Perinatal healthcare for women at risk of children's social care involvement: a qualitative survey of professionals in England.

BACKGROUND: Women with complex health needs are more at risk of having children's social care involvement with their newborns than other mothers. Around the time of pregnancy, there are opportunities for health services to support women with these needs and mitigate the risk of mother-baby separation. Yet little is known about healthcare professionals' experiences of providing this support. METHODS: We administered an online survey to perinatal healthcare professionals across England (n=70 responders), including midwives, obstetricians, perinatal psychologists/psychiatrists and health visitors. We asked about their experiences of providing care for pregnant women with chronic physical conditions, mental health needs, intellectual/developmental disabilities and substance use disorders, who might be at risk of children's social care involvement. We conducted a framework analysis. RESULTS: We constructed five themes from participant data. These include (1) inaccessible healthcare for women with complex needs, (2) the challenges and importance of restoring trust, (3) services focusing on individuals, not families, (4) the necessity and caution around multidisciplinary support and (5) underfunded services inhibiting good practice. CONCLUSIONS: Women who are at risk of children's social care involvement will likely experience perinatal healthcare inequities. Our findings suggest that current perinatal healthcare provision for this population is inadequate and national guidelines need updated to inform support.

'On paper, you're normal': narratives of unseen health needs among women who have had children removed from their care.

BACKGROUND: Mothers who have children removed from their care often have complex needs. These women have poor health outcomes and are dying earlier than their peers from preventable and amenable causes. Yet there is little known about how health care services might mitigate these risks. This study aimed to listen to the voices of women who had children removed from their care to understand their experiences of health and healthcare. METHODS: We used a narrative approach to collect and analyse interview data with six mothers who had experienced child removal in England. Each participant was asked to reflect on their life and main health challenges. RESULTS: Three narrative subplots were developed to consolidate experiences of unmet health need: (i) 'on paper you're normal': narratives of complex need, (ii) 'in my family, everyone had issues': narratives of whole family need and (iii) 'I'm still mummy, no matter where they are': narratives of maternal identity and health. CONCLUSIONS: Findings highlight limitations within current systems of support, including a culture of distrust and women falling between the gaps of services. Women's narratives illustrate opportunities for health intervention, especially immediately following child removal.

Parental health in the context of public family care proceedings: A scoping review of evidence and interventions.

BACKGROUND: Child protective services (CPS), or their equivalent, have statutory power to remove children from birth parents in instances of child abuse, neglect, or concerns around parenting capacity via public family care proceedings. Parents who have children subject to proceedings, 'birth parents', often have complex health and social care needs. OBJECTIVE: We aimed to review what is known about the health needs of birth parents and the interventions implemented to support these health needs. METHODS: We searched PubMed, Scopus, and grey literature using a systematic strategy of key concepts "health", "care proceedings", and "parents". We included all publications in English that reported parental health in the context of care proceedings from the 1st of January 2000 to the 1st of March 2021. RESULTS: Included studies (n = 61) reported on maternal health (57 %) or the health of both parents (40 %), with only one study reporting on fathers alone. We conceptually categorised parental health need (n = 41) into i) mental health, ii) physical health, iii) substance misuse, iv) developmental disorders, and v) reproductive health. Health inequities and poor access to services were described across all categories, with longstanding issues often pre-dating proceedings or the child's birth. All interventions supporting parental health (n = 20) were targeted at mothers, with some supporting fathers (n = 8), formally or informally. We grouped similar interventions into three types: alternative family courts, wrap-around services, and specialist advocacy/peer support. CONCLUSIONS: Parents who have children subject to care proceedings have complex health needs that pre-date CPS concerns. The studies included in our review strongly suggest that health issues are exacerbated by child removal, triggering deteriorations in mental health, poor antenatal health for subsequent pregnancies, and avoidable mortality. Findings highlight the need for targeted and timely intervention for parents to improve whole-family outcomes. There are models that have been designed, implemented, and tested using relationship-based, trauma-informed, multidisciplinary, family-focused, and long-term approaches.

