Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

Postnatal corticosteroid response in neonates < 32 weeks and relation with placental pathology.

Acute chorioamnionitis and maternal vascular malperfusion are associated with an increased risk of bronchopulmonary dysplasia. To prevent bronchopulmonary dysplasia, postnatal corticosteroids are given to preterm neonates. Clinical observations indicate not all neonates respond to corticosteroids, the so-called non-responders. This study aimed to investigate the association between placental pathology and short-term response to postnatal corticosteroids in neonates < 32 weeks postconceptional age at risk for bronchopulmonary dysplasia. All neonates < 32 weeks born between 2009 and 2016, receiving corticosteroids in the course of BPD, were included. The preterm neonates were divided into three groups depending on placental histology: acute chorioamnionitis, maternal vascular malperfusion, or no placental pathology. Respiratory support was assessed prior to treatment and at days 4 and 7. A responder was defined as extubation within 7 days after starting corticosteroid treatment. In total, 52% of the chorioamnionitis neonates, 67% of the maternal vascular malperfusion neonates, and 58% of neonates in the no pathology group were responders. The odds ratio for extubation was 0.53 (0.18-1.55) at day 4 and 0.66 (0.23-1.97) at day 7, in the chorioamnionitis group compared to the maternal vascular malperfusion. CONCLUSION: Short-term response to postnatal corticosteroids did not significantly differ between premature neonates born after acute chorioamnionitis, maternal vascular malperfusion, or no placenta pathology. However, a trend of better corticosteroid response in maternal vascular malperfusion neonates was found, potentially due to differences in prenatal pulmonary development and postnatal cortisol. WHAT IS KNOWN: • Bronchopulmonary dysplasia is related to chorioamnionitis and maternal vascular malperfusion. • Corticosteroids remain an important treatment in the course of bronchopulmonary dysplasia despite conflicting results and non-responsiveness in some preterm neonates. WHAT IS NEW: • Non-responsiveness might be related to differences in pulmonary inflammation and systemic cortisol due to predispositions triggered by chorioamnionitis or maternal vascular malperfusion. • Neonates born after maternal vascular malperfusion seem to respond better to postnatal corticosteroid treatment.

Determinants of label non-adherence to non-vitamin K oral anticoagulants in patients with newly diagnosed atrial fibrillation.

Aims: To evaluate the extent and determinants of off-label non-vitamin K oral anticoagulant (NOAC) dosing in newly diagnosed Dutch AF patients. Methods and results: In the DUTCH-AF registry, patients with newly diagnosed AF (<6 months) are prospectively enrolled. Label adherence to NOAC dosing was assessed using the European Medicines Agency labelling. Factors associated with off-label dosing were explored by multivariable logistic regression analyses. From July 2018 to November 2020, 4500 patients were registered. The mean age was 69.6 ± 10.5 years, and 41.5% were female. Of the 3252 patients in which NOAC label adherence could be assessed, underdosing and overdosing were observed in 4.2% and 2.4%, respectively. In 2916 (89.7%) patients with a full-dose NOAC recommendation, 4.6% were underdosed, with a similar distribution between NOACs. Independent determinants (with 95% confidence interval) were higher age [odds ratio (OR): 1.01 per year, 1.01-1.02], lower renal function (OR: 0.96 per ml/min/1.73 m2, 0.92-0.98), lower weight (OR: 0.98 per kg, 0.97-1.00), active malignancy (OR: 2.46, 1.19-5.09), anaemia (OR: 1.73, 1.08-2.76), and concomitant use of antiplatelets (OR: 4.93, 2.57-9.46). In the 336 (10.3%) patients with a reduced dose NOAC recommendation, 22.9% were overdosed, most often with rivaroxaban. Independent determinants were lower age (OR: 0.92 per year, 0.88-0.96) and lower renal function (OR: 0.98 per ml/min/1.73 m2, 0.96-1.00). Conclusion: In newly diagnosed Dutch AF patients, off-label dosing of NOACs was seen in only 6.6% of patients, most often underdosing. In this study, determinants of off-label dosing were age, renal function, weight, anaemia, active malignancy, and concomitant use of antiplatelets.

