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This nationwide multidisciplinary survey found dissatisfaction among physicians with current osteoporotic vertebral compression fracture care, revealing significant disparities in diagnosis, treatment, and follow-up practices. Issues include poor communication and differing guidelines. Improving interdisciplinary collaboration and standardized care strategies is essential for better patient outcomes., Purpose: This survey aims to assess current preferred care practices for symptomatic osteoporotic vertebral compression fractures (OVCF) in the Netherlands, focusing on guideline adherence, identifying knowledge gaps, and clarifying consensus and collaboration across medical disciplines in OVCF treatment., Methods: This cross-sectional study was conducted via Qualtrics (Provo, UT) using a self-administered online survey distributed to 238 general practitioners and physicians in orthopedics, traumatology, internal medicine, rheumatology, and geriatrics working at 51 hospitals in the Netherlands. The survey, conducted in Dutch, included 36 multiple-choice and two open questions and was accessible via an anonymous email link or QR code. General practitioners received additional questions specific to their role. Data was anonymized, stored securely, and analyzed using descriptive statistics in Microsoft Excel and SPSS (Version 24). Open-ended responses were coded and categorized. The survey was conducted prior to the publication of the updated Federation of Medical Specialists guidelines in 2024., Results: Physicians across various disciplines uniformly expressed dissatisfaction with current OVCF care. The survey highlighted significant disparities in diagnosis, treatment, and follow-up practices. A lack of communication between primary and secondary care providers and differing guidelines further complicate OVCF management. These issues point to considerable variation in clinical practice and gaps in interdisciplinary collaboration., Conclusion: Addressing the identified issues requires fostering interdisciplinary collaboration and creating cohesive care strategies. Ensuring access to diagnostic resources in both primary and secondary care and establishing coordinated care models promises more structured and standardized treatment. These steps are crucial for enhancing patient outcomes in OVCF management., (© 2024. The Author(s).)

Background: The Netherlands is one of few countries worldwide which has used the bivalent HPV vaccine for girls-only for over a decade. This allows assessment of vaccine effectiveness (VE) against female genital HPV DNA-positivity of this vaccine in an observational post-licencing real-world setting. Additionally, it is unclear whether catch-up vaccination campaigns result in similar VE as routine vaccination. Therefore, type-specific and grouped VE were assessed and compared for women who had been eligible for catch-up vaccination at 13-16 years with those who had been eligible for routine vaccination at 12 years., Methods: PASSYON is a Dutch biennial repeated cross-sectional (2011-2021) study among sexual health clinic clients aged 16-24 years old. Women provided self-collected vaginal samples, questionnaires on demographics and sexual behaviour were administered, and women self-reported HPV vaccination status. Samples were analysed using a PCR-based assay (SPF 10 -LiPA 25 ). Type-specific and grouped VE estimates, adjusted with propensity score stratification, were assessed against genital positivity for 14 HPV types. VE for targeted and non-targeted genotypes were compared between women who had been eligible for the catch-up and those who had been eligible for routine vaccination., Results: The study included 4488 female participants who had been eligible for HPV vaccination and provided genital swabs (1561 eligible for catch-up, 2927 for routine vaccination). Very high VE against genital HPV-16 and HPV-18 was observed (resp. 93.5% and 89.5%) and significant cross-protection against six other genotypes (HPV-31/33/35/45/52/58), varying from 18.0% (HPV-52) to 79.6% (HPV-45). VE estimates were comparable between women who had been eligible for the catch-up campaign and those eligible for routine vaccination: VE HPV-16/HPV-18: 92.2% (95%CI: 87.9-94.9) vs. 91.8% (95%CI: 86.0-95.2)., Conclusions: In real-world settings, the VE of bivalent vaccine is high against targeted genotypes, with cross-protection against 6 other genotypes. Catch-up campaigns up to age 16 years can be as effective as routine vaccination at age 12, although it is recommendable to provide HPV vaccination at an age at which most are likely not sexually active yet. This may inform countries considering catch-up campaigns when introducing or extending the use of HPV vaccination within their national immunisation programmes., (© 2024. The Author(s).)

Previous studies demonstrated limited efficacy of immune checkpoint inhibitors in unresectable acral melanoma (AM); it remains unclear how this translates to the adjuvant setting. This study investigates clinical outcomes of acral compared to cutaneous melanoma (CM) patients treated with adjuvant anti-PD-1 after complete resection. All stages III-IV AM and CM patients receiving adjuvant anti-PD-1 after complete resection between 2018 and 2022 were included from the prospective nationwide Dutch Melanoma Treatment Registry. We analyzed recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS). A multivariable Cox regression analysis of RFS was performed to adjust for potential confounders. We included 1958 (86 AM and 1872 CM) patients. At baseline, AM patients more frequently had KIT mutations, higher disease stages, and Eastern Cooperative Oncology Group Performance Status, and fewer BRAF and NRAS mutations. Median RFS was 14.8 months (95% confidence interval [CI]: 11.5-29.3) in AM and 37.4 months (95% CI: 34.6 to not reached) in CM (p = .002). After correcting for potential confounders, AM remained associated with a higher risk of recurrence (HR adj 1.53; 95% CI: 1.07-2.17; p = .019). Two-year DMFS tended to be worse for AM than for CM: 64.5% versus 79.7% (p = .050). Two-year OS was significantly lower in AM (71.5% vs. 84.3%; p = .027). The results of this study suggest a poorer outcome of adjuvant-treated AM compared to CM. Studies assessing the added value of adjuvant treatment in AM are needed. Future research should investigate alternative treatment strategies to improve outcomes of high-risk AM., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = -2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: A previous cohort study in the US found that women with higher cardiovascular risk were more likely to have a history of migraine but less likely to have active migraine. Extrapolating these results to men and European individuals is crucial to understanding the complex association between migraine activity status and vascular health in other populations., Objective: To evaluate the association pattern between a cardiovascular risk score, the most recent European version of the Systematic Coronary Risk Evaluation 2 (SCORE2) risk estimation system, and migraine activity status in Dutch men and women., Design, Setting, and Participants: The prospective population-based Lifelines cohort consists of community-dwelling adults residing in the northern part of the Netherlands. Individuals with a terminal illness, incapacitated individuals, including those with a severe mental illness, or who were unable to visit their general practitioner or complete the questionnaires were excluded from participation within Lifelines. Participants whose data on the cardiovascular risk scores and migraine status were complete were included in the analysis. Data on baseline characteristics were collected between November 1, 2006, to December 31, 2014. Cross-sectional and follow-up analyses were conducted within the prospective cohort. Questionnaires were sent approximately every 1.5 to 2.5 years, and the last self-reported migraine assessment took place between October 1, 2019, and January 31, 2021. Data were analyzed from March 1, 2022, to August 16, 2024., Exposures: The SCORE2 is a sex-specific European cardiovascular risk score that includes age, cholesterol levels, smoking status, diabetes, and systolic blood pressure., Main Outcomes and Measures: The primary outcome was the association pattern between cardiovascular risk scores and migraine activity status. SCORE2 risk scores were measured once at baseline; groups of the SCORE2 (<1.0%, 1.0% to <2.5%, 2.5% to <5.0%, 5.0% to <7.5%, 7.5% to <10.0%, and ≥10.0%) were created based on the sum of points of individual risk factors. Migraine activity status was assessed using self-reported questionnaires and classified as (1) prevalent (ie, migraine at baseline), (2) incident (ie, no migraine at baseline but migraine in ≥1 follow-up), and (3) none. To evaluate the influence of age, we conducted stratified analyses of the SCORE2 by age categories (<40, 40-49, and ≥50 years)., Results: The total study population consisted of 140 915 individuals at baseline with a mean (SD) age of 44.4 (12.7) years, of whom 58.5% were women. In total, 25 915 individuals (18.4% of the total population) had prevalent migraine and 2224 (1.9% of the 115 000 without prevalent migraine) had incident migraine. The odds of having prevalent and incident migraine, compared with individuals with a SCORE2 category of less than 1.0%, varied and decreased with increasing SCORE2 categories, with odds ratios (ORs) for prevalent migraine ranging from 0.93 (95% CI, 0.90-0.96) for a SCORE2 category of 1.0% to less than 2.5% to 0.43 (95% CI, 0.39-0.48) for a SCORE2 category of at least 10.0% and, for incident migraine, from 0.63 (95% CI, 0.57-0.69) for a SCORE2 category of 1.0% to less than 2.5% to 0.17 (95% CI, 0.10-0.27) for a SCORE2 category of at least 10.0%. A similar pattern was observed in both sexes but more profound in women. In women, ORs for prevalent migraine ranged from 1.21 (95% CI, 1.16-1.25) to 0.70 (95% CI, 0.58-0.83) (vs 1.19 [95% CI, 1.09-1.29] to 0.84 [95% CI, 0.72-0.99] in men) and, for incident migraine, 0.72 (95% CI, 0.64-0.80) to 0.20 (95% CI, 0.07-0.43) (vs 1.18 [95% CI, 0.92-1.52] to 0.44 [95% CI, 0.22-0.78] in men). Models with incident migraine as the outcome showed lower ORs across the ascending cardiovascular risk score categories. Age stratification suggested that the association between cardiovascular risk scores and migraine activity status were unlikely to be strongly influenced by age., Conclusions and Relevance: In this cohort study of community-dwelling Dutch adults, the odds of having prevalent or incident migraine decreased with increasing cardiovascular risk score categories. These results support the hypothesis that a relatively healthy cardiovascular system increases the probability of having active or developing migraine in the future, especially among women. Sex differences might play a pathophysiological role in the association between migraine activity and vascular health.

