Elkerliek Ziekenhuis

Accurate quantification of neonatal bilirubin remains a perennial challenge. To monitor analytical performance of total bilirubin measurements across hospitals in the Netherlands, a dedicated neonatal external quality assessment (EQA) program is in place. We retrospectively analyzed Dutch EQA data from 2013 until 2025. Each year, the 81 participating laboratories received 24 pooled adult blood serum samples spiked with unconjugated bilirubin (range 100-400 µmol/L or 5.85-23.40 mg/dL). Bias from the target value determined by the reference measurement procedure (RMP) and the coefficient of variation (CV) were established for both unfactored and factored measurements. In total, 25 983 bilirubin measurements were analyzed. Three analytical principles were used on 12 platforms from 6 manufacturers. Diazo-based methods exhibited the lowest median bias (+0.4% in 2024), alongside spectrophotometric methods (-3.8% in 2024). Vanadate-based methods showed a bias of +19.5% in 2024 that was reduced to +3.0% for factored measurements. Substantial differences in bias were observed among manufacturers and platforms, with some exhibiting concentration dependency. Comparable patterns were seen for CVs, which generally remained below 5%. EQA results demonstrated temporal variability in bias across all analytical principles, manufacturers, and platforms used for neonatal bilirubin assays. Bias was found to vary with bilirubin concentration. Standardization of neonatal bilirubin assays is urgently needed to ensure more reliable and accurate measurements across different systems. Meanwhile, EQA programs are important in monitoring future assay adjustments to ensure appropriate and consistent management of neonatal hyperbilirubinemia.

Introduction and aim Refractory dyspnea is a common symptom in advanced COPD, with a high negative impact. As treatment for refractory dyspnea, opioids -mostly morphine- have been investigated and made their way into palliative care guidelines. But in recent years there have been multiple negative studies in COPD. Furthermore, there is no RCT investigating transdermal fentanyl. We aimed to investigate whether both morphine and fentanyl are more effective than placebo for refractory dyspnea in COPD. <bold>Methods:</bold> This was a multicenter, cross-over, dubbel-dummy RCT, investigating fentanyl (patch,12mcg/hr), morphine (10 mg p.o. bid) and placebo, during 3 periods of 2 weeks (incl. 3 days wash out). Patients with stable COPD, FEV1<50%, and mMRC score≥3 with refractory dyspnea caused by COPD despite optimal therapy were included. <bold>Results:</bold> Between 2019 and 2024, 59 participants were included (69±7 years, 54% female, FEV1 33±10%), of which 37 completed all three study periods. The main reasons for discontinuation were exacerbations (n=13) and side effects (n=7). There were no significant differences between both fentanyl and morphine compared to placebo with respect to mean and worst dyspnea, sleep quality, health-related quality of life, mastery, anxiety or capillary blood gas analysis (table 1). <bold>Conclusion:</bold> This study demonstrated no positive effect of both morphine and fentanyl compared to placebo in the treatment of refractory dyspnea in COPD. <fig><object-id>erj;66/suppl_69/OA1188/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

BackgroundWe aimed to describe real-world complete response (CR) rates, predictors of CR, and survival outcomes in patients treated with first-line pertuzumab, trastuzumab, and chemotherapy for HER2-positive (HER2+) metastatic breast cancer (MBC).MethodsPatients with HER2+ MBC who started first-line pertuzumab, trastuzumab, and chemotherapy in 2013–2021 were selected from the SONABRE Registry (NCT-03577197), involving eleven Dutch hospitals. CR was defined as no evidence of disease on imaging during first-line systemic therapy with or without local therapy (surgery and/or radiotherapy). Multivariable logistic regression was used to identify predictors for CR. Progression-free survival (PFS) and overall survival (OS) from the start of first-line pertuzumab, trastuzumab, and chemotherapy were computed with the Kaplan-Meier method.ResultsWe included 244 patients treated with first-line pertuzumab, trastuzumab, and chemotherapy, with a median follow-up duration of 71 months (interquartile range: 60–82 months). A CR during first-line systemic therapy was reached in 63 patients (26 %). Patients younger than 65 years (odds ratio (OR) = 5.24, 95 %CI:1.49–18.44, p = 0.01), those with de Novo MBC (OR = 2.48, 95 %CI:1.24–4.93, p = 0.01), or those with a single metastatic site (OR = 3.81, 95 %CI:1.83–7.96, p < 0.001) were more likely to reach CR than their counterparts. The 5-year PFS and OS rates were, respectively, 63 % (95 %CI:48 %–75 %) and 85 % (95 %CI:72 %–92 %) in patients with a CR and 10 % (95 %CI:6 %–16 %) and 36 % (95 %CI:28 %–44 %) in patients without a CR.ConclusionsIn the real world, one in four patients treated with first-line pertuzumab, trastuzumab, chemotherapy, with or without local therapy, reached CR. Two third of patients with a CR were still free of progression after five years.

