Considering multifetal pregnancy reduction in triplet pregnancies: do we forget the emotional impact on fathers? A qualitative study from The Netherlands.

STUDY QUESTION: What factors influence the decision-making process of fathers regarding multifetal pregnancy reduction or maintaining a triplet pregnancy, and how do these decisions impact their psychological well-being? SUMMARY ANSWER: For fathers, the emotional impact of multifetal pregnancy reduction or caring for triplets is extensive and requires careful consideration. WHAT IS KNOWN ALREADY: Multifetal pregnancy reduction is a medical procedure with the purpose to reduce the number of fetuses to improve chances of a healthy outcome for both the remaining fetus(es) and the mother, either for medical reasons or social considerations. Aspects of the decision whether to perform multifetal pregnancy reduction have been rarely investigated, and the impact on fathers is unknown. STUDY DESIGN, SIZE, DURATION: Qualitative study with semi-structured interviews between October 2021 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fathers either after multifetal pregnancy reduction from triplet to twin or singleton pregnancy or ongoing triplet pregnancies 1-6 years after the decision were included. The interview schedule was designed to explore key aspects related to (i) the decision-making process whether to perform multifetal pregnancy reduction and (ii) the emotional aspects and psychological impact of the decision. Thematic analysis was used to identify patterns and trends in the father's data. The process involved familiarization with the data, defining and naming themes, and producing a final report. This study was a collaboration between a regional secondary hospital (OLVG) and a tertiary care hospital (Amsterdam University Medical Center, Amsterdam UMC), both situated in Amsterdam, The Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: Data saturation was achieved after 12 interviews. Five main themes were identified: (i) initial responses and emotional complexity, (ii) experiencing disparities in counselling quality and post-decision care, (iii) personal influences on the decision journey, (iv) navigating parenthood: choices, challenges, and emotional adaptation, and (v) shared wisdom and lessons. For fathers, the decision whether to maintain or reduce a triplet pregnancy is complex, in which medical, psychological but mainly social factors play an important role. In terms of psychological consequences after the decision, this study found that fathers after multifetal pregnancy reduction often struggled with difficult emotions towards the decision; some expressed feelings of doubt or regret and were still processing these emotions. Several fathers after an ongoing triplet had experienced a period of severe stress in the first years after the pregnancy, with major consequences for their mental health. Help in emotional processing was not offered to any of the fathers after the decision or birth. LIMITATION, REASONS FOR CAUTION: While our study focuses on the multifetal pregnancy reduction process in the Amsterdam region, we recognize the importance of further investigation into how this process may vary across different regions in The Netherlands and internationally. We acknowledge the potential of selection bias, as fathers with more positive experiences might have been more willing to participate. Caution is needed in interpreting the role of the mother in the recruitment process. Additionally, the time span of 1-6 years between the decision and the interviews may have influenced emotional processing and introduced potential reporting bias. WIDER IMPLICATIONS OF THE FINDINGS: The emotional impact of multifetal pregnancy reduction or caring for triplets is significant, emphasizing the need for awareness among caregivers regarding the emotional challenges faced by fathers. A guided trajectory might optimize the decision-making and primarily facilitate the provision of appropriate care thereafter to optimize outcomes around decisions with potential traumatic implications. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Screening for adolescent idiopathic scoliosis is more accurate when performed by healthcare professionals compared to untrained parents: a diagnostic accuracy study.

BACKGROUND: Many countries ended their professional scoliosis screening due to ongoing controversies. Discontinuation resulted in a shift of screening responsibility from trained healthcare professionals to untrained parents. PURPOSE: To compare the diagnostic accuracy of picture-based scoliosis screening between parents and healthcare professionals. METHODS: In this cross-sectional diagnostic accuracy study, parents and healthcare professionals assessed pictures of 28 children (20 AIS & 8 non-scoliosis). Each child had two photographs (standing position & full-flexion during forward-bending test) that were presented simultaneously. Lumbar and thoracic curves were represented with a range in severity (10 to > 40°). The assessors had to answer whether they detected an abnormality that ought to be referred to a specialist. Measures of accuracy were calculated for both groups and various curve severities. RESULTS: All pictures were assessed by 101 parents and 122 healthcare professionals. The sensitivity for detecting scoliosis was significantly lower in untrained parents (63.8%, [95% CI: 61.7-65.9%]) compared to healthcare professionals (73.4%, [95% CI: 71.6-75.2%]; p < 0.001), while the specificity was not significantly different (63.6%, [95% CI: 60.2-66.9%] vs. 65.3%, [95% CI: 62.2-68.3%]; p = 0.49). Healthcare professionals consistently recognized the gibbus as a warning sign when referring patients, while untrained parents highlighted various regions, including the spine, gibbus and scapula regions. CONCLUSION: The sensitivity of screening for scoliosis was significantly lower when it was performed by parents, while the false-positive rate was similar to healthcare professionals. The window of opportunity for conservative treatment may be missed when parents rather than professionals are responsible for screening.

