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BACKGROUND: Individuals with genetic neurodevelopmental disorders (GNDs) or intellectual disability (ID) are often affected by complex neuropsychiatric comorbidities. Targeted treatments are increasingly available, but due to the heterogeneity of these patient populations, choosing a key outcome and corresponding outcome measurement instrument remains challenging. OBJECTIVES: The aim of this scoping review was to describe the research on outcomes and instruments used in clinical trials in GNDs and ID. ELIGIBILITY CRITERIA: Clinical trials in individuals with GNDs and ID for any intervention over the past 10 years were included in the review. SOURCES OF EVIDENCE: MEDLINE, PsycINFO, and Cochrane CENTRAL were searched. Titles and abstracts were independently screened for eligibility with a subsample of 10% double-screening for interrater reliability. Data from full texts were independently reviewed. Discrepancies were discussed until consensus was reached. CHARTING METHODS: Information was recorded on patient populations, interventions, designs, outcomes, measurement instruments, and type of reporter when applicable. Qualitative and descriptive analyses were performed. RESULTS: We included 312 studies reporting 91 different outcomes, with cognitive function most frequently measured (28%). Various outcome measurement instruments (n = 457) were used, with 288 in only a single clinical trial. There were 18 genetic condition-specific instruments and 16 measures were designed ad-hoc for one particular trial. Types of report included proxy-report (39%), self-report (22%), clinician-report (16%), observer-report (6%), self-assisted report (1%), or unknown (16%). CONCLUSION: This scoping review of current practice reveals a myriad of outcomes and outcome measurement instruments for clinical trials in GNDs and ID. This complicates generalization, evidence synthesis, and evaluation. It underlines the need for consensus on suitability, validity, and relevancy of instruments, ultimately resulting in a core outcome set. A series of steps is proposed to move from the myriad of measures to a more unified approach.

Aysun Damci,1,2 Janneke GJ Hoeijmakers,1,2 Marlies den Hollander,3– 5 Catharina G Faber,1,2 Sophie Waardenburg,6,7 Charlotte CM van Laake-Geelen,3– 5 Albère JA Köke,3,4 Jeanine AMCF Verbunt3– 5 1MHeNS, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, 6200 MD, The Netherlands; 2Department of Neurology, Maastricht University Medical Center+, Maastricht, 6229 HX, The Netherlands; 3Care and Public Health Research Institute, Maastricht university, Maastricht, 6200 MD, The Netherlands; 4Department of Rehabilitation Medicine, Maastricht University Medical Center+, Maastricht, 6229 HX, The Netherlands; 5Adelante Zorggroep, Center of Rehabilitation Medicine, Hoensbroek, 6432 CC, The Netherlands; 6Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center+, Maastricht, 6229 HX, The Netherlands; 7Department of Anesthesiology and Pain Medicine, Maastricht University Medical Center+, Maastricht, 6229 HX, The NetherlandsCorrespondence: Aysun Damci, Department of Neurology, Maastricht University Medical Centre+, P.O. Box 5800, Maastricht, 6202 AZ, The Netherlands, Tel +31-43-3877059, Fax +31-43-3877055, Email aysun.damci@mumc.nlPurpose: Small fiber neuropathy (SFN) is characterized by neuropathic pain, associated with decreased quality of life (QOL). It remains unclear which psychosocial factors play a role in SFN. The experience sampling method (ESM) allows a profound understanding of the real-time fluctuations in reaction to events. The main goal of this study was to increase knowledge of the interrelationships between pain intensity, physical activity, and psychosocial factors in patients with SFN in daily practice over time.Patients and Methods: A prospective observational ESM study with the PsyMate© application (smart-eHealth GmbH, Luxembourg) was conducted at the Adelante location of Maastricht University Medical Center+ in the Netherlands. Participants with idiopathic SFN, older than 18 years, with an indication for rehabilitation, were included. Pain intensity, fatigue, positive and negative affect, physical activity, avoidance behavior, and pain catastrophic thoughts were incorporated into the ESM questions. Participants received 10 beep signals per day followed by the above-mentioned questions, for consecutive 7 days. The results were analyzed with linear mixed-effect models.Results: Twenty-one participants were included with a mean age of 48.24 (SD ± 13.89) years, of whom 76.2% were female. More pain (now) resulted in more physical activity (later) (a) and more physical activity (now) resulted in more pain (later) (b). The first association (a) is influenced by pain catastrophic thoughts and fatigue, and the second (b) by an increase in affective states and a lower level of avoidance behavior.Conclusion: In idiopathic SFN, pain intensity, and physical activity showed a 2-sided association, influenced by catastrophic thoughts, fatigue, affective states, and avoidance behavior.Keywords: chronic pain, rehabilitation therapy, biopsychosocial factors, small fiber neuropathy