Objective: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS)., Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.004)., Results: A total of 1382 CCS participated, all diagnosed ≥ 15 years ago. The mean age of participating CCS was 36 years, and 51% were female. Perceived benefit and burden, acceptance, and helplessness, self-esteem and social support were associated with the psychosocial outcomes. In the models including all psychosocial factors, most associations with psychosocial outcomes were seen for self-esteem (10×), and perceived burden (9×). Self-esteem (all β ≤ 0.47) and perceived burden (all β ≤ 0.38) demonstrated strongest associations of medium/large size., Conclusions: Perceptions of childhood cancer, illness cognitions, self-esteem, and social support play a role in explaining psychosocial functioning in CCS, outweighing the influence of socio-demographic and medical variables. Addressing negative perceptions and reducing feelings of helplessness, while promoting acceptance, self-esteem, and social support, could provide intervention targets for CCS who encounter psychosocial challenges., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Background: High and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients., Methods: This is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2., Results: Distribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48-8.04 mg/day) vs. 9.15 mg/day (IQR:8.33-9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69-1.003)., Conclusion: This large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Ruben Malmberg has received payment for lectures from BMS. Roelof van Leeuwen has received grants from BMS and Pfizer, consulting fees from BMS, MDS, Pfizer, Pierre Fabre, AstraZeneca, and Roche, and payment for presentations and attending meetings from AstraZeneca. Hans Smit is a member on the advisory board of BMS and MSD and is a member representative of the Dutch scientific committee for pulmonary disease (no payments involved). Juliëtte Zwaveling has received a grant from AstraZeneca. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aortic stiffness, a consequence of vascular aging, is an independent predictor of cardiovascular morbidity and mortality. However, the impact of age and sex on its predictive performance remains unclear. We have included 6046 individuals from the population-based Rotterdam study. Survival analyses were performed to investigate the impact of age and sex on the link between aortic stiffness and outcomes, including coronary heart disease (CHD), stroke, cardiovascular disease (CVD), cardiovascular and all-cause mortality. The added predictive value of aortic stiffness across age categories and by sex was assessed by using explained variation, Harrell's C index and Integrated Discrimination Improvement (IDI). Aortic stiffness was independently associated with all outcomes [hazard ratio (95% confidence interval; CI): 1.16 (1.04-1.22) for CHD, 1.09 (1.00-1.19) for stroke, 1.11 (1.05-1.18) for CVD, 1.14 (1.05-1.23) for cardiovascular mortality, 1.08 (1.03-1.13) for all-cause mortality]. The strength of the association between aortic stiffness and stroke, cardiovascular and all-cause mortality decreased significantly by advancing age. The variance of the outcome (R2) explained by aortic stiffness alone was noticeable in individuals younger than 60 years and negligible in the other age categories. The association of aortic stiffness and CHD was stronger in women than in men. Similarly, the difference in R2 between women and men was greater for CHD than for the other considered outcomes. Our findings suggest that the gain in explained variation caused by aortic stiffness for CVD and mortality might be limited to individuals younger than 60 years., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To identify differences in levels of serum biomarkers associated with atherosclerosis between anti-citrullinated protein antibodies (ACPA) positive groups., Methods: Cross-sectional data were used from the Dutch Lifelines Cohort Study combined with data derived from RA risk and early RA studies conducted at the University Medical Center Groningen (UMCG). Serum biomarkers of inflammation, endothelial cell activation, tissue remodeling and adipokine, which were previously associated with atherosclerosis, were measured with Luminex in four ACPA positive groups with different characteristics: without joint complaints, with joint complaints, RA risk and early RA groups., Results: Levels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor Receptor 1 (TNFR1) and vascular endothelial growth factor (VEGF) were significantly higher in the RA risk and early RA groups compared to the joint complaints and the no joint complaints groups. The difference remained statistically significant after correcting for renal function, smoking and hypertension in multivariate logistic regression analysis, with focus on ACPA positive with joint complaints group versus RA risk group: CRP OR = 2.67, p = 0.033; IL-6 OR = 3.73, p = 0.019; TNFR1 OR = 1.003, p < 0.001; VGEF OR = 8.59, p = 0.019., Conclusion: Individuals at risk for RA have higher levels of inflammatory markers and VEGF, which suggests that they might also have a risk of higher cardiovascular disease (CVD); however, this does not apply to individuals with ACPA positivity with self-reported joint complaints or without joint complaints only. Therefore, it is important that individuals with RA risk are referred to a rheumatologist to rule in or out arthritis/development of RA and discuss CVD risk., (© 2024. The Author(s).)

Objectives: Blood cultures (BCs) are commonly ordered in emergency departments (EDs), while a minority yields a relevant pathogen. Diagnostic stewardship is needed to safely reduce unnecessary BCs. We aimed to develop and validate a bacteremia prediction model for ED patients, with specific focus on the benefit of incorporating procalcitonin., Methods: We included adult patients with suspected bacteremia from a Dutch ED for a one-year period. We defined 23 candidate predictors for a "full model", of which nine were used for an automatable "basic model". Variations of both models with C-reactive protein and procalcitonin were constructed using LASSO regression, with bootstrapping for internal validation. External validation was done in an independent cohort of patients with confirmed infection from 71 Spanish EDs. We assessed discriminative performance using the C-statistic and calibration with calibration curves. Clinical usefulness was evaluated by sensitivity, specificity, saved BCs, and Net Benefit., Results: Among 2111 patients in the derivation cohort (mean age 63 years, 46% male), 273 (13%) had bacteremia, versus 896 (20%) in the external cohort (n = 4436). Adding procalcitonin substantially improved performance for all models. The basic model with procalcitonin showed most promise, with a C-statistic of 0.87 (0.86-0.88) upon external validation. At a 5% risk threshold, it showed a sensitivity of 99% and could have saved 29% of BCs while only missing 10 out of 896 (1.1%) bacteremia patients., Conclusions: Procalcitonin-based bacteremia prediction models can safely reduce unnecessary BCs at the ED. Further validation is needed across a broader range of healthcare settings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ES received royalties from Springer Verlag for his book “Clinical Prediction Models. AJJ declares to have received payments for presentations and lectures for Roche Diagnostics, Thermo Fisher Scientific, B.R.A.H.M.S. AG, Biomerieux and Virogates. All other authors reported no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Familial hypercholesterolemia (FH) is a genetic disorder marked by high LDL cholesterol and an increased premature coronary artery disease (CAD) risk. Current dichotomous classification of LDL receptor gene (LDLR) variants may inadequately capture patient variability in LDL cholesterol levels and CAD risk. This study assessed a novel approach for determining LDLR variant severity using variant-specific LDL cholesterol percentiles., Methods: Participants of the Dutch FH cascade screening program were screened for 456 LDLR variants. For each LDLR variant carrier, a sex- and age-specific LDL cholesterol percentile was derived from the LDL cholesterol level measured at study entry, i.e. generally from the blood drawn for DNA analysis. These percentiles were used to calculate the mean LDL cholesterol percentile for each variant. Based on the variant-specific LDL cholesterol percentiles, carriers were grouped into the following LDL cholesterol strata: <75th, 75th-88th, 88th-92nd, 92nd-96.5th, 96.5th-98th, and ≥98th percentile. Additionally, variants were categorized into class 1 (LDLR deficient) and non-class 1 (often LDLR defective) variants. CAD risk between carriers in the different LDL cholesterol strata and non-carriers was compared using a Cox proportional hazard model., Results: Out of 35,067 participants, 12,485 (36 %) LDLR variant carriers (mean age 38.0 ± 20.0 years, 47.7 % male) were identified. Carriers had a 5-fold higher CAD risk compared with non-carriers. Hazard ratios for CAD increased gradually from 2.2 (95%CI 0.97-5.0) to 12.0 (95%CI 5.5-24.8) across the LDL cholesterol strata. A 7.3-fold and 3.9-fold increased CAD risk was observed in carriers of class 1 and non-class 1 LDLR variants, respectively., Conclusions: This study presents a refined approach for classifying LDLR variants based on their impact on LDL cholesterol levels, allowing for more precise, genotype-specific CAD risk estimation in FH patients compared with traditional methods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: LFR is cofounder of Lipid Tools and reports speakers fee from Ultragenyx, Novartis, and Daiichi Sankyo. JJPK is part time CSO of New Amsterdam Pharma and part time CMO of Staten Biotech and a consultant to AgBio, Scribe, Cincor, CSL Behring, CiVi Biopharma, Draupnir, Esperion Therapeutics, Madrigal, Menarini, Omeicos, Silence Therapeutics, Sirnaomics, TTxD and North Sea Therapeutics. GKH reports research grants from the Netherlands Organization for Scientific Research (vidi 016.156.445), CardioVascular Research Initiative, European Union and the Klinkerpad fonds, institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker's bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron until April 2019 (fees paid to the academic institution); and part-time employment and stock holder of at Novo Nordisk A/S, Denmark since April 2019. ESGS has received ad-board/lecturing fees, paid to the institution, from: Amgen, Sanofi, Astra-Zeneca, Esperion, Daiichi Sankyo, NovoNordisk, Ionis/Akcea, Amarin. The other authors report no disclosures., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To determine patients' perspectives on home monitoring at emergency department (ED) presentation and shortly after admission and compare these with their physicians' perspectives. Methods: Forty Dutch hospitals participated in this prospective flash mob study. Adult patients with acute medical conditions, treated by internal medicine specialties, presenting at the ED or admitted at the admission ward within the previous 24 h were included. The primary outcome was the proportion of patients who were able and willing to undergo home monitoring. Secondary outcomes included identifying barriers to home monitoring, patient's prerequisites, and assessing the agreement between the perspectives of patients and treating physicians. Results: On February 2, 2023, in total 665 patients [median age 69 (interquartile range: 55-78) years; 95.5% community dwelling; 29.3% Modified Early Warning Score ≥3; 29.5% clinical frailty score ≥5] were included. In total, 19.6% of ED patients were admitted and 26% of ward patients preferred home monitoring as continuation of care. Guaranteed readmission (87.8%), ability to contact the hospital 24/7 (77.3%), and a family caregiver at home (55.7%) were the most often reported prerequisites. Barriers for home monitoring were feeling too severely ill (78.8%) and inability to receive the required treatment at home (64.4%). The agreement between patients and physicians was fair (Cohens kappa coefficient 0.26). Conclusions: A substantial proportion of acutely ill patients stated that they were willing and able to be monitored at home. Guaranteed readmission, availability of a treatment team (24/7), and a home support system are needed for successful implementation of home monitoring in acute care.

