In risiko’s denken is niet zonder risiko

Thinking in terms of risk is in itself not without it risk. If we label something as risky we'll start perceiving and treating that 'something' differently. This paper in Dutch highlights this phenomenon in relation to pregnancy and childbirth

The influence of preferred place of birth on the course of pregnancy and labor among healthy nulliparous women: a prospective cohort study

__Abstract__ BACKGROUND: Most studies on birth settings investigate the association between planned place of birth at the start of labor and birth outcomes and intervention rates. To optimize maternity care it also is important to pay attention to the entire process of pregnancy and childbirth. This study explores the association between the initial preferred place of birth and model of care, and the course of pregnancy and labor in low-risk nulliparous women in the Netherlands. METHODS: As part of a Dutch prospective cohort study (2007-2011), we compared medical indications during pregnancy and birth outcomes of 576 women who initially preferred a home birth (n = 226), a midwife-led hospital birth (n = 168) or an obstetrician-led hospital birth (n = 182). Data were obtained by a questionnaire before 20 weeks of gestation and by medical records. Analyses were performed according to the initial preferred place of birth. RESULTS: Low-risk nulliparous women who preferred a home birth with midwife-led care were less likely to be diagnosed with a medical indication during pregnancy compared to women who preferred a birth with obstetrician-led care (OR 0.41 95% CI 0.25-0.66). Preferring a birth with midwife-led care - both at home and in hospital - was associated with lower odds of induced labor (OR 0.51 95% CI 0.28-0.95 respectively OR 0.42 95% CI 0.21-0.85) and epidural analgesia (OR 0.32 95% CI 0.18-0.56 respectively OR 0.34 95% CI 0.19-0.62) compared to preferring a birth with obstetrician-led care. In addition, women who preferred a home birth were less likely to experience augmentation of labor (OR 0.54 95% CI 0.32-0.93) and narcotic analgesia (OR 0.41 95% CI 0.21-0.79) compared to women who preferred a birth with obstetrician-led care. We observed no significant association between preferred place of birth and mode of birth. CONCLUSIONS: Nulliparous women who initially preferred a home birth were less likely to be diagnosed with a medical indication during pregnancy. Women who initially preferred a birth with midwife-led care - both at home and in hospital - experienced lower rates of interventions during labor. Although some differences can be attributed to the model of care, we suggest that characteristics and attitudes of women themselves also play an important role

A robust pipeline with high replication rate for detection of somatic variants in the adaptive immune system as a source of common genetic variation in autoimmune disease

The role of somatic variants in diseases beyond cancer is increasingly being recognized, with potential roles in autoinflammatory and autoimmune diseases. However, as mutation rates and allele fractions are lower, studies in these diseases are substantially less tolerant of false positives, and bio-informatics algorithms require high replication rates. We developed a pipeline combining two variant callers, MuTect2 and VarScan2, with technical filtering and prioritization. Our pipeline detects somatic variants with allele fractions as low as 0.5% and achieves a replication rate of > 55%. Validation in an independent data set demonstrates excellent performance (sensitivity > 57%, specificity > 98%, replication rate > 80%). We applied this pipeline to the autoimmune disease multiple sclerosis (MS) as a proof-of-principle. We demonstrate that 60% of MS patients carry 2-10 exonic somatic variants in their peripheral blood T and B cells, with the vast majority (80%) occurring in T cells and variants persisting over time. Synonymous variants significantly co-occur with non-synonymous variants. Systematic characterization indicates somatic variants are enriched for being novel or very rare in public databases of germline variants and trend towards being more damaging and conserved, as reflected by higher phred-scaled combined annotation-dependent depletion (CADD) and genomic evolutionary rate profiling (GERP) scores. Our pipeline and proof-of-principle now warrant further investigation of common somatic genetic variation on top of inherited genetic variation in the context of autoimmune disease, where it may offer subtle survival advantages to immune cells and contribute to the capacity of these cells to participate in the autoimmune reaction.Peer reviewe

