This study aimed to identify determinants that hinder or facilitate implementation of the Feverkidstool, a clinical decision support tool offering a quantitative, evidence-based approach, to manage children with fever in the emergency department (ED) setting.

Qualitative study using semistructured interviews, analysed through directed content analysis guided by the Consolidated Framework for Implementation Research (CFIR).

Secondary and tertiary paediatric emergency departments in three hospitals in the Netherlands.

Eighteen potential end users of the Feverkidstool, including paediatricians and paediatric residents working in the ED and involved in the care of febrile children, participated in the study.

Determinants of Feverkidstool implementation, categorised by CFIR domains: intervention characteristics, outer setting, inner setting, characteristics of individuals and implementation process.

Respondents (n=18) perceived the evidence-based guidance by the Feverkidstool and its potential to reduce antibiotic use as valuable. However, concerns were raised about its applicability to critically ill children and those with comorbidities. User-friendliness was seen as a facilitator, whereas the need for C reactive protein testing and lack of integration with electronic health records were mentioned as barriers. The ability to standardise care for febrile children was considered an important benefit of using the Feverkidstool.

Barriers and facilitators across all CFIR domains are identified. Addressing these will facilitate implementation. When effectively implemented, the Feverkidstool has the potential to improve care for children presenting with fever in the ED. This may potentially lead to a more standardised approach and reduce unnecessary antibiotic prescriptions.

The predictive value of carotid-femoral pulse wave velocity (cfPWV) for cardiovascular (CV) events in individuals with blood pressure (BP) 120–159/80–99 mm Hg, where more accurate risk stratification has the greatest clinical effect, is unknown. This study aims to determine whether cfPWV improves the prediction of CV events beyond traditional risk factors in individuals with moderate BP.

A systematic review and meta-analysis.

PubMed and EMBASE were searched through April 2023.

We included prospective, population-based cohort studies with ≥1 year follow-up that directly measured cfPWV as an index of arterial stiffness and reported incident CV disease (CVD), atherosclerotic CVD (ASCVD), coronary heart disease, stroke or all-cause mortality outcomes.

Individual participant data from 11 cohorts (n=15 987) were harmonised and analysed using two-stage random-effects meta-analysis. Incremental predictive and clinical utility analyses compared 10-year risk models with and without cfPWV.

There were 1279 first atherosclerotic CV events over a median follow-up of 9.9 years. A 1-SD increase in log_e(cfPWV) was associated with a 1.21-fold (95% CI 1.08 to 1.36) increase in risk of ASCVD. Adding cfPWV to traditional risk factors improved ASCVD prediction: change in discrimination (C-index): 0.0048 (95% CI 0.0002 to 0.0094), p=0.041. In hypothetical populations of 100 000 individuals with moderate BP, cfPWV-guided treatment could reduce event rates by 2.7% and 3.1% under European and US guidelines, respectively.

Adding cfPWV to traditional CV risk factors may improve the prediction and classification of first CV events in individuals with moderate BP. Additional screening with cfPWV could enhance risk stratification for antihypertensive treatment initiations.

Gastroenteropancreatic neuroendocrine tumours (GEP NET) are malignant neoplasms that impact survival. Somatostatin analogues (SSA) are used for treating hormonal symptoms caused by GEP NET and have antiproliferative effects. They are used as first-line therapy in patients with advanced GEP NET, but disease control is limited to a median progression-free survival (mPFS) of 14–32 months. Second-line treatment options include targeted therapy (everolimus or sunitinib), or peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE. In patients suffering from a NET-related hormonal syndrome, SSA is generally continued life-long. However, there is no consensus on whether it is beneficial to continue SSA in non-functional NET upon disease progression. Due to the ongoing activity of the somatostatin receptor pathway in GEP NET progressing on first-line SSA, we hypothesise that SSA have an added efficacy in second-line therapy.

The SAUNA trial is an international, multicentre, open-label, randomised, controlled, pragmatic clinical trial. 270 patients with advanced, non-functional GEP NET and progression under first-line SSA will be included in substudy 1 (PRRT; n=142) or substudy 2 (targeted therapy (everolimus/sunitinib); n=128) per investigator’s choice of second-line therapy and will be randomised (1:1) per substudy between SSA continuation or SSA withdrawal arms. Co-primary endpoints are the difference in progression-free survival (PFS) according to the RECIST (Response Evaluation Criteria In Solid Tumours) V.1.1 criteria and difference in time to deterioration (TTD) in quality of life (QoL) per substudy after initiating second-line therapy with or without SSA. Secondary endpoints include the PFS rate at 18 months, the difference in pooled PFS and TTD combining both substudies, overall survival, response rates, QoL, costs, cost-effectiveness and toxicity. The study design was developed in cooperation with the Belgium and Dutch patient organisations.

The study has been approved on 31 May 2023 by the Ethical Committees and Regulatory Authorities of the concerned member states (EU CT number 2022-502703-30-00). Both the trial management group and the steering committee will oversee good governance of this trial. Results of the study will be published in peer-reviewed international journals and presented at international conferences.

NCT05701241.