Factors facilitating and hindering the implementation of the European Society of Cardiology Syncope Guidelines at the Emergency Department: A nationwide qualitative study.

AIMS: Syncope care is often fragmented and inefficient. Structuring syncope care through implementation of guidelines and Syncope Units has been shown to improve diagnostic yield, reduce costs and improve quality of life. We implemented the European Society of Cardiology (ESC) 2018 syncope guidelines at the Emergency Departments (ED) and established Syncope Units in five Dutch hospitals. We evaluated the implementation process by identifying factors that hinder ('barriers') and facilitate ('facilitators') the implementation. METHODS AND RESULTS: We conducted, recorded and transcribed semi-structured interviews with 19 specialists and residents involved in syncope care from neurology, cardiology, internal medicine and emergency medicine. Two researchers independently classified the reported barriers and facilitators, according to the framework of qualitative research (Flottorp), which distinguished several separate fields ('levels'). Software package Atlas.ti was used for analysis. We identified 31 barriers and 22 facilitators. Most barriers occurred on the level of the individual health care professional (e.g. inexperienced residents having to work with the guideline at the ED) and the organizational context (e.g. specialists not relinquishing preceding procedures). Participants reported most facilitators at the level of innovation (e.g. structured work-flow at the ED). The multidisciplinary Syncope Unit was welcomed as useful solution to a perceived need in clinical practice. CONCLUSION: Implementing ESC syncope guidelines at the ED and establishing Syncope Units facilitated a structured multidisciplinary work-up for syncope patients. Most identified barriers related to the individual health care professional and the organizational context. Future implementation of the multidisciplinary guideline should be tailored to address these barriers.

Characteristics of patients with atrial fibrillation prescribed edoxaban in Belgium and the Netherlands: insights from the ETNA-AF-Europe study.

BACKGROUND: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. METHODS: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p­glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). RESULTS: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. CONCLUSION: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. TRIAL REGISTRATION: NCT02944019; Date of registration 24 October 2016.

[Contraindications to DOACs in atrial fibrillation]. / Contra-indicaties voor DOAC's bij atriumfibrilleren.

Sometimes there is doubt as to whether or not anticoagulants should be initiated, and if so which ones, in patients with atrial fibrillation and advanced age, increased frailty, or fall risk, kidney, or liver impairment, alcohol abuse, uncontrolled hypertension, or a history of major bleeding. These subgroups have increased risk of haemorrhage as well as thromboembolism. Treatment with anticoagulants is indicated in the vital elderly, preferably with direct oral anticoagulants as demonstrated by robust data. The available study results for the other subgroups may not be (fully) generalisable to clinical practice. In such patients, a comprehensive risk assessment is therefore advised; as is discussing the pros and cons of (not) using anticoagulants and of both type of anticoagulants. Only in exceptional cases is it justified not to use anticoagulants.

Antithrombotic management of patients with atrial fibrillation-Dutch anticoagulant initiatives anno 2020.

In recent years, as more and more experience has been gained with prescribing direct oral anticoagulants (DOACs), new research initiatives have emerged in the Netherlands to improve the safety and appropriateness of DOAC treatment for stroke prevention in patients with atrial fibrillation (AF). These initiatives address several contemporary unresolved issues, such as inappropriate dosing, non-adherence and the long-term management of DOAC treatment. Dutch initiatives have also contributed to the development and improvement of risk prediction models. Although fewer bleeding complications (notably intracranial bleeding) are in general seen with DOACs in comparison with vitamin K antagonists, to successfully identify patients with high bleeding risk and to tailor anticoagulant treatment accordingly to mitigate this increased bleeding risk, is one of the research aims of recent and future years. This review highlights contributions from the Netherlands that aim to address these unresolved issues regarding the anticoagulant management in AF in daily practice, and provides a narrative overview of contemporary stroke and bleeding risk assessment strategies.

Complex clinical scenarios with the use of direct oral anticoagulants in patients with atrial fibrillation: a multidisciplinary expert advisory board.