Impact of counselling provision in primary schools on child and adolescent mental health service referral rates: a longitudinal observational cohort study.

BACKGROUND: In the United Kingdom, schools play an increasingly important role in supporting young peoples' mental health. While there is a growing evidence base to support the effectiveness of school-based interventions, less is known about how these provisions impact on local Child and Adolescent Mental Health Service (CAMHS) referral rates. There is a concern that an increase in school-based provision might lead to an increase in CAMHS referrals and overwhelm services. We aimed to examine the longitudinal association between Place2Be counselling provision in primary schools on CAMHS referral rates in South London. METHOD: This was a retrospective cohort study using linked data from the National Pupil Database (NPD) and CAMHS referrals to the South London and Maudsley's NHS Foundation Trust (SLaM) identified through the Clinical Record Interactive Search (CRIS) tool. The cohort included a total of 285 state-maintained primary schools in four London boroughs for the academic years of 2007-2012. During the study period, 23 of these schools received school-based mental health provision from Place2Be. The primary outcome was the incident rate ratio (IRR) of school-level accepted CAMHS referrals in 2012/13 in schools with, or without, Place2Be provision. RESULTS: There was no significant association between elevated rates of CAMHS referral and Place2Be provision, even after comprehensive adjustment for school-level and pupil characteristics (IRR 0.91 (0.67-1.23)). School-level characteristics, including higher proportion of white-British pupils (IRR 1.009 (1.002-1.02)), medical staff ratio (IRR 6.49 (2.05-20.6)) and poorer Ofsted school inspection ratings (e.g. IRR 1.58 (1.06-2.34) for 'Requires Improvement' vs. 'Outstanding') were associated with increased CAMHS referral rates. CONCLUSIONS: Place2Be provision did not result in increased specialist mental health referrals; however, other school-level characteristics did. Future research should investigate pupils' Place2Be clinical outcomes, as well the outcomes of individuals referred to CAMHS to better understand which needs are being met by which services.

Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.

PURPOSE: Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings'). METHODS: This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings. RESULTS: Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age. CONCLUSION: Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.

ABCB4 Mutations in Adults Cause a Spectrum Cholestatic Disorder Histologically Distinct from Other Biliary Disease.

BACKGROUND: Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood. AIMS: We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined. METHODS: Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed. RESULTS: Two novel pathogenic ABCB4 variants were identified: c.620 T > G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis. CONCLUSIONS: Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.

What are the perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays? A systematic review of the literature.

OBJECTIVE: To identify the attitudes and perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays. DESIGN: Systematic Literature Review. METHOD: An electronic search of databases Scopus, CINAHL, MEDLINE, PEDro, Speechbite, OTseeker and ScienceDirect was undertaken in October 2020. Articles were compared with eligibility criteria by 2 authors. All articles were appraised for quality and level of evidence. FINDINGS: Fourteen studies were deemed to be eligible. Results were synthesised using a narrative analysis. The themes identified were technology, self-efficacy, replacement of face-to-face services, time management, relationships, access and family-centred care. Each of these themes was seen as both a potential barrier and a facilitator when trying to provide services via telehealth. CONCLUSIONS: The results in this review cannot be generalised due to small sampling size, low response rates, lack of maximum variation sampling and under-representation of occupational therapists and physiotherapists. Study design was either mixed-methods survey or interview or only survey or interview. Risk of bias in studies was high. Further research is required including comparison studies and cost-benefit analysis.

Parenting interventions for people with schizophrenia or related serious mental illness.