Introduction: During the COVID19 pandemic, older patients hospitalized for COVID-19 exhibited an increased mortality risk compared to younger patients. While ageing is associated with compromised immune responses and frailty, their contributions and interplay remain understudied. This study investigated the association between inflammatory markers and mortality and potential modification by frailty among older patients hospitalized for COVID-19., Methods: Data were from three multicenter Dutch cohorts (COVID-OLD, CliniCo, Covid-Predict). Patients were 70 years or older, hospitalized for COVID-19and categorized into three frailty groups: fit (Clinical frailty score (CFS) 1-3), pre-frail (CFS 4-5), and frail (CFS 6-9). Immunological markers (lymphocyte count, neutrophil count, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammation index (SII)) were measured at baseline. Associations with in hospital mortality were examined using logistic regression., Results: A total of 1697 patients were included from COVID-OLD, 656 from Covid-Predict, and 574 from CliniCo. The median age was 79, 77, and 78 years for each cohort. Hospital mortality rates were 33 %, 27 % and 39 % in the three cohorts, respectively. A lower CRP was associated with a higher frailty score in all three cohorts (all p < 0.01). Lymphocyte count, neutrophil count, NLR, PLR, or SII, were similar across frailty groups. Higher CRP levels were associated with increased in-hospital mortality risk across all frailty groups, across all cohorts (OR (95 % CI), 2.88 (2.20-3.78), 3.15 (1.95-5.16), and 3.28 (1.87-5.92)), and frailty did not modify the association between inflammatory markers and in-hospital mortality (all p-interaction>0.05)., Conclusion: While frailty is a significant factor in determining overall outcomes in older patients, our study suggests that the elevated risk of mortality in older patients with frailty compared to fit patients is likely not explained by difference in inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The global population is ageing rapidly. As a result, an increasing number of older patients with traumatic spine injuries are seen in hospitals worldwide. However, it is unknown how the incidence of traumatic spinal injury has developed over the past decade. Therefore, this study aimed to determine the incidence and characteristics of traumatic spinal injury in patients aged under and above 65 years., Methods: During three time periods: 2009-2010, 2014-2015 and 2019-2020, all adult patients with traumatic spinal injury in the Netherlands were identified from the Dutch National Trauma Registry. Patient-related characteristics and 1-year mortality were collected from a subgroup of patients treated at a level-1 trauma centre, and patients aged ≥ 65 years were compared to patients aged < 65 years., Results: In the Dutch National Trauma Registry 25,737 patients with traumatic spinal injury were identified. The incidence of spine injury in patients > 65 years was 49.5/100,000/yr in 2009-2010, 68.8 in 2014-2015 and 65.9 in 2019-2020. The percentage of patients ≥ 65 years increased from 37% in 2009-2010, to 43% in 2014-2015, and to 47% in 2019-2020. In the subgroup of 1054 patients treated in a level-1 trauma centre, a similar increasing incidence was seen in patients aged ≥ 65 years. In these patients low energy falls were the most common trauma mechanism and the cervical spine was the most commonly injured region. Moreover, patients ≥ 65 years had significantly higher 1-year mortality compared with patients aged < 65 years, 22.7% versus 9.2%., Conclusion: The incidence of traumatic spinal injury in older patients in the Netherlands has increased over the last 12 years. Almost half of the patients with traumatic spinal injury are currently aged ≥ 65 years. The increasing incidence and the high 1-year mortality highlight the need to modify existing treatment protocols for these patients., (© 2024. The Author(s).)

Purpose: A significant proportion of cancer patients suffer from chemotherapy-induced peripheral neuropathy (CIPN). This descriptive study aimed to examine patients' experience of CIPN symptoms, daily limitations, involvement of healthcare professionals, and social support., Methods: Cross-sectional data have been collected in the Netherlands via a national online questionnaire comprising closed items only (February 2021)., Results: Out of 3752 respondents, 1975 received chemotherapy only (i.e., without targeted therapy) and were therefore included. The majority (71.2%) reported symptoms in both hands and feet (e.g., tingling and loss of sensation or diminished sensation). Participants reported most limitations in household chores, social activities, hobbies, sports, walking, and sleeping and least in family/(taking care of) children, cycling, driving, self-care, eating and drinking, and sexuality and intimacy. Many patients indicated that their healthcare professionals informed them about the possibility of CIPN development before treatment (58.4%), and they paid attention to CIPN during and after treatment (53.1%). However, many patients (43%) reported a lack of information on what to do when CIPN develops. Few participants (22%) visited their general practitioner (GP) for CIPN. In general, patients' social environments sometimes to always showed empathy to patients., Conclusions: Symptoms of CIPN are frequently reported and can result in various daily limitations. Support from professionals and peers is crucial in managing CIPN, which is sometimes lacking. Appropriate guidance and support should be provided to patients to decrease the impact of CIPN on daily life. Future research should investigate differences in chemotherapeutic agents and the resulting symptoms and consequences., (© 2023. The Author(s).)

Background: This study aims to assess the lifetime cost-effectiveness of a multi-component adherence intervention (MCAI), including a patient decision aid and motivational interviewing, compared to usual care in patients with a recent fracture attending fracture liaison services (FLS) and eligible for anti-osteoporosis medication (AOM)., Research Design and Methods: Data on AOM initiation and one-year persistence were collected from a quasi-experimental study conducted between 2019 and 2023 in two Dutch FLS centers. An individual level, state-transition Markov model was used to simulate lifetime costs and quality-adjusted life years (QALYs) with a societal perspective of MCAI vs usual care. One-way and probabilistic sensitivity analyses were conducted including variation in additional FLS and MCAI costs (no MCAI cost in baseline)., Results: MCAI was associated with gain in QALYs (0.0012) and reduction in costs (-€16) and is therefore dominant. At the Dutch willingness-to-pay threshold of €50,000/QALY, MCAI remained cost-effective when increasing costs of the FLS visit or the yearly maintenance cost for MCAI up to +€60. Probabilistic sensitivity analysis demonstrated MCAI to be dominant in 54% of the simulations and cost-effective in 87% with a threshold of €50,000/QALY., Conclusions: A MCAI implemented in FLS centers may lead to cost-effective allocation of resources in FLS care, depending on extra costs.

Objectives: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care., Methods: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS)., Results: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903])., Conclusions: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Diabetes mellitus is a major cause of death. Outpatients with diabetes have more complications than patients in general practice; mortality patterns have only been studied in the total diabetes population. This study aims to assess mortality, causes, and predictors in outpatients with diabetes., Materials and Methods: A cohort study, included people with diabetes mellitus from the nationwide Dutch Paediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2016-2020. DPARD data were linked to Statistics Netherlands (CBS), comprising data on mortality, ethnicity and education. All-cause and cardiovascular mortality rates were estimated using Cox proportional hazard regression., Results: During a median follow-up of 3.1 years among 12 992 people with diabetes, mortality rates per 10 000 person-years were 67.7 in adult type 1 diabetes and 324.2 in type 2 diabetes. The major cause of non-cardiovascular death was malignancy. During the pandemic years of influenza (2018) and COVID (2020), mortality rates peaked. Age, smoking and an estimated glomerular filtration rate of <60 ml/min were associated with all-cause mortality. In type 2 diabetes, additional factors were male sex, body mass index <20 kg/m 2 , diabetes duration <1 year and hypertension., Conclusions: Mortality among Dutch outpatients with diabetes is high. Smoking and renal failure were associated with mortality in both types. Further focus on early detection and treatment of mortality-associated factors may improve clinical outcomes., (© 2024 John Wiley & Sons Ltd.)

