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Introduction: The Netherlands Study of Depression and Anxiety (NESDA, www.nesda.nl) is a longitudinal, multi-site, naturalistic, case-control cohort study set up to examine the etiology, course and consequences of depressive and anxiety disorders. This paper presents a cohort profile of NESDA.Methods and Results: The NESDA sample recruited initially 2329 persons with a remitted or current DSM-IV based depressive (major depressive disorder, dysthymia) and/or anxiety disorder (panic disorder, social phobia, agoraphobia, generalized anxiety disorder), 367 of their siblings and 652 healthy controls, yielding a total of 3348 participants. Half-day face-to-face assessments of participants started in 2004 and since then have been repeated six times over a period of 9 years. A 13-year follow-up assessment is ongoing, at what time we also recruit offspring of participants. Retention rates are generally high, ranging from 87.1% (after 2 years) to 69.4% (after 9 years). Psychiatric diagnostic interviews have been administered at all face-to-face assessments, as was monitoring of clinical characteristics, psychosocial functioning and somatic health. Assessed etiological factors include e.g. early and current environmental risk factors, psychological vulnerability and resilience factors as well as (neuro)biology through hypothesis-driven biomarker assessments, genome-wide and large-scale '-omics' assessments, and neuroimaging assessments.Limitations: The naturalistic design allows research into course and consequences of affective disorders but is limited in treatment response interpretation.Conclusions: NESDA provides a strong research infrastructure for research into depressive and/or anxiety disorders. Its data have been used for many scientific papers describing either NESDA-based analyses or joint collaborative consortia-projects, and are in principle available to researchers outside the NESDA consortium. [ABSTRACT FROM AUTHOR]

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The objective of the paper is to assess the cost-effectiveness of targeted respiratory syncytial virus (RSV) prophylaxis based on a validated prediction rule with 1-year time horizon in moderately preterm infants compared to no prophylaxis. Data on health care consumption were derived from a randomised clinical trial on wheeze reduction following RSV prophylaxis and a large birth cohort study on risk prediction of RSV hospitalisation. We calculated the incremental cost-effectiveness ratio (ICER) of targeted RSV prophylaxis vs. no prophylaxis per quality-adjusted life year (QALYs) using a societal perspective, including medical and parental costs and effects. Costs and health outcomes were modelled in a decision tree analysis with sensitivity analyses. Targeted RSV prophylaxis in infants with a first-year RSV hospitalisation risk of > 10% resulted in a QALY gain of 0.02 (0.931 vs. 0.929) per patient against additional cost of €472 compared to no prophylaxis (ICER €214,748/QALY). The ICER falls below a threshold of €80,000 per QALY when RSV prophylaxis cost would be lowered from €928 (baseline) to €406 per unit. At a unit cost of €97, RSV prophylaxis would be cost saving.Conclusions: Targeted RSV prophylaxis is not cost-effective in reducing RSV burden of disease in moderately preterm infants, but it can become cost-effective if lower priced biosimilar palivizumab or a vaccine would be available. [ABSTRACT FROM AUTHOR]

Resistance exercise training is effective to counteract the adverse effects of androgen deprivation therapy (ADT) on body composition, muscle mass and leg strength in prostate cancer patients (PCa). However, it is unknown whether these effects can be autonomously maintained after cessation of the supervised program. Sixty‐eight PCa patients on ADT were included. The exercise intervention group (EX, n = 37) performed 20 weeks of supervised resistance exercise training. Thereafter, patients were advised to autonomously continue exercise training. The control group (CON, n = 31) only received usual care. Outcome measures were compared between baseline and after 1 year. Changes during the intervention (baseline vs. 20 weeks) and follow‐up period (20 weeks vs. 1 year) were descriptively explored. In EX, 83% reported to have continued exercise training themselves. After 1 year, fat mass gains were attenuated in EX compared to CON (1.2 ± 2.6 and 2.8 ± 1.9 kg, respectively; time × treatment effect p = 0.032). The fat percentage increased, and lean mass and quadriceps muscle cross‐sectional area decreased over time, with no differences between groups (overall 1.6 ± 2.1%, −0.7 ± 2.3 kg and −2.2 ± 2.9 cm2, respectively; time effects, all p < 0.05). For muscle strength, an increase of ∼5% in EX was observed, significantly different from the ∼10% decrease in CON (p < 0.001). Subsequent analyses showed that the initial exercise training‐obtained gains in lean mass, muscle mass and strength in EX compared to CON, declined during the follow‐up period. In conclusion, PCa patients on ADT are not capable to autonomously maintain the exercise‐obtained gains of a 20‐week supervised training program over a subsequent 1‐year period. Highlights: ADT for prostate cancer results in many side effects, including muscle mass lossA supervised resistance exercise training program can counteract many side effectsAfter cessation of the supervised program, exercise benefits are not effectively preservedMore focus on sustainability of exercise programs during ADT is required [ABSTRACT FROM AUTHOR]

Background: Approximately 20 % of children and adolescents who have sustained mild traumatic brain injuries may experience long-term consequences, including cognitive problems, post-traumatic stress symptoms and reduced load-bearing capacity. The underestimation and belated recognition of these long-term consequences may lead to chronic and disruptive problems, such as participation problems in school and in social relationships. The aim of this study is to examine the level of activities and participation of children and adolescents up to 6 months after a mild traumatic brain injury and to identify possible outcome predictors. Another aim is to investigate the effectiveness of an early psychoeducational intervention and compare the results with those obtained with usual care.Methods/design: This paper presents the Brains Ahead! study design, a randomised controlled trial nested within a multicentre, longitudinal, prospective cohort study. The eligible participants include children and adolescents between 6 and 18 years of age who have experienced a mild traumatic brain injury within the last 2 weeks. The cohort study will include 500 children and adolescents with a mild traumatic brain injury and their caregivers. A subset of 140 participants and their caregivers will be included in the randomised controlled trial. Participants in the randomised controlled trial will be randomly assigned to either the psychoeducational intervention group or the usual care control group. The psychoeducational intervention involves one face-to-face contact and one phone contact with the interventionist, during which the consequences of mild traumatic brain injury and advice for coping with these consequences to prevent long-term problems will be discussed. Information will be provided both verbally and in a booklet. The primary outcome domain is activities and participation, which will be evaluated using the Child and Adolescent Scale of Participation. Participants are evaluated 2 weeks, 3 months and 6 months after the mild traumatic brain injury.Discussion: The results of this study will provide insight into which children with mild traumatic brain injury are at risk for long-term participation problems and may benefit from a psychoeducational intervention.Trial Registration: Netherlands Trial Register identifier NTR5153 . Registered on 17 Apr 2015. [ABSTRACT FROM AUTHOR]

Background: Over 30 % of older patients experience hospitalization-associated disability (HAD) (i.e., loss of independence in Activities of Daily Living (ADLs)) after an acute hospitalization. Despite its high prevalence, the mechanisms that underlie HAD remain elusive. This paper describes the protocol for the Hospital-Associated Disability and impact on daily Life (Hospital-ADL) study, which aims to unravel the potential mechanisms behind HAD from admission to three months post-discharge.Methods/design: The Hospital-ADL study is a multicenter, observational, prospective cohort study aiming to recruit 400 patients aged ≥70 years that are acutely hospitalized at departments of Internal Medicine, Cardiology or Geriatrics, involving six hospitals in the Netherlands. Eligible are patients hospitalized for at least 48 h, without major cognitive impairment (Mini Mental State Examination score ≥15), who have a life expectancy of more than three months, and without disablement in all six ADLs. The study will assess possible cognitive, behavioral, psychosocial, physical, and biological factors of HAD. Data will be collected through: 1] medical and demographical data; 2] personal interviews, which includes assessment of cognitive impairment, behavioral and psychosocial functioning, physical functioning, and health care utilization; 3] physical performance tests, which includes gait speed, hand grip strength, balance, bioelectrical impedance analysis (BIA), and an activity tracker (Fitbit Flex), and; 4] analyses of blood samples to assess inflammatory and metabolic markers. The primary endpoint is additional disabilities in ADLs three months post-hospital discharge compared to ADL function two weeks prior to hospital admission. Secondary outcomes are health care utilization, health-related quality of life (HRQoL), physical performance tests, and mortality. There will be at least five data collection points; within 48 h after admission (H1), at discharge (H3), and at one (P1; home visit), two (P2; by telephone) and three months (P3; home visit) post-discharge. If the patient is admitted for more than five days, additional measurements will be planned during hospitalization on Monday, Wednesday, and Friday (H2).Discussion: The Hospital-ADL study will provide information on cognitive, behavioral, psychosocial, physical, and biological factors associated with HAD and will be collected during and following hospitalization. These data may inform new interventions to prevent or restore hospitalization-associated disability. [ABSTRACT FROM AUTHOR]

Background: The preconception period provides a window of opportunity for interventions aiming to reduce unhealthy lifestyle behaviours and their negative effect on pregnancy outcomes. This study aimed to assess the effectiveness of a locally tailored preconception care (PCC) intervention in a hybrid-II effectiveness implementation design.Methods: A stepped-wedge cluster randomized controlled trial was performed in four Dutch municipalities. The intervention contained a social marketing strategy aiming to improve the uptake (prospective parents) and the provision (healthcare providers) of PCC. Prospective parents participated by administering a questionnaire in early pregnancy recalling their preconceptional behaviours. Experiences of healthcare providers were also evaluated through questionnaires. The composite primary outcome was adherence to at least three out of four preconceptional lifestyle recommendations (early initiation of folic acid supplements, healthy nutrition, no smoking or alcohol use). Secondary outcomes were preconceptional lifestyle behaviour change, (online) reach of the intervention and improved knowledge among healthcare providers.Results: A total of 850 women and 154 men participated in the control phase and 213 women and 39 men in the intervention phase. The composite primary outcome significantly improved among women participating in the municipality where the reach of the intervention was highest (Relative Risk (RR) 1.57 (95% Confidence Interval (CI) 1.11-2.22). Among women, vegetable intake had significantly improved in the intervention phase (RR 1.82 (95%CI 1.14-2.91)). The aimed online reach- and engagement rate of the intervention was achieved most of the time. Also, after the intervention, more healthcare providers were aware of PCC-risk factors (54.5% vs. 47.7%; p = 0.040) and more healthcare providers considered it easier to start a conversation about PCC (75.0% vs. 47.9%; p = 0.030).Conclusion: The intervention showed some tentative positive effects on lifestyle behaviours among prospective parents. Primarily on vegetable intake and the knowledge and competence of healthcare providers. The results of this study contribute to the evidence regarding successfully implementing PCC-interventions to optimize the health of prospective parents and future generations.Trial Registration: Dutch Trial Register: NL7784 (Registered 06/06/2019). [ABSTRACT FROM AUTHOR]