Serum Levels of α-Fetoprotein Increased More Than 10 Years Before Detection of Hepatocellular Carcinoma.

BACKGROUND & AIMS: Ultrasound (US)-based screening has been recommended for patients with an increased risk of hepatocellular carcinoma (HCC). US analysis, however, is limited in patients who are obese or have small tumors. The addition of serum level of α-fetoprotein (AFP) measurements to US analysis can increase detection of HCC. We analyzed data from patients with chronic liver disease, collected over 15 years in an HCC surveillance program, to develop a model to assess risk of HCC. METHODS: We collected data from 3450 patients with chronic liver disease undergoing US surveillance in Japan from March 1998 through April 2014, and followed them up for a median of 8.83 years. We performed longitudinal discriminant analysis of serial AFP measurements (median number of observations/patient, 56; approximately every 3 months) to develop a model to determine the risk of HCC. We validated the model using data from 2 cohorts of patients with chronic liver disease in Japan (404 and 2754 patients) and 1 cohort in Scotland (1596 patients). RESULTS: HCC was detected in 413 patients (median tumor diameter, 1.8 cm), during a median follow-up time of 6.60 years. In the development data set, the model identified patients who developed HCC with an area under the curve of 0.78; it correctly identified 74.3% of patients who did develop HCC, and 72.9% of patients who did not. Overall, 73.1% of patients were classified correctly. The model could be used to assign patients to a high-risk group (27.5 HCCs/1000 patient-years) vs a low-risk group (4.9 HCCs/1000 patient-years). A similar performance was observed when the model was used to assess patients with cirrhosis. Analysis of the validation cohorts produced similar results. CONCLUSIONS: We developed and validated a model to identify patients with chronic liver disease who are at risk for HCC based on change in serum AFP level over time. The model could be used to assign patients to high-risk vs low-risk groups, and might be used to select patients for surveillance.

The cost-effectiveness of dapagliflozin compared to DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in the Netherlands.

AIM: When glycaemic control for people with type 2 diabetes is not achieved with metformin and sulfonylurea alone, adding another oral anti-diabetes drug, such as a sodium-glucose co-transporter 2 (SGLT2) or dipeptidyl peptidase-4 (DPP-4) inhibitor, is an alternative to starting insulin. The aim of this study is to determine the cost-effectiveness of dapagliflozin (an SGLT2 inhibitor) compared with DPP-4 inhibitors when added to metformin and sulfonylurea in people with type 2 diabetes in the Netherlands. METHODS: A cost-utility analysis is performed using the Cardiff diabetes model, a fixed-time increment stochastic simulation model informed by 'United Kingdom Prospective Diabetes Study 68' risk equations. The base-case analysis uses a 40-year time horizon, a Dutch societal perspective and differential discounting (4% for costs, 1.5% for effects). Inputs are obtained from the literature and Dutch price lists. Univariate and probabilistic sensitivity analysis are performed. RESULTS: Dapagliflozin is dominant compared with DPP-4 inhibitors, resulting in a €990 cost saving and a 0.28 quality-adjusted life year gain over 40 years. Cost savings are associated mainly with treatment costs and a reduced incidence of micro- and macrovascular complications, among others nephropathy, myocardial infarction and stroke. Results are robust to changes in input parameters. CONCLUSIONS: Dapagliflozin is a cost-saving alternative to DPP-4 inhibitors when added to metformin and sulfonylurea. The incidence of micro- and macrovascular complications is lower for people treated with dapagliflozin. Uncertainty around this outcome is low.

Direct observation of surface charge redistribution in active nanoscale conducting channels by Kelvin Probe Force Microscopy.