Background Patient reported outcomes are used to assess the impact of medical interventions on perceived health in both clinical trials and daily care. Further, patient-reported outcome measures (PROMs) optimize the consultation. However, patient completion of PROMs before their consultation, and healthcare provider's (HCP) use of PROMs in their consultation are suboptimal. In this cross-sectional study, we examined whether viewing a PROM dashboard before or during consultation consecutively resulted in higher patient completion of PROMs. Methods As part of regular care, patients were asked to fill out PROMs prior their consultation. HCPs’ dashboard views were logged. A chi-square test was performed on dashboard viewed (yes/no) with consecutively filling out PROMs (yes/no). The odds ratio (OR) of consecutively filling out PROMs after a dashboard view was calculated. Results 38.016 consecutive appointments were linked to a previous appointment in which a dashboard could be viewed. In 2740 cases, a dashboard was viewed by the HCP, against 35.276 cases in which a dashboard was not viewed. Follow-up adherence in completing PROMs was 49%. The chi-square test showed statistical significance of p

Abstract Malignant plasma cells in multiple myeloma patients reside in the bone marrow and continuously interact with local immune cells. Progression and therapy response are influenced by this immune environment, highlighting the need for a detailed understanding of endogenous immune responses to malignant plasma cells. Here we used the 5TGM1 murine transfer model of multiple myeloma to dissect early immune responses to myeloma cells. We modeled stable and progressive disease by transferring 5TGM1 murine myeloma cells into C57Bl/6 mice and KaLwRij mice, respectively. We used flow cytometry and single‐cell and bulk transcriptomic analyses to characterize differential immune responses in stable and progressive disease. Transfer of 5TGM1 cells in C57Bl/6 mice led to stable disease with low tumor burden in a subset of animals. Stable disease was associated with sustained activation and expansion of NK cells, ILC1, and CD8+ T cells, a response that was lost upon disease progression. Single‐cell RNA‐sequencing of immune cells and bulk RNA sequencing of immune and mesenchymal stromal cells implicated the activation of interferon responses as a central immune pathway during stable disease. Experimentally, neutralization of IFNγ significantly increased myeloma development and progression in C57Bl/6 mice, testifying to the importance of this pathway in early disease control. In conclusion, we provide a framework for studying immune responses to multiple myeloma progression in immunocompetent and genetically modifiable mice and highlight the importance of bone marrow immunity in tumor control.

BackgroundSmall fiber neuropathy (SFN) is a chronic neuropathic pain condition that can lead to a decreased quality of life (QOL) and disability. Current pain treatment is mainly symptomatic, consisting of analgesics, with often disappointing results. There is a need for new, more effective treatment modality. Treatment based on a biopsychosocial approach on SFN-related pain may be a promising alternative. A rehabilitation treatment study protocol is presented with the following main objective: to test the effect of a tailored interdisciplinary rehabilitation treatment targeting both cognitive and psychological factors related to pain, in decreasing disability, and improving QOL in SFN.MethodsSingle-case experimental design. Ten participants with SFN will be included. Every patient will be offered a personalized program based on one of three rehabilitation treatment modules (graded activity, exposure in vivo or acceptance and commitment therapy) depending on the most prominent factor maintaining disability. Treatment will be provided for at least 8 weeks with 2 sessions a week.Discussion/conclusionThis is the first study investigating personalized rehabilitation treatment in patients with idiopathic SFN. The findings are expected to result in an effective treatment for SFN with an increase in QOL and a decrease in disability.Clinical trial registrationClinicalTrials.gov, identifier NCT05798949.

