Search

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]

This study set out to understand how representational practices of journalism and age congregate in the fiction movie The French Dispatch. Employing textual analysis, we found that the film engages with three overlapping tropes in which journalism and age congregate. First, it represents journalists as different from “normal civilians” especially in their state of loneliness which is a constant throughout the narrative. This difference narrative is especially invigorated for journalists that demographically deviate from the norm in which older women are labeled as “old maids.” Second, the film represents an intergenerational conflict, specifically in relation to explorations of journalistic neutrality. Last, the commercial nature of journalism is addressed through the representation of an older mentoring editor-in-chief who protects journalistic quality against commercial pressures. By combining the lens of journalism and ageism, we uncovered how both concepts congregate and create a unique romanticized perspective on the profession as “it used to be.” [ABSTRACT FROM AUTHOR]

When COVID-19 vaccines were implemented, nursing home residents (NHRs) and staff (NHS) in Belgium were prioritized for vaccination. To characterize the vaccine response over time in this population and to identify poorly responding groups, we assessed antibody concentrations two (T1), four (T2) and six months (T3) after primary course BNT162b2 vaccination in six groups of infection-naive/infection-primed NHRs/NHS, with/without comorbidity (NHRs only). Participant groups (N = 125 per group) were defined within a national serosurveillance study in nursing homes, based on questionnaire data. Dried blood spots were analyzed using ELISA for the quantification of SARS-CoV-2 S1RBD IgG antibodies. Among all groups, antibody concentrations significantly decreased between T1 and T2/T3, all with a ≥70% decrease at T3, except for infection-primed staff (−32%). Antibody concentrations among infection-naive NHRs were 11.96 times lower than those among infection-primed NHR, while the latter were comparable (x1.05) to infection-primed NHS. The largest proportion [13% (95% CI: 11–24%)] of vaccine non-responders was observed in the group of infection-naive NHRs with comorbidities. A longer interval between infection and vaccination (≥3 months) elicited higher antibody responses. Our data retrospectively show the necessity of timely COVID-19 booster vaccination. Infection-naive NHRs require special attention regarding immune monitoring in future epidemics or pandemics. [ABSTRACT FROM AUTHOR]

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.

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

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 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.

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.