Surface-exposed uniformly doped silicon-on-insulator channels are fabricated to evaluate the accuracy of Kelvin Probe Force Microscopy (KPFM) measured surface potential and reveals the role of surface charge on the exposed channel operated in the ambient environment. First, the quality of the potential profile probed in the vacuum environment is assessed by the consistency of converted resistivity from KPFM result to the resistivity extracted by the other three methods. Second, in contrast to the simulated and vacuum surface potential profile and image, the ambient surface potential is bent excessively at the terminals of the channel. The excessive bending can be explained by the movement of surface charge under the drive of geometry induced strong local electric field from the channel and results in non-uniform distribution. The dynamic movement of surface charges is proved by the observation of time-dependent potential drift in the ambient measurement. The result suggests the surface charge effect should be taken into account of the measurement of the surface potential in the ambient environment and the design of charge sensitive devices whose surfaces are exposed to air or in ambient conditions in their operation.

Progesterone for prevention of preterm birth in women with short cervical length: 2-year infant outcomes.

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

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.

Strongly coupled evenly divided disks: a new compact and tunable platform for plasmonic Fano resonances.

Plasmonic artificial molecules are promising platforms for linear and nonlinear optical modulation at various regimes including the visible, infrared and terahertz bands. Fano resonances in plasmonic artificial structures are widely used for controlling spectral lineshapes and tailoring of near-field and far-field optical response. Generation of a strong Fano resonance usually relies on strong plasmon coupling in densely packed plasmonic structures. Challenges in reproducible fabrication using conventional lithography significantly hinders the exploration of novel plasmonic nanostructures for strong Fano resonance. In this work, we propose a new class of plasmonic molecules with symmetric structure for Fano resonances, named evenly divided disk, which shows a strong Fano resonance due to the interference between a subradiant anti-bonding mode and a superradiant bonding mode. We successfully fabricated evenly divided disk structures with high reproducibility and with sub-20 nm gaps, using our recently developed sketch and peel lithography technique. The experimental spectra agree well with the calculated response, indicating the robustness of the Fano resonance for the evenly divided disk geometry. Control experiments reveal that the strength of the Fano resonance gradually increases when increasing the number of split parts on the disk from three to eight individual segments. The Fano-resonant plasmonic molecules that can also be reliably defined by our unique fabrication approach open up new avenues for application and provide insight into the design of artificial molecules for controlling light-matter interactions.

Towards a 3D GeSbTe phase change memory with integrated selector by non-aqueous electrodeposition.

We have recently reported a new method for the electrodeposition of thin film and nanostructured phase change memory (PCM) devices from a single, highly tuneable, non-aqueous electrolyte. The quality of the material was confirmed by phase cycling via electrical pulsed switching of both 100 nm nano-cells and thin film devices. This method potentially allows deposition into extremely small confined cells down to less than 5 nm, 3D lay-outs that require non-line-of-sight techniques, and seamless integration of selector devices. As electrodeposition requires a conducting substrate, the key condition for electronic applications based on this method is the use of patterned metal lines as the working electrode during the electrodeposition process. In this paper, we show the design and fabrication of a 2D passive memory matrix in which the word lines act as the working electrode and nucleation site for the growth of confined cells of Ge-Sb-Te. We will discuss the precursor requirement for deposition from non-aqueous, weakly coordinating solvents, show the transmission electron microscopy analysis of the electrodeposition growth process and elemental distribution in the deposits, and show the fabrication and characterisation of the Ge-Sb-Te memory matrix.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Selecting the optimal position of CDK4/6 inhibitors in hormone receptor-positive advanced breast cancer - the SONIA study: study protocol for a randomized controlled trial.

BACKGROUND: Combining cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with endocrine therapy is an effective strategy to improve progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. There is a lack of comparative data to help clinicians decide if CDK4/6 inhibitors can best be added to first- or second-line endocrine therapy. Improvement in median progression-free survival in first-line studies is larger than in second-line studies, but CDK4/6 inhibitors have not consistently shown to improve overall survival or quality of life. They do come with added toxicity and costs, and many patients have lasting disease remission on endocrine therapy alone. No subgroup has been identified to select patients who are most likely to benefit from the addition of CDK4/6 inhibition in any line of treatment. Altogether, these factors make that the optimal strategy for using CDK4/6 inhibitors in clinical practice is unknown. METHODS: The SONIA study is an investigator-initiated, multicenter, randomized phase III study in patients with HR+/HER2-negative advanced breast cancer. Patients are randomly assigned to receive either strategy A (first-line treatment with a non-steroidal aromatase inhibitor combined with CDK4/6 inhibition, followed on progression by fulvestrant) or strategy B (first-line treatment with a non-steroidal aromatase inhibitor, followed on progression by fulvestrant combined with CDK4/6 inhibition). The primary objective is to test whether strategy A is more effective than strategy B. The primary endpoint is time from randomization to second objective progression (PFS2). Secondary endpoints include overall survival, safety, quality of life, and cost-effectiveness. Five-hundred seventy-four events yield 89% power to show that strategy A has statistically significant, clinically meaningful superior PFS2 (according to ESMO-MCBS) in a log-rank test at the two-sided 95% confidence level. Given an accrual period of 42 months and an additional 18 months follow-up, inclusion of 1050 evaluable patients is required. DISCUSSION: This study design represents daily clinical practice, and the results will aid clinicians in deciding when adding CDK4/6 inhibitors to endocrine therapy will benefit their patients most. Additional biomarker analyses may help to optimize patient selection. TRIAL REGISTRATION: http://clinicaltrials.gov: NCT03425838 (8 February 2018). EudraCT-number: 2017-002334-23 (29 September 2017).