BackgroundDespite the increasing use of patient-reported outcome measures (PROMs) for collecting self-reported data among hospital outpatients, clinicians’ use of these data remains suboptimal. Insight into this issue and strategies to enhance the use of PROMs are critical but limited. ObjectiveThis study aimed to examine clinicians’ use of PROM data for value-based outpatient consultations and identify efforts to enhance their use of PROMs in a Dutch university hospital. First, we aimed to investigate clinicians’ use of outpatients’ PROM data in 2023, focusing on adoption, implementation, and maintenance. Second, we aimed to develop insights into the organizational-level strategies implemented to enhance clinicians’ use of PROM data from 2020 to 2023. This included understanding the underlying rationales for these strategies and identifying strategies that appeared to be missing to address barriers or leverage facilitators. Third, we aimed to explore the key factors driving and constraining clinicians’ use of PROMs in 2023. MethodsWe integrated data from 4 sources: 1-year performance data on clinicians’ use of PROMs (n=70 subdepartments), internal hospital documents from a central support team (n=56), a survey among clinicians (n=47), and interviews with individuals contributing to the organizational-level implementation of PROMs (n=20). The Reach, Effectiveness, Adoption, Implementation, and Maintenance framework was used to analyze clinicians’ adoption, implementation, and maintenance of PROMs. Strategies were analyzed using the Expert Recommendations for Implementing Change taxonomy, and results were structured around the constructs of capability, opportunity, and motivation. ResultsOn average, around 2023, clinicians accessed PROM data for approximately 3 of 20 (14%) patients during their outpatient consultation, despite numerous strategies to improve this practice. We identified issues in adoption, implementation, and maintenance. The hospital’s strategies, shaped organically and pragmatically, were related to 27 (37%) out of 73 Expert Recommendations for Implementing Change strategies. These strategies focused on enhancing clinicians’ capability, opportunity, and motivation. We found shortcomings in the quality of execution and completeness of strategies in relation to addressing all barriers and leveraging facilitators. We identified variations in the factors influencing the use of PROMs among frequent PROM users, occasional users, and nonusers. Challenges to effective facilitation were apparent, with certain desired strategies being unfeasible or impeded. ConclusionsEnhancing clinicians’ use of PROMs has remained challenging despite various strategies aimed at improving their capability, opportunity, and motivation. The use of PROMs may require more substantial changes than initially expected, necessitating a shift in clinicians’ professional attitudes and practices. Hospitals can facilitate rather than manage clinicians’ genuine use of PROMs. They must prioritize efforts to engage clinicians with PROMs for value-based outpatient care. Specific attention to their professionalization may be warranted. Tailored strategies, designed to address within-group differences in clinicians’ needs and motivation, hold promise for future efforts.

Introduction While secondhand smoke exposure in outdoor spaces has been investigated before, no data on outdoor secondhand smoke exposure have been collected in the Netherlands. Such data could help policymakers gain support for smoke-free outdoor public spaces. Methods Between May and November 2021, we visited 25 outdoor locations across the Netherlands. At each location, we conducted four measurements with smokers and one measurement without smokers. During each measurement, we counted the number of smokers present and we rated tobacco smell intensity on a fivepoint scale. Airborne nicotine and 3-ethenylpyridine (3-EP) data were collected through active sampling on thermal desorption tubes. The contents of these tubes were later analyzed using gas chromatography-mass spectrometry. Using linear mixed models, we investigated the association between levels of nicotine and the presence of smokers, the number of smokers, and the intensity of tobacco smell. We also investigated these association with levels of 3-EP. Results Nicotine levels were higher when smokers were present (B=1.40; 95% CI: 0.69– 2.11, p