BACKGROUND: Around a third of people with schizophrenia or related serious mental illness will be a parent. Both the parents and the children in this population are at increased risk of adverse outcomes due to parental mental illness. Parenting interventions are known to improve parenting skills and decrease child disruptive behaviour. This systematic review aimed to synthesise the evidence base for parenting interventions designed specifically for parents who have schizophrenia or related serious mental illness. OBJECTIVES: To assess the effects of parenting interventions for people with schizophrenia or related serious mental illness. SEARCH METHODS: On 10 February 2021 we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on the following: Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.Gov, Embase, International Standard Randomised Controlled Trial Number (ISRCTN), MEDLINE, PsycINFO, PubMed, and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) that compared parenting interventions with a control condition for people with schizophrenia or related serious mental illness with a child between the ages of 0 and 18 years. DATA COLLECTION AND ANALYSIS: We independently inspected citations, selected studies, extracted data and appraised study quality. We assessed risk of bias for included studies. MAIN RESULTS: We only included one trial (n = 50), and it was not possible to extract any data because the authors did not provide any means and standard deviations for our outcomes of interest; they only reported whether outcomes were significant or not at the 0.05 level. Three domains of the trial were rated as having a high risk of bias. AUTHORS' CONCLUSIONS: The only included trial provided inconclusive evidence. There is insufficient evidence to make recommendations to people with schizophrenia (or related serious mental illness) or clinicians, or for policy changes. Although there is no RCT evidence, parenting interventions for people with schizophrenia or related serious mental illness have been developed. Future research should test these in RCTs in order to improve the evidence base for this population.

Preterm birth prediction in asymptomatic women at mid-gestation using a panel of novel protein biomarkers: the Prediction of PreTerm Labor (PPeTaL) study.

BACKGROUND: Accurate prediction of spontaneous preterm labor/preterm birth in asymptomatic women remains an elusive clinical challenge because of the multi-etiological nature of preterm birth. OBJECTIVE: The aim of this study was to develop and validate an immunoassay-based, multi-biomarker test to predict spontaneous preterm birth. MATERIALS AND METHODS: This was an observational cohort study of women delivering from December 2017 to February 2019 at 2 maternity hospitals in Melbourne, Australia. Cervicovaginal fluid samples were collected from asymptomatic women at gestational week 16+0-24+0, and biomarker concentrations were quantified by enzyme-linked immunosorbent assay. Women were assigned to a training cohort (n = 136) and a validation cohort (n = 150) based on chronological delivery dates. RESULTS: Seven candidate biomarkers representing key pathways in utero-cervical remodeling were discovered by high-throughput bioinformatic search, and their significance in both in vivo and in vitro studies was assessed. Using a combination of the biomarkers for the first 136 women allocated to the training cohort, we developed an algorithm to stratify term birth (n = 124) and spontaneous preterm birth (n = 12) samples with a sensitivity of 100% (95% confidence interval, 76-100%) and a specificity of 74% (95% confidence interval, 66-81%). The algorithm was further validated in a subsequent cohort of 150 women (n = 139 term birth and n = 11 preterm birth), achieving a sensitivity of 91% (95% confidence interval, 62-100%) and a specificity of 78% (95% confidence interval, 70-84%). CONCLUSION: We have identified a panel of biomarkers that yield clinically useful diagnostic values when combined in a multiplex algorithm. The early identification of asymptomatic women at risk for preterm birth would allow women to be triaged to specialist clinics for further assessment and appropriate preventive treatment.

User Perspectives of Mood-Monitoring Apps Available to Young People: Qualitative Content Analysis.