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

Prognostic accuracy of cerebroplacental ratio and middle cerebral artery Doppler for adverse perinatal outcome: systematic review and meta-analysis.

OBJECTIVE: Doppler ultrasonographic assessment of the cerebroplacental ratio (CPR) and middle cerebral artery (MCA) is widely used as an adjunct to umbilical artery (UA) Doppler to identify fetuses at risk of adverse perinatal outcome. However, reported estimates of its accuracy vary considerably. The aim of this study was to review systematically the prognostic accuracies of CPR and MCA Doppler in predicting adverse perinatal outcome, and to compare these with UA Doppler, in order to identify whether CPR and MCA Doppler evaluation are of added value to UA Doppler. METHODS: PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, from inception to June 2016, for studies on the prognostic accuracy of UA Doppler compared with CPR and/or MCA Doppler in the prediction of adverse perinatal outcome in women with a singleton pregnancy of any risk profile. Risk of bias and concerns about applicability were assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) tool. Meta-analysis was performed for multiple adverse perinatal outcomes. Using hierarchal summary receiver-operating characteristics meta-regression models, the prognostic accuracy of CPR vs MCA Doppler was compared indirectly, and CPR and MCA Doppler vs UA Doppler compared directly. RESULTS: The search identified 4693 articles, of which 128 studies (involving 47 748 women) were included. Risk of bias or suboptimal reporting was detected in 120/128 studies (94%) and substantial heterogeneity was found, which limited subgroup analyses for fetal growth and gestational age. A large variation was observed in reported sensitivities and specificities, and in thresholds used. CPR outperformed UA Doppler in the prediction of composite adverse outcome (as defined in the included studies) (P < 0.001) and emergency delivery for fetal distress (P = 0.003), but was comparable to UA Doppler for the other outcomes. MCA Doppler performed significantly worse than did UA Doppler in the prediction of low Apgar score (P = 0.017) and emergency delivery for fetal distress (P = 0.034). CPR outperformed MCA Doppler in the prediction of composite adverse outcome (P < 0.001) and emergency delivery for fetal distress (P = 0.013). CONCLUSION: Calculating the CPR with MCA Doppler can add value to UA Doppler assessment in the prediction of adverse perinatal outcome in women with a singleton pregnancy. However, it is unclear to which subgroup of pregnant women this applies. The effectiveness of the CPR in guiding clinical management needs to be evaluated in clinical trials. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Health-related quality of life and its determinants in patients with metastatic renal cell carcinoma.

PURPOSE: Based on improvements of progression-free survival (PFS), new agents for metastatic renal cell carcinoma (mRCC) have been approved. It is assumed that one of the benefits is a delay in health-related quality of life (HRQoL) deterioration as a result of a delay in progression of disease. However, little data are available supporting this relationship. This study aims to provide insight into the most important determinants of HRQoL (including progression of disease) of patients with mRCC. METHODS: A patient registry (PERCEPTION) was created to evaluate treatment of patients with (m)RCC in the Netherlands. HRQoL was measured, using the EORTC QLQ-C30 and EQ-5D-5L, every 3 months in the first year of participation in the study, and every 6 months in the second year. Participation started as soon as possible following a diagnosis of (m)RCC. Random effects models were used to study associations between HRQoL and patient and disease characteristics, symptoms and treatment. RESULTS: Eighty-seven patients with mRCC completed 304 questionnaires. The average EORTC QLQ-C30 global health status was 69 (SD, 19) before progression and 61 (SD, 22) after progression of disease. Similarly, the average EQ-5D utility was 0.75 (SD, 0.19) before progression and 0.66 (SD, 0.30) after progression of disease. The presence of fatigue, pain, dyspnoea, and the application of radiotherapy were associated with significantly lower EQ-5D utilities. CONCLUSIONS: Key drivers for reduced HRQoL in mRCC are disease symptoms. Since symptoms increase with progression of disease, targeted therapies that increase PFS are expected to postpone reductions in HRQoL in mRCC.