Objectives The primary objective of this study was to describe the self-reported reproductive health of retired elite women’s footballers with specific reference to menstrual function, pregnancy and motherhood, contraceptive use and pelvic floor function.Methods An electronic survey was disseminated to women’s footballers (18 years or older) who had retired from elite football within 10 years of completing the survey.Results 69 respondents completed the survey (mean age 35.8 years, mean age at retirement 30.3 years). One-third of participants self-reported experiencing at least one episode of amenorrhoea (>3 months without menstruation) for reasons other than hormonal contraceptive use or pregnancy. Three participants (mean age of 41 years, range 30–54) reported having reached menopause at the time of the study. 54 (78.3%) participants were not using any form of contraception. 17 (24.6%) of the participants are mothers (range 1–3 children). 51 of the participants (73.9%) had never been pregnant, and the majority of those who had been pregnant (86.7%) became pregnant in less than 2 years following the onset of desire for pregnancy. Four of the retired players gave birth during their playing career, and the mean time to return to competitive matches following delivery was 22 weeks. The mean Pelvic Floor Distress Inventory-20 score for participants was 72.Conclusion These insights can be used to inform future efforts to promote positive reproductive health outcomes for current, former and future women’s footballers. Research efforts should focus on improving the understanding of how to effectively support women’s footballers in the perinatal period. Best practice guidelines on the use of menstrual cycle monitoring and pelvic health support would improve standards of care for women’s footballers. Stakeholders should consider gender-specific postretirement care for women’s footballers.

Age-related macular degeneration (AMD) is a disease that affects the macula - the central part of the retina. It is a leading cause of irreversible vision loss in the elderly. AMD onset is marked by the presence of lipid- and protein-rich extracellular deposits beneath the retinal pigment epithelium (RPE), a monolayer of polarized, pigmented epithelial cells located between the photoreceptors and the choroidal blood supply. Progression of AMD to the late nonexudative "dry" stage of AMD, also called geographic atrophy, is linked to progressive loss of areas of the RPE, photoreceptors, and underlying choriocapillaris leading to a severe decline in patients' vision. Differential susceptibility of macular RPE in AMD and the lack of an anatomical macula in most lab animal models has promoted the use of in vitro models of the RPE. In addition, the need for high throughput platforms to test potential therapies has driven the creation and characterization of in vitro model systems that recapitulate morphologic and functional abnormalities associated with human AMD. These models range from spontaneously formed cell line ARPE19, immortalized cell lines such as hTERT-RPE1, RPE-J, and D407, to primary human (fetal or adult) or animal (mouse and pig) RPE cells, and embryonic and induced pluripotent stem cell (iPSC) derived RPE. Hallmark RPE phenotypes, such as cobblestone morphology, pigmentation, and polarization, vary significantly betweendifferent models and culture conditions used in different labs, which would directly impact their usability for investigating different aspects of AMD biology. Here the AMD Disease Models task group of the Ryan Initiative for Macular Research (RIMR) provides a summary of several currently used in vitro RPE models, historical aspects of their development, RPE phenotypes that are attainable in these models, their ability to model different aspects of AMD pathophysiology, and pros/cons for their use in the RPE and AMD fields. In addition, due to the burgeoning use of iPSC derived RPE cells, the critical need for developing standards for differentiating and rigorously characterizing RPE cell appearance, morphology, and function are discussed.

Infections with Campylobacter species mainly cause gastrointestinal disease and are usually self-limiting. Systemic complications such as bacteremia and osteoarticular infections are rare. Here we report a very rare case of a vertebral osteomyelitis due to C. jejuni, and we reviewed the literature for similar cases, identifying six other cases. Therapy should be guided on resistance testing if available due to emerging resistance rates, especially to fluoroquinolones. Azithromycin may be a treatment option for C. jejuni spondylodiscitis.