BACKGROUND: Mobile health apps are increasingly available and used in a clinical context to monitor young people's mood and mental health. Despite the benefits of accessibility and cost-effectiveness, consumer engagement remains a hurdle for uptake and continued use. Hundreds of mood-monitoring apps are publicly available to young people on app stores; however, few studies have examined consumer perspectives. App store reviews held on Google and Apple platforms provide a large, rich source of naturally generated, publicly available user reviews. Although commercial developers use these data to modify and improve their apps, to date, there has been very little in-depth evaluation of app store user reviews within scientific research, and our current understanding of what makes apps engaging and valuable to young people is limited. OBJECTIVE: This study aims to gain a better understanding of what app users consider useful to encourage frequent and prolonged use of mood-monitoring apps appropriate for young people. METHODS: A systematic approach was applied to the selection of apps and reviews. We identified mood-monitoring apps (n=53) by a combination of automated application programming interface (API) methods. We only included apps appropriate for young people based on app store age categories (apps available to those younger than 18 years). We subsequently downloaded all available user reviews via API data scraping methods and selected a representative subsample of reviews (n=1803) for manual qualitative content analysis. RESULTS: The qualitative content analysis revealed 8 main themes: accessibility (34%), flexibility (21%), recording and representation of mood (18%), user requests (17%), reflecting on mood (16%), technical features (16%), design (13%), and health promotion (11%). A total of 6 minor themes were also identified: notification and reminders; recommendation; privacy, security, and transparency; developer; adverts; and social/community. CONCLUSIONS: Users value mood-monitoring apps that can be personalized to their needs, have a simple and intuitive design, and allow accurate representation and review of complex and fluctuating moods. App store reviews are a valuable repository of user engagement feedback and provide a wealth of information about what users value in an app and what user needs are not being met. Users perceive mood-monitoring apps positively, but over 20% of reviews identified the need for improvement.

Informing the development of an E-platform for monitoring wellbeing in schools: involving young people in a co-design process.

BACKGROUND: The use of new technologies and methodologies in young people's mental health research is needed to allow more frequent and reliable sampling. Mobile applications and e-platforms create exciting potential for the collection of large-scale cohort data, however there are various feasibility and ethical issues to consider. Consultation with young people is needed to inform the research agenda, and ensure these technologies are engaging, useful and safe. This article describes the process of Public and Patient Involvement (PPI) with a sample of young people in London, with the aim of i) informing the development of a mood-monitoring e-platform, and ii) providing feedback and advice for researchers developing web-based technologies in the mental health field. METHODS: A total of 26 young people were consulted across four advisory group co-design sessions. All young people were students enrolled at one of the participating London based sixth form colleges, and voluntarily attended a workshop session. Audio recordings of the sessions were analysed using a thematic analysis framework. RESULTS: We found that young people were engaged in discussions around mobile health technologies and valued the opportunity to collaborate throughout the early stages of the development process The advisory groups identified key considerations for future web-development work to encourage engagement and prolonged use, including, the promotion of trust and transparency, consideration of accessibility, provision of support, production of engaging and functional design, and acknowledgment of specific contextual influences surrounding young people's wellbeing. CONCLUSIONS: Involving young people in the development process of e-health technologies contributes to optimising the successful adoption and prolonged usage of new methodologies. The thematic map and informant examples can be used to guide researchers interested in developing web-based technologies in the mental health field and will be directly applicable to the development of a mood-monitoring e-platform.

Effects of a monocarboxylate transport 1 inhibitor, AZD3965, on retinal and visual function in the rat.

BACKGROUND AND PURPOSE: Inhibition of monocarboxylate transport 1 (MCT1) is of interest in targeting highly glycolytic tumours. However, MCT1 is expressed in retina, and so inhibition of MCT1 could affect retinal function. EXPERIMENTAL APPROACH: AZD3965, an MCT1 inhibitor selected for clinical development, and two additional MCT1 inhibitors were evaluated for effects on visual acuity in albino (Han Wistar) rats. The effects of AZD3965 on visual acuity and electroretinography (ERG) were further investigated in pigmented (Long-Evans) rats, with dosing for up to 7 days. KEY RESULTS: All three MCT1 inhibitors reduced visual acuity within 2 h of dosing, suggesting a class effect. The deficit caused by AZD3965 (1,000 mg·kg-1 p.o. per day for 4 days) in Long Evans rats recovered to pre-dose levels 7 days after cessation of dosing. AZD3965 (50 to 1,000 mg·kg-1 p.o.) reduced the amplitude of scotopic a- and b-waves, and photopic b-wave of the ERG in a dose-related fashion, within 2 h of dosing. The effects on the scotopic ERG had diminished by Day 7 of dosing, demonstrating partial restoration of function despite continued treatment. Seven days after cessation of dosing at the highest dose tested (1,000 mg·kg-1 ), there was recovery of both scotopic a- and b- waves and, to a lesser extent, photopic b-wave. ERG was affected at lower plasma exposures than was visual function. CONCLUSIONS AND IMPLICATIONS: This study clarifies the role of the MCT1 transporter in retinal function. The monitorability of the functional effects on the retina enabled safe clinical use of AZD3965.