Telemonitoring to improve nutritional status in community-dwelling elderly: design and methods for process and effect evaluation of a non-randomized controlled trial.

BACKGROUND: A good nutritional status is key for maintaining health and quality of life in older adults. In the Netherlands, 11 to 35% of the community-dwelling elderly are undernourished. Undernutrition or the risk of it should be signalled as soon as possible to be able to intervene at an early stage. However, in the context of an ageing population health care resources are scarce, evoking interest in health enabling technologies such as telemonitoring. This article describes the design of an intervention study focussing at telemonitoring and improving nutritional status of community-dwelling elderly. METHODS: The PhysioDom Home Dietary Intake Monitoring intervention was evaluated using a parallel arm pre-test post-test design including 215 Dutch community-dwelling elderly aged > 65 years. The six-month intervention included nutritional telemonitoring, television messages, and dietary advice by a nurse or a dietician. The control group received usual care. Measurements were performed at baseline, after 4.5 months, and at the end of the study, and included the primary outcome nutritional status and secondary outcomes behavioural determinants, diet quality, appetite, body weight, physical activity, physical functioning, and quality of life. Furthermore, a process evaluation was conducted to provide insight into intervention delivery, feasibility, and acceptability. DISCUSSION: This study will improve insight into feasibility and effectiveness of telemonitoring of nutritional parameters in community-dwelling elderly. This will provide relevant insights for health care professionals, researchers, and policy makers. TRIAL REGISTRATION: The study was retrospectively registered at Clinical-Trials.gov (identifier NCT03240094 ) since August 3, 2017.

The impact of protein quantity during energy restriction on genome-wide gene expression in adipose tissue of obese humans.

BACKGROUND: Overweight and obesity is a growing health problem worldwide. The most effective strategy to reduce weight is energy restriction (ER). ER has been shown to be beneficial in disease prevention and it reduces chronic inflammation. Recent studies suggest that reducing the protein quantity of a diet contributes to the beneficial effects by ER. The organ most extensively affected during ER is white adipose tissue (WAT). OBJECTIVE: The first objective was to assess changes in gene expression between a high-protein diet and a normal protein diet during ER. Second, the total effect of ER on changes in gene expression in WAT was assessed. METHODS: In a parallel double-blinded controlled study, overweight older participants adhered to a 25% ER diet, either combined with high-protein intake (HP-ER, 1.7 g kg-1 per day), or with normal protein intake (NP-ER, 0.9 g kg-1 per day) for 12 weeks. From 10 HP-ER participants and 12 NP-ER participants subcutaneous WAT biopsies were collected before and after the diet intervention. Adipose tissue was used to isolate total RNA and to evaluate whole-genome gene expression changes upon a HP-ER and NP-ER diet. RESULTS: A different gene expression response between HP-ER and NP-ER was observed for 530 genes. After NP-ER, a downregulation in expression of genes linked to immune cell infiltration, adaptive immune response and inflammasome was found, whereas no such effect was found after HP-ER. HP-ER resulted in upregulation in expression of genes linked to cell cycle, GPCR signalling, olfactory signalling and nitrogen metabolism. Upon 25% ER, gene sets related to energy metabolism and immune response were decreased. CONCLUSIONS: Based on gene expression changes, we concluded that consumption of normal protein quantity compared with high-protein quantity during ER has a more beneficial effect on inflammation-related gene expression in WAT.

Nanoscale modeling of electro-plasmonic tunable devices for modulators and metasurfaces.