Background: MPS IIIA is a rare, degenerative pediatric genetic disease characterized by symptoms impacting cognition, mobility and behavior; the mean age of death is around 15 years of age. Currently, there are no approved therapies for MPS IIIA.Methods: A two-year, multi-center, prospective, descriptive cohort study was conducted to document the natural history course of MPS IIIA. In the context of this study, semi-structured interviews were performed with parents of children at study entry and one year later. Interview transcripts were analyzed using thematic analysis methods to identity concepts of interest to children and parents, identify what factors impacted parents' burden the most, and develop qualitatively-derived disease severity stages. Children were sorted into these stages according to the symptoms their parents described at the entry interview. This sorting was compared quantitatively to the sorting of children at baseline according to the child's calendar age and their BSID development quotient (DQ).Results: 22 parents in France, Germany, the Netherlands and the UK were interviewed. Children ranged in age from 28 to 105 months (mean 61.4 months). The conceptual models for children's symptoms and impacts and parents' impacts provided a detailed and comprehensive picture of what it is like for children of various ages and their parents to live with MPS IIIA. Four factors were identified as mediating the burden perceived by parents: state support, family support, time since diagnosis, and parent coping strategy. Four disease stages were developed, accounting for both the presence and the severity of MPS IIIA symptoms. The comparison of children's sorting into these stages with the BSID DQ and the child's calendar age showed strong statistical associations.Conclusions: The findings of this qualitative research embedded in a natural history study add to the current understanding of MPS IIIA as a complex disease that impacts every aspect of the lives of children and their families. This study demonstrates the unique potential of mixed methods research in rare diseases to address some of the current limitations of more traditional quantitative approaches by providing an individualized, detailed understanding of the patient experience. [ABSTRACT FROM AUTHOR]

Background Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child's sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs). Methods We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales. Results Our analyses included data from children with a history of iGBS in Denmark (period 1997 -2017; n = 1432) and the Netherlands (2000 -2017; n = 697) and from 21 172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. Boys had a higher risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction = 1.28; 95% confidence interval [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands. Conclusion Boys are at higher risk of NDI ; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex. [ABSTRACT FROM AUTHOR]

Background: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health.Objective: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association.Methods: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor).Results: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk.Conclusion: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms. [ABSTRACT FROM AUTHOR]

Death or myocardial infarction, the most serious clinical consequences of atherosclerosis, often result from plaque rupture at non-flow limiting lesions. Current diagnostic imaging with coronary angiography only detects large plaques that already impinge on the lumen and cannot accurately identify those that have a propensity to cause unheralded events. Accurate evaluation of the composition or of the biomechanical characteristics of plaques with invasive or non-invasive methods, alone or in conjunction with assessment of circulating biomarkers, could help identify high-risk patients, thus providing the rationale for aggressive treatments in order to reduce future clinical events. The IBIS (Integrated Biomarker and Imaging Study) study is a prospective, single-center, non-randomized, observational study conducted in Rotterdam. The aim of the IBIS study is to evaluate both invasive (quantitative coronary angiography, intravascular ultrasound (IVUS) and palpography) and non-invasive (multislice spiral computed tomography) imaging techniques to characterize non-flow limiting coronary lesions. In addition, multiple classical and novel biomarkers will be measured and their levels correlated with the results of the different imaging techniques. A minimum of 85 patients up to a maximum of 120 patients will be included. This paper describes the study protocol and methodological solutions that have been devised for the purpose of comparisons among several imaging modalities. It outlines the analyses that will be performed to compare invasive and non-invasive imaging techniques in conjunction with multiple biomarkers to characterize non-flow limiting subclinical coronary lesions. [ABSTRACT FROM AUTHOR]

Study Question: Does septum resection improve reproductive outcomes in women with a septate uterus?Summary Answer: Hysteroscopic septum resection does not improve reproductive outcomes in women with a septate uterus.What Is Known Already: A septate uterus is a congenital uterine anomaly. Women with a septate uterus are at increased risk of subfertility, pregnancy loss and preterm birth. Hysteroscopic resection of a septum may improve the chance of a live birth in affected women, but this has never been evaluated in randomized clinical trials. We assessed whether septum resection improves reproductive outcomes in women with a septate uterus, wanting to become pregnant.Study Design, Size, Duration: We performed an international, multicentre, open-label, randomized controlled trial in 10 centres in The Netherlands, UK, USA and Iran between October 2010 and September 2018.Participants/materials, Setting, Methods: Women with a septate uterus and a history of subfertility, pregnancy loss or preterm birth were randomly allocated to septum resection or expectant management. The primary outcome was conception leading to live birth within 12 months after randomization, defined as the birth of a living foetus beyond 24 weeks of gestational age. We analysed the data on an intention-to-treat basis and calculated relative risks with 95% CI.Main Results and the Role Of Chance: We randomly assigned 80 women with a septate uterus to septum resection (n = 40) or expectant management (n = 40). We excluded one woman who underwent septum resection from the intention-to-treat analysis, because she withdrew informed consent for the study shortly after randomization. Live birth occurred in 12 of 39 women allocated to septum resection (31%) and in 14 of 40 women allocated to expectant management (35%) (relative risk (RR) 0.88 (95% CI 0.47 to 1.65)). There was one uterine perforation which occurred during surgery (1/39 = 2.6%).Limitations, Reasons For Caution: Although this was a major international trial, the sample size was still limited and recruitment took a long period. Since surgical techniques did not fundamentally change over time, we consider the latter of limited clinical significance.Wider Implications Of the Findings: The trial generated high-level evidence in addition to evidence from a recently published large cohort study. Both studies unequivocally do not reveal any improvements in reproductive outcomes, thereby questioning any rationale behind surgery.Study Funding/competing Interest(s): There was no study funding. M.H.E. reports a patent on a surgical endoscopic cutting device and process for the removal of tissue from a body cavity licensed to Medtronic, outside the scope of the submitted work. H.A.v.V. reports personal fees from Medtronic, outside the submitted work. B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. M.G. reports several research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the scope of the submitted work. The remaining authors have nothing to declare.Trial Registration Number: Dutch trial registry: NTR 1676.Trial Registration Date: 18 February 2009.Date Of First Patient’s Enrolment: 20 October 2010. [ABSTRACT FROM AUTHOR]

Background: Hospital readmission after transplantation is common in kidney transplant recipients (KTRs). In this study, we aim to compare the risk of 3-month hospital readmission after kidney transplantation with different donor types in the overall population and in both young (< 65 years) and elderly (≥65 years) KTRs.Methods: We included all first-time adult KTRs from 2016 to 2018 in the Netherlands Organ Transplant Registry. Multivariable logistic regression models were used to estimate the effect while adjusting for baseline confounders.Results: Among 1917 KTRs, 615 (32.1%) had at least one hospital readmission. Living donor kidney transplantation (LDKT) recipients had an adjusted OR of 0.76 (95%CI, 0.61 to 0.96; p = 0.02) for hospital readmission compared to deceased donor kidney transplantation (DDKT) recipients. In the young and elderly, the adjusted ORs were 0.69 (95%CI, 0.52 to 0.90, p = 0.01) and 0.93 (95%CI, 0.62 to 1.39, p = 0.73) and did not differ significantly from each other (p-value for interaction = 0.38). In DDKT, the risk of hospital readmission is similar between recipients with donation after cardiac death (DCD) or brain death (DBD) and the risk was similar between the young and elderly.Conclusion: A lower risk of post-transplant 3-month hospital readmission was found in recipients after LDKT compared to DDKT, and this benefit of LDKT might be less dominant in elderly patients. In DDKT, having either DCD or DBD donors is not associated with post-transplant 3-month hospital readmission, regardless of age. Tailored patient management is needed for recipients with DDKT and elderly KTRs. [ABSTRACT FROM AUTHOR]

