Effectiveness of score card-based antenatal risk selection, care pathways, and multidisciplinary consultation in the Healthy Pregnancy 4 All study (HP4ALL): Study protocol for a cluster randomized controlled trial

Background: Promotion of healthy pregnancies has gained high priority in the Netherlands because of relatively unfavorable perinatal outcomes. In response, a nationwide study, 'Healthy Pregnancy 4 All' (HP4ALL), has been initiated. Part of this study involves systematic and broadened antenatal risk assessment (the Risk Assessment substudy). Risk selection in current clinical practice is mainly based on medical risk factors. Despite the increasing evidence for the influence of nonmedical risk factors (social status, lifestyle or ethnicity) on perinatal outcomes, these risk factors remain highly unexposed. Systematic risk selection, combined with customized care pathways to reduce or treat detected risks, and regular and structured consultation between community midwives, gynecologists and other care providers such as social workers, is part of this study. Methods/Design: Neighborhoods in 14 municipalities with adverse perinatal outcomes above national and municipal averages are selected for participation. The study concerns a cluster randomized controlled trial. Municipalities are randomly allocated to intervention (n = 3,500 pregnant women) and control groups (n = 3,500 pregnant women). The intervention consists of systematic risk selection with th

Design and outline of the healthy pregnancy 4 all study

Background: Promotion of healthy pregnancies has gained high priority in the Netherlands because of the relatively unfavourable perinatal health outcomes. In response a nationwide study Healthy Pregnancy 4 All was initiated. This study combines public health and epidemiologic research to evaluate the effectiveness of two obstetric interventions before and during pregnancy: (1) programmatic preconception care (PCC) and (2) systematic antenatal risk assessment (including both medical and non-medical risk factors) followed by patient-tailored multidisciplinary care pathways. In this paper we present an overview of the study setting and outlines. We describe the selection of geographical areas and introduce the design and outline of the preconception care and the antenatal risk assessment studies.Methods/design: A thorough analysis was performed to identify geographical areas in which adverse perinatal outcomes were high. These areas were regarded as eligible for either or both sub-studies as we hypothesised studies to have maximal effect there. This selection of municipalities was based on multiple criteria relevant to either the preconception care intervention or the antenatal risk assessment intervention, or to both. The preconception care intervention was designed as a prospective community-based cohort study. The antenatal risk assessment intervention was designed as a cluster randomised controlled trial - where municipalities are randomly allocated to intervention and control.Discussion: Optimal linkage is sought between curative and preventive care, public health, government, and social welfare organisations. To our knowledge, this is the first study in which these elements are combined

Barriers in the Uptake and Delivery of Preconception Care: Exploring the Views of Care Providers

Objectives To examine health care professionals’ views of their role and responsibilities in providing preconception care and identify barriers that affect the delivery and uptake of preconception care. Methods Twenty health care professionals who provide preconception care on a regular basis were interviewed using semi-structured interviews. Results We interviewed twelve community midwives, three General Practitioners, three obstetricians, one cardiologist specialized in congenital heart diseases and one gastroenterologist.We identified four barriers affecting the uptake and delivery of preconception care (PCC): (1) lack of a comprehensive preconception care program; (2) limited awareness of most future parents about the benefits of preconception care, hesitance of GP’s about the necessity and effectiveness of PCC; (3) poor coordination and organization of preconception care; (4) conflicting views of health care professionals on pregnancy, reproductive autonomy of patients and professional responsibility. Conclusion We have identified four barriers in the uptake and delivery of preconception care. Our findings support the timely implementation of a comprehensive program of PCC (already advocated by the Health Council of the Netherlands) and increasing awareness and knowledge of PCC from care providers and future parents. We emphasize the need for further research on how organizational barriers lead to suboptimal PCC and how interdisciplinary collaboration and referral can lead to optimally tailored intervention approaches

Impact of Intracranial Volume and Brain Volume on the Prognostic Value of Computed Tomography Perfusion Core Volume in Acute Ischemic Stroke

Background: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. Materials and Methods: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy.Results: In 200 patients, the median core volume was 13 (5–41) mL. Median ICV and TBV were 1377 (1283–1456) mL and 1108 (1020–1197) mL. Median ICVcore and TBVcore were 0.9 (0.4–2.8)% and 1.7 (0.5–3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33–0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35–0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33–0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. Conclusion:Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.</p

SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes

Dravet syndrome is a severe epileptic encephalopathy, characterized by (febrile) seizures, behavioural problems and developmental delay. Eighty per cent of patients with Dravet syndrome have a mutation in SCN1A, encoding Nav1.1. Milder clinical phenotypes, such as GEFS+ (generalized epilepsy with febrile seizures plus), can also arise from SCN1A mutations. Predicting the clinical phenotypic outcome based on the type of mutation remains challenging, even when the same mutation is inherited within one family. This clinical and genetic heterogeneity adds to the difficulties of predicting disease progression and tailoring the prescription of anti-seizure medication. Understanding the neuropathology of different SCN1A mutations may help to predict the expected clinical phenotypes and inform the selection of best-fit treatments. Initially, the loss of Na+-current in inhibitory neurons was recognized specifically to result in disinhibition and consequently seizure generation. However, the extent to which excitatory neurons contribute to the pathophysiology is currently debated and might depend on the patient clinical phenotype or the specific SCN1A mutation. To examine the genotype-phenotype correlations of SCN1A mutations in relation to excitatory neurons, we investigated a panel of patient-derived excitatory neuronal networks differentiated on multi-electrode arrays. We included patients with different clinical phenotypes, harbouring various SCN1A mutations, along with a family in which the same mutation led to febrile seizures, GEFS+ or Dravet syndrome. We hitherto describe a previously unidentified functional excitatory neuronal network phenotype in the context of epilepsy, which corresponds to seizurogenic network prediction patterns elicited by proconvulsive compounds. We found that excitatory neuronal networks were affected differently, depending on the type of SCN1A mutation, but did not segregate according to clinical severity. Specifically, loss-of-function mutations could be distinguished from missense mutations, and mutations in the pore domain could be distinguished from mutations in the voltage sensing domain. Furthermore, all patients showed aggravated neuronal network responses at febrile temperatures compared with controls. Finally, retrospective drug screening revealed that anti-seizure medication affected GEFS+ patient- but not Dravet patient-derived neuronal networks in a patient-specific and clinically relevant manner. In conclusion, our results indicate a mutation-specific excitatory neuronal network phenotype, which recapitulates the foremost clinically relevant features, providing future opportunities for precision therapies.</p