The interest in plasmonic electro-optical modulators with nanoscale footprint and ultrafast low-energy performance has generated a demand for precise multiphysics modeling of the electrical and optical properties of plasmonic nanostructures. We perform combined simulations that account for the interaction of highly confined nearfields with charge accumulation and depletion on the nanoscale. Validation of our numerical model is done by comparison to a recently published reflective meta-absorber. The simulations show excellent agreement to the experimental mid-infrared data. We then use our model to propose electro-optical modulation of the extinction cross-section of a gold dimer nanoantenna at the telecom wavelength of 1550 nm. An ITO gap-loaded nanoantenna structure allows us to achieve a normalized modulation of 45% at 1550 nm, where the gap-load design circumvents resonance pinning of the structure. Resonance pinning limits the performance of simplistic designs such as a uniform coating of the nanoantenna with a sheet of indium tin oxide, which we also present for comparison. This large value is reached by a reduction of the capacitive coupling of the antenna arms, which breaks the necessity of a large volume overlap between the charge distribution and the optical nearfield. A parameter exploration shows a weak reliance on the exact device dimensions, as long as strong coupling inside the antenna gap is ensured. These results open the way for a new method in electro-optical tuning of plasmonic structures and can readily be adapted to plasmonic waveguides, metasurfaces and other electro-optical modulators.

High-fidelity phase and amplitude control of phase-only computer generated holograms using conjugate gradient minimisation.

We demonstrate simultaneous control of both the phase and amplitude of light using a conjugate gradient minimisation-based hologram calculation technique and a single phase-only spatial light modulator (SLM). A cost function, which incorporates the inner product of the light field with a chosen target field within a defined measure region, is efficiently minimised to create high fidelity patterns in the Fourier plane of the SLM. A fidelity of F = 0.999997 is achieved for a pattern resembling an LG10 mode with a calculated light-usage efficiency of 41.5%. Possible applications of our method in optical trapping and ultracold atoms are presented and we show uncorrected experimental realisation of our patterns with F = 0.97 and 7.8% light efficiency.

Maternal and neonatal outcomes in women with severe early onset pre-eclampsia before 26 weeks of gestation, a case series.

OBJECTIVE: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation. DESIGN: Nationwide case series. SETTING: All Dutch tertiary perinatal care centres. POPULATION: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014. METHODS: Women were identified through computerised hospital databases. Data were collected from medical records. MAIN OUTCOME MEASURES: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival). RESULTS: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days. CONCLUSIONS: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling. TWEETABLE ABSTRACT: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival.

Influence of cut-off value on prevalence of short cervical length.

OBJECTIVE: To assess the distribution of cervical length (CL) in a large cohort of asymptomatic low-risk women with singleton pregnancy and no previous preterm birth and to explain the low prevalence of short CL ≤ 30 mm in this cohort. METHODS: This was a secondary analysis of a multicenter cohort study with an embedded randomized controlled trial (Triple P trial; NTR-2078) on the prevention of preterm birth with progesterone. In the cohort study, CL was measured in asymptomatic low-risk women with singleton pregnancy to investigate its predictive capacity to identify those at increased risk for preterm birth. A short CL was defined by a cut-off value of ≤ 30 mm, based on existing literature. Women with a short CL were subsequently included in a randomized controlled trial evaluating the effect of progesterone, compared with placebo, on preterm birth. In total, 57 centers and 20 234 women participated in the study. Normal distributions for CL were simulated based on the mean and SD of the original data. The distribution of CL was assessed for each individual center and measurements were compared between levels of care: primary (29 ultrasound centers), secondary (21 general hospitals) and tertiary (seven university medical centers) care institutions. Comparison was also performed between centers with low, intermediate and high volume of CL measurements. CL distributions before (n = 12 284 women) and after (n = 7950 women) a national symposium, at which the prevalence of short CL measurements was addressed publicly, were analyzed. RESULTS: Between November 2009 and August 2013, 20 234 women had CL measurements, of whom 367 (1.8%) had a short CL. Mean ± SD CL was 44.2 ± 7.8 mm. A 'dip' in the distribution of CL measurements between 20 and 30 mm was observed, defined by a ratio of < 50% when comparing the number of measurements in observed and simulated normal distributions. The dip was present in 89% of participating centers. All centers showed a dip in the distribution of measurements ≤ 30 mm when analyzed according to the level of care and volume of measurements. A significant difference was found when comparing the distribution before and after publicly addressing the low prevalence of short CL (1.7% vs 2.0% of measurements were ≤ 30 mm, respectively; P < 0.001). CONCLUSIONS: A cut-off value of 30 mm for CL was used to include women in a randomized clinical trial that was embedded in a cohort study. We suggest that the use of a predefined cut-off value for a short cervix influences the distribution of the CL measurements. Since the measurement is not blinded, preference of assessors for the control or intervention arms may have introduced selection bias. This might have resulted in fewer measurements around the cut-off value. Other trials using similar designs could benefit from this observation and take precautions to avoid selection bias. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.