Creating an Optimality Index – Netherlands: a validation study

Abstract Background At present, the maternity care system in the Netherlands is being reorganized into an integrated model of care, shifting the focus of midwives to include increasing numbers of births in hospital settings and clients with medium risk profiles. In light of these changes, it is useful for midwives to have a tool which may help them in reflecting upon care practices that promote physiological childbirth practices. The Optimality Index-US is an evidence based tool, designed to measure optimal perinatal care processes and outcomes. It has been validated for use in the United States (OI-US), United Kingdom (OI-UK) and Turkey (OI-TR). The objective of this study was to adapt the OI-US for the Dutch maternity care setting (OI-NL). Methods Translation and back translation were applied to create the OI-NL. A panel of maternity care experts (n = 10) provided input for face validation items in the OI-NL. Assessment of inter-rater reliability and ease of use was also conducted. Following this, the OI-NL was used prospectively to collect data on 266 women who commenced intrapartum care under the responsibility of a midwife. Twice groups were compared, based on parity and on care-setting at birth. Mean scores between these groups, corrected for perinatal background factors were assessed for discriminant validity. Results Face validity was established for OI-NL on the basis of expert input. Discriminant validity was confirmed by conducting multiple regressions analyses for parity (β = 6.21, P = 0.00) and for care-setting (β = 12.1, p = 0.00). Inter-rater reliability was 98%, with one item (Apgar score) sensitive to scoring differences. Conclusion OI-NL is a valid and reliable tool for use in the Dutch maternity care setting. In addition to its value for assessing evidence-based maternity care processes and outcomes, there is potential for use for learning and reflection. Against the backdrop of a changing maternity care system, and due to the specificity of its items OI-NL may be of value as a tool for detecting subtle changes indicative of escalating medicalization of childbirth in the Netherlands.https://deepblue.lib.umich.edu/bitstream/2027.42/143165/1/12884_2018_Article_1735.pd

CFTR Function Restoration upon Elexacaftor/Tezacaftor/Ivacaftor Treatment in Patient-Derived Intestinal Organoids with Rare CFTR Genotypes

Cystic fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. The combination of the CFTR modulators elexacaftor, tezacaftor, and ivacaftor (ETI) enables the effective rescue of CFTR function in people with the most prevalent F508del mutation. However, the functional restoration of rare CFTR variants remains unclear. Here, we use patient-derived intestinal organoids (PDIOs) to identify rare CFTR variants and potentially individuals with CF that might benefit from ETI. First, steady-state lumen area (SLA) measurements were taken to assess CFTR function and compare it to the level observed in healthy controls. Secondly, the forskolin-induced swelling (FIS) assay was performed to measure CFTR rescue within a lower function range, and to further compare it to ETI-mediated CFTR rescue in CFTR genotypes that have received market approval. ETI responses in 30 PDIOs harboring the F508del mutation served as reference for ETI responses of 22 PDIOs with genotypes that are not currently eligible for CFTR modulator treatment, following European Medicine Agency (EMA) and/or U.S. Food and Drug Administration (FDA) regulations. Our data expand previous datasets showing a correlation between in vitro CFTR rescue in organoids and corresponding in vivo ppFEV1 improvement upon a CFTR modulator treatment in published clinical trials, and suggests that the majority of individuals with rare CFTR variants could benefit from ETI. CFTR restoration was further confirmed on protein levels using Western blot. Our data support that CFTR function measurements in PDIOs with rare CFTR genotypes can help to select potential responders to ETI, and suggest that regulatory authorities need to consider providing access to treatment based on the principle of equality for people with CF who do not have access to treatment.</p

The Knight of Malta

BACKGROUND: For most women, participation in decision-making during maternity care has a positive impact on their childbirth experiences. Shared decision-making (SDM) is widely advocated as a way to support people in their healthcare choices. The aim of this study was to identify quality criteria and professional competencies for applying shared decision-making in maternity care. We focused on decision-making in everyday maternity care practice for healthy women. METHODS: An international three-round web-based Delphi study was conducted. The Delphi panel included international experts in SDM and in maternity care: mostly midwives, and additionally obstetricians, educators, researchers, policy makers and representatives of care users. Round 1 contained open-ended questions to explore relevant ingredients for SDM in maternity care and to identify the competencies needed for this. In rounds 2 and 3, experts rated statements on quality criteria and competencies on a 1 to 7 Likert-scale. A priori, positive consensus was defined as 70% or more of the experts scoring >/=6 (70% panel agreement). RESULTS: Consensus was reached on 45 quality criteria statements and 4 competency statements. SDM in maternity care is a dynamic process that starts in antenatal care and ends after birth. Experts agreed that the regular visits during pregnancy offer opportunities to build a relationship, anticipate situations and revisit complex decisions. Professionals need to prepare women antenatally for unexpected, urgent decisions in birth and revisit these decisions postnatally. Open and respectful communication between women and care professionals is essential; information needs to be accurate, evidence-based and understandable to women. Experts were divided about the contribution of professional advice in shared decision-making and about the partner's role. CONCLUSIONS: SDM in maternity care is a dynamic process that takes into consideration women's individual needs and the context of the pregnancy or birth. The identified ingredients for good quality SDM will help practitioners to apply SDM in practice and educators to prepare (future) professionals for SDM, contributing to women's positive birth experience and satisfaction with care

Balancing restrictions and access to maternity care for women and birthing partners during the COVID-19 pandemic: the psychosocial impact of suboptimal care