Study Question: Does assisted reproduction, such as ovarian stimulation and/or laboratory procedures, have impact on perinatal outcomes of singleton live births compared to natural conception in couples with unexplained subfertility?Summary Answer: Compared to natural conception, singletons born after intrauterine insemination with ovarian stimulation (IUI-OS) had a lower birthweight, while singletons born after IVF had comparable birthweights, in couples with unexplained subfertility.What Is Known Already: Singletons conceived by assisted reproduction have different perinatal outcomes such as low birthweight and a higher risk of premature birth than naturally conceived singletons. This might be due to the assisted reproduction, such as laboratory procedures or the ovarian stimulation, or to an intrinsic factor in couples with subfertility.Study Design, Size, Duration: We performed a prospective cohort study using the follow-up data of two randomized clinical trials performed in couples with unexplained subfertility. We evaluated perinatal outcomes of 472 live birth singletons conceived after assisted reproduction or after natural conception within the time horizon of the studies.Participants/materials, Setting, Methods: To assess the possible impact of ovarian stimulation we compared the singletons conceived after IUI with FSH or clomiphene citrate (CC) and IVF in a modified natural cycle (IVF-MNC) or standard IVF with single embryo transfer (IVF-SET) to naturally conceived singletons in the same cohorts. To further look into the possible effect of the laboratory procedures, we put both IUI and IVF groups together into IUI-OS and IVF and compared both to singletons born after natural conception. We only included singletons conceived after fresh embryo transfers. The main outcome was birthweight presented as absolute weight in grams and gestational age- and gender-adjusted percentiles. We calculated differences in birthweight using regression analyses adjusted for maternal age, BMI, smoking, parity, duration of subfertility and child gender.Main Results and the Role Of Chance: In total, there were 472 live birth singletons. Of the 472 singleton pregnancies, 209 were conceived after IUI-OS (136 with FSH and 73 with CC as ovarian stimulation), 138 after IVF (50 after IVF-MNC and 88 after IVF-SET) and 125 were conceived naturally.Singletons conceived following IUI-FSH and IUI-CC both had lower birthweights compared to naturally conceived singletons (adjusted difference IUI-FSH -156.3 g, 95% CI -287.9 to -24.7; IUI-CC -160.3 g, 95% CI -316.7 to -3.8). When we compared IVF-MNC and IVF-SET to naturally conceived singletons, no significant difference was found (adjusted difference IVF-MNC 75.8 g, 95% CI -102.0 to 253.7; IVF-SET -10.6 g, 95% CI -159.2 to 138.1). The mean birthweight percentile was only significantly lower in the IUI-FSH group (-7.0 percentile, 95% CI -13.9 to -0.2). The IUI-CC and IVF-SET group had a lower mean percentile and the IVF-MNC group a higher mean percentile, but these groups were not significant different compared to the naturally conceived group (IUI-CC -5.1 percentile, 95% CI -13.3 to 3.0; IVF-MNC 4.4 percentile, 95% CI -4.9 to 13.6; IVF-SET -1.3 percentile, 95% CI -9.1 to 6.4).Looking at the laboratory process that took place, singletons conceived following IUI-OS had lower birthweights than naturally conceived singletons (adjusted difference -157.7 g, 95% CI -277.4 to -38.0). The IVF group had comparable birthweights with the naturally conceived group (adjusted difference 20.9 g, 95% CI -110.8 to 152.6). The mean birthweight percentile was significantly lower in the IUI-OS group compared to the natural group (-6.4 percentile, 95% CI -12.6 to -0.1). The IVF group was comparable (0.7 percentile, 95% CI -6.1 to 7.6).Limitations, Reasons For Caution: The results are limited by the number of cases. The data were collected prospectively alongside the randomized controlled trials, but analyzed as treated.Wider Implications Of the Findings: Our data suggest IUI in a stimulated cycle may have a negative impact on the birthweight of the child and possibly on pre-eclampsia. Further research should look into the effect of different methods of ovarian stimulation on placenta pathology and pre-eclampsia in couples with unexplained subfertility using naturally conceived singletons in the unexplained population as a reference.Study Funding/competing Interest(s): Both initial trials were supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (INeS 120620027, SUPER 80-83600-98-10192). The INeS study also had a grant from Zorgverzekeraars Nederland, the Dutch association of healthcare insurers (09-003). B.W.J.M. is supported by an NHMRC investigator Grant (GNT1176437) and reports consultancy for ObsEva, Merck Merck KGaA, Guerbet and iGenomix, outside the submitted work. A.H. reports grants from Ferring Pharmaceutical company (the Netherlands), outside the submitted work. F.J.M.B. receives monetary compensation as a member of the external advisory board for Merck Serono (the Netherlands), Ferring Pharmaceutics BV (the Netherlands) and Gedeon Richter (Belgium), he receives personal fees from educational activities for Ferring BV (the Netherlands) and for advisory and consultancy work for Roche and he receives research support grants from Merck Serono and Ferring Pharmaceutics BV, outside the submitted work. The remaining authors have nothing to disclose.Trial Registration Number: INeS study Trial NL915 (NTR939); SUPER Trial NL3895 (NTR4057). [ABSTRACT FROM AUTHOR]

Previous studies showed that prolonged breastfeeding increases the risk of caries. However, the observed associations were mainly based on non-European populations, and important confounding and mediating factors like socioeconomic position (SEP) and diet were often neglected. The aim of this study was to investigate the role of breastfeeding and bottle-feeding practices on dental caries during childhood while accounting for SEP, ethnic background, and sugar intake. This study was part of the Generation R Study, a prospective multiethnic cohort study conducted in Rotterdam, The Netherlands. In total, 4,146 children were included in the analyses. Information about feeding practices was derived from delivery reports and questionnaires during infancy. Caries was measured via intraoral photographs at the age of 6 years and defined as decayed, missing, and filled teeth (dmft). Negative binomial hurdle regression analyses were used to study the associations between several infant feeding practices and childhood caries. The prevalence of dental caries at the age of 6 years was 27.9% (n = 1,158). Prolonged breastfeeding (for >12 months) was associated with dental caries (OR 1.35, 95% CI 1.04-1.74) and the number of teeth affected by dental caries (RR 1.27, 95% CI 1.03-1.56). Furthermore, nocturnal bottle-feeding was associated with dental caries (OR 1.52, 95% CI 1.20-1.93). All associations were independent of family SEP, ethnic background, and sugar intake. Results from this Dutch cohort study confirmed the previously observed associations between prolonged breastfeeding and nocturnal bottle-feeding and the increased risk of childhood dental caries, even after proper adjustments for indicators of SEP, ethnic background, and sugar intake. Future studies are encouraged to elaborate further on possible explanations for the observed relationships. Healthcare professionals should be aware and advise caregivers about the potential risk of prolonged breastfeeding on caries development by applying the current recommendations on breastfeeding, oral hygiene, and feeding frequency. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the rate of preterm birth (PTB) in a subsequent pregnancy in women who had undergone term induction using a Foley catheter compared with prostaglandins.Methods: This was a follow-up study of two large randomized controlled trials (PROBAAT-1 and PROBAAT-2). In the original trials, women with a term singleton pregnancy with the fetus in cephalic presentation and with an indication for labor induction were randomized to receive either a 30-mL Foley catheter or prostaglandins (vaginal prostaglandin E2 in PROBAAT-1 and oral misoprostol in PROBAAT-2). Data on subsequent ongoing pregnancies > 16 weeks' gestation were collected from hospital charts from clinics participating in this follow-up study. The main outcome measure was preterm birth < 37 weeks' gestation in a subsequent pregnancy.Results: Fourteen hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 572 had been allocated to induction of labor using a Foley catheter and 570 to induction of labor using prostaglandins. Of these, 162 (14%) were lost to follow-up. In total, 251 and 258 women had a known subsequent pregnancy > 16 weeks' gestation in the Foley catheter and prostaglandin groups, respectively. There were no differences in baseline characteristics between the groups. The overall rate of PTB in a subsequent pregnancy was 9/251 (3.6%) in the Foley catheter group vs 10/258 (3.9%) in the prostaglandin group (relative risk (RR), 0.93; 95% CI, 0.38-2.24), and the rate of spontaneous PTB was 5/251 (2.0%) vs 5/258 (1.9%) (RR, 1.03; 95% CI, 0.30-3.51).Conclusion: In women with term singleton pregnancy, induction of labor using a 30-mL Foley catheter is not associated with an increased risk of PTB in a subsequent pregnancy, as compared to induction of labor using prostaglandins. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: Spontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patients to assess clearance using a conventional definition (no total CT-DNA, assessed by routine quantitative PCR methods) and a definition accounting for viability, assessed by viability PCR testing.Methods: Three outpatient STI clinics included CT-diagnosed women (The Netherlands, 2016-2017, FemCure study); participants had vaginal CT (vCT) and rectal CT (rCT) (group A: n=155), vCT and were rectally untested (group B: n=351), single vCT (group C: n=25) or single rCT (group D: n=29). Follow-up (median interval 9 days) vaginal and rectal samples underwent quantitative PCR testing (detecting total CT-DNA). When PCR positive, samples underwent V-PCR testing to detect 'viable CT' (CT-DNA from intact CT organisms; V-PCR positive). 'Clearance' was the proportion PCR-negative patients and 'clearance of viable CT' was the proportion of patients testing PCR negative or PCR positive but V-PCR negative. We used multivariable logistic regression analyses to assess diagnosis group (A-D), age, days since initial CT test (diagnosis) and study site (STI clinic) in relation to clearance and clearance of viable CT.Results: Clearance and clearance of viable CT at both anatomic sites were for (A) 0.6% and 3.9%; (B) 5.4% and 9.4%; (C) 32.0% and 52.0% and (D) 27.6% and 41.4%, respectively. In multivariate analyses, women with single infections (groups C and D) had higher likelihood of clearance than women concurrently infected with vCT and rCT (p<0.001).Of rectally untested women (group B), 76.9% had total CT-DNA and 46.7% had viable CT (V-PCR positive) at the rectal site.Conclusions: Of untreated female vCT patients who had CT also at the rectal site, or who were rectally untested, only a small proportion cleared CT (in fact many had viable CT) at their follow-up visit (median 9 days). Among single site infected women clearance was much higher.Trial Registration Number: NCT02694497. [ABSTRACT FROM AUTHOR]