Abstract Background Obese RA patients have higher disease activity scores (DAS). Previous research showed that obese RA patients have higher tender joint count (TJC) and VAS general health. However, it remains unclear whether DAS components measuring local and systemic inflammation (swollen joint count (SJC), CRP) are increased and if this is present in the total RA population or confined to an ACPA subgroup. As ACPA is suggested to enhance inflammatory responses, we hypothesized that the association of obesity with SJC and CRP is present especially in ACPA-positive RA. We therefore studied associations of obesity with courses of DAS components in ACPA subgroups. Methods We studied 649 RA patients (291 ACPA-positive), included in the Leiden Early Arthritis Clinic. Five-year courses of DAS44 and DAS44 components (SJC—44, TJC—53, CRP, VAS (0–100)) were compared between RA patients with normal weight (BMI 18.5–24.9), overweight (25.0–29.9), and obesity (≥ 30.0), stratified for ACPA. Linear/Poisson mixed models with a knot at 4 months were used. Results Obese RA patients had + 0.32 higher DAS compared to normal weight during the 5-year follow-up. In ACPA-positive RA, obese patients had + 0.43 (95% CI: 0.22, 0.64) higher DAS, whereas in ACPA-negative RA, this difference was smaller and not statistically significant: + 0.19 (95% CI: − 0.01, 0.38). In ACPA-positive RA, all DAS components were significantly higher in obese patients compared to normal weight: SJC + 60% (IRR1.60; 95% CI: 1.18, 2.16), CRP + 3.7 mg/L (95% CI:0.95, 6.53), TJC + 55% (IRR1.55; 95% CI:1.15, 2.10), and VAS + 9 (95% CI: 4.0, 14.2). ACPA-negative obese RA patients tended to have higher TJC (IRR1.22; 95% CI: 0.96, 1.55) and VAS (β4.3; 95% CI: − 0.4, 9.0), while SJC (IRR1.07; 95% CI:0.85, 1.33) and CRP (β0.24; 95% CI: − 1.29, 3.32) were unaffected. Conclusion The association of obesity with a worse DAS course is mainly present in ACPA-positive RA; especially SJC and CRP levels remain higher in ACPA-positive RA patients with obesity but not ACPA-negative RA patients. This is the first demonstration that obesity influences the disease course of ACPA-positive and ACPA-negative RA differently.

Background: Glioblastoma is an aggressive and incurable type of brain cancer. Little progress has been made in the development of effective new therapies in the past decades. The blood–brain barrier (BBB) and drug efflux pumps, which together hamper drug delivery to these tumors, play a pivotal role in the gap between promising preclinical findings and failure in clinical trials. Therefore, selecting drugs that can reach the tumor region in pharmacologically effective concentrations is of major importance. Methods: In the current study, we utilized a drug selection platform to identify candidate drugs by combining in vitro oncological drug screening data and pharmacokinetic (PK) profiles for central nervous system (CNS) penetration using the multiparameter optimization (MPO) score. Furthermore, we developed intracranial patient-derived xenograft (PDX) models that recapitulated the in situ characteristics of glioblastoma and characterized them in terms of vascular integrity, BBB permeability and expression of ATP-binding cassette (ABC) transporters. Omacetaxine mepesuccinate (OMA) was selected as a proof-of-concept drug candidate to validate our drug selection pipeline. Results: We assessed OMA’s PK profile in three different orthotopic mouse PDX models and found that OMA reaches the brain tumor tissue at concentrations ranging from 2- to 11-fold higher than in vitro IC50 values on patient-derived glioblastoma cell cultures. Conclusions: This study demonstrates that OMA, a drug selected for its in vitro anti-glioma activity and CNS- MPO score, achieves brain tumor tissue concentrations exceeding its in vitro IC50 values in patient-derived glioblastoma cell cultures, as shown in three orthotopic mouse PDX models. We emphasize the importance of such approaches at the preclinical level, highlighting both their significance and limitations in identifying compounds with potential clinical implementation in glioblastoma.