The role of the social environment can facilitate positive health outcomes through active community engagement, normalization of healthy behaviors, and stress buffering. We aim to examine the associations of neighborhood social cohesion with changes in BMI over time. A total of 7641 participants from The Maastricht Study between the ages of 40 and 75 years were analyzed. Weight and height were measured at baseline, and weight was self-reported annually up to 10 years of follow-up (median = 4.7 years). Perceived social cohesion was obtained by questionnaire. Home addresses for each participant were linked to geographic information system data from the Geoscience and Health Cohort Consortium to create neighborhood exposure variables including area level social cohesion, neighborhood walkability, and food environment within a 1000 m Euclidian buffer. Linear regression analyses were performed with BMI adjusted for socioeconomic variables. A mixed model analysis was carried out to examine changes in BMI. Living in the highest quartile area of individually perceived social cohesion was associated with lower BMI (Q4 B: -.53; 95% CI = -.79, -.28) compared to the lowest quartile. Similar findings were discovered using the area level measure (Q4 B: -.97; 95% CI = -1.29, -.65). There was no longitudinal association between social cohesion and BMI. Neighborhood social cohesion was associated with lower BMI classifying it as an obesogenic area characteristic that influences weight, independent of conventional built environment features., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Rationale: Healthcare systems remain disease oriented despite growing sustainability concerns caused by inadequate management of patients with multimorbidity. Comprehensive care programmes (CCPs) can play an important role in streamlining care delivery, but large differences in setup and results hinder firm conclusions on their effectiveness. Many elements for successful implementation of CCPs are identified, but strategies to overcome barriers and embed programmes within health systems remain unknown., Aims and Objectives: To address this knowledge gap through a detailed study of implementing a CCP in a Dutch hospital setting, including patient experiences, facilitators, barriers and ways to overcome those barriers. Additionally, this study aims to explore effects on patient satisfaction and healthcare use., Methods: A qualitative study design with 39 semistructured interviews and focus groups between July 2020 and February 2023 with 16 patients and 17 involved professionals. Additionally, effects on quantitative outcomes for patient satisfaction (PACIC-20) and healthcare use were explored., Results: Professionals expressed a wide range of topics related to implementation and ways to overcome barriers at hospital and system level. Alterations in the design to accommodate varying care demands, focus on inclusions through referrals, and lack of long-term support and appropriate financing were key topics. Patients expressed varying experiences, stated a strong desire for comprehensive information, and emphasised the importance of trust in caregivers. Patient satisfaction showed no effects, while healthcare use showed slight decreases in trends, but patient numbers were limited., Conclusion: The introduction of a CCP is feasible, and exploratory analysis on effectiveness shows lower hospital care use without decreasing patient satisfaction. However, this is accompanied by several challenges that show current fragmented systems still do not support implementation of integrated care initiatives. Overcoming those comes with substantial costs and may require a strong bottom-up implementation within a motivated team and actions on all levels of healthcare systems., (© 2024 The Author(s). Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Background: Outpatient Clinics (OCs) are under pressure because of increasing patient volumes and provider shortages. At the same time, many patients with chronic diseases receive routine follow-up consultations that are not always necessary. These patients block access to care for patients that are in actual need for care. Pre-assessing patient charts has shown to reduce unnecessary outpatient visits. However, the resulting late cancellations due to the pre-assessment, challenge efficient alignment of capacity with actual patient demand, leading to either empty slots or overtime. This study aims to develop a method to analyse the effect of pre-assessing patients before inviting them to the OC. This involves 1) to select who should come and 2) to optimize the impact of pre-assessment on the schedule and efficient use of OC staff., Methods: This prospective mixed-methods evaluation study consists of 1) an expert meeting to determine a pre-assessment strategy; 2) a retrospective cohort study to review the impact of this strategy (12 months of a Dutch nephrology OC); 3) mathematical optimization to develop an optimal criteria-based scheduling strategy; and 4) a computer simulation to evaluate the developed strategy. Primary outcomes are the staff idle time and staff overtime. Secondary outcomes evaluate the number of weekly offered appointments., Results: The expert group reached consensus about the pre-assessment criteria. 875 (18%) of the realized appointments in 2022 did not meet the OC visit pre-assessment criteria. In the best performing scheduling strategy, 94 slots (87% of the available capacity) should be scheduled on a weekly basis. For this schedule, 26.8% of the OC weeks will experience idle time ( μ =2.51, σ =1.44 appointment slots), and 21% of the OC weeks will experience overtime ( μ =2.26, σ =1.65 appointment slots) due to the variation in patient appointment requests. Using the pre-assessment strategy combined with the best performing scheduling strategy under full capacity (108 slots), up to 20% increase in patient demand can be handled with equal operational performance., Conclusions: This evaluation study allows OC managers to virtually test operational impact of pre-assessment strategies on the capacity of their OC, and shows the potential of increasing efficient use of scarce healthcare capacity., Trial Registration: Not applicable., (© 2024. The Author(s).)

Background: Enteric hepatitis A virus (HAV) infections during childhood are often asymptomatic but may cause severe illness in adults. To improve public health surveillance we assessed the applicability of sewage monitoring during an HAV outbreak at a primary school., Methods: Between October 19 and December 27, 2022, five symptomatic HAV cases were notified to the Public Health Service Amsterdam; all attended the same primary school. Passive samplers, small absorbent tools, were deployed in sewage near the school from November 14, 2022, to March 22, 2023. The absorbents were subjected to RNA extraction, HAV PCR testing, and, if positive, sequencing. PCR and sequencing were also performed on plasma and feces samples of HAV cases., Results: In 22 out of 88 (25%) of sewage samples, HAV RNA was detected. All HAV-RNA-positive sewage samples until 8 February 2023 were subgenotype IB, matching the strain detected in all cases. Another strain of HAV (subgenotype IA) was detected in sewage from 15 February 2023 onwards, without associated cases., Conclusions: Passive sampler-based sewage monitoring is an effective method to rapidly detect HAV shedding linked to diagnosed cases. It detects unnoticed viral infections and allows monitoring of outbreaks. This suggests that passive sampler-based monitoring is a promising tool supporting the public health response during HAV and other outbreaks., (© 2024. The Author(s).)

Background: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis., Methods: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as the outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination., Results: SNR was split into an urban development cohort with 4771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912, respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration., Conclusion: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Discussions about care decisions, including code status documentation and advance care planning, are crucial components of patient-centred care. However, due to numerous barriers, these discussions are often avoided by both physicians and patients. As a result, these discussions often take place at the emergency department (ED). We aimed to improve the quality of care decision conversations in the internal medicine ED., Methods: This pre-post intervention study was conducted at the internal medicine ED of a tertiary hospital in the Netherlands. Two interventions were implemented simultaneously: physician training and patient education. Physician training included an e-learning module and simulated patient sessions. Patients received a leaflet providing information about care decisions. Primary outcome was patient satisfaction with the care decision discussions, assessed using the Quality of Communication questionnaire. Secondary outcomes included the percentage of patients recalling a care decision discussion, initiator of the discussion, leaflet recall, leaflet evaluation, prior care decision discussions and perceived appropriate timing for discussions., Results: 333 patients participated, 149 before and 184 after the interventions. Postintervention, there were significant improvements in patient-reported quality of care decision communication (p<0.001) and more patients recalled having care decision discussions (63.7% vs 45.9%, p=0.001). However, only 12% of patients recalled receiving the leaflet., Conclusions: Implementation of physician training and patient education significantly improved the quality of care decision conversations in our internal medicine ED. Despite low leaflet recall, the interventions demonstrated a notable impact on patient satisfaction with care decision discussions. Future research could explore alternative patient education methods and involve other healthcare professionals in initiating discussions. These findings underscore the importance of ongoing efforts to enhance communication in healthcare settings, particularly in emergency care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

First-line treatment for advanced-stage diffuse large B-cell lymphoma (DLBCL) typically involves 6x R-CHOP21 or 6x R-CHOP21 with two additional rituximab administrations (6x R-CHOP21 + 2 R). In contemporary practice, this treatment choice might be guided by interim PET scan results. This nationwide, population-based study investigates the comparative effectiveness of these treatment regimens in an era where interim PET-guided treatment decisions were not standard practice. Utilizing the Netherlands Cancer Registry, we identified 1577 adult patients diagnosed with advanced-stage DLBCL between 2014-2018 who completed either 6x R-CHOP21 (43%) or 6x R-CHOP21 + 2 R (57%). We used propensity scores to assess differences in event-free survival (EFS) and overall survival (OS). At five years, EFS (hazard ratio of 6x R-CHOP21 + 2 R versus 6x R-CHOP21 [HR] = 0.89; 95% confidence interval [CI], 0.72-1.09) and OS (HR = 0.93; 95% CI, 0.73-1.18) were not significantly different between both regimens. In exploratory risk-stratified analysis according to the International Prognostic Index (IPI), high-IPI patients (i.e., scores of 4-5) benefit most from 6x R-CHOP21 + 2 R (5-year absolute risk difference of EFS = 16.8%; 95% CI, -0.4%-34.1% and OS = 12.1%; 95% CI, -5.4-29.6%). Collectively, this analysis reveals no significant differences on average in EFS and OS between the two treatments. However, the potential benefits for high-risk patients treated with 6x R-CHOP21 + 2 R underscore the need for future research., (© 2024. The Author(s).)

Sarcoidosis and tuberculosis (TB) are two granulomatous diseases that often share overlapping clinical features, including uveitis. We measured 368 inflammation-related proteins in serum in both diseases, with and without uveitis from two distinct geographically separated cohorts: sarcoidosis from the Netherlands and TB from Indonesia. A total of 192 and 102 differentially expressed proteins were found in sarcoidosis and active pulmonary TB compared to their geographical healthy controls, respectively. While substantial overlap exists in the immune-related pathways involved in both diseases, activation of B cell activating factor (BAFF) signaling and proliferation-inducing ligand (APRIL) mediated signaling pathways was specifically associated with sarcoidosis. We identified a B-lymphocyte activation signature consisting of BAFF, TNFRSF13B/TACI, TRAF2, IKBKG, MAPK9, NFATC1, and DAPP1 that was associated with sarcoidosis, regardless of the presence of uveitis. In summary, a difference in B-lymphocyte activation is a key discriminative immunological feature between sarcoidosis/ocular sarcoidosis (OS) and TB/ocular TB (OTB)., (© 2024. The Author(s).)

Background: Epidemiological and toxicological studies indicate that increased exposure to air pollutants can lead to neurodegenerative diseases. To further confirm this relationship, we evaluated the association between exposure to ambient air pollutants and corneal nerve measures as a surrogate for neurodegeneration, using corneal confocal microscopy., Methods: We used population-based observational cross-sectional data from The Maastricht Study including N = 3635 participants (mean age 59.3 years, 51.6% were women, and 19.9% had type 2 diabetes) living in the Maastricht area. Using the Geoscience and hEalth Cohort COnsortium (GECCO) data we linked the yearly average exposure levels of ambient air pollutants at home address-level [particulate matter with diameters of ≤ 2.5 µm (PM2.5), and ≤ 10.0 µm (PM10), nitrogen dioxide (NO2), and elemental carbon (EC)]. We used linear regression analysis to study the associations between Z-score for ambient air pollutants concentrations (PM 2.5 , PM 10 , NO 2 , and EC) and Z-score for individual corneal nerve measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length, and fractal dimension)., Results: After adjustment for potential confounders (age, sex, level of education, glucose metabolism status, corneal confocal microscopy lag time, inclusion year of participants, smoking status, and alcohol consumption), higher Z-scores for PM 2.5 and PM 10 were associated with lower Z-scores for corneal nerve bifurcation density, nerve density, nerve length, and nerve fractal dimension [stβ (95% CI): PM 2.5 -0.10 (-0.14; -0.05), -0.04 (-0.09; 0.01), -0.11 (-0.16; -0.06), -0.20 (-0.24; -0.15); and PM 10 -0.08 (-0.13; -0.03), -0.04 (-0.09; 0.01), -0.08 (-0.13; -0.04), -0.17 (-0.21; -0.12)], respectively. No associations were found between NO 2 and EC and corneal nerve measures., Conclusions: Our population-based study demonstrated that exposure to higher levels of PM 2.5 and PM 10 are associated with higher levels of corneal neurodegeneration, estimated from lower corneal nerve measures. Our results suggest that air pollution may be a determinant for neurodegeneration assessed in the cornea and may impact the ocular surface health as well., (© 2024. The Author(s).)