Introduction: Doppler ultrasound cardiotocography is a non-invasive alternative that, despite its poor specificity, is often first choice for intrapartum monitoring. Doppler ultrasound suffers from signal loss due to fetal movements and is negatively correlated with maternal body mass index (BMI). Reported accuracy of fetal heart rate monitoring by Doppler ultrasound varies between 10.6 and 14.3 bpm and reliability between 62.4% and 73%. The fetal scalp electrode (FSE) is considered the reference standard for fetal monitoring but can only be applied after membranes have ruptured with sufficient cervical dilatation and is sometimes contra-indicated. A non-invasive alternative that overcomes the shortcomings of Doppler ultrasound, providing reliable information on fetal heart rate, could be the answer. Non-invasive fetal electrocardiography (NI-fECG) uses a wireless electrode patch on the maternal abdomen to obtain both fetal and maternal heart rate signals as well as an electrohysterogram. We aimed to validate a wireless NI-fECG device for intrapartum monitoring in term singleton pregnancies, by comparison with the FSE.Material and Methods: We performed a multicenter cross-sectional observational study at labor wards of 6 hospitals located in the Netherlands, Belgium, and Spain. Laboring women with a healthy singleton fetus in cephalic presentation and gestational age between 36 and 42 weeks were included. Participants received an abdominal electrode patch and FSE after written informed consent. Accuracy, reliability, and success rate of fetal heart rate readings were determined, using FSE as reference standard. Analysis was performed for the total population and measurement period as well as separated by labor stage and BMI class (≤30 and >30 kg/m2 ).Results: We included a total of 125 women. Simultaneous registrations with NI-fECG and FSE were available in 103 women. Overall accuracy is -1.46 bpm and overall reliability 86.84%. Overall success rate of the NI-fECG is around 90% for the total population as well as for both BMI subgroups. Success rate dropped to 63% during second stage of labor, similar results are found when looking at the separate BMI groups.Conclusions: Performance measures of the NI-fECG device are good in the overall group and the separate BMI groups. Compared with Doppler ultrasound performance measures from the literature, NI-fECG is a more accurate alternative. Especially, when women have a higher BMI, NI-fECG performs well, resembling FSE performance measures. [ABSTRACT FROM AUTHOR]

Background: Individual differences in the risk to develop dementia remain poorly understood. These differences may partly be explained through reserve, which is the ability to buffer cognitive decline due to neuropathology and age.Objective: To determine how much early and late-life cognitive reserve (CR) and brain reserve (BR) contribute to the risk of dementia.Methods: 4,112 dementia-free participants (mean age = 66.3 years) from the Rotterdam Study were followed up for on average 6.0 years. Early-life CR and BR were defined as attained education and intracranial volume, respectively. Late-life CR was derived through variance decomposition based on cognition. Late-life BR was set as the total non-lesioned brain volume divided by intracranial volume.Results: Higher early-life CR (hazard ratio = 0.48, 95% CI = [0.21; 1.06]) but not early-life BR associated with a lower risk of incident dementia. Higher late-life CR (hazard ratio = 0.57, 95% CI = [0.48; 0.68]) and late-life BR (hazard ratio = 0.54, 95% CI = [0.43; 0.68]) also showed lower levels of dementia. Combining all proxies into one model attenuated the association between early-life CR and dementia (hazard ratio = 0.56, 95% CI = [0.25; 1.25]) whereas the other associations were unaffected. These findings were stable upon stratification for sex, age, and APOEɛ4. Finally, high levels of late-life CR and BR provided additive protection against dementia.Conclusion: The findings illustrate the importance of late-life over early-life reserve in understanding the risk of dementia, and show the need to study CR and BR conjointly. [ABSTRACT FROM AUTHOR]

Study Question: Does septum resection improve reproductive outcomes in women with a septate uterus?Summary Answer: In women with a septate uterus, septum resection does not increase live birth rate nor does it decrease the rates of pregnancy loss or preterm birth, compared with expectant management.What Is Known Already: The septate uterus is the most common uterine anomaly with an estimated prevalence of 0.2-2.3% in women of reproductive age, depending on the classification system. The definition of the septate uterus has been a long-lasting and ongoing subject of debate, and currently two classification systems are used worldwide. Women with a septate uterus may be at increased risk of subfertility, pregnancy loss, preterm birth and foetal malpresentation. Based on low quality evidence, current guidelines recommend removal of the intrauterine septum or, more cautiously, state that the procedure should be evaluated in future studies.Study Design, Size, Duration: We performed an international multicentre cohort study in which we identified women mainly retrospectively by searching in electronic patient files, medical records and databases within the time frame of January 2000 until August 2018. Searching of the databases, files and records took place between January 2016 and July 2018. By doing so, we collected data on 257 women with a septate uterus in 21 centres in the Netherlands, USA and UK.Participants/materials, Setting, Methods: We included women with a septate uterus, defined by the treating physician, according to the classification system at that time. The women were ascertained among those with a history of subfertility, pregnancy loss, preterm birth or foetal malpresentation or during a routine diagnostic procedure. Allocation to septum resection or expectant management was dependent on the reproductive history and severity of the disease. We excluded women who did not have a wish to conceive at time of diagnosis. The primary outcome was live birth. Secondary outcomes included pregnancy loss, preterm birth and foetal malpresentation. All conceptions during follow-up were registered but for the comparative analyses, only the first live birth or ongoing pregnancy was included. To evaluate differences in live birth and ongoing pregnancy, we used Cox proportional regression to calculate hazard rates (HRs) and 95% CI. To evaluate differences in pregnancy loss, preterm birth and foetal malpresentation, we used logistic regression to calculate odds ratios (OR) with corresponding 95% CI. We adjusted all reproductive outcomes for possible confounders.Main Results and the Role Of Chance: In total, 257 women were included in the cohort. Of these, 151 women underwent a septum resection and 106 women had expectant management. The median follow-up time was 46 months. During this time, live birth occurred in 80 women following a septum resection (53.0%) compared to 76 women following expectant management (71.7%) (HR 0.71 95% CI 0.49-1.02) and ongoing pregnancy occurred in 89 women who underwent septum resection (58.9%), compared to 80 women who had expectant management (75.5%) (HR 0.74 (95% CI 0.52-1.06)). Pregnancy loss occurred in 51 women who underwent septum resection (46.8%) versus 31 women who had expectant management (34.4%) (OR 1.58 (0.81-3.09)), while preterm birth occurred in 26 women who underwent septum resection (29.2%) versus 13 women who had expectant management (16.7%) (OR 1.26 (95% CI 0.52-3.04)) and foetal malpresentation occurred in 17 women who underwent septum resection (19.1%) versus 27 women who had expectant management (34.6%) (OR 0.56 (95% CI 0.24-1.33)).Limitations, Reasons For Caution: Our retrospective study has a less robust design compared with a randomized controlled trial. Over the years, the ideas about the definition of the septate uterus has changed, but since the 257 women with a septate uterus included in this study had been diagnosed by their treating physician according to the leading classification system at that time, the data of this study reflect the daily practice of recent decades. Despite correcting for the most relevant patient characteristics, our estimates might not be free of residual confounding.Wider Implications Of the Findings: Our results suggest that septum resection, a procedure that is widely offered and associated with financial costs for society, healthcare systems or individuals, does not lead to improved reproductive outcomes compared to expectant management for women with a septate uterus. The results of this study need to be confirmed in randomized clinical trials.Study Funding/competing Interest(s): A travel for JFWR to Chicago was supported by the Jo Kolk Studyfund. Otherwise, no specific funding was received for this study. The Department of Obstetrics and Gynaecology, University Medical Centre, Groningen, received an unrestricted educational grant from Ferring Pharmaceutical Company unrelated to the present study. BWM reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck, personal fees from Guerbet, other payment from Guerbet and grants from Merck, outside the submitted work. The other authors declare no conficts of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Introduction: We performed an independent validation study of all published first trimester prediction models, containing non-invasive predictors, for the risk of gestational diabetes mellitus. Furthermore, the clinical potential of the best performing models was evaluated.Material and Methods: Systemically selected prediction models from the literature were validated in a Dutch prospective cohort using data from Expect Study I and PRIDE Study. The predictive performance of the models was evaluated by discrimination and calibration. Clinical utility was assessed using decision curve analysis. Screening performance measures were calculated at different risk thresholds for the best model and compared with current selective screening strategies.Results: The validation cohort included 5260 women. Gestational diabetes mellitus was diagnosed in 127 women (2.4%). The discriminative performance of the 12 included models ranged from 68% to 75%. Nearly all models overestimated the risk. After recalibration, agreement between the observed outcomes and predicted probabilities improved for most models.Conclusions: The best performing prediction models showed acceptable performance measures and may enable more personalized medicine-based antenatal care for women at risk of developing gestational diabetes mellitus compared with current applied strategies. [ABSTRACT FROM AUTHOR]

Introduction: Low-dose aspirin (LDA) prophylaxis has been shown to reduce women's preeclampsia risk. Evidence regarding LDA adherence rates of pregnant women is based almost exclusively on clinical trials, giving a potentially biased picture. Moreover, these studies do not report on determinants of adherence. Since 2017, obstetric healthcare professionals in a Dutch region have assessed women's preeclampsia risk by means of a prediction tool and counseled those with an above-population average risk on LDA as a prophylactic measure.Material and Methods: From 2017 to 2018, 865 women were recruited in multiple centers and prospectively followed using web-based surveys (Expect Study II). Rates and determinants of LDA usage among women with an increased preeclampsia risk in daily practice were assessed. Results were compared with findings in a similar cohort from a care-as-usual setting lacking risk-based counseling (Expect Study I, n = 2614). Netherlands Trial Register NTR4143.Results: In total, 306 women had a predicted increased preeclampsia risk. LDA usage was higher for women receiving risk-based care than care-as-usual (29.4% vs 1.5%, odds ratio 19.1, 95% confidence interval 11.2-32.5). Daily LDA usage was positively correlated with both predicted risk and women's concerns regarding preeclampsia. Most reported reasons for non- or incomplete use were unawareness of LDA as a preventive intervention, concerns about potential adverse effects and doubts regarding the benefits.Conclusions: Risk-based counseling was associated with a higher prevalence of LDA usage, but general usage rates were low. Future research regarding potential factors improving the usage of LDA during pregnancy is necessary. [ABSTRACT FROM AUTHOR]