Abstract Background Access to HIV testing is crucial for detection, linkage to treatment, and prevention. In less urbanised areas, reliance on general practitioners (GPs) for HIV testing is probable, as sexual health centres (SHC) are mostly located within urbanised areas. Limited insight into individuals undergoing HIV testing stems from sparse standard registration of demographics at GPs. This cross-sectional study aims (1) to assess and compare HIV testing at the GP and SHC, and (2) to assess population- and provider-specific HIV incidence. Methods Individual HIV testing data of GPs and SHC were linked to population register data (aged ≥ 15 years, Rotterdam area, 2015–2019). We reported the proportion HIV tested, and compared GP and SHC testing rates with negative binomial generalised additive models. Data on new HIV diagnoses (2015–2019) from the Dutch HIV Monitoring Foundation relative to the population were used to assess HIV incidence. Results The overall proportion HIV tested was 1.14% for all residents, ranging from 0.41% for ≥ 40-year-olds to 4.70% for Antilleans. The GP testing rate was generally higher than the SHC testing rate with an overall rate ratio (RR) of 1.61 (95% CI: 1.56–1.65), but not for 15-24-year-olds (RR: 0.81, 95% CI: 0.74–0.88). Large differences in HIV testing rate (1.36 to 39.47 per 1,000 residents) and GP-SHC ratio (RR: 0.23 to 7.24) by geographical area were observed. The GPs’ contribution in HIV testing was greater for GP in areas further away from the SHC. In general, population groups that are relatively often tested are also the groups with most diagnoses and highest incidence (e.g., men who have sex with men, non-western). The overall incidence was 10.55 per 100,000 residents, varying from 3.09 for heterosexual men/women to 24.04 for 25–29-year-olds. Conclusions GPs have a pivotal role in HIV testing in less urbanised areas further away from the SHC, and among some population groups. A relatively high incidence often follows relatively high testing rates. Opportunities to improve HIV testing have been found for migrants, lower-educated individuals, in areas less urbanised areas and further away from GP/SHC. Strategies include additional targeted testing, via for example SHC branch locations and outreach activities.

Abstract Background Recovery Colleges (RCs) have spread across the globe as a new way of supporting people with mental vulnerabilities in their recovery journey. RCs focus on ‘learning’ rather than ‘curing’ and in that line facilitate a transition from being a passive, dependent patient/client to an active, empowered student learning to live life, despite vulnerabilities. Peer support and co-creation are central in RCs, as peers learn from each other by sharing personal experiences with mental vulnerabilities in an accessible, inspiring and stimulating atmosphere. The implementation of RCs is highly encouraged internationally, and as a result RCs and related self-help initiatives increasingly emerge. However, high-quality research on RCs is scarce and there is a call for thorough investigation of (cost-)effectiveness, mechanisms of action, cross-border fidelity and positioning of RCs. In response, this research project aims to fill these gaps. Methods This research project entails (1) a prospective quasi-experimental effectiveness study and economic evaluation, (2) a multifaceted qualitative study to elaborate on the mechanisms of action of RCs for those involved (3) a study to develop a (Dutch) Fidelity Measure of Recovery Colleges, and (4) an organisational case study to describe the positioning of RCs in relation to other mental health care services and community-based initiatives. Following the ideals of co-creation and empowerment in RCs we conduct this research project in co-creation with RC students from Enik Recovery College in Utrecht, the Netherlands. Discussion This research project will lead to one of the first longitudinal controlled quantitative evaluations of both cost-effectiveness and effectiveness of RC attendance in a broad sense (beyond attending courses alone). Moreover, we will gather data on a micro level (i.e., impact on RC students), meso level (i.e., organisational fidelity) and macro level (i.e., positioning in the care and support domain), capturing all important perspectives when scrutinizing the impact of complex systems. Finally, we will demonstrate the validity and value of embracing experiential knowledge in science as a complementary source of information, leading to a more profound understanding of what is researched. Trial registration The prospective quasi-experimental study has been pre-registered at clinicaltrails.gov (#NCT05620212).