Decidual mesenchymal stem/stromal cell-derived extracellular vesicles ameliorate endothelial cell proliferation, inflammation, and oxidative stress in a cell culture model of preeclampsia.

Oxidative stress and endothelial dysfunction contribute substantially to the pathogenesis of preeclampsia (PE). Decidual mesenchymal stem/stromal cells (DMSC), reportedly reduce endothelial cell dysfunction and alleviate PE-like symptoms in a murine model. However, as a therapeutic strategy, the use of whole DMSC presents significant technical limitations, which may be overcome by employing DMSC-secreted extracellular vesicles (DMSC_EV). DMSC_EV restoration of endothelial dysfunction through a paracrine effect may alleviate the clinical features of PE. OBJECTIVE: To determine whether DMSC-secreted, extracellular vesicles (DMSC_EV) restore endothelial cell function and reduce oxidative stress. METHODS: DMSC were isolated from the placentae of uncomplicated term pregnancies and DMSC_EV prepared by ultracentrifugation. Human umbilical vein endothelial cells (HUVEC) were treated with bacterial lipopolysaccharide (LPS), or with serum from PE patients, to model the effects of PE. DMSC_EV were then added to treated HUVEC and their growth profiles, inflammatory state, and oxidative stress levels measured. RESULTS: DMSC_EV displayed characteristic features of extracellular vesicles. In both LPS- and PE serum-treatment models, addition of DMSC_EV significantly increased HUVEC cell attachment and proliferation, and significantly reduced production of pro-inflammatory cytokine IL-6. The addition of DMSC_EV to LPS-treated HUVEC had no significant effect on total antioxidant capacity, superoxide dismutase levels or on lipid peroxidation levels. In contrast, the addition of DMSC_EV to PE serum-treated HUVEC resulted in a significant reduction in levels of lipid peroxidation. CONCLUSION: Addition of DMSC_EV had beneficial effects in both LPS- and PE serum- treated HUVEC but the two treatment models to induce endothelial cell dysfunction showed differences. The LPS treatment of HUVEC model may not accurately model the endothelial cell dysfunction characteristic of PE. Human cell culture models of PE show that DMSC_EV improve endothelial cell dysfunction in PE, but testing in in vivo models of PE is required.

Arts-Based Interventions for Professionals in Caring Roles During and After Crisis: A Systematic Review of the Literature.

Crisis events, such as the COVID-19 pandemic, can have a devastating effect on communities and the care professionals within them. Over recent years, arts-based interventions have helped in a wide range of crisis situations, being recommended to support the workforce during and after complex crisis but there has been no systematic review of the role of arts-based crisis interventions and whether there are cogent themes regarding practice elements and outcomes. We, therefore, conducted a systematic review to (i) define the arts-based change process used during and after crisis events, and (ii) explore the perceptions of intermediate and long-term mental health benefits of arts-based interventions for professionals in caring roles. Our search yielded six studies (all qualitative). All data were thematically aggregated and meta-synthesized, revealing seven practice elements (a safe place, focusing on strengths and protective factors, developing psychosocial competencies to support peers, emotional expression and processing, identifying and naming the impact of the crisis, using an integrative creative approach, and cultural and organizational sensitivity) applied across all six studies, as well as a range of intermediate and long-term benefits shared common features (adapting, growing, and recovering; using the community as a healing resource; reducing or preventing symptoms of stress or trauma reactions, psychophysiological homeostasis). The ways in which these studies were designed independently from one another and yet used the same practice elements in their crisis interventions indicates that there is comparability about how and why the arts-based practice elements are being used and to what effect. Our findings provide a sound basis and meaningful parameters for future research incorporating quantitative and qualitative approaches to firmly establish the effectiveness of art-based interventions, and how arts can support cultural sensitivity, acceptability and indicated outcomes, particularly those relating to stress and trauma during or following a crisis.