Background: Perception by workers of their health problems as work-related is possibly associated with sickness absence (SA). The aim of this study was to to study the relationship between perceived work-relatedness of health problems and SA among workers who visit their GP, taking the influence of other potential determinants into account and to study the influence of these determinants on SA. Design and setting prospective cohort study in 32 Dutch GP practices.Methods: A secondary analysis of RCT data among workers, aged 18-63 years, who visited their GP. We measured self-reported SA days in 12 months and high SA (>20 days in 12 months) and compared workers who perceived work-relatedness (WR+) with workers who did not (WR-). With multivariable linear and logistic regression models, we analyzed the influence of age, gender, experienced health, chronic illness, prior SA, number of GP consultations and perceived work ability.Results: We analyzed data of 209 workers, 31% perceived work-relatedness. Geometric mean of SA days was 1.6 (95% CI: 0.9-3.0) for WR+- workers and 1.2 (95% CI: 0.8-1.8) for WR- workers (P = 0.42). Incidence of high SA was 21.5 and 13.3%, respectively (odds ratio 1.79; 95% CI: 0.84-3.84). SA was positively associated with chronic illness, prior SA, low perceived work ability and age over 50.Conclusions: Perceived work-relatedness was not associated with SA. SA was associated with chronic illness, prior SA, low perceived work ability and age over 50. [ABSTRACT FROM AUTHOR]

Background: Chronotype is an individual's preferred timing of sleep and activity, and is often referred to as a later chronotype (or evening-type) or an earlier chronotype (or morning-type). Having an evening chronotype is associated with more severe depressive and anxiety symptoms. Based on these findings it is has been suggested that chronotype is a stable construct associated with vulnerability to develop depressive or anxiety disorders. To examine this, we test the stability of chronotype over 7 years, and its longitudinal association with the change in severity of depressive and anxiety symptoms.Methods: Data of 1,417 participants with a depressive and/or anxiety disorder diagnosis and healthy controls assessed at the 2 and 9-year follow-up waves of the Netherlands Study of depression and anxiety were used. Chronotype was assessed with the Munich chronotype questionnaire. Severity of depressive and anxiety symptoms were assessed with the inventory of depressive symptomatology and Beck anxiety inventory.Results: Chronotype was found to be moderately stable (r = 0.53) and on average advanced (i.e., became earlier) with 10.8 min over 7 years (p < .001). Controlling for possible confounders, a decrease in severity of depressive symptoms was associated with an advance in chronotype (B = 0.008, p = .003). A change in severity of anxiety symptoms was not associated with a change in chronotype.Conclusion: Chronotype was found to be a stable, trait-like construct with only a minor level advance over a period of 7 years. The change in chronotype was associated with a change in severity of depressive, but not anxiety, symptoms. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of providing free fruit and snack vegetables at a university on students' fruit intake, snack vegetable intake and total vegetable intake.Design: Free fruit and raw snack vegetables (e.g. bite-sized tomatoes) were provided in a stand in the form of a miniature wooden house located in the central hall of the university's main building, which students regularly pass through on their way to lectures and the cafeteria. Three interventions tested with a pre-test/post-test design were performed. In these three interventions, small changes to the appearance of the stand were made, such as placing potted plants around it. Demographic characteristics and fruit and vegetable intakes were assessed with questionnaires.Setting: A Dutch university of applied science.Participants: Intervention 1 included 124 students; Intervention 2 included ninety-two students; Intervention 3 included 237 students.Results: Longitudinal linear regression analyses showed that post-test snack vegetable intake was consistently higher compared with pre-test. In the three interventions, post-test snack vegetable intakes were between 11 and 14 g/d higher than at the pre-test, which is comparable to three bite-sized tomatoes. No differences in fruit intake or total vegetable intake were found. Subgroup analyses showed that, in all three interventions, students with the lowest pre-test fruit intake and total vegetable intake reported the largest increase in fruit intake and snack vegetable intake after the interventions.Conclusions: Providing free fruit and vegetables to students at their university might be beneficial for those with low habitual intakes. [ABSTRACT FROM AUTHOR]

Background: It is unclear what session frequency is most effective in cognitive-behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression.Aims: Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression.Method: We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16-24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted.Results: Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00-2.18).Conclusions: In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes. [ABSTRACT FROM AUTHOR]

There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4±9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population. [ABSTRACT FROM AUTHOR]

Background: Few large-scale epidemiologic studies evaluate the clinical and economic burden of appendicitis. These data may impact future research and treatment strategies. In this study, the objective was to determine the burden of appendectomy for appendicitis in terms of incidence rates, length of hospital stay (LOS) and hospital costs on a national level. In addition, outcomes were compared for subgroups based on surgical treatment, age and hospital setting.Methods: Observational retrospective population-based cohort study using the national Dutch healthcare reimbursement registry, which covers hospital registration and reimbursement for 17 million inhabitants. Patients with a diagnosis of appendicitis who underwent appendectomy between 2006 and 2016 were included. Primary outcomes were incidence rates, LOS and hospital costs.Results: A total of 135,025 patients were included. Some 53% of patients was male, and 64% was treated in a general hospital. The overall incidence rate of appendectomy was 81 per 100,000 inhabitants and showed a significant decreasing trend across time and age. Mean ± SD LOS per patient was 3.66 ± 3.5 days. LOS showed a significant increase with age and was significantly longer for open versus minimally invasive appendectomy. Mean ± SD hospital costs per patient were €3700 ± 1284. Costs were initially lower for open compared to minimally invasive appendectomy, but were similar from 2012 onward. Compared to non-university hospitals, patients treated in university hospitals had a significantly longer LOS and higher costs.Conclusions: Appendectomy for appendicitis represents a substantial clinical and economic burden in the Netherlands. A preference for minimally invasive technique seems justified. [ABSTRACT FROM AUTHOR]

Introduction: The common genetic variant (rs1051730) in the 15q24 nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 was associated with smoking quantity and has been reported to be associated also with reduced ability to quit smoking in pregnant women but results were inconsistent in nonpregnant women. The aim of this study was to explore the association between rs1051730 and smoking cessation during pregnancy in a sample of Dutch women.Methods: Data on smoking during pregnancy were available from 1337 women, who ever smoked, registered at the Netherlands Twin Register (NTR). Logistic regression was used to assess evidence for the association of rs1051730 genotype on smoking during pregnancy. In a subsample of 561 women, we investigated the influence of partner's smoking. Educational attainment and year of birth were used as covariates in both analyses.Results: There was evidence for a significant association between having one or more T alleles of the rs1051730 polymorphism and the likelihood of smoking during pregnancy (p = .03, odds ratio = 1.28, 95% CI = 1.02 to 1.61). However, this association attenuated when adjusting for birth cohort and educational attainment (p = .37, odds ratio = 1.12, 95% CI = 0.87 to 1.43). In the subsample, smoking spouse was highly associated with smoking during pregnancy, even when educational attainment and birth cohort were included in the model.Conclusions: Our results did not support a strong association between this genetic variant and smoking during pregnancy. However, a strong association was observed with the smoking behavior of the partner, regardless of the genotype of the women.Implications: The present study emphasizes the importance of social influences like spousal smoking on the smoking behavior of pregnant women. Further research is needed to address the role of rs1051730 genetic variant in influencing smoking cessation and the interaction with important environmental factors like the smoking behavior of the partner. [ABSTRACT FROM AUTHOR]

Aim: Recent evidence is emerging indicating long-term effects in infants born after an episode of preterm labour (PTL), even if birth is at term. This population-based study compared long-term rates of outcomes and health-care utilisation (HCU) in children born following spontaneous preterm labour, irrespective of gestational age at delivery or of an uncomplicated pregnancy (SPTLu), with children born following full-term labour (FTL), overall stratified by comorbidity status and assessed using a composite morbidity measure (CM).Methods: Retrospective data on mother-neonate pairs were collected from a patient-linked dataset from the Netherlands Perinatal Registry and the PHARMO Database Network. Children born between 2000 and 2010 were followed until 2012.Results: Of pregnancies in 134 006 mother-neonate pairs, 122 894 (92%) pregnancies resulted in FTL, and 11 112 (8%) resulted in PTL. Of the PTL pregnancies, 6599 (59%) were SPTLu. Mean follow-up after birth was 6.6-6.7 years. Children from SPTLu pregnancies were at increased risk of neurodevelopmental and respiratory conditions compared with those from FTL pregnancies. In children from SPTLu pregnancies, the presence of the CM was associated with an increased risk of respiratory conditions and failure to thrive. Post-natal hospitalisations (incidence rate (IR) per 100 patient-years: 18.1 vs. 11.7) and specialist referrals (IR per 1000 patient-years: 290.6 vs. 184.5) occurred significantly more frequently in children from SPTLu versus FTL pregnancies.Conclusion: The increased risk of morbidities and HCU in children born following SPTLu pregnancy in this population-based setting reinforces the need for safe interventions that can effectively halt labour and lead to an improvement in childhood outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the external validity of all published first-trimester prediction models based on routinely collected maternal predictors for the risk of small- and large-for-gestational-age (SGA and LGA) infants. Furthermore, the clinical potential of the best-performing models was evaluated.Design: Multicentre prospective cohort.Setting: Thirty-six midwifery practices and six hospitals (in the Netherlands).Population: Pregnant women were recruited at <16 weeks of gestation between 1 July 2013 and 31 December 2015.Methods: Prediction models were systematically selected from the literature. Information on predictors was obtained by a web-based questionnaire. Birthweight centiles were corrected for gestational age, parity, fetal sex, and ethnicity.Main Outcome Measures: Predictive performance was assessed by means of discrimination (C-statistic) and calibration.Results: The validation cohort consisted of 2582 pregnant women. The outcomes of SGA <10th percentile and LGA >90th percentile occurred in 203 and 224 women, respectively. The C-statistics of the included models ranged from 0.52 to 0.64 for SGA (n = 6), and from 0.60 to 0.69 for LGA (n = 6). All models yielded higher C-statistics for more severe cases of SGA (<5th percentile) and LGA (>95th percentile). Initial calibration showed poor-to-moderate agreement between the predicted probabilities and the observed outcomes, but this improved substantially after recalibration.Conclusion: The clinical relevance of the models is limited because of their moderate predictive performance, and because the definitions of SGA and LGA do not exclude constitutionally small or large infants. As most clinically relevant fetal growth deviations are related to 'vascular' or 'metabolic' factors, models predicting hypertensive disorders and gestational diabetes are likely to be more specific.Tweetable Abstract: The clinical relevance of prediction models for the risk of small- and large-for-gestational-age is limited. [ABSTRACT FROM AUTHOR]

