Centralisation of acute obstetric care in the Netherlands : a qualitative study to explore the experiences of stakeholders with adaptations in organisation of care

Background: In the past decade, acute obstetric care (AOC) has become centralised in many high-income countries. In this qualitative study, we explored how stakeholders in maternity care perceived and experienced adaptations in the organisation of maternity care in areas in the Netherlands where AOC was centralised. Methods: A heterogenic group of fifteen maternity care stakeholders, including patients, were purposively selected for semi-structured interviews. An inductive thematic analysis was used. Results: Three main themes were identified: (1) lack of involvement. (2) the process of making adaptations in the organisation of maternity care. (3) maintaining quality of care. Stakeholders in this study were highly motivated to maintain a high quality of maternity care and therefore made adaptations at several organisational levels. However, they felt a lack of involvement during the planning of centralisation of AOC and highlighted the importance of a collaborative process when making adaptations after centralisation of AOC. Conclusions: Regions with AOC centralisation plans should invest time and money in change management, encourage early involvement of all maternity care stakeholders and acknowledge centralisation of AOC as a professional life event with associated emotions, including a feeling of unsafety

Perpendicular diffusion of solar energetic particles: When is the diffusion approximation valid?

Abstract: Multi-spacecraft observations of widespread solar energetic particle (SEP) events indicate that perpendicular (to the mean field) diffusion is an important SEP transport mechanism. However, this is in direct contrast to so-called spike and drop-out events, which indicate very little lateral transport. To better understand these seemingly incongruous observations, we discuss the recent progress made towards understanding and implementing perpendicular diffusion in transport models of SEP electrons. This includes a re-derivation of the relevant focused transport equation, a discussion surrounding the correct form of the pitch-angle dependent perpendicular diffusion coefficient and what turbulence quantities are needed as input, and how models lead to degenerate solutions of the particle intensity. Lastly, we evaluate the validity of a diffusion approach to SEP transport and conclude that it is valid when examining a large number of (an ensemble of) events, but that individual SEP events may exhibit coherent structures related to the magnetic field turbulence at short timescales that cannot be accounted for in this modelling approach

Consumption of nitrate-rich beetroot juice with or without vitamin C supplementation increases the excretion of urinary nitrate, nitrate, and N-nitroso compounds in humans

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances

Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy

BACKGROUND AND OBJECTIVES: To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN. METHODS: iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed. RESULTS: iPSC-derived MNs moderately express the complement regulatory proteins CD46 and CD55 and strongly expressed CD59. Furthermore, MNs express C3aR, C5aR, and complement receptor 1. IgM anti-GM1 antibodies in serum from patients with MMN bind to MNs and induce C3 and C4 fixation on incubation with fresh serum. ARGX-117 inhibits complement activation downstream of C4 induced by patient-derived anti-GM1 antibodies bound to MNs. DISCUSSION: Binding of IgM antibodies from patients with MMN to iPSC-derived MNs induces complement activation. By expressing complement regulatory proteins, particularly CD59, MNs are protected against complement-mediated lysis. Yet, because of expressing C3aR, the function of these cells may be affected by complement activation upstream of membrane attack complex formation. ARGX-117 inhibits complement activation upstream of C3 in this disease model for MMN and therefore represents an intervention strategy to prevent harmful effects of complement in MMN

IgM anti-GM2 antibodies in patients with multifocal motor neuropathy target Schwann cells and are associated with early onset

BACKGROUND: Multifocal motor neuropathy (MMN) is a rare, chronic immune-mediated polyneuropathy characterized by asymmetric distal limb weakness. An important feature of MMN is the presence of IgM antibodies against gangliosides, in particular GM1 and less often GM2. Antibodies against GM1 bind to motor neurons (MNs) and cause damage through complement activation. The involvement of Schwann cells (SCs), expressing GM1 and GM2, in the pathogenesis of MMN is unknown. METHODS: Combining the data of our 2007 and 2015 combined cross-sectional and follow-up studies in Dutch patients with MMN, we evaluated the presence of IgM antibodies against GM1 and GM2 in serum from 124 patients with MMN and investigated their binding to SCs and complement-activating properties. We also assessed the relation of IgM binding and complement deposition with clinical characteristics. RESULTS: Thirteen out of 124 patients (10%) had a positive ELISA titer for IgM anti-GM2. Age at onset of symptoms was significantly lower in MMN patients with anti-GM2 IgM. IgM binding to SCs correlated with IgM anti-GM2 titers. We found no correlation between IgM anti-GM2 titers and MN binding or with IgM anti-GM1 titers. IgM binding to SCs decreased upon pre-incubation of serum with soluble GM2, but not with soluble GM1. IgM anti-GM2 binding to SCs correlated with complement activation, as reflected by increased C3 fixation on SCs and C5a formation in the supernatant. CONCLUSION: Circulating IgM anti-GM2 antibodies define a subgroup of patients with MMN that has an earlier onset of disease. These antibodies probably target SCs specifically and activate complement, similarly as IgM anti-GM1 on MNs. Our data indicate that complement activation by IgM antibodies bound to SCs and MNs underlies MMN pathology

