified; it is culture-independent, reducing exposure for research and/or clinical personnel and allowing genomic information to be obtained from samples that do not yield isolates; and the resulting comprehensive data not only provide robust means to confirm the presence of a target species in a sample, but also can provide data useful for source attribution, which is important from a genomic epidemiology perspective.

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA).

Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs.

Measuring psychosocial determinants of vaccination behavior in healthcare professionals: validation of the Pro-VC-Be short-form questionnaire.

BACKGROUND: Vaccine confidence among health care professionals (HCPs) is a key determinant of vaccination behaviors. We validate a short-form version of the 31-item Pro-VC-Be (Health Professionals Vaccine Confidence and Behaviors) questionnaire that measures HCPs' confidence in and commitment to vaccination. RESEARCH DESIGN AND METHODS: A cross-sectional survey among 2,696 HCPs established a long-form tool to measure 10 dimensions of psychosocial determinants of vaccination behaviors. Confirmatory factor analysis (CFA) models tested the construct validity of 69,984 combinations of items in a 10-item short form tool. The criterion validity of this tool was tested with four behavioral and attitudinal outcomes using weighted modified Poisson regressions. An immunization resource score was constructed from summing the responses of the dimensions that can influence HCPs' pro-vaccination behaviors: vaccine confidence, proactive efficacy, and trust in authorities. RESULTS: The short-form tool showed good construct validity in CFA analyses (RMSEA = 0.035 [0.024; 0.045]; CFI = 0.956; TLI = 0.918; SRMR 0.027) and comparable criterion validity to the long-form tool. The immunization resource score showed excellent criterion validity. CONCLUSIONS: The Pro-VC-Be short-form showed good construct validity and criterion validity similar to the long-form and can therefore be used to measure determinants of vaccination behaviors among HCPs.

Co-Occurrence of Francisella, Spotted Fever Group Rickettsia, and Midichloria in Avian-Associated Hyalomma rufipes.

The migratory behavior of wild birds contributes to the geographical spread of ticks and their microorganisms. In this study, we aimed to investigate the dispersal and co-occurrence of Francisella and spotted fever group Rickettsia (SFGR) in ticks infesting birds migrating northward in the African-Western Palaearctic region (AWPR). Birds were trapped with mist nests across the Mediterranean basin during the 2014 and 2015 spring migration. In total, 575 ticks were collected from 244 birds. We screened the ticks for the species Francisella tularensis, the genus Francisella, and SFGR by microfluidic real-time PCR. Confirmatory analyses and metagenomic sequencing were performed on tick samples that putatively tested positive for F. tularensis during initial screenings. Hyalomma rufipes was the most common tick species and had a high prevalence of Francisella, including co-occurrence of Francisella and SFGR. Metagenomic analysis of total DNA extracted from two H. rufipes confirmed the presence of Francisella, Rickettsia, and Midichloria. Average nucleotide identity and phylogenetic inference indicated the highest identity of the metagenome-assembled genomes to a Francisella-like endosymbiont (FLE), Rickettsia aeschlimannii, and Midichloria mitochondrii. The results of this study suggest that (i) FLE- and SFGR-containing ticks are dispersed by northbound migratory birds in the AWPR, (ii) H. rufipes likely is not involved in transmission of F. tularensis in the AWPR, and (iii) a dual endosymbiosis of FLEs and Midichloria may support some of the nutritional requirements of H. rufipes.

Attitudes towards mandatory vaccination and sanctions for vaccination refusal.

AIMS: Investigating attitudes towards mandatory vaccination and sanctions for vaccination refusal in an area with insufficient vaccination coverage may help health authorities to assess which strategies for increasing vaccination coverage are appropriate. This study examines attitudes to vaccine mandates and asks questions regarding what kinds of sanctions could legitimately result from vaccination refusal. It seeks to find out if people's attitudes towards mandates and towards sanctions for vaccination refusal are related to their attitudes to vaccines and the degree of trust they feel towards health care professionals and health care authorities. The study also discusses how the observed attitudes towards mandates may be related to perceptions of autonomy, responsibility, and equitability. METHODS: Data collection was carried out in Finland through an online survey in a region with suboptimal vaccine uptake. Statistical analysis was conducted on a sample of 1101 respondents, using confirmatory factor analysis and structural regression analysis. RESULTS: Persons hold different views on mandates and sanctions. Importantly, the persons who support vaccination mandates and sanctions for vaccination refusal are to a great degree the same people who have positive attitudes to vaccines and high trust in health care professionals and health authorities. CONCLUSION: Trust is a key factor which has a bearing on people's attitudes towards mandates and sanctions for noncompliance. A focus on the reasons for lack of trust, and on how to enhance trust, is a more feasible long-term way (than mandates) to promote large- scale compliance with childhood vaccine programmes in the studied country context.

Acquired spherocytosis in the setting of myelodysplasia.

Hereditary spherocytosis (HS) is the most prevalent red blood cell (RBC) membrane disorder. We report a rare case of acquired SPTB spherocytosis coinciding with a myelodysplastic syndrome associated U2AF1 mutation, neither found in germline DNA. The diagnosis was confirmed by Eosin-5-Maleimide binding assay and Next Generation Sequencing (NGS). The patient recovered quickly after splenectomy, which confirms that his myelodysplastic syndrome (MDS)-associated U2AF1 mutation did not affect the clinical picture. This case highlights the essence of thoroughly examining the etiology of hemolytic indices, despite bone marrow morphology and myeloid gene panel supporting a diagnosis of MDS with single line dysplasia.

An instrument to measure psychosocial determinants of health care professionals' vaccination behavior: Validation of the Pro-VC-Be questionnaire.

OBJECTIVES: The lack of validated instruments assessing vaccine hesitancy/confidence among health care professionals (HCPs) for themselves, and their patients led us to develop and validate the Pro-VC-Be instrument to measure vaccine confidence and other psychosocial determinants of HCPs' vaccination behavior among diverse HCPs in different countries. METHODS: Cross-sectional survey in October-November 2020 among 1,249 GPs in France, 432 GPs in French-speaking parts of Belgium, and 1,055 nurses in Quebec (Canada), all participating in general population immunization. Exploratory and confirmatory factor analyses evaluated the instrument's construct validity. We used HCPs' self-reported vaccine recommendations to patients, general immunization activity, self-vaccination, and future COVID-19 vaccine acceptance to test criterion validity. RESULTS: The final results indicated a 6-factor structure with good fit: vaccine confidence (combining complacency, perceived vaccine risks, perceived benefit-risk balance, perceived collective responsibility), trust in authorities, perceived constraints, proactive efficacy (combining commitment to vaccination and self-efficacy), reluctant trust, and openness to patients. The instrument showed good convergent and criterion validity and adequate discriminant validity. CONCLUSIONS: This study found that the Pro-VC-Be is a valid instrument for measuring psychosocial determinants of HCPs' vaccination behaviors in different settings. Its validation is currently underway in Europe among various HCPs in different languages.