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OBJECTIVE: To investigate if cerebroplacental ratio (CPR) adds to the predictive value of umbilical artery pulsatility index (UA PI) alone - standard of practice - for adverse perinatal outcome in singleton pregnancies. DESIGN AND SETTING: Meta-analysis based on individual participant data (IPD). POPULATION OR SAMPLE: Ten centres provided 17 data sets for 21 661 participants, 18 731 of which could be included. Sample sizes per data set ranged from 207 to 9215 individuals. Patient populations varied from uncomplicated to complicated pregnancies. METHODS: In a collaborative, pooled analysis, we compared the prognostic value of combining CPR with UA PI, versus UA PI only and CPR only, with a one-stage IPD approach. After multiple imputation of missing values, we used multilevel multivariable logistic regression to develop prediction models. We evaluated the classification performance of all models with receiver operating characteristics analysis. We performed subgroup analyses according to gestational age, birthweight centile and estimated fetal weight centile. MAIN OUTCOME MEASURES: Composite adverse perinatal outcome, defined as perinatal death, caesarean section for fetal distress or neonatal unit admission. RESULTS: Adverse outcomes occurred in 3423 (18%) participants. The model with UA PI alone resulted in an area under the curve (AUC) of 0.775 (95% CI 0.709-0.828) and with CPR alone in an AUC of 0.778 (95% CI 0.715-0.831). Addition of CPR to the UA PI model resulted in an increase in the AUC of 0.003 points (0.778, 95% CI 0.714-0.831). These results were consistent across all subgroups. CONCLUSIONS: Cerebroplacental ratio added no predictive value for adverse perinatal outcome beyond UA PI, when assessing singleton pregnancies, irrespective of gestational age or fetal size. TWEETABLE ABSTRACT: Doppler measurement of cerebroplacental ratio in clinical practice has limited added predictive value to umbilical artery alone.

The ultrafast concentration of electromagnetic energy in nanoscale volumes is one of the key features of optical nanoantennas illuminated at their surface plasmon resonances. Here, we drive the insulator to metal phase transition in vanadium dioxide (VO2) using a laser-induced pumping effect obtained by positioning a single gold nanoantenna in proximity to a VO2 thermochromic material. We explore how the geometry of the single nanoantenna affects the size and permittivity of the nanometer-scale VO2 regions featuring phase transition under different pumping conditions. The results reveal that a higher VO2 phase transition effect is obtained for pumping of the longitudinal or transversal localized surface plasmon depending on the antenna length. This characterization is of paramount importance since the single nanoantennas are the building blocks of many plasmonic nanosystems. Finally, we demonstrate the picosecond dynamics of the VO2 phase transition characterizing this system, useful for the realization of fast nano-switches. Our work shows that it is possible to miniaturize the hybrid plasmonic-VO2 system down to the single-antenna level, still maintaining a controllable behavior, fast picosecond dynamics, and the features characterizing its optical and thermal response.

BACKGROUND: The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs.MATERIALS AND METHODS: Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan-Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis.RESULTS: Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million.CONCLUSION: Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma.

BACKGROUND: The introduction of adjuvant systemic treatment has significantly improved recurrence-free survival in patients with resectable high-risk melanoma. Adjuvant treatment with immune checkpoint inhibitors and targeted therapy, however, substantially impacts health care budgets, while the number of patients with melanoma who are treated in the adjuvant setting is still increasing. To evaluate the socioeconomic impact of the three adjuvant treatments, a cost-effectiveness analysis (CEA) was carried out.MATERIALS AND METHODS: Data were obtained from the three pivotal registration phase III clinical trials on the adjuvant treatment of patients with resected high-risk stage III in melanoma (KEYNOTE-054, CheckMate 238, and COMBI-AD). For this CEA, a Markov model with three health states (no evidence of disease, recurrent/progressive disease, and death) was applied. From a societal perspective, different adjuvant strategies were compared according to total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. To evaluate model uncertainty, sensitivity analyses (deterministic and probabilistic) were carried out.RESULTS: In the adjuvant setting, total costs (per patient) were €168 826 for nivolumab, €194 529 for pembrolizumab, and €211 110 for dabrafenib-trametinib. These costs were mainly determined by drug acquisition costs, whereas routine surveillance costs varied from €126 096 to €134 945. Compared with routine surveillance, LYs improved by approximately 1.41 for all therapies and QALYs improved by 2.02 for immune checkpoint inhibitors and 2.03 for targeted therapy. This resulted in incremental cost-effectiveness ratios of €21 153 (nivolumab), €33 878 (pembrolizumab), and €37 520 (dabrafenib-trametinib) per QALY gained.CONCLUSIONS: This CEA compared the three EMA-approved adjuvant systemic therapies for resected stage III melanoma. Adjuvant treatment with nivolumab was the most cost-effec

Background: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. Methods: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015–2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. Results: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015–2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). Conclusion: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

Background: Persons with multiple sclerosis (MS) take their treatment via pills, injections or infusions. A novel mode of disease-modifying treatment administration, an implantable device, is under development. This study determined MS patient preferences for three modes of first-line treatment administration (implant, pills, injectables), and trade-offs regarding treatment characteristics. Methods: A survey including a discrete choice experiment was conducted among MS patients in the Netherlands, France, and the United Kingdom. Respondents had to repeatedly choose between various treatment scenarios with four treatment characteristics: risk of relapse, reduction of disease progression, risk of side effects and mode of administration. Data was analysed using a panel latent class logit model. Results: Based on the preferences of 753 MS patients (response rate 7%: 753/11202), two latent classes were identified (class probability of 74% vs 26%). Persons with relapsing-remitting MS and who administered medication via injections generally preferred any treatment over no treatment. Patients who could walk without an aid were more likely to prefer no treatment. Reducing disease progression was the most important treatment characteristic class 1. Mode of administration was the most important characteristic in class 2. Patients were willing to accept an increase in risk of relapse and disease progression to get their treatment via an implant rather than injections. Predicted uptake was the highest for the implant, followed by pills, injections, and no treatment. Conclusion: We found that a drug-delivery implant could be a potential addition to the MS treatment landscape: MS patients are willing to trade-off risk of relapse and disease progression for an implant, and predicted uptake for an implant is relatively high.

Klimaatverandering, verdroging en verzuring hebben grote effecten op de Nederlandse bossen, zeker op de zandgronden. Een deel van deze bossen is bovendien kwetsbaar door een eenzijdige boomsoortensamenstelling. Daar komt bij dat verschillende veel voorkomende boom-soorten, zoals fijnspar, gewone es en lariks onder druk staan door klimaatverandering en ziekten. Nieuwe of minder gangbare boomsoorten kunnen helpen om de menging te vergroten en daarmee ook de veerkracht van de Nederlandse bossen. In opdracht van het ministerie van LNV brachten wij vijf potentieel interessante nieuwe en/of minder gangbare boomsoorten in beeld voor de zandgronden.