In-hospital informal caregivers' needs as perceived by themselves and by the nursing staff in Northern Greece: A descriptive study

<p>Abstract</p> <p>Background</p> <p>Informal care is common in many countries, especially in Greece, where families provide care in hospitals. Health education and informational needs are important factors for family members which are often underestimated by nursing staff. The aim of this study was to compare the perceptions of the nurses and the in-hospital informal caregivers about the in-hospital informal caregivers' knowledge and informational needs, as well as the factors that influence these perceptions.</p> <p>Methods</p> <p>This was a non-experimental descriptive study conducted in three general hospitals in Greece. The sample consisted of 320 nurses and 370 in-hospital informal caregivers who completed questionnaires. Descriptive statistics were analyzed using t-tests; group comparisons were conducted using ANOVA.</p> <p>Results</p> <p>The score of the questionnaire for health education and informational needs was significantly greater for informal caregivers (57.1 ± 6.9 and 26.6 ± 2.8) than for nurses (53.4 ± 5.7 and 22.4 ± 3.1) (p < 0.001). For the nursing staff, the factors that influence the informational needs of patients' caregivers were <it>level of education </it>and <it>working experience</it>, while for the caregivers the <it>level of education </it>was independently associated with the score for the health education needs. Finally, <it>age, marital status</it>, and <it>level of education </it>of informal caregivers' were independently associated with informational needs.</p> <p>Conclusions</p> <p>The in-hospital informal caregivers perceived that they have more educational and informational needs than the nurses did. The findings of this study also show that the nursing staff has to identify the needs of in-hospital informal caregivers in order to be able to meet these needs.</p

The United Kingdom and the Netherlands maternity care responses to COVID-19: A comparative study

BackgroundThe national health care response to coronavirus (COVID-19) has varied between countries. The United Kingdom (UK) and the Netherlands (NL) have comparable maternity and neonatal care systems, and experienced similar numbers of COVID-19 infections, but had different organisational responses to the pandemic. Understanding why and how similarities and differences occurred in these two contexts could inform optimal care in normal circumstances, and during future crises.AimTo compare the UK and Dutch COVID-19 maternity and neonatal care responses in three key domains: choice of birthplace, companionship, and families in vulnerable situations.MethodA multi-method study, including documentary analysis of national organisation policy and guidance on COVID-19, and interviews with national and regional stakeholders.FindingsBoth countries had an infection control focus, with less emphasis on the impact of restrictions, especially for families in vulnerable situations. Differences included care providers’ fear of contracting COVID-19; the extent to which community- and personalised care was embedded in the care system before the pandemic; and how far multidisciplinary collaboration and service-user involvement were prioritised.ConclusionWe recommend that countries should 1) make a systematic plan for crisis decision-making before a serious event occurs, and that this must include authentic service-user involvement, multidisciplinary collaboration, and protection of staff wellbeing 2) integrate women’s and families’ values into the maternity and neonatal care system, ensuring equitable inclusion of the most vulnerable and 3) strengthen community provision to ensure system wide resilience to future shocks from pandemics, or other unexpected large-scale events

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Making maternity and neonatal care personalised in the COVID-19 pandemic: Results from the Babies Born Better survey in the UK and the Netherlands

Background The COVID-19 pandemic had a severe impact on women’s birth experiences. To date, there are no studies that use both quantitative and qualitative data to compare women’s birth experiences before and during the pandemic, across more than one country. Aim To examine women’s birth experiences during the COVID-19 pandemic and to compare the experiences of women who gave birth in the United Kingdom (UK) or the Netherlands (NL) either before or during the pandemic. Method This study is based on analyses of quantitative and qualitative data from the online Babies Born Better survey. Responses recorded by women giving birth in the UK and the NL between June and December 2020 have been used, encompassing women who gave birth between 2017 and 2020. Quantitative data were analysed descriptively, and chi-squared tests were performed to compare women who gave birth pre- versus during pandemic and separately by country. Qualitative data was analysed by inductive thematic analysis. Findings Respondents in both the UK and the NL who gave birth during the pandemic were as likely, or, if they had a self-reported above average standard of life, more likely to rate their labour and birth experience positively when compared to women who gave birth pre-pandemic. This was despite the fact that those labouring in the pandemic reported a lack of support and limits placed on freedom of choice. Two potential explanatory themes were identified in the qualitative data: respondents had lower expectations of care during the pandemic, and they appreciated the efforts of staff to give individualised care, despite the rules. Conclusion Our study implies that many women labouring during the COVID-19 pandemic experienced restrictions, but their experience was mitigated by staff actions. However, personalised care should not be maintained by the good will of care providers, but should be a priority in maternity care policy to benefit all service users equitably