Abstract Introduction During the COVID-19 pandemic, elective surgeries including hernia repairs, were postponed, or cancelled completely. However, it has been stated previously that the volume of surgical emergency hernia repairs did not drop during this period. Due to the disruption in elective surgeries, waiting lists have increased rapidly, causing a suspected treatment delay. To gain improve preoperative patient prioritization, the aim of this multicenter study was to track volumes of hernia surgery before, during and after the pandemic to investigate for a shift from elective towards emergency hernia surgery. Methods A retrospective study using hernia databases from four regional hospitals to account for altered referral patterns (elective versus emergent), capturing patients’ admissions and surgery times for both groin and ventral hernia repair was conducted. Study period was predefined from March 2019 to March 2023. Data are presented as descriptive statistics. Results During the historic period, 106 of 2267 hernia surgeries (4.7%) performed were defined as emergency repairs. During the pandemic, 1551 elective surgeries were executed, of which 103 (6.6%) emergencies. During the current period, the portion of emergencies dropped to 5% (205 emergency hernia repairs); (p = 0.039). A significant increase in emergent hernia cicatricalis repair during the pandemic period was found: chronologically 9.9%, 19.2% and 9.3% emergent repairs (p = 0.005). Discussion Regionwide data showed a 34% decline in hernia repairs during the pandemic compared to historical levels. Surgery rates are still convalescent, with a persistent proportion of emergent surgeries. These numbers emphasize the challenges in selecting patient whose hernia repair should not be postponed.