Objective: To examine timing of eating across ten European countries.Design: Cross-sectional analysis of the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study using standardized 24 h diet recalls collected during 1995-2000. Eleven predefined food consumption occasions were assessed during the recall interview. We present time of consumption of meals and snacks as well as the later:earlier energy intake ratio, with earlier and later intakes defined as 06.00-14.00 and 15.00-24.00 hours, respectively. Type III tests were used to examine associations of sociodemographic, lifestyle and health variables with timing of energy intake.Setting: Ten Western European countries.Subjects: In total, 22 985 women and 13 035 men aged 35-74 years (n 36 020).Results: A south-north gradient was observed for timing of eating, with later consumption of meals and snacks in Mediterranean countries compared with Central and Northern European countries. However, the energy load was reversed, with the later:earlier energy intake ratio ranging from 0·68 (France) to 1·39 (Norway) among women, and from 0·71 (Greece) to 1·35 (the Netherlands) among men. Among women, country, age, education, marital status, smoking, day of recall and season were all independently associated with timing of energy intake (all P<0·05). Among men, the corresponding variables were country, age, education, smoking, physical activity, BMI and day of recall (all P<0·05).Conclusions: We found pronounced differences in timing of eating across Europe, with later meal timetables but greater energy load earlier during the day in Mediterranean countries compared with Central and Northern European countries. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to assess charts proposed for international use in the Intergrowth-21st Project.Methods: Ultrasound data were collected from 43,923 healthy singleton pregnancies examined at 18-23 weeks of gestation in the Netherlands. Fetal measurements were converted into Z-scores using previous and current Dutch reference charts and Intergrowth charts. The distributions of the Z-scores were compared with the expected standard normal distribution.Results: In the Dutch population, Intergrowth curves perform well for head circumference and biparietal diameter, but not for abdominal circumference (AC, Z- score = 0.43) and femur length (FL, Z-score = 0.26). Similar findings have been reported in other European countries. Compared with the population in the Intergrowth study, Dutch women are relatively tall (170 vs. 162 cm) and sturdy (67 vs. 61 kg) with a moderately high BMI. Maternal size, in particular maternal height, is positively correlated with birthweight.Conclusions: Whilst the establishment of the Intergrowth charts is an important step towards worldwide uniformity, for now locally derived charts still perform better, especially for AC and FL. Results from our validation study indicate that distinction between normal and pathologically small babies may be improved by taking maternal size into account. [ABSTRACT FROM AUTHOR]

Study Question: Does starting IUI with ovarian stimulation (IUI-OS) within 1.5 years after completion of the fertility workup increase ongoing pregnancy rates compared to expectant management in couples with unexplained subfertility?Summary Answer: IUI-OS is associated with higher chances of ongoing pregnancy compared to expectant management in unexplained subfertile couples, specifically those with poor prognoses of natural conception, i.e. <15% over 6 months or <25% over 1 year.What Is Known Already: IUI-OS is often the first-line treatment for couples with unexplained subfertility. Two randomized controlled trials compared IUI-OS to expectant management using different thresholds for the prognosis of natural conception as inclusion criteria and found conflicting results. A cohort of couples with unexplained subfertility exposed to expectant management and IUI-OS offers an opportunity to determine the chances of conception after both strategies and to evaluate whether the effect of IUI-OS depends on a couple's prognosis of natural conception.Study Design, Size, Duration: A prospective cohort study on couples with unexplained or mild male subfertility who could start IUI-OS at any point after completion of the fertility workup, recruited in seven Dutch centres between January 2002 and February 2004. Decisions regarding treatment were subject to local protocols, the judgement of the clinician and the wishes of the couple. Couples with bilateral tubal occlusion, anovulation or a total motile sperm count <1 × 106 were excluded. Follow up was censored at the start of IVF, after the last IUI cycle or at last contact and truncated at a maximum of 1.5 years after the fertility workup.Participants/materials, Setting, Methods: The endpoint was time to conception leading to an ongoing pregnancy. We used the sequential Cox approach comparing in each month ongoing pregnancy rates over the next 6 months of couples who started IUI-OS to couples who did not. We calculated the prognosis of natural conception for individual couples, updated this over consecutive failed cycles and evaluated whether prognosis modified the effect of starting IUI-OS. We corrected for known predictors of conception using inverse probability weighting.Main Results and the Role Of Chance: Data from 1896 couples were available. There were 800 couples whom had at least one IUI-OS cycle within 1.5 years post fertility workup of whom 142 couples conceived (rate: 0.50 per couple per year, median follow up 4 months). The median period between fertility workup completion and starting IUI-OS was 6.5 months. Out of 1096 untreated couples, 386 conceived naturally (rate: 0.31 per couple per year, median follow up 7 months). Starting IUI-OS was associated with a higher chance of ongoing pregnancy by a pooled, overall hazard ratio of 1.96 (95% CI: 1.47-2.62) compared to expectant management. The effect of treatment was modified by a couple's prognosis of achieving natural conception (P = 0.01), with poorer prognoses or additional failed natural cycles being associated with a stronger effect of treatment. The predicted 6-month ongoing pregnancy rate for a couple with a prognosis of 25% at completion of the fertility workup over the next six cycles (~40% over 1 year) was 25% (95% CI: 21-28%) for expectant management and 24% (95% CI: 9-36%) when starting IUI-OS directly. For a couple with a prognosis of 15% (25% over 1 year), these predicted rates were 17% (95% CI: 15-19%) for expectant management and 24% (95% CI: 15-32%) for starting IUI-OS.Limitations, Reasons For Caution: The effect estimates are based on a prospective cohort followed up for 1.5 years after completion of the fertility workup. Although we balanced the known predictors of conception between treated and untreated couples using inverse probability weighting, observational data may be subject to residual confounding. The results need to be confirmed in external datasets.Wider Implications Of the Findings: These results explain the discrepancies between previous trials that compared IUI-OS to expectant management, but further studies are required to establish the threshold at which IUI-OS is (cost-)effective.Study Funding/competing Interest(s): This study was facilitated by (Grant 945/12/002) from ZonMW, The Netherlands Organization for Health Research and Development, The Hague, The Netherlands. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. S.B. reports acting as Editor-in-Chief of HROpen. The other authors have no conflicts of interest. [ABSTRACT FROM AUTHOR]

Information on the safety of medication use during pregnancy and breastfeeding is scarce, yet use of medication among pregnant and breastfeeding women is widespread. The pREGnant, the Dutch Pregnancy Drug Register, was set up to obtain insight into medication use among pregnant and breastfeeding women and potential effects on maternal and fetal/infant health. The systematically documented, good quality data on medication use during pregnancy and lactation in pREGnant will be used in signal detection, epidemiologic studies and counseling of healthcare providers and patients. The register has a prospective cohort design. The population is derived from pregnant women throughout the Netherlands. Data collection started in April 2014 and enrollment of women is continuous and is characterized by a relative high proportion of women born in the Netherlands with a high education compared with the general Dutch pregnant population. Data on current pregnancy, obstetric history, maternal lifestyle, health and medication use, delivery, and infant health are collected through web-based questionnaires completed by the participating women (three times during pregnancy and three times during the infant's first year of life). If permission is given, the self-reported data can be complemented with information retrieved from Perined, the perinatal registry of the Netherlands, and from obstetric and medical records, and/or pharmacy records. Here, we provide detailed information on the design of the pREGnant, the Dutch Pregnancy Drug Register, as well as descriptive information on characteristics of the participants so far. Currently, steps are being taken to implement the register on a large scale in the Netherlands. [ABSTRACT FROM AUTHOR]

Aims: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist-to-hip ratio (WHR), BMI and all-cause mortality in patients with HF.Methods and Results: For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37-3.63; P =0.001], whereas no significant association was found in men (HR 0.87, 95% CI 0.63-1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men.Conclusions: A higher WHR was associated with a higher risk of death in female but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF. [ABSTRACT FROM AUTHOR]

Background/objectives: Many diet quality scores exist, but fully food-based scores based on contemporary evidence are scarce. Our aim was to develop a food-based diet score based on international literature and examine its discriminative capacity and socio-demographic determinants.Subjects/methods: Between 2006 and 2013, dietary intake of 129,369 participants of the Lifelines Cohort (42% male, 45 ± 13 years (range 18-93)) was assessed with a 110-item food frequency questionnaire. Based on the 2015 Dutch Dietary Guidelines and underlying literature, nine food groups with positive (vegetables, fruit, whole grain products, legumes&nuts, fish, oils&soft margarines, unsweetened dairy, coffee and tea) and three food groups with negative health effects (red&processed meat, butter&hard margarines and sugar-sweetened beverages) were identified. Per food group, the intake in grams per 1000 kcal was categorized into quintiles, awarded 0 to 4 points (negative groups scored inversely) and summed. Food groups with neutral, unknown or inconclusive evidence are described but not included.Results: The Lifelines Diet Score (LLDS) discriminated well between high and low consumers of included food groups. This is illustrated by e.g. a 2-fold higher vegetable intake in the highest, compared to the lowest LLDS quintile. Differences were 5.5-fold for fruit, 3.5-fold for fish, 3-fold for dairy and 8-fold for sugar-sweetened beverages. The LLDS was higher in females and positively associated with age and educational level.Conclusions: The LLDS is based on the latest international evidence for diet-disease relations at the food group level and has high capacity to discriminate people with widely different intakes. Together with the population-based quintile approach, this makes the LLDS a flexible, widely applicable tool for diet quality assessment. [ABSTRACT FROM AUTHOR]