BackgroundIn the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known.AimWe assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands.MethodsData on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree.ResultsData on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs.ConclusionThe prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.

Background: Robust evidence for interventions to improve health-related quality of life (HRQoL) in people who receive a kidney transplant is scarce. We aimed to assess the effects of a lifestyle intervention in this context., Methods: We conducted a multicentre, open-label, parallel-group, randomised controlled trial among people who have received a kidney transplant. Participants from six hospitals across the Netherlands were randomly assigned 1:1:1 by an independent company into: usual care, exercise, and exercise plus diet. The exercise intervention encompassed two phases, a 3-month supervised exercise programme (twice weekly) followed by 12 months of lifestyle coaching, with 15 months of additional dietary counselling (12 sessions) for the exercise plus diet group. The primary outcome was HRQoL-domain physical functioning, assessed using the 36-item Short Form Survey at 15 months., Findings: From Oct 12, 2010 to Nov 18, 2016, 221 participants who had received a kidney transplant (138 [62%] male and 83 [38%] female, with a mean age of 52·5 [SD 13·5] years, who were a median of 5·5 [IQR 3·6-8·4] months post-transplant) were included and randomly assigned to usual care (n=74), exercise intervention (n=77), and exercise plus diet intervention (n=70). In the intention-to-treat analyses, at 15 months post-baseline, no significant differences in HRQoL-domain physical functioning were found for the exercise group (5·3 arbitrary units, 95% CI -4·2 to 14·9; p=0·27), and the exercise plus diet group (5·9 arbitrary units, -4·1 to 16·0; p=0·25) compared with control. Safety outcomes showed no safety concerns. After 3 months of supervised exercise intervention, HRQoL-domain physical functioning improved in the exercise group (7·3 arbitrary units, 95% CI 1·2 to 13·3; p=0·018) but not in the exercise plus diet group (5·8 arbitrary units, -0·5 to 12·1; p=0·072)., Interpretation: A lifestyle intervention is safe and feasible in people who have received kidney transplants, paving the way for lifestyle intervention studies in other multimorbid populations with polypharmacy. However, improving HRQoL for people who have received a kidney transplant is challenging. The lifestyle interventions in the current study did not show significant improvements in HRQoL at the end of the study at the total group level., Funding: Dutch Kidney Foundation, Innovation Fund of the Dutch Medical Insurance Companies, and University Medical Center Groningen., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: In the current exploratory study we estimate comorbidity rates between FDs [fibromyalgia (FM), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and irritable bowel syndrome (IBS)]-and IDs-[major depressive disorder (MDD) and generalized anxiety disorder (GAD)] by using self-reported diagnostic criteria., Method: We analyzed data from 107,849 participants (mean age = 49.3 (SD = 13.0), 58.6% women) of the Lifelines Cohort Study. Lifelines is a prospective population-based cohort study in the northeast of the Netherlands. Current IDs were assessed using the Mini-International Neuropsychiatric Interview. Current FM, ME/CFS, and IBS were assessed according to the 2010 American College of Rheumatology criteria, the 1994 Centers for Disease Control and Prevention criteria and the ROME IV criteria, respectively. We estimated tetrachoric correlations between diagnoses and tested for sex differences. Additionally, we estimated the ratio of observed-to-expected frequency for combinations of diagnoses., Results: FDs and IDs are highly comorbid (odds ratios: 3.2-12.6) with associations stronger among men. Participants with at least three disorders/diagnoses were more prevalent than expected by chance., Conclusion: Studies that aim to explain sex differences and the comorbidity of specific combinations of IDs and FDs will be an important contribution to understanding the etiology of these conditions., Competing Interests: Declaration of competing interest Nathaniel S. Thomas, Nathan A. Gillespie, Kenneth S. Kendler, Albertine J. Oldehinkel, Judith G.M. Rosmalen and Hanna M. van Loo declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Chronic nonbacterial osteitis (CNO) is a rare bone disease causing pain and functional impairment. We aimed to explore the application of physical therapy (PT) for adult CNO from the patients' and primary care therapists' perspective., Method: Cross-sectional study among the Dutch adult CNO cohort (1992-present). A survey on PT-use for axial spondylarthritis was adapted for CNO. Patients using PT in the past 2 years (recent PT-users) were asked about modalities, perceived effects, satisfaction, and preferences for provision. Their current physical therapists were invited to complete a self-developed survey covering therapy details and educational preferences., Results: 80/199 invited patients and 14/16 invited therapists completed the survey respectively. 41 (51%) patients used PT for CNO in the preceding 2 years, 14 (18%) used PT >2 years back, and 25 (31%) never used PT. Recent PT-users (n=41) reported diverse treatment modalities, involving massage (61%), joint mobilizations (44%), breathing exercises (49%), muscle strengthening (32%) and counselling through of home-exercises (46%) and pain education (32%). 64% of all patients desired greater emphasis from physicians regarding the role of PT. Most therapists would appreciate referral letters with CNO-specific information (93%), and consultations with specialized therapists (86%)., Conclusions: In this study, two-third of adult CNO patients had -ever or recently- used PT, which involved variable therapeutic modalities. Most patients were receptive to a larger role of PT in CNO-management and most therapists preferred CNO-specific information to optimize their care. These findings provide a foundation for the development and systematic evaluation of CNO-specific PT.

People with HIV continue to experience HIV stigma. Quantitative data on HIV stigma perpetrated by healthcare providers of hospitals providing HIV care in high-income countries are limited. The aim of this study is to investigate factors associated with HIV stigma in Dutch healthcare settings from the healthcare providers' perspective. We conducted a cross-sectional study using the questionnaire 'Measuring HIV Stigma and Discrimination Among Health Facility Staff - Monitoring Tool for Global Indicators' to assess HIV stigma among healthcare providers (n = 405) in two academic hospitals. Healthcare providers licensed to provide medical care were eligible for inclusion. The primary outcome was the self-reported prevalence of at least one manifestation of HIV stigma measured by six stigma indicators (four individual, two institutional). Secondary outcomes were the prevalence of HIV stigma per indicator, per occupation, per department, and factors associated with individual stigma indicators. HIV stigma was prevalent among 88.1% (95%CI 84.5% - 91.2%) of participants. Stigma was mostly driven by negative attitudes towards people with HIV and worry to acquire HIV. Multivariate analysis showed that several factors were associated with HIV stigma, including younger age, male sex, working at one of the surgical departments, and working as a nurse. Having received any training on HIV stigma and/or discrimination was associated with less HIV stigma among all indicators. In conclusion, HIV stigma is highly prevalent among Dutch healthcare providers. Targeted approaches, including training on HIV stigma and discrimination, are needed to reduce HIV stigma in healthcare and should, among others, focus on younger healthcare providers., (© 2024. The Author(s).)

Purpose: To study trends in incidence and outcome of patients with traumatic spinal cord injury (TSCI) in the Netherlands before, during and after implementation of the Advanced Trauma Life Support (ATLS ® ) and Pre-Hospital Trauma Life Support (PHTLS ® )- Spinal Motion Restriction(SMR) protocol., Methods: In an observational database we studied national hospital admission and emergency department databases to analyse incidence rates and outcome of traumatic spinal cord injury and spinal fractures in the emergency department and in admittances in The Netherlands between 1986 and 2021., Results: A significant increase of 39% in TSCI in admitted patients with spinal fractures over the past 35 years (p < 0.001). This increase was especially prevalent in cervical spinal fractures (132%), while thoracic and lumbosacral spinal fractures showed a decrease in accompanied TSCI (64% and 88% respectively). The overall increase in spinal fractures was not significant. The duration of hospital admission decreased for spinal fractures without TSCI and with TSCI (66% and 56% respectively)., Conclusion: Since implementation of the SMR-protocol was aiming to limit TSCI in patients who suffered a spinal fracture, the increase in TSCI is an unexpected finding. Exact explanation for this increase is unclear and the contribution of the SMR-protocol is not fully understood due to confounders in the used datasets. Either way, the scientific evidence supporting this costly time- and labor-intensive SMR-protocol remains debated, along with evidence contradicting it. Therefore it stresses the need for clear, evidencebased reasoning for spinal immobilization according to ATLS, as this is currently lacking., (© 2024. The Author(s).)