For distal forearm fractures in children, it has been shown that a below-elbow cast is an adequate treatment that overcomes the discomfort of an above-elbow cast and unnecessary immobilization of the elbow. For reduced diaphyseal both-bone forearm fractures, our previous randomized controlled trial (RCT)-which compared an above-elbow cast with early conversion to a below-elbow cast-revealed no differences in the risk of redisplacement or functional outcomes at short-term follow-up. Although studies with a longer follow-up after diaphyseal both-bone forearm fractures in children are scarce, they are essential, as growth might affect the outcome. In this secondary analysis of an earlier RCT, we asked: (1) Does early conversion from an above-elbow to a below-elbow cast in children with reduced, stable diaphyseal forearm fractures result in worse clinical and radiological outcome? (2) Does a malunion result in inferior clinical outcomes at 7.5 years of follow-up? In this study, we evaluated children at a minimum of 5 years of follow-up who were included in a previous RCT. The median (range) duration of follow-up was 7.5 years (5.2 to 9.9). The patients for this RCT were included from the emergency departments of four different urban hospitals. Between January 2006 and August 2010, we treated 128 patients for reduced diaphyseal both-bone forearm fractures. All 128 patients were eligible; 24% (31) were excluded because they were lost before the minimum study follow-up or had incomplete datasets, leaving 76% (97) for secondary analysis. The loss in the follow-up group was comparable to the included population. Eligible patients were invited for secondary functional and radiographic assessment. The primary outcome was the difference in forearm rotation compared with the uninjured contralateral arm. Secondary outcomes were the ABILHAND-kids and QuickDASH questionnaire, loss of flexion and extension of the elbow and wrist compared with the contralateral forearm, JAMAR grip strength ratio, and radiological assessment of residual deformity. The study was not blinded regarding the children, parents, and clinicians. At 7.5-year follow-up, there were no differences in ABILHAND-kids questionnaire score (above-elbow cast: 41 ± 2.4 versus above/below-elbow cast: 41.7 ± 0.7, mean difference -0.7 [95% confidence interval (CI) -1.4 to 0.04]; p = 0.06), QuickDASH (above-elbow cast: 5.8 ± 9.6 versus 2.9 ± 6.0 for above-/below-elbow cast, mean difference 2.9 [95% CI -0.5 to 6.2]; p = 0.92), and grip strength (0.9 ± 0.2 for above-elbow cast versus 1 ± 0.2 for above/below-elbow cast, mean difference -0.04 [95% CI -1 to 0.03]; p = 0.24). Functional outcomes showed no difference (loss of forearm rotation: above-elbow cast 7.9 ± 17.7 versus 4.1 ± 6.9 for above-/below-elbow cast, mean difference 3.8 [95% CI -1.7 to 9.4]; p = 0.47; arc of motion: above-elbow cast 152° ± 21° versus 155° ± 11° for the above/below-elbow cast group, mean difference -2.5 [95% CI -9.3 to -4.4]; p = 0.17; loss of wrist flexion-extension: above-elbow cast group 1.0° ± 5.0° versus 0.6° ± 4.2° for above/below-elbow cast, mean difference 0.4° [95% CI -1.5° to 2.2°]; p = 0.69). The secondary follow-up showed improvement in forearm rotation in both groups compared with the rotation at 7 months. For radiographical analysis, the only difference was in AP ulna (above-elbow cast: 6° ± 3° versus above/below-elbow cast: 5° ± 2°, mean difference 1.8° [0.7° to 3°]; p = 0.003), although this is likely not clinically relevant. There were no differences in the other parameters. Thirteen patients with persistent malunion at 7-month follow-up showed no clinically relevant differences in functional outcomes at 7.5-year follow-up compared with children without malunion. The loss of forearm rotation was 5.5ׄ° ± 9.1° for the malunion group compared with 6.0° ± 13.9° in the no malunion group, with a mean difference of 0.4 (95% CI of -7.5 to 8.4; p = 0.92). In light of these results, we suggest that surgeons perform an early conversion to a below-elbow cast for reduced diaphyseal both-bone forearm fractures in children. This study shows that even in patients with secondary fracture displacement, remodeling occurred. And even in persistent malunion, these patients mostly showed good-to-excellent final results. Future studies, such as a meta-analysis or a large, prospective observational study, would help to establish the influence of skeletal age, sex, and the severity and direction of malunion angulation of both the radius and ulna on clinical result. Furthermore, a similar systematic review could prove beneficial in clarifying the acceptable angulation for pediatric lower extremity fractures. Level I, therapeutic study.

To describe the 12-month mortality of Dutch COVID-19 intensive care unit patients, the total COVID-19 population and various subgroups on the basis of the number of comorbidities, age, sex, mechanical ventilation, and vasoactive medication use. We included all patients admitted with COVID-19 between March 1, 2020, and March 29, 2022, from the Dutch National Intensive Care (NICE) database. The crude 12-month mortality rate is presented via Kaplan-Meier survival curves for each patient subgroup. We used Cox regression models to analyze the effects of patient characteristics on 12-month mortality after hospital discharge. We included 16,605 COVID-19 patients. The in-hospital mortality rate was 28.1%, and the 12-month mortality rate after intensive care unit admission was 29.8%. Among hospital survivors, 12-month mortality after hospital discharge was 2.5% (300/11,931). The hazard of death at 12 months after hospital discharge was greater in patients between 60 and 79 years (HR 4.74; 95%CI 2.23 - 10.06) and ≥ 80 years (HR 22.77; 95%CI 9.91 - 52.28) than in patients < 40 years of age; in male patients than in female patients (HR 1.38; 95%CI 1.07 - 1.78); and in patients with one (adjusted HR 1.95; 95%CI 1.5 - 2.53), two (adjusted HR 4.49; 95%CI 3.27 - 6.16) or more than two comorbidities (adjusted HR 4.99; 95%CI 2.62 - 9.5) than in patients with no comorbidities. Neither vasoactive medication use nor mechanical ventilation resulted in statistically significant results. For Dutch COVID-19 intensive care unit patients, most deaths occurred during their hospital stay. For hospital survivors, the crude 12-month mortality rate was low. Patient age (older than 60), sex and the number of comorbidities were associated with a greater hazard of death at 12 months after hospital discharge, whereas mechanical ventilation and vasoactive medication were not.