Background/objectives: We studied the ecologic relationships of food groups, macronutrients, eating patterns, and an a priori food pattern score (Mediterranean Adequacy Index: MAI) with long-term CHD mortality rates in the Seven Countries Study.Subjects/methods: Sixteen cohorts (12,763 men aged 40-59 years) were enrolled in the 1960s in seven countries (US, Finland, The Netherlands, Italy, Greece, former Yugoslavia: Croatia/Serbia, Japan). Dietary surveys were carried out at baseline and only in a subsample of each cohort. The average food consumption of each cohort was chemically analyzed for individual fatty acids and carbohydrates.Results: Ecologic correlations of diet were computed across cohorts for 50-year CHD mortality rates; 97% of men had died in cohorts with 50-year follow-up. CHD death rates ranged 6.7-fold among cohorts. At baseline, hard fat was greatest in northern Europe, olive oil in Greece, meat in the US, sweet products in northern Europe and the US, and fish in Japan. The MAI was high in Mediterranean and Japanese cohorts. The 50-year CHD mortality rates of the cohorts were closely positively ecologically correlated (r = 0.68-0.92) with average consumption of hard fat, sweet products, animal foods, saturated fat, and sucrose, but not with naturally occurring sugars. Vegetable foods, starch, and the a priori pattern MAI were inversely correlated (r = -0.59 to -0.91) with CHD mortality rates.Conclusions: Long-term CHD mortality rates had statistically significant ecologic correlations with several aspects of diet consumed in the 1960s, the traditional Mediterranean and Japanese patterns being rich in vegetable foods, and low in sweet products and animal foods. [ABSTRACT FROM AUTHOR]

In medical school selection, non-cognitive performance in particular correlates with performance in clinical practice. It is arguable, therefore, that selection should focus on non-cognitive aspects despite the predictive value of prior cognitive performance for early medical school performance. The aim of this study at Radboud University Medical Center, the Netherlands, is to determine the effects of admitting students through an autonomous non-cognitive procedure on early medical school performance. We compared their performance to the performance of students selected through an autonomous cognitive selection procedure, enrolling in the Bachelor's curriculum simultaneously. 574 students (2013 and 2014 cohorts), admitted through non-cognitive selection (based on portfolio, CASPer and MMI, n = 135) or cognitive selection (curriculum sample selection, n = 439) were included in the study. We compared dropout rates, course credits and grades, using logistic and linear regression. The dropout rate was the highest in the non-cognitive selection group (p < 0.001). Students admitted through non-cognitive selection more often obtained the highest grade for the nursing attachment (p = 0.02) and had a higher mean grade for the practical clinical course in year 3 (p = .04). No differences in course grades were found. The results indicate that students perform best on the elements of the curriculum that are represented most strongly in the selection procedure they had participated in. We recommend the use of curriculum sample procedures, resembling the early medical school curriculum,-whether it has a more cognitive or a more non-cognitive focus-, to select the students who are likely to be successful in the subsequent curriculum. [ABSTRACT FROM AUTHOR]

Background A 'Patient-Reported Outcome Measure, Inquiry into Side Effects' (PROMISE) instrument was developed for patients to report common symptoms in clinical medication reviews. Objective To determine changes in patient-reported drug-associated symptoms collected by PROMISE before and after community pharmacist-led clinical medication reviews compared with usual care. Setting Community pharmacies in the Netherlands. Methods Patients were randomised into an intervention group (IG) and a control group (CG). PROMISE was used to collect symptoms experienced during the previous month, and any suspected drug-associated symptoms from both groups at baseline and at follow-up after 3 months. IG patients received a one-time clinical medication review, while CG patients received usual care. Main outcome measure Mean number of drug-associated symptoms at follow-up. Results Measurements were completed by 78 IG and 67 CG patients from 15 community pharmacies. Mean numbers of drug-associated symptoms per patient at follow-up were 4.0 in the IG and 5.0 in the CG, with an incident rate ratio between the groups of 0.90 (95% CI 0.62-1.33). Mean numbers of drug-associated symptoms per patient reported at follow-up and persisting since baseline were 2.1 in the IG and 2.6 in the CG, with an incident rate ratio of 0.85 (95% CI 0.43-1.42). The lowest percentages of persisting drug-associated symptoms detected in the IG were 'palpitations' and 'stomach pain, dyspepsia' while in the CG they were 'stomach pain, dyspepsia' and 'trembling, shivering'. Conclusion PROMISE provided meaningful information on drug-associated symptoms in clinical medication reviews, however the number of drug-associated symptoms was not reduced by performing clinical medication reviews compared with usual care. [ABSTRACT FROM AUTHOR]

Objective: Observational study of patients with chest pain in primary care: determination of incidence, referral rate, diagnostic tests and (agreement between) working and final diagnoses.Methods: 118 general practitioners (GPs) in the Netherlands and Belgium recorded all patient contacts during  2weeks. Furthermore, patients presenting with chest pain were registered extensively. A follow-up form was filled in after 30 days.Results: 22 294 patient contacts were registered. In 281 (1.26%), chest pain was a reason for consulting the GP (mean age for men 54.4/women 53 years). In this cohort of 281 patients, in 38.1% of patients, acute coronary syndrome (ACS) was suspected at least temporarily during consultation, 40.2% of patients were referred to secondary care and 512 diagnostic tests were performed by GPs and consulted specialists. Musculoskeletal pain was the most frequent working (26.1%) and final diagnoses (33.1%). Potentially life-threatening diseases as final diagnosis (such as myocardial infarction) accounted for 8.4% of all chest pain cases. In 23.1% of cases, a major difference between working and final diagnoses was found, in 0.7% a severe disease was initially missed by the GP.Conclusion: Chest pain was present in 281 patients (1.26% of all consultations). Final diagnoses were mostly non-life-threatening. Nevertheless, in 8.4% of patients with chest pain, life-threatening underlying causes were identified. This seems reflected in the magnitude and wide variety of diagnostic tests performed in these patients by GPs and specialists, in the (safe) overestimation of life-threatening diseases by GPs at initial assessment and in the high referral rate we found. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to investigate the nature, management, and outcome of major injuries related to equestrian sports and to define the at-risk groups for serious and life-threatening injuries.Methods: We analyzed demographic, pre-hospital, clinical, and outcome data from an international population-based prospective trauma database (TraumaRegister DGU®). Patients with major injuries (Injury Severity Score [ISS] ≥9 points) related to equestrian sports activities were included (January 1, 1993, to December 31, 2012). Clinical and outcome parameters were stratified for four different types of injury mechanisms: fall from horse (FFH), horse-kick (HK), horse crush (HC), and carriage-related accidents (CRA). Participating countries included Germany, Austria, Switzerland, Finland, Slovenia, Belgium, Luxembourg, and The Netherlands. Statistical analyses were performed with SPSS (Version 22, IBM Inc., Armonk, NY).Results: The Database identified 122,000 documented patients, of whom 679 were equestrian incidents. Among these, the four major injury mechanisms were: FFH (n = 427), HK (n = 188), HC (n = 34), and the CRA (n = 30). Females were more likely to sustain FFH (75.5%, p < 0.001), leading to head injuries (n = 204, 47.8%) and spinal fractures (n = 109, 25.5%). HK injuries often resulted in facial fractures (29.3%, p < 0.001). Individuals sustaining HC injuries had a high risk for pelvic (32.4%, p < 0.001) and abdominal injuries (35.2%, p < 0.001). In contrast to the FFH cohort, the CRA cohort involved older males (57 ± 13 years), with chest (63.3% p = 0.001), and extremity injuries, resulting in significant injury severity (ISS 20.7 ± 10.6). In the CRA cohort, 16% were in haemorrhagic shock on scene, and also the highest in-hospital mortality (14.8%, p = 0.006) was observed.Conclusions: Young female riders are at risk from falling, horse-kicks, and crush-injuries. Older males in carriage-related accidents sustained the highest injury severity and mortality rate, and must specifically be targeted by future prevention initiatives. Level of evidence Descriptive Epidemiologic Study, Level II. [ABSTRACT FROM AUTHOR]

Objective: To update the Dutch Healthy Diet index, a measure of diet quality, to reflect adherence to the Dutch dietary guidelines 2015 and to evaluate against participants' characteristics and nutrient intakes with the score based on 24 h recall (24 hR) data and FFQ data.Design: The Dutch Healthy Diet index 2015 (DHD15-index) consists of fifteen components representing the fifteen food-based Dutch dietary guidelines of 2015. Per component the score ranges between 0 and 10, resulting in a total score between 0 (no adherence) and 150 (complete adherence).Setting: Wageningen area, the Netherlands, 2011-2013.Subjects: Data of 885 men and women, aged 20-70 years, participating in the longitudinal NQplus study, who filled out two 24 hR and one FFQ, were used.Results: Mean (sd) score of the DHD15-index was 68·7 (16·1) for men and 79·4 (16·0) for women. Significant inverse trends were found between the DHD15-index and BMI, smoking, and intakes of energy, total fat and saturated fat. Positive trends were seen across sex-specific quintiles of the DHD15-index score with energy-adjusted micronutrient intakes. Mean DHD15-index score of the FFQ data was 15·5 points higher compared with 24 hR data, with a correlation coefficient of 0·56 between the scores. Observed trends of the DHD15-index based on FFQ with participant characteristics, macronutrient and energy-adjusted micronutrient intakes were similar to those with the DHD15-index based on 24 hR.Conclusions: The DHD15-index score assesses adherence to the Dutch dietary guidelines 2015 and indicates diet quality. The DHD15-index score can be based on 24 hR data and on FFQ data. [ABSTRACT FROM AUTHOR]