BackgroundRecent studies have shown positive, though small, clinical effects of digital smoking cessation (SC) interventions for cancer survivors. However, research on associations among participant characteristics, intervention engagement, and outcomes is limited. ObjectiveThis study aimed to explore the predictors and moderators of engagement and outcome of MyCourse-Quit Smoking (in Dutch: “MijnKoers-Stoppen met Roken”), a digital minimally guided intervention for cancer survivors. MethodsA secondary analysis of data from the randomized controlled trial was performed. The number of cigarettes smoked in the past 7 days at 6-month follow-up was the primary outcome measure. We analyzed interactions among participant characteristics (11 variables), intervention engagement (3 variables), and outcome using robust linear (mixed) modeling. ResultsIn total, 165 participants were included in this study. Female participants accessed the intervention less often than male participants (B=–11.12; P=.004). A higher Alcohol Use Disorders Identification Test score at baseline was associated with a significantly higher number of logins (B=1.10; P

Objectives Rheumatoid arthritis (RA) mainly affects small joints. Despite the mechanical function of joints, the role of mechanical stress in the development of arthritis is insufficiently understood. We hypothesised that mechanical stress/physical strain is a risk factor for joint inflammation in RA. Therefore, we studied work-related physical strain in subjects with clinically suspected arthralgia (CSA) as a risk factor for the presence of imaging-detected subclinical joint inflammation and the development of clinical arthritis/RA.Methods In 501 CSA patients and 155 symptom-free persons’ occupation-related physical strain was quantified using the International Standard Classification of Occupations. Contrast-enhanced hand-MRIs were made and evaluated for joint inflammation (sum of synovitis/tenosynovitis/osteitis). CSA patients were followed on RA development. Age relationship was studied using an interaction term of physical strain with age.Results The degree of physical strain in CSA is associated with the severity of joint inflammation, independent of educational-level/BMI/smoking (interaction physical strain-age p=0.007; indicating a stronger association with increasing age). Physical strain is associated with higher tenosynovitis scores, in particular. In symptom-free persons, physical strain was not associated with imaging-detected joint inflammation. Higher degrees of physical strain also associated with higher risks for RA development in an age-dependent manner (HR=1.20 (1.06–1.37)/10-year increase in age), independent of educational-level/BMI/smoking. This association was partly mediated by an effect via subclinical joint inflammation.Conclusions Work-related physical strain increases the risk of subclinical joint inflammation and of developing RA. The age relationship suggests an effect of long-term stress or that tenosynovium is more sensitive to stress at older age. Together, the data indicate that mechanical stress contributes to the development of arthritis in RA.

Abstract Background Behavioural symptoms and frontotemporal hypometabolism overlap between behavioural variant of frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD), hampering diagnostic distinction. Voxel-wise comparisons of brain metabolism might identify specific frontotemporal-(hypo)metabolic regions between bvFTD and PPD. We investigated brain metabolism in bvFTD and PPD and its relationship with behavioural symptoms, social cognition, severity of depressive symptoms and cognitive functioning. Results Compared to controls, bvFTD showed decreased metabolism in the dorsal anterior cingulate cortex (dACC) (p

There are concerns over the impact of the congested international match calendar on professional footballers’ physical and mental well-being, and injury susceptibility. This study aimed to determine whether there were differences in match workload and international travel between injured and non-injured male football players over two elite competition seasons. An observational, retrospective, case–control study was conducted using data from the 2021/2022 and 2022/2023 seasons of five top-tier European men’s football leagues. Student t-tests were used to compare cumulative match workload and international travel data over a 28-day period preceding 1270 injuries and 2540 controls. There were significant differences in match workload and international travel variables between the injured groups (all injuries and hamstring injuries) and the control group. Match workload variables were higher (p < 0.01), recovery variables lower (p < 0.01), and international travel variables higher (p < 0.01). An overload of match workload and international travel contribute to increased injury susceptibility in professional men’s football. This emphasizes the need to address international match calendar concerns, including the number of games per season, the frequency of back-to-back games, and international travel requirements. Additionally, the findings highlight the importance of monitoring player match workloads, and implementing squad rotations and tailored training programs to mitigate injury risks.