Aims: Common genetic variations in the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT-interval shortening in digoxin users. As QT-interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different NOS1AP rs10494366 genotypes., Methods: We included 11 377 individuals from the prospective population-based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time-dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose-dependent, comparing high dosage (≥ 0.250 mg), moderate dosage (0.125 mg ≤ dose< 0.250 mg) and low dosage (< 0.125 mg) digoxin users with non-users., Results: The median baseline age of the total study population was 62 (interquartile range [IQR] 58-71) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow-up of 11.5 (IQR 6.5-17) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38-3.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98-8.21] in the minor homozygous GG, 3.46 [95% CI: 2.37-5.04] in the heterozygous TG and 2.56 [95%CI: 1.70-3.86] in the homozygous TT genotype groups. Compared to low- and moderate-dose, high-dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34-23.47])., Conclusions: Current use of digoxin is associated with a significantly increased risk of SCD. The NOS1AP gene rs10494366 variant did not modify the digoxin-associated risk of SCD in a population of European ancestry., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: Obesity may promote kidney damage through hemodynamic and hormonal effects. We investigated the association between body mass index (BMI), total body fat (TBF) and chronic kidney disease (CKD) and whether hypertension, diabetes, leptin and adiponectin mediated these associations., Methods: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study, 6671 participants (45-65 y) were included. We defined CKD as eGFR <60 ml/min/1.73 m 2 and/or moderately increased albuminuria. The percentage of mediation was calculated using general structural equation modeling, adjusted for potential confounding factors age, sex, smoking, ethnicity, physical activity and Dutch healthy diet index., Results: At baseline mean (SD) age was 56 (6), BMI 26.3 (4.4), 44% men, and 4% had CKD. Higher BMI and TBF were associated with 1.08 (95%CI 1.05; 1.11) and 1.05-fold (95%CI 1.02; 1.08) increased odds of CKD, respectively. As adiponectin was not associated with any of the outcomes, it was not studied further as a mediating factor. The association between BMI and CKD was 8.5% (95%CI 0.5; 16.5) mediated by diabetes and 22.3% (95%CI 7.5; 37.2) by hypertension. In addition, the association between TBF and CKD was 9.6% (95%CI -0.4; 19.6) mediated by diabetes and 22.4% (95%CI 4.2; 40.6) by hypertension. We could not confirm mediation by leptin in the association between BMI and CKD (35.6% [95%CI -18.8; 90.3]), nor between TBF and CKD (59.7% [95%CI -7.1; 126.6])., Conclusion: Our results suggest that the relations between BMI, TBF and CKD are in part mediated by diabetes and hypertension., (© 2024. The Author(s).)

Patients with high-consequence infectious diseases (HCIDs) require high-quality care by specially trained staff in a high-level isolation unit (HLIU) that follows strict infection prevention and control (IPC) measures. Caring for patients with (suspected) HCID is challenging, mainly because of the strict personal protective equipment (PPE) and IPC protocols healthcare workers (HCW) must adhere to for protection. The Radboud University Medical Center, located in Nijmegen, the Netherlands, has been a dedicated HLIU facility since 2008. A newly built HLIU opened in May 2022, and encouraged us to review the existing PPE selection, IPC protocols, and HCID training program to improve safety and comfort for HCWs working in the HLIU. Based on a systematic search through (inter)national HCID PPE guidelines and semistructured interviews with end users, we selected an improved, more comfortable set of PPE. Additionally, we developed a more concise and easier-to-use patient care process flow and implemented a new teaching strategy. The new way of working was tested in October 2022 when the first 2 patients with suspected HCID were admitted to our unit. We used surveys to evaluate the experiences of HCWs involved in this care to further improve the workflow of the unit. When optimizing safety and comfort for HCWs, it is important to consider (inter)national guidelines as well as user preferences. By systematically evaluating recent experiences of patient admission to the HLIU and then adjusting protocols and training, we can ensure that the quality of provided healthcare and the safety of HCWs working in the HLIU remains high.

Objective: To analyze the impact of noninvasive and early invasive treatments on health status in patients with lower extremity peripheral arterial disease (PAD) without and with chronic total occlusions (CTOs) after 12 months of follow-up., Methods: Using the international (the United States, the Netherlands, and Australia) observational longitudinal Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories registry, we included patients with recent PAD symptoms between June 2011 and December 2015. We assessed the PAD-specific health status at initial visit and the 3-, 6-, and 12-month follow-up using the Peripheral Arterial Questionnaire. On a propensity matched-weighted cohort, we compared patients' characteristics by CTO status and treatment groups as early invasive (revascularization in the 3 months) vs noninvasive (exercise, medical therapies, or smoking cessation). We then assessed the health status trajectory over 12 months, as a three-way interaction between CTO status, treatment groups, and months, using a multilevel generalized linear regression model for repeated measures adjusted for baseline health status with random effects at the site and patient levels., Results: We included 581 participants, with a mean age of 66.62 ± 9.33 years, 34.3% female, and 90.8% White, of whom 353 (60.8%) were without and 228 (39.2%) had a CTO lesion. Respectively, 96 (27.2%) and 70 (30.7%) patients underwent early invasive treatment (d = 0.07). Although patients with CTO were more likely to have lower resting ABI, multilevel disease, and to experience severe claudication vs their counterparts (|d| ≥ 0.20), patient health status at baseline with CTO was not different from those without CTO, with mean summary scores of 45.14 ± 20.26 vs 45.90 ± 21.24 (d = 0.04), respectively. The trajectory did not differ by CTO status (interaction CTO status × month; P = .517) and was higher in early invasive vs noninvasive treatment (treatment × month; P < .001), regardless of CTO status (CTO status × treatment; P = .981 and CTO status × treatment × month; P = .264). The score increased over time with the largest improvement occurring at 3 months in both noninvasive (non-CTO, +7.82 [95% confidence interval (CI), 4.03-11.60] and CTO, +9.27 95% CI, 4.45-14.09) and early invasive (non-CTO, +26.17 [95% CI, 20.06-32.28] and CTO, +24.52 [95% CI, 17.40-31.64] groups. The mean score in CTO vs non-CTO groups did not differ at each timepoint, with a 12-month mean score of 70.26 (95% CI, 67.87-74.65) vs 71.17 (95% CI, 65.91-76.44) (P = .99) in the noninvasive treatment and 84.93 (95% CI, 78.90-90.97) vs 79.20 (95% CI, 72.77-86.14) (P = .31) in the early invasive treatment., Conclusions: Patients with symptomatic PAD undergoing early revascularization exhibited better health status over time vs those undergoing noninvasive treatment strategy, irrespective of the presence of CTOs. The degree of the improvement was greater in the 3 months after the initial visit, especially in patients undergoing early revascularization., Competing Interests: Disclosures C.M.-H. reports unrestricted research grants from Philips, Shockwave, Abbott, and Merck; he is a consultant for Abbott, Terumo, and Cook. K.S. reports unrestricted research grants Philips, Shockwave, Abbott, J&J, and Merck; she is a consultant for Cook, Terumo, and Happify., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts., Methods: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards., Findings: We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities., Interpretation: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections., Funding: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation., Competing Interests: Declaration of interests DM owns stock in and is a consultant for Biomesense. AHMvdZ reports grants from Health Hjolland, GSK, Boehringer Ingelheim, and Vertx; consulting fees from Boehringer Ingelheim and AstraZeneca; and honoraria from GSK, all outside the submitted work; and is a chair of the data safety monitoring board of a study on bronchopulmonary dysplasia in neonates. B-JvdB is the chair of the cardiovasular theme of HELIUS, the Netherlands Society of Hypertension, and Amsterdam Cardiovascular Sciences; and participates on the committee of the Dutch Cardiovascular Alliance. RK is on the Scientific Advisory Board of Gencirq, Cybele, DayTwo, Biomesense, and Micronoma; owns stock in Gencirq, Cybele, Biomesense, Micronoma, and Biota; is a consultant for DayTwo and Biomesense; and is a cofounder of Micronoma and Biota. MN is on the Scientific Advisory Board of Caelus Pharmaceuticals. TN reports grants from the Finnish Research Council, Emil Aaltonen Foundation, Sigrid Jusélius Foundation, and Finnish Foundation for Cardiovascular Research; and honoraria from Servier Finland and AstraZeneca. WJW reports grants from ZonMw/NWO and EU (Eurostars); and ad hoc consultancy for AstraZeneca and Shionogi, outside the submitted work. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The Value-Based Health Care (VBHC) model of care provides insights into patient characteristics, outcomes, and costs of care delivery that help clinicians counsel patients. This study compares the allocation and value of curative oncological treatment in frail and fit older patients with esophageal cancer in a dedicated VBHC pathway., Materials and Methods: Data was collected from patients with primary esophageal cancer without distant metastases, aged 70 years or older, and treated at a Dutch tertiary care hospital between 2015 and 2019. Geriatric assessment (GA) was performed. Outcomes included treatment discontinuation, mortality, quality of life (QoL), and physical functioning over a one-year period. Direct hospital costs were estimated using activity-based costing., Results: In this study, 89 patients were included with mean age 75 years. Of 56 patients completing GA, 19 were classified as frail and 37 as fit. For frail patients, the treatment plan was chemoradiotherapy and surgery (CRT&S) in 68% (13/19) and definitive chemoradiotherapy (dCRT) in 32% (6/19); for fit patients, CRT&S in 84% (31/37) and dCRT in 16% (6/37). Frail patients discontinued chemotherapy more often than fit patients (26% (5/19) vs 11% (4/37), p = 0.03) and reported lower QoL after six months (mean 0.58 [standard deviation (SD) 0.35] vs 0.88 [0.25], p < 0.05). After one year, 11% of frail and 30% of fit patients reported no decline in physical functioning and QoL and survived. Frail and fit patients had comparable mean direct hospital costs (€24 K [SD €13 K] vs €23 K [SD €8 K], p = 0.82)., Discussion: The value of curative oncological treatment was lower for frail than for fit patients because of slightly worse outcomes and comparable costs. The utility of the VBHC model of care depends on the availability of sufficient data. Real-world evidence in VBHC can be used to inform treatment decisions and optimization in future patients by sharing results and monitoring performance over time., Trial Registration: The study was retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107 (date of registration: 22-10-2019)., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In the recent years, digital intensive care unit (ICU) diaries have emerged as more advantageous than paper diaries. Despite the advantages of digital diaries, the successful implementation and maintenance of this digital intervention present significant challenges in clinical practice. Therefore, understanding the facilitators and barriers among stakeholders influencing this process becomes imperative for devising a tailored strategy to integrate digital diaries effectively within ICU settings., Aim/objective: The aim of this study was to explore facilitators and barriers for implementation of a digital ICU diary from the perspectives of ICU professionals, ICU survivors, and their relatives., Methods: A qualitative design was used, incorporating focus-group interviews with professionals from four Dutch ICUs, along with individual interviews with ICU survivors and relatives. The study spanned from October 2022 to April 2023. Data analysis utilised a mixed inductive-deductive approach, particularly through directed content analysis. The Consolidated Framework for Implementation Research 2.0 guided both data collection and analysis processes., Findings: We conducted five focus-group interviews among ICU professionals (n = 32) and 10 individual or dual interviews involving five ICU survivors and nine relatives. Key facilitators for implementing a digital diary according to ICU professionals encompassed a user-friendly interface accessible independent of time and place, with a seamless login process requiring minimal steps, comprehensive training covering all aspects of its use, and feedback from the experiences of both patients and relatives. Barriers for ICU professionals included many steps required to access the digital diary, as well as resistance to (co)writing diary entries. In contrast, professionals' involvement in writing diary entries was highly appreciated among ICU survivors and relatives. An ambiguous factor arose regarding sharing the digital diary with others; both ICU survivors and relatives found it valuable, yet it also raised privacy concerns., Conclusions: This study offers insights into the most important factors influencing the implementation of a digital ICU diary. Strikingly, some factors serve as both barriers and facilitators. When developing the implementation strategy, the identified facilitators can be used to overcome the barriers faced by ICU professionals, ICU survivors, and their relatives in adopting a digital diary., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Asymptomatic bacteriuria (ASB) - the presence of bacteria in urine without urinary tract infection (UTI) related signs & symptoms (S&S) - is common in the elderly bladder and is not considered pathogenic for UTI. We hypothesise that colonisation with non-uropathogenic bacteria could protect the bladder from invasion of more harmful bacteria. The exact role and dynamics of bacteriuria in the relation to the development of a UTI is still unknown. We aim to provide insight into the course of bacteriuria in the elderly bladder and its relation to UTI in frail older adults., Methods and Analysis: A prospective observational cohort study is being conducted in Dutch nursing homes (NHs) between February 2024 and December 2025. Urine samples and case report forms (CRF) on UTI-related S&S will be collected from each consenting NH resident every 3 months for a follow-up period of 18 months. Whenever a UTI-suspicion occurs in between the 3 monthly time points, additional data and a urine sample will be collected. Urine samples undergo several urinalyses (e.g. dipstick and bacterial culture). Additional molecular analysis will be conducted on a selection of cultured Escherichia coli (E. coli) for virulence genes. Primary analyses will be conducted between residents with and without ASB at each time point. The primary outcome is UTI incidence during follow-up. In secondary analyses we will also take into account the low versus high presence of virulence genes of the E. coli., Discussion: The combination of high ASB prevalence and a reduced ability of frail older adults to express UTI-related S&S may lead to UTI misdiagnosis and inappropriate antibiotic use. To our knowledge, this is the first study to investigate the dynamics and role of bacteriuria in the elderly bladder and their potential protective effect on the development of UTI. The study findings with comprehensive analysis of epidemiological, clinical and molecular data could set the fundamental base for future guidelines and studies, and contribute to improving prevention, diagnosis and treatment of UTI in frail older adults, in addition to contributing to antibiotic stewardship in NHs., (© 2024. The Author(s).)