Smoking and caffeine consumption show a strong positive correlation, but the mechanism underlying this association is unclear. Explanations include shared genetic/environmental factors or causal effects. This study employed three methods to investigate the association between smoking and caffeine. First, bivariate genetic models were applied to data of 10 368 twins from the Netherlands Twin Register in order to estimate genetic and environmental correlations between smoking and caffeine use. Second, from the summary statistics of meta-analyses of genome-wide association studies on smoking and caffeine, the genetic correlation was calculated by LD-score regression. Third, causal effects were tested using Mendelian randomization analysis in 6605 Netherlands Twin Register participants and 5714 women from the Avon Longitudinal Study of Parents and Children. Through twin modelling, a genetic correlation of r0.47 and an environmental correlation of r0.30 were estimated between current smoking (yes/no) and coffee use (high/low). Between current smoking and total caffeine use, this was r0.44 and r0.00, respectively. LD-score regression also indicated sizeable genetic correlations between smoking and coffee use (r0.44 between smoking heaviness and cups of coffee per day, r0.28 between smoking initiation and coffee use and r0.25 between smoking persistence and coffee use). Consistent with the relatively high genetic correlations and lower environmental correlations, Mendelian randomization provided no evidence for causal effects of smoking on caffeine or vice versa. Genetic factors thus explain most of the association between smoking and caffeine consumption. These findings suggest that quitting smoking may be more difficult for heavy caffeine consumers, given their genetic susceptibility. [ABSTRACT FROM AUTHOR]

Objective: To investigate outpatient follow-up after mild traumatic brain injury (mTBI) by various medical specialists, for both hospitalized and non-hospitalized patients, and to study guideline adherence regarding hospital admission.Methods: Patients (n= 1151) with mTBI recruited from the emergency department received questionnaires 2 weeks (n= 879), 3 months (n= 780) and 6 months (n= 668) after injury comprising outpatient follow-up by various health care providers, and outcome defined by the Glasgow Outcome Scale Extended (GOS-E) after 6 months.Results: Hospitalized patients (60%) were older (46.6 ± 19.9 vs. 40.6 ± 18.5 years), more severely injured (GCS <15, 50% vs. 13%) with more Computed Tomography (CT) abnormalities on admission (21% vs. 2%) compared to non-hospitalized patients (p< 0.01) . Almost half of the patients visited a neurologist at the outpatient clinic within six months (60% of the hospitalized and 25% of the non-hospitalized patients (χ2= 67.10,p< 0.01)), and approximately ten per cent consulted a psychiatrist/psychologist. Outcome was unfavourable (GOS-E <7) in 34% of hospitalized and 21% of non-hospitalized patients (χ2= 11.89,p< 0.01).Conclusion: Two-thirds of all mTBI patients consult one or more specialists within six months after injury, with 30% having an unfavourable outcome. A quarter of non-hospitalized patients was seen at the outpatient neurology clinic, underling the importance of regular follow-up of mTBI patients irrespective of hospital admittance. [ABSTRACT FROM PUBLISHER]

Objectives: To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women.Methods: This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups.Results: Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure ≥ 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged ≥ 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged ≥ 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208).Conclusion: The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether cemented or uncemented hemiarthroplasty is the best treatment option in elderly patients with displaced femoral neck fractures. Previous randomized trials comparing cemented and uncemented hemiarthroplasty have conflicting results. We conducted a randomized controlled trial to compare cemented and uncemented hemiarthroplasty.Methods: This multicenter parallel-randomized controlled trial included patients of 70 years and older with a displaced femoral neck fracture (Garden type III or IV). Inclusion was between August 2008 and June 2012. Patients were randomized between a cemented hemiarthroplasty, type Müller Straight Stem or an uncemented hemiarthroplasty, type DB-10. Primary outcomes were complications, operation time, functional outcome (measured by Timed-Up-and-Go (TUG) and Groningen Activity Restriction Scale (GARS)) and mid-thigh pain. Health Related Quality of Life (HRQoL, expressed with the SF-12) was measured as an secondary outcome. Follow up was 1 year.Results: In total 201 patients were included in the study (91 uncemented, 110 cemented hemiarthroplasties) The uncemented group showed more major local complications (intra- and postoperative fractures and dislocations) odds ratio (95% confidence interval) 3.36 (1.40 to 8.11). There was no difference in mean operation time (57.3 vs 55.4 min). There were no differences in functional outcomes (TUG 12.8 (9.4) vs. 13.9 (9.0), GARS 43.2 (19.7) vs. 39.2 (16.5)) and mid-thigh pain (18.6 vs 21.6%). Physical component SF-12 HRQoLwas lower in the uncemented group (30.3 vs. 35.3 p < 0.05 after six weeks, 33.8 vs 38.5 p < 0.05 after 12 weeks).Conclusion: A cemented hemiarthroplasty in elderly patients with a displaced femoral neck fracture results in less complications compared to an uncemented hemiarthroplasty.Trial Registration: Netherlands Trial Registry; NTR 1508 , accepted date 27 okt 2008. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic surgery is associated with a shallow learning curve. AnubiFiX embalming technique enables laparoscopic surgical training on supple embalmed and hence insufflatable human specimens in the dissection room. Aim of the present trial is to test whether dissection-based anatomy education is superior to classical frontal classroom education on the short and long term.Methods: A total of 112 medical students were randomized in three groups. Group I attended classroom education, group II laparoscopic dissection-based education and group III received both. All groups completed an anatomy test on human specimens before, immediately after and 3 weeks after the anatomy training.Results: Group II and III scored significantly better compared to group I immediately after the anatomy training (p I-II < 0.001, p I-III < 0.001). This difference was still significant after 3 weeks (p I-II < 0.001, p I-III < 0.001). No significant difference was found between group II and group III immediately after the course (p = 0.86), nor at the follow-up (p = 0.054).Conclusions: The AnubiFiX™ embalming technique enables laparoscopic anatomy education in human specimens, with superior outcomes on the short and long term, as compared to classical frontal classroom education. [ABSTRACT FROM AUTHOR]

Background: Social exclusion (SE) refers to the inability of certain groups or individuals to fully participate in society. SE is associated with socioeconomic inequalities in health, and its measurement in routine public health monitoring is considered key to designing effective health policies. In an earlier retrospective analysis we demonstrated that in all four major Dutch cities, SE could largely be measured with existing local public health monitoring data. The current prospective study is aimed at constructing and validating an extended national measure for SE that optimally employs available items.Methods: In 2012, a stratified general population sample of 258,928 Dutch adults completed a version of the Netherlands Public Health Monitor (PHM) questionnaire in which 9 items were added covering aspects of SE that were found to be missing in our previous research. Items were derived from the SCP social exclusion index, a well-constructed 15-item instrument developed by the Netherlands Institute for Social Research (SCP). The dataset was randomly divided into a development sample (N =129,464) and a validation sample (N = 129,464). Canonical correlation analysis was conducted in the development sample. The psychometric properties were studied and compared with those of the original SCP index. All analyses were then replicated in the validation sample.Results: The analysis yielded a four dimensional index, the Social Exclusion Index for Health Surveys (SEI-HS), containing 8 SCP items and 9 PHM items. The four dimensions: "lack of social participation", "material deprivation", "lack of normative integration" and "inadequate access to basic social rights", were each measured with 3 to 6 items. The SEI-HS showed adequate internal consistency for both the general index and for two of four dimension scales. The internal structure and construct validity of the SEI-HS were satisfactory and similar to the original SCP index. Replication of the SEI-HS in the validation sample confirmed its generalisability.Conclusion: This study demonstrates that the SEI-HS offers epidemiologists and public health researchers a uniform, reliable, valid and efficient means of assessing social exclusion and its underlying dimensions. The study also provides valuable insights in how to develop embedded measures for public health surveillance. [ABSTRACT FROM AUTHOR]

Background: Guidelines for treatment of the posterior fracture fragment in trimalleolar fractures are scarce and show varying advices. Did the increasing size of the posterior fragment seem to relate to worse outcome in the past, nowadays this has changed to the amount of dislocation of the posterior fragment post-operatively. Despite many retrospective cohort studies and some prospective cohort studies, no consistent guideline could be derived from the current literature.Methods: The POSTFIX-study is designed as a multicenter randomized clinical trial to analyse the effects of anatomical reduction and fixation of the posterior fragment in AO 44-B3 fractures with medium-sized posterior fragment. A total of 84 patients will be included and online allocated to either anatomical reduction and fixation of the posterior fragment via the posterolateral approach (n = 42) or no fixation of the posterior fragment (n = 42). The concomitant fractured medial and lateral malleoli are treated according to the AO-principles. Functionality of the ankle as measured by the AAOS-questionnaire (American Association of Orthopaedic Surgeons) 1 year post-operatively was set as primary outcome. Main secondary outcome measures are the AAOS-questionnaire 5 years postoperatively and osteoarthritis as measured on plain radiographs 1 year and 5 years post-operatively. The Olerud and Molander score, the AOFAS-score, the VAS-pain, the Euroqol-5D and Range of Motion by physical examination will also be evaluated during the follow-up period.Discussion: The POSTFIX-trial is the first high quality multicenter randomized clinical trial worldwide to analyse the effects of anatomical fixation of the posterior fragment in trimalleolar fractures. New guidelines on anatomical reduction and fixation of the posterior fragment can in future be based on the results of this trial.Trial Registration: This trial is registered on ClinicalTrials.gov with reference number: NCT02596529 . Registered 3 November 2015, retrospectively registered. [ABSTRACT FROM AUTHOR]