ObjectivePrehospital risk stratification and triage are currently not performed in patients suspected of non-ST-segment elevation acute coronary syndrome (NSTE-ACS). This may lead to prolonged time to revascularisation, increased duration of hospital admission and higher healthcare costs. The preHEART score (prehospital history, ECG, age, risk factors and point-of-care troponin score) can be used by emergency medical services (EMS) personnel for prehospital risk stratification and triage decisions in patients with NSTE-ACS. The aim of the current study was to evaluate the effect of prehospital risk stratification and direct transfer to a percutaneous coronary intervention (PCI) centre, based on the preHEART score, on time to final invasive diagnostics or culprit revascularisation.MethodsProspective, multicentre, two-cohort study in patients with suspected NSTE-ACS. The first cohort is observational (standard care), while the second (interventional) cohort includes patients who are stratified for direct transfer to either a PCI or a non-PCI centre based on their preHEART score. Risk stratification and triage are performed by EMS personnel. The primary endpoint of the study is time from first medical contact until final invasive diagnostics or revascularisation. Secondary endpoints are time from first medical contact until intracoronary angiography (ICA), duration of hospital admission, number of invasive diagnostics, number of inter-hospital transfers and major adverse cardiac events at 7 and 30 days.ResultsA total of 1069 patients were included. In the interventional cohort (n=577), time between final invasive diagnostics or revascularisation (42 (17–101) hours vs 20 (5–44) hours, p<0.001) and length of hospital admission (3 (2–5) days vs 2 (1–4) days, p=0.007) were shorter than in the observational cohort (n=492). In patients with NSTE-ACS in need for ICA or revascularisation, healthcare costs were reduced in the interventional cohort (€5599 (2978–9625) vs €4899 (2278–5947), p=0.02).ConclusionPrehospital risk stratification and direct transfer to a PCI centre, based on the preHEART score, reduces time from first medical contact to final invasive diagnostics and revascularisation, reduces duration of hospital admission and decreases healthcare costs in patients with NSTE-ACS in need for ICA or revascularisation.Trial registrationNCT05243485.

PurposeThis study determines the prognostic impact of body mass index (BMI) in patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2−) advanced (i.e., metastatic) breast cancer (ABC).MethodsAll patients with HR+/HER2− ABC who received endocrine therapy +—a cyclin-dependent kinase 4/6 inhibitor as first-given systemic therapy in 2007–2020 in the Netherlands were identified from the Southeast Netherlands Advanced Breast Cancer (SONABRE) registry (NCT03577197). Patients were categorised as underweight (BMI: < 18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥ 30.0 kg/m2). Overall survival (OS) and progression-free survival (PFS) were compared between BMI classes using multivariable Cox regression analyses.ResultsThis study included 1456 patients, of whom 35 (2%) were underweight, 580 (40%) normal weight, 479 (33%) overweight, and 362 (25%) obese. No differences in OS were observed between normal weight patients and respectively overweight (HR 0.99; 95% CI 0.85–1.16; p = 0.93) and obese patients (HR 1.04; 95% CI 0.88–1.24; p = 0.62). However, the OS of underweight patients (HR 1.45; 95% CI 0.97–2.15; p = 0.07) tended to be worse than the OS of normal weight patients. When compared with normal weight patients, the PFS was similar in underweight (HR 1.05; 95% CI 0.73–1.51; p = 0.81), overweight (HR 0.90; 95% CI 0.79–1.03; p = 0.14), and obese patients (HR 0.88; 95% CI 0.76–1.02; p = 0.10).ConclusionIn this study among 1456 patients with HR+/HER2− ABC, overweight and obesity were prevalent, whereas underweight was uncommon. When compared with normal weight, overweight and obesity were not associated with either OS or PFS. However, underweight seemed to be an adverse prognostic factor for OS.

BackgroundIn women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study.MethodsThis study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated.DiscussionThe H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice.Trial registration numberThe study was prospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).