Quantified health and cost effects of faster endovascular treatment for large vessel ischemic stroke patients in the Netherlands

BACKGROUND: The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. METHODS: A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. RESULTS: EVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. CONCLUSION: One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs

Cost-effectiveness of CT perfusion for the detection of large vessel occlusion acute ischemic stroke followed by endovascular treatment:a model-based health economic evaluation study

Objectives:CT perfusion (CTP) has been suggested to increase the rate of large vessel occlusion (LVO) detection in patients suspected of acute ischemic stroke (AIS) if used in addition to a standard diagnostic imaging regime of CT angiography (CTA) and non-contrast CT (NCCT). The aim of this study was to estimate the costs and health effects of additional CTP for endovascular treatment (EVT)–eligible occlusion detection using model-based analyses. Methods: In this Dutch, nationwide retrospective cohort study with model-based health economic evaluation, data from 701 EVT-treated patients with available CTP results were included (January 2018–March 2022; trialregister.nl:NL7974). We compared a cohort undergoing NCCT, CTA, and CTP (NCCT + CTA + CTP) with a generated counterfactual where NCCT and CTA (NCCT + CTA) was used for LVO detection. The NCCT + CTA strategy was simulated using diagnostic accuracy values and EVT effects from the literature. A Markov model was used to simulate 10-year follow-up. We adopted a healthcare payer perspective for costs in euros and health gains in quality-adjusted life years (QALYs). The primary outcome was the net monetary benefit (NMB) at a willingness to pay of €80,000; secondary outcomes were the difference between LVO detection strategies in QALYs (ΔQALY) and costs (ΔCosts) per LVO patient. Results: We included 701 patients (median age: 72, IQR: [62–81]) years). Per LVO patient, CTP-based occlusion detection resulted in cost savings (ΔCosts median: € − 2671, IQR: [€ − 4721; € − 731]), a health gain (ΔQALY median: 0.073, IQR: [0.044; 0.104]), and a positive NMB (median: €8436, IQR: [5565; 11,876]) per LVO patient. Conclusion: CTP-based screening of suspected stroke patients for an endovascular treatment eligible large vessel occlusion was cost-effective. Clinical relevance statement.: Although CTP-based patient selection for endovascular treatment has been recently suggested to result in worse patient outcomes after ischemic stroke, an alternative CTP-based screening for endovascular treatable occlusions is cost-effective. Key Points: • Using CT perfusion to detect an endovascular treatment-eligible occlusions resulted in a health gain and cost savings during 10 years of follow-up. • Depending on the screening costs related to the number of patients needed to image with CT perfusion, cost savings could be considerable (median: € − 3857, IQR: [€ − 5907; € − 1916] per patient). • As the gain in quality adjusted life years was most affected by the sensitivity of CT perfusion-based occlusion detection, additional studies for the diagnostic accuracy of CT perfusion for occlusion detection are required.</p

Value of Automatically Derived Full Thrombus Characteristics:An Explorative Study of Their Associations with Outcomes in Ischemic Stroke Patients

(1) Background: For acute ischemic strokes caused by large vessel occlusion, manually assessed thrombus volume and perviousness have been associated with treatment outcomes. However, the manual assessment of these characteristics is time-consuming and subject to inter-observer bias. Alternatively, a recently introduced fully automated deep learning-based algorithm can be used to consistently estimate full thrombus characteristics. Here, we exploratively assess the value of these novel biomarkers in terms of their association with stroke outcomes. (2) Methods: We studied two applications of automated full thrombus characterization as follows: one in a randomized trial, MR CLEAN-NO IV (n = 314), and another in a Dutch nationwide registry, MR CLEAN Registry (n = 1839). We used an automatic pipeline to determine the thrombus volume, perviousness, density, and heterogeneity. We assessed their relationship with the functional outcome defined as the modified Rankin Scale (mRS) at 90 days and two technical success measures as follows: successful final reperfusion, which is defined as an eTICI score of 2b-3, and successful first-pass reperfusion (FPS). (3) Results: Higher perviousness was significantly related to a better mRS in both MR CLEAN-NO IV and the MR CLEAN Registry. A lower thrombus volume and lower heterogeneity were only significantly related to better mRS scores in the MR CLEAN Registry. Only lower thrombus heterogeneity was significantly related to technical success; it was significantly related to a higher chance of FPS in the MR CLEAN-NO IV trial (OR = 0.55, 95% CI: 0.31–0.98) and successful reperfusion in the MR CLEAN Registry (OR = 0.88, 95% CI: 0.78–0.99). (4) Conclusions: Thrombus characteristics derived from automatic entire thrombus segmentations are significantly related to stroke outcomes.</p