Person-centred care (PCC) is associated with improved patient well-being and higher levels of satisfaction with care but its impact on individuals living with obesity is not well-established. The main aim of this study was to assess the relationship between PCC and the physical and social well-being of patients living with obesity, as well as their satisfaction with care. This study is based on a cross-sectional, web-based survey administered among a representative panel of Dutch individuals living with obesity. The primary outcomes were physical and social well-being and satisfaction with care. The primary exposure was a rating of overall PCC, encompassing its eight dimensions. In addition, covariates considered in the analyses included sex, age, marital status, education level, body mass index, and chronic illness. The data from a total of 590 participants were analysed using descriptive statistics, correlation analyses, and multiple regression analyses. Among PCC dimensions, participants rated 'access to care' the highest (M 4.1, SD 0.6), while 'coordination of care' (M 3.5, SD 0.8) was rated lower than all other dimensions. Participants' overall PCC ratings were positively correlated with their physical (r = 0.255, P < .001) and social well-being (r = 0.289, P < .001) and their satisfaction with care (r = 0.788, P < .001), as were the separate dimension scores. After controlling for sex, age, marital status, education level, body mass index, and chronic illness in the regression analyses, participants' overall PCC ratings were positively related to their physical (β = 0.24, P < .001) and social well-being (β = 0.26, P < .001), and satisfaction with care (β = 0.79, P < .001). PCC holds promise for improved outcomes among patients living with obesity, both in terms of physical and social well-being, as well as satisfaction with care. This is an important finding, particularly when considering the profound physical, social, and psychological consequences associated with obesity. In addition to highlighting the potential benefits of PCC in the healthcare of individuals living with obesity, the findings offer valuable insights into strategies for further refining the provision of PCC to meet the specific needs of these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Quality in Health Care.)

Background: Individual differences in susceptibility to developing asthma, a heterogeneous chronic inflammatory lung disease, are poorly understood. Whether genetics can predict asthma risk and how genetic variants modulate the complex pathophysiology of asthma are still debated., Aim: To build polygenic risk scores for asthma risk prediction and epigenomically link predictive genetic variants to pathophysiological mechanisms., Methods: Restricted polygenic risk scores were constructed using single nucleotide variants derived from genome-wide association studies and validated using data generated in the Rotterdam Study, a Dutch prospective cohort of 14 926 individuals. Outcomes used were asthma, childhood-onset asthma, adulthood-onset asthma, eosinophilic asthma and asthma exacerbations. Genome-wide chromatin analysis data from 19 disease-relevant cell types were used for epigenomic polygenic risk score partitioning., Results: The polygenic risk scores obtained predicted asthma and related outcomes, with the strongest associations observed for childhood-onset asthma (2.55 odds ratios per polygenic risk score standard deviation, area under the curve of 0.760). Polygenic risk scores allowed for the classification of individuals into high-risk and low-risk groups. Polygenic risk score partitioning using epigenomic profiles identified five clusters of variants within putative gene regulatory regions linked to specific asthma-relevant cells, genes and biological pathways., Conclusions: Polygenic risk scores were associated with asthma(-related traits) in a Dutch prospective cohort, with substantially higher predictive power observed for childhood-onset than adult-onset asthma. Importantly, polygenic risk score variants could be epigenomically partitioned into clusters of regulatory variants with different pathophysiological association patterns and effect estimates, which likely represent distinct genetically driven disease pathways. Our findings have potential implications for personalised risk mitigation and treatment strategies., Competing Interests: Conflict of interest: G. Brusselle has received fees for lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Sanofi Regeneron; and honoraria for participating on advisory boards from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck Sharp & Dohme, Novartis and Sanofi Regeneron. The remaining authors declare no conflicts of interest., (Copyright ©The authors 2024.)

Background and Objectives: Although several lines of evidence suggest a link between migraine and cardiovascular events, less is known about the association between cardiovascular risk factors (CVRFs) and migraine. This knowledge is clinically important to provide directions on mitigating the cardiovascular risk in patients with migraine. We hypothesized that CVRFs are associated with a higher migraine prevalence. Therefore, our primary objective was to investigate sex-specific associations between CVRFs and lifetime prevalence of migraine., Methods: We performed cross-sectional analyses within an ongoing population-based cohort study (Rotterdam Study), including middle-aged and elderly individuals. By means of (structured) interviews, physical examinations, and blood sampling, we obtained information on the lifetime prevalence of migraine and the following traditional CVRFs: current smoking, obesity, hypercholesterolemia, hypertension, and diabetes mellitus. Similarly, we obtained information on quantitative component data on these CVRFs, including pack-years of smoking, lipid levels, systolic and diastolic blood pressure (BP), body mass index, and fasting glucose levels. Patients with migraine were age-matched to individuals without migraine, and we performed conditional logistic regression analyses to investigate the sex-stratified association of CVRFs with migraine., Results: In total, 7,266 community-dwelling middle-aged and elderly persons were included (median age 66.6 [IQR 56.4-74.8] years, 57.5% females). The lifetime prevalence of migraine was 14.9%. In females, current smoking (odds ratio (OR) 0.72, 95% CI 0.58-0.90), more pack-years (OR per SD increase 0.91, 95% CI 0.84-1.00), diabetes mellitus (OR 0.74, 95% CI 0.56-0.98), and higher fasting glucose levels (OR per SD increase in glucose 0.90, 95% CI 0.82 - 0.98) were all related to a lower migraine prevalence while a higher diastolic BP related to a higher migraine prevalence (OR per SD increase 1.16, 95% CI 1.04-1.29). In males, no significant associations between CVRFs and migraine were observed., Discussion: Traditional CVRFs were either unrelated or inversely related to migraine in middle-aged and elderly individuals, but only in females. In males, we did not find any association between CVRFs and migraine. Because only an increased diastolic BP was related to a higher migraine prevalence in females, our study contributes to the hypothesis that migraine is not directly associated with traditional CVRFs. Future studies are warranted to extrapolate these findings to younger populations.