Renal Perfusion during Hemodialysis: Intradialytic Blood Flow Decline and Effects of Dialysate Cooling.

BACKGROUND: Residual renal function (RRF) confers survival in patients with ESRD but declines after initiating hemodialysis. Previous research shows that dialysate cooling reduces hemodialysis-induced circulatory stress and protects the brain and heart from ischemic injury. Whether hemodialysis-induced circulatory stress affects renal perfusion, and if it can be ameliorated with dialysate cooling to potentially reduce RRF loss, is unknown. METHODS: We used renal computed tomography perfusion imaging to scan 29 patients undergoing continuous dialysis under standard (36.5°C dialysate temperature) conditions; we also scanned another 15 patients under both standard and cooled (35.0°C) conditions. Imaging was performed immediately before, 3 hours into, and 15 minutes after hemodialysis sessions. We used perfusion maps to quantify renal perfusion. To provide a reference to another organ vulnerable to hemodialysis-induced ischemic injury, we also used echocardiography to assess intradialytic myocardial stunning. RESULTS: During standard hemodialysis, renal perfusion decreased 18.4% (P<0.005) and correlated with myocardial injury (r=-0.33; P<0.05). During sessions with dialysis cooling, patients experienced a 10.6% decrease in perfusion (not significantly different from the decline with standard hemodialysis), and ten of the 15 patients showed improved or no effect on myocardial stunning. CONCLUSIONS: This study shows an acute decrease in renal perfusion during hemodialysis, a first step toward pathophysiologic characterization of hemodialysis-mediated RRF decline. Dialysate cooling ameliorated this decline but this effect did not reach statistical significance. Further study is needed to explore the potential of dialysate cooling as a therapeutic approach to slow RRF decline.

The functional observational battery and modified Irwin test as global neurobehavioral assessments in the rat: Pharmacological validation data and a comparison of methods.

BACKGROUND: Evaluation of the effects of candidate drugs on the nervous system in preclinical safety pharmacology studies utilises a global neurobehavioral assessment, usually in the rat. This either takes the form of the functional observational battery (FOB) or modified Irwin Test, both of which evaluate effects across 4 functional domains: autonomic, neuromuscular, sensorimotor and behavioral. Although there is a great deal of overlap in the parameters they address, the two tests approach the assessments slightly differently. We undertook a broad pharmacological validation of both the FOB and the Irwin test, and compared the two outcomes. METHODS: Male rats (6 per treatment group) were used to assess each of 12 reference drugs alongside vehicle controls in separate FOB and Irwin studies. The drugs compared in the two study types were chlorpromazine, chlordiazepoxide, clonidine, baclofen, (+)-amphetamine, harmaline, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, physostigmine, picrotoxin, yohimbine and atropine. There is a high degree of semantic equivalence in the parameters assessed in the autonomic domain between the two tests, with a lower degree of equivalence for neuromuscular and behavioral domains, whereas sensorimotor reflex testing in the FOB is far more extensive than in the Irwin test. RESULTS: Across the set of reference drugs, concordance between the two tests was generally good across the 4 functional domains at the 'domain' level (i.e., detecting 'an effect'), whereas there was generally a poor concordance at the individual parameter level. However, this was partially explained by variability between repeated studies on a single reference drug using the same test (FOB or Irwin). CONCLUSIONS: Both tests are 'fit-for-purpose' in detecting effects of candidate drugs on the nervous system. We would encourage the global safety pharmacology community to consider whether (a) the tests could be combined into one industry standard; (b) candidate drugs could be triaged according to CNS penetration, with the level of scrutiny in the CNS core battery assessment adjusted accordingly and (c) whether new home cage technology could be applied to semi-automate the preclinical neurobehavioral assessment.