The women's right to respectful and dignified care during labour and childbirth is strategically accepted. As management committee members of the EU COST Action CA18211 network ('DEVOTION') focused on traumatic childbirth (www.ca18211.eu), we are concerned with ensuring a positive birth experience for all. We work on a pan-European level to ensure women's rights to give birth in a clinically and psychologically safe environment including during the current COVID-19 pandemic

Traumatic birth and childbirth-related post-traumatic stress disorder: International expert consensus recommendations for practice, policy, and research

Background Research suggests 1 in 3 births are experienced as psychologically traumatic and about 4% of women and 1% of their partners develop post-traumatic stress disorder (PTSD) as a result. Aim To provide expert consensus recommendations for practice, policy, and research and theory. Method Two consultations (n = 65 and n = 43) with an international group of expert researchers and clinicians from 33 countries involved in COST Action CA18211; three meetings with CA18211 group leaders and stakeholders; followed by review and feedback from people with lived experience and CA18211 members (n = 238). Findings Recommendations for practice include that care for women and birth partners must be given in ways that minimise negative birth experiences. This includes respecting women’s rights before, during, and after childbirth; and preventing maltreatment and obstetric violence. Principles of trauma-informed care need to be integrated across maternity settings. Recommendations for policy include that national and international guidelines are needed to increase awareness of perinatal mental health problems, including traumatic birth and childbirth-related PTSD, and outline evidence-based, practical strategies for detection, prevention, and treatment. Recommendations for research and theory include that birth needs to be understood through a neuro-biopsychosocial framework. Longitudinal studies with representative and global samples are warranted; and research on prevention, intervention and cost to society is essential. Conclusion Implementation of these recommendations could potentially reduce traumatic births and childbirth-related PTSD worldwide and improve outcomes for women and families. Recommendations should ideally be incorporated into a comprehensive, holistic approach to mental health support for all involved in the childbirth process

Seasonal Growth Rate of the Sponge Haliclona oculata (Demospongiae: Haplosclerida)

The interest in sponges has increased rapidly since the discovery of potential new pharmaceutical compounds produced by many sponges. A good method to produce these compounds by using aquaculture of sponges is not yet available, because there is insufficient knowledge about the nutritional needs of sponges. To gain more insight in the nutritional needs for growth, we studied the growth rate of Haliclona oculata in its natural environment and monitored environmental parameters in parallel. A stereo photogrammetry approach was used for measuring growth rates. Stereo pictures were taken and used to measure volumetric changes monthly during 1 year. Volumetric growth rate of Haliclona oculata showed a seasonal trend with the highest average specific growth rate measured in May: 0.012 ± 0.004 day−1. In our study a strong positive correlation (p < 0.01) was found for growth rate with temperature, algal biomass (measured as chlorophyll a), and carbon and nitrogen content in suspended particulate matter. A negative correlation (p < 0.05) was found for growth rate with salinity, ammonium, nitrate, nitrite, and phosphate. No correlation was found with dissolved organic carbon, suggesting that Haliclona oculata is more dependent on particulate organic carbon

Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice

Background & Aims: The bile acid (BA)-activated farnesoid X receptor (FXR) controls hepatic BA synthesis and cell proliferation via the intestinal hormone fibroblast growth factor 19. Because cystic fibrosis (CF) is associated with intestinal dysbiosis, anomalous BA handling, and biliary cirrhosis, we investigated FXR signaling in CF. Methods: Intestinal and hepatic expression of FXR target genes and inflammation markers was assessed in Cftr null mice and controls. Localization of the apical sodium-dependent BA transporter was assessed, and BAs in gastrointestinal tissues were analyzed. The CF microbiota was characterized and FXR signaling was investigated in intestinal tissue and organoids. Results: Ileal murine fibroblast growth factor 19 ortholog (Fgf15) expression was strongly reduced in CF mice, compared with controls. Luminal BA levels and localization of apical sodium-dependent BA transporter was not affected, and BAs induced Fgf15 up to normal levels in CF ileum, ex vivo, and CF organoids. CF mice showed a dysbiosis that was associated with a marked up-regulation of genes involved in host–microbe interactions, including those involved in mucin glycosylation, antimicrobial defense, and Toll-like receptor signaling. Antibiotic treatment reversed the up-regulation of inflammatory markers and restored intestinal FXR signaling in CF mice. Conversely, FXR-dependent gene induction in ileal tissue and organoids was repressed by bacterial lipopolysaccharide and proinflammatory cytokines, respectively. Loss of intestinal FXR activity was associated with a markedly blunted hepatic trophic response to oral BA supplementation, and with impaired repression of Cyp7a1, the gene encoding the rate-limiting enzyme in BA synthesis. Conclusions: In CF mice, the gut microbiota represses intestinal FXR activity, and, consequently, FXR-dependent hepatic cell proliferation and feedback control of BA synthesis