Objective: To address the relationship between tissue accumulation of advanced glycation end-products, assessed by skin autofluorescence (SAF), and subclinical atherosclerosis quantified with coronary artery calcium score (CACS) in the general Dutch population., Methods: A total of 3,839 participants of the LifeLines Cohort Study without diabetes or cardiovascular disease were included in this cross-sectional evaluation. They underwent SAF measurement and cardiac computed tomography to measure CACS. Associations between SAF and CACS was assessed using regression models. Participants at elevated risk for cardiovascular disease were selected by either CACS≥100, or SAF value in the top 15%; overlap and cardiovascular risk profile of these participants were compared., Results: In univariate analysis, every 1 arbitrary unit (AU) increase in SAF resulted in an odds ratio of 2.91 (95% confidence interval 2.44-3.48, p<0.001) for coronary calcification. After adjustment for cardiovascular risk factors, there was still 20% higher odds of coronary calcification with 1 AU increase in SAF, but significance was lost. In total, 1025 (27%) participants either had high SAF and/or high CACS, of these 441 (12%) had only high SAF, 450 (12%) had only high CACS and 134 (3%) participants had high SAF and high CACS., Conclusion: In a population-based Dutch cohort, SAF was associated with the degree of coronary calcification. This association was largely explained by classical cardiovascular risk factors. Limited overlap was found in subgroups with high SAF or high CACS, indicating that SAF and CACS may have complementary role in identifying individuals at elevated cardiovascular risk., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: A.J. Smit is founder and shareholder in Diagnoptics Technologies (Groningen, the Netherlands), manufacturer of the AGE reader that was used in the present study. M. Oudkerk is involved in the company iDNA BV. M. Vonder is a consultant for iDNA BV. All other authors declare that there is no duality of interest associated with this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Boersma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited., Objectives: This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and to identify its associated factors in individuals aged > 50 years., Methods: Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological and nondermatological factors were recorded. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: In total, 5246 eligible participants were included (age range 51-100 years, median age 67; 56.0% women). The results revealed a -lifetime prevalence of 33.7% for itch with skin conditions. Factors significantly associated with itch were female sex (OR 1.26, 95% CI 1.11-1.43), body mass index (1.02, 1.01-1.03), self-reported atopic dermatitis (4.29, 3.74-4.92), presence of atopic dermatitis (1.97, 1.60-2.43), self--reported psoriasis (2.31, 1.77-3.01), presence of psoriasis (2.11, 1.55-2.87), self-reported dry skin (1.95, 1.73-2.20), self-reported asthma (1.40, 1.08-1.83), renal impairment (1.45, 1.17-1.79), and clinically relevant depressive (1.85, 1.52-2.25) and anxiety symptoms (1.36, 1.11-1.66)., Conclusions: This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged > 50 years. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, nondermatological factors, including renal impairment, imply additional contributors to induction or persistence of itch in individuals with skin conditions., Competing Interests: Conflicts of interest No products produced by Unilever were tested in this study. However, it is possible that this study could be used to promote products and services in the future, leading to financial gain. L.M.P. has received consulting fees from Centogene. L.C. has received flash glucose sensors for research ­purposes. Other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: Diagnostic errors have been attributed to reasoning flaws caused by cognitive biases. While experiments have shown bias to cause errors, physicians of similar expertise differed in susceptibility to bias. Resisting bias is often said to depend on engaging analytical reasoning, disregarding the influence of knowledge. We examined the role of knowledge and reasoning mode, indicated by diagnosis time and confidence, as predictors of susceptibility to anchoring bias. Anchoring bias occurs when physicians stick to an incorrect diagnosis triggered by early salient distracting features (SDF) despite subsequent conflicting information., Methods: Sixty-eight internal medicine residents from two Dutch university hospitals participated in a two-phase experiment. Phase 1: assessment of knowledge of discriminating features (ie, clinical findings that discriminate between lookalike diseases) for six diseases. Phase 2 (1 week later): diagnosis of six cases of these diseases. Each case had two versions differing exclusively in the presence/absence of SDF. Each participant diagnosed three cases with SDF (SDF+) and three without (SDF-). Participants were randomly allocated to case versions. Based on phase 1 assessment, participants were split into higher knowledge or lower knowledge groups., Main Outcome Measurements: frequency of diagnoses associated with SDF; time to diagnose; and confidence in diagnosis., Results: While both knowledge groups performed similarly on SDF- cases, higher knowledge physicians succumbed to anchoring bias less frequently than their lower knowledge counterparts on SDF+ cases (p=0.02). Overall, physicians spent more time (p<0.001) and had lower confidence (p=0.02) on SDF+ than SDF- cases (p<0.001). However, when diagnosing SDF+ cases, the groups did not differ in time (p=0.88) nor in confidence (p=0.96)., Conclusions: Physicians apparently adopted a more analytical reasoning approach when presented with distracting features, indicated by increased time and lower confidence, trying to combat bias. Yet, extended deliberation alone did not explain the observed performance differences between knowledge groups. Success in mitigating anchoring bias was primarily predicted by knowledge of discriminating features of diagnoses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Haematology patients with high-risk neutropenia are prone to mucosal-barrier injury-associated laboratory-confirmed bloodstream infections (MBI-LCBI). We assessed risk factors for MBI-LCBI including candidaemia in neutropenic haematology patients with fever., Methods: This prospective observational study was performed in six dedicated haematology units in the Netherlands. Eligible haematology patients had neutropenia < 500/mL for ≥ 7 days and had fever. MBI-LCBIs were classified according to Centers for Disease Control (CDC) definitions and were followed until the end of neutropenia > 500/mL or discharge., Results: We included 416 patients from December 2014 until August 2019. We observed 63 MBI-LCBIs. Neither clinical mucositis scores nor the blood level of citrulline at fever onset was associated with MBI-LCBI. In the multivariable analysis, MASCC-score (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05 to 1.29 per point decrease), intensive chemotherapy (OR 3·81, 95% CI 2.10 to 6.90) and Pichia kudriavzevii (formerly Candida krusei) colonisation (OR 5.40, 95% CI 1.75 to 16.7) were retained as risk factors for MBI-LCBI, while quinolone use seemed protective (OR 0.42, 95% CI 0.20 to 0.92). Citrulline level (OR 1.57, 95% CI 1.07 to 2.31 per µmol/L decrease), active chronic obstructive pulmonary disease (OR 15.4, 95% CI 1.61 to 14.7) and colonisation with fluconazole-resistant Candida (OR 8.54, 95% CI 1.51 to 48.4) were associated with candidaemia., Conclusion: In haematology patients with fever during neutropenia, hypocitrullinaemia at fever onset was associated with candidaemia, but not with bacterial MBI-LCBI. Patients with intensive chemotherapy with a low MASCC-score and colonisation with Pichia kudriavzevii had the highest risk of MBI-LCBI., Trial Registration: ClinicalTrials.gov (NCT02149329) at 19-NOV-2014., (© 2024. The Author(s).)

The primary aim of this study was to evaluate computed tomography (CT)-based bone density analysis at the level of thoracic vertebra 12 (Th12) as a screening method for decreased bone density in patients admitted to the intensive care unit (ICU). Interobserver variability was analyzed. Secondary aims were to assess the prevalence of CT-based low bone density upon ICU admission in a cohort of COVID-19 patients and to assess the potential effect of long-term ICU stay on bone density in these patients. Retrospective single-center cohort study. ICU of the Leiden University Medical Center (LUMC), the Netherlands. Patients admitted to the ICU of the LUMC between March 1st, 2020 and February 1st, 2022 with a diagnosis of COVID-19, and a length of ICU stay of ≥ 21 days. In the included patients both baseline chest CT scans (obtained upon ICU admission) and follow-up chest CT scans (obtained ≥ 21 days after ICU admission) were available for analysis. A total of 118 CT scans in 38 patients were analyzed. There was a good interobserver variability, with an overall mean absolute difference (between measurements of three observers) of 9.7 Hounsfield Units (HU) and an intraclass correlation coefficient (ICC) of 0.93 (95% CI 0.88-0.96). The effect of intravenous contrast administration on bone density measurements was small (+ 7.5 HU (95% CI 3.4-11.5 HU)) higher in contrast enhanced CT images compared to non contrast enhanced CT images). Thirty-seven percent of patients had a bone density < 140 HU, suggestive of osteoporosis. No significant difference was found between bone density upon ICU admission and bone density at follow-up (≥ 21 days after ICU admission). Vertebral CT-based bone density analysis using routine CT scans is an easily applicable method to identify ICU patients with decreased bone density, which could enable enrollment in osteoporosis prevention programs. A high prevalence of low bone density was found in our cohort of ICU patients. There were no changes observed in bone density between baseline and follow-up measurements., (© 2024. The Author(s).)

Background: There are increased indications that physical activity timing, irrespective of intensity, impacts insomnia and circadian clock function. Here, we describe the rationale and design of a randomized cross-over study, called ON TIME, to examine the effects of (changing) physical activity timing on insomnia severity and on multiple exploratory outcomes that are linked to circadian clock function., Methods: We will conduct a randomized cross-over trial in 40 healthy older adults (aged 65 to 75 years) with subclinical or clinical insomnia (Insomnia Severity Index (ISI) scores of ≥ 10) from the Dutch municipality of Leiden and surroundings. Participants will undergo 3 intervention periods (14 days each) consecutively: one sedentary period and two periods of increased physical activity (one period with morning activity and one period with evening activity). The intervention periods are separated by a wash-out period of 1 week. In both active intervention arms, participants will follow coached or uncoached outdoor physical exercise sessions comprising endurance, strength, and flexibility exercises for 14 days. The primary outcome is change in insomnia severity as measured by the ISI. Additional exploratory outcomes include multiple components of objective sleep quality measured with tri-axial accelerometry and subjective sleep quality assessed by questionnaires as well as dim light melatonin onset and 24-h rhythms in heart rate, heart rate variability, breathing rate, oxygen saturation, mood, and objective emotional arousal and stress. Additionally, we will collect diary data on eating patterns (timing and composition). Finally, fasting blood samples will be collected at baseline and after each intervention period for measurements of biomarkers of metabolic and physiological functioning and expression of genes involved in regulation of the biological clock., Discussion: We anticipate that this study will make a significant contribution to the limited knowledge on the effect of physical activity timing. Optimizing physical activity timing has the potential to augment the health benefits of increased physical exercise in the aging population., Trial Registration: Trial was approved by the Medical Ethics Committee Leiden, The Hague, Delft, The Netherlands (June, 2023). The trial was registered in the CCMO-register https://www.toetsingonline.nl/to/ccmo&#95;search.nsf/Searchform?OpenForm under study ID NL82335.058.22 and named ("Ouderen op tijd in beweging" or in English "Older adults exercising on time"). At time of manuscript submission, the trial was additionally registered at ClinicalTrials.gov under study ID: NL82335.058.22 and is awaiting approval., (© 2024. The Author(s).)