Time to endoscopy for acute upper gastrointestinal bleeding: Results from a prospective multicentre trainee-led audit.

Background: Endoscopy within 24 h of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24 h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between November and December 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2 h (IQR 12.0-35.7), comprising median admission to referral and referral to endoscopy times of 8.1 h (IQR 3.7-18.1) and 6.7 h (IQR 3.0-23.1), respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0-87.5%, p = 0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7:00 and 19:00 hours or via the emergency department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1 d; p = 0.004), but not 30-d mortality (p = 0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Hepato-splanchnic circulatory stress: An important effect of hemodialysis.

The gastro-intestinal tract is being increasingly recognized as the site of key pathophysiological processes in the hemodialysis patient. Intestinal dysbiosis, increased intraluminal toxin production, and increased intestinal permeability are commonly observed processes which contribute to the pathogenesis of cardiovascular disease and thus elevated mortality. The acute circulatory effects of dialysis itself may contribute significantly to the development of gastrointestinal dysfunction as a result of both local and distant effects. Additionally, the liver, a relatively unknown entity in this process, has a substantial role as a functional barrier between the portal and systemic circulation and in the metabolism of pathogenic gut-derived uremic toxins. Here we summarize the evidence for acute gastro-intestinal and hepatic effects of hemodialysis and identify gaps in knowledge to date which require further study.

White Female Bystanders' Responses to a Black Woman at Risk for Sexual Assault: Positive Effects of Intergroup Contact.

Although much research suggests that intergroup contact reduces prejudice, less research has examined the effects of contact on prosocial intergroup bystander behaviors. The current study examined mediators between White undergraduate women's (N = 139) contact with racial/ethnic minority group members and their intent to help a Black woman at risk for sexual assault. As expected, White women who had more frequent and higher quality contact reported greater intent to intervene. Results showed that the effect of quality intergroup contact was mediated by diversity beliefs, or the attitude that cultural heterogeneity leads to favorable outcomes. These results suggest that promoting high-quality opportunities for intergroup contact and education regarding cultural diversity could promote the safety of racially and ethnically diverse students on predominantly White campuses.

Effect of ultrafiltration during hemodialysis on hepatic and total-body water: an observational study.

BACKGROUND: The hepatic circulation is involved in adaptive systemic responses to circulatory stress. However, it is vulnerable to both chronic hypervolemia and cardiac dysfunction. The influence of hemodialysis (HD) and ultrafiltration (UF) upon liver water content has been understudied. We conducted a detailed pilot study to characterize the effects of HD upon liver water content and stiffness, referenced to peripheral fluid mobilization and total body water. METHODS: We studied 14 established HD patients without liver disease. Magnetic resonance imaging (MRI) together with ultrasound-based elastography and bioimpedance assessment were employed to measure hepatic water content and stiffness, body composition, and water content in the calf pre- and post-HD. RESULTS: Mean UF volume was 8.13 ± 4.4 mL/kg/hr. Fluid removal was accompanied with effective mobilization of peripheral water (measured with MRI within the thigh) from 0.85 ± 0.21 g/mL to 0.83 ± 0.18 g/mL, and reduction in total body water (38.9 ± 9.4 L to 37.4 ± 8.6 L). However, directly-measured liver water content did not decrease (0.57 ± 0.1 mL/g to 0.79 ± 0.3 m L/g). Liver water content and IVC diameter were inversely proportional (r = - 0.57, p = 0.03), a relationship which persisted after dialysis. CONCLUSIONS: In contrast to the reduced total body water content, liver water content did not decrease post-HD, consistent with a diversion of blood to the hepatic circulation, in those with signs of greater circulatory stress. This novel observation suggests that there is a unique hepatic response to HD with UF and that the liver may play a more important role in intradialytic hypotension and fluid shifts than currently appreciated.