The risk of developing atrial fibrillation (AF) and the risk of stroke both increase with advancing age. As such, many individuals have, or will develop, an indication for oral anticoagulation to reduce the risk of stroke. Currently, a large number of anticoagulants are available, including vitamin K antagonists, direct thrombin or factor Xa inhibitors (the last two also referred to as direct oral anticoagulants or DOACs), and different dosages are available. Of the DOACs, rivaroxaban can be obtained in the most different doses: 2.5 mg, 5 mg, 15 mg and 20 mg. Many patients develop co-morbidities and/or undergo procedures that may require the temporary combination of anticoagulation with antiplatelet therapy. In daily practice, clinicians encounter complex scenarios that are not always described in the treatment guidelines, and clear recommendations are lacking. Here, we report the outcomes of a multidisciplinary advisory board meeting, held in Utrecht (The Netherlands) on 3 June 2019, on decision making in complex clinical situations regarding the use of DOACs. The advisory board consisted of Dutch cardiovascular specialists: (interventional) cardiologist, internist, neurologist, vascular surgeon and general practitioners invited according to personal title and specific field of expertise.

Changes in anticoagulant prescription in Dutch patients with recent-onset atrial fibrillation: observations from the GARFIELD-AF registry.

BACKGROUND: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. METHODS: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. RESULTS: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. CONCLUSIONS: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

Trends in direct oral anticoagulant (DOAC) use: health benefits and patient preference.

In 2012, the Dutch Health Council published a report addressing barriers for an early and broad introduction of direct oral anticoagulants (DOACs). The report raised concerns about the lack of an antidote, adherence, lack of monitoring in the case of overdose and the increased budget impact at DOAC introduction. In the past decade, international studies have shown that DOACs can provide healthcare benefits for a large number of patients. This has led to an increase in the prescription of DOACs, as they are an effective and user-friendly alternative to vitamin K antagonists (VKAs). Unlike VKAs, DOACs do not need monitoring of the international normalized ratio due to more predictable pharmacokinetics. However, the number of prescriptions of DOACs in the Netherlands is still lagging, compared to other European countries. This article highlights the potential health gains in the Netherlands if the use of DOACs were to increase, based on current international experience.

Magnetic resonance imaging in patients with cardiac implantable electronic devices.

In recent years the prevalence of implantation of a cardiac implantable electronic device (CIED) has increased due to expanding implantation indications and prolonged life expectancy. Diagnostic strategies increasingly employ magnetic resonance imaging (MRI) to aid therapeutic strategies. In earlier guidelines, MRI was contra-indicated in patients with CIEDs, mainly due to previous reports of severe complications. With the development of MRI-conditional CIEDs and recent evidence concerning non-MRI-conditional CIEDs, MRIs in CIED patients can be safely performed in many hospitals.However, there are several questions that need to be addressed. Which patients can we scan? How can the scans be performed safely? And last but not least, can cardiac MRI provide diagnostic yield in patients with CIEDs?Current European guidelines are rather outdated and vague about patient selection and practical issues. There are national guidelines on this topic but several issues need extra attention and those are addressed in this point of view. It is important to create an environment with proper patient selection without unnecessary MRI scans in CIED patients, but also without unnecessary fear of complications, preventing access to MRI in patients who can benefit from this powerful diagnostic tool.

Optimal long-term antithrombotic management of atrial fibrillation: life cycle management.

Optimal antithrombotic management of atrial fibrillation equals balancing between prevention of arterial thromboembolism, predominantly ischaemic stroke, and haemorrhagic complications. Over time different antithrombotic agents and strategies have been developed. At present, non-vitamin K antagonist oral anticoagulants (NOACs) are the first-line therapy for stroke prevention in patients with non-valvular atrial fibrillation (i.e. without a mechanical valve prosthesis or rheumatic heart disease). Considering the impact of the suboptimal adoption of recommended oral anticoagulant therapy, as experienced with the previous first-line vitamin K antagonists, this review focuses on adequate use of NOACs. As such, we address the most important and clinically challenging issues in the antithrombotic life cycle management for long-term stroke prevention in atrial fibrillation.