The significance of meeting Dawes-Redman criteria in computerised antenatal fetal heart rate assessment.

OBJECTIVE: To investigate the significance of not meeting Dawes-Redman criteria on computerised cardiotocography in high-risk pregnancies. DESIGN: Retrospective observational study. SETTING: UK university hospital. POPULATION: High-risk pregnancies undergoing antenatal assessment. METHODS: We interrogated the database for records of computerised fetal heart rate assessment and pregnancy outcomes. MAIN OUTCOME MEASURES: Neonatal outcome and stillbirths. RESULTS: Excluding duplicate assessment in the same pregnancy, 14 025 records with complete information on the criteria of normality having been met and the outcome of the pregnancy were available. Criteria were not met for 907 records (6.46%). The gestational age of assessment was lower in the group not meeting criteria of normality. Overall, 32 stillbirths occurred in normally formed fetuses (2.28/1000). Stillbirths were more frequent in the group not meeting criteria (odds ratio [OR] 8.78, 95% CI 4.28-18.02). This finding persisted even after records with abnormally low short-term variation (STV) were excluded. The confidence intervals around the rate of stillbirth in the two groups overlapped beyond an STV of 8 ms. CONCLUSIONS: Approximately 1:16 pregnancies do not meet the criteria of normality. The criteria are not met more often at preterm gestation than at term. The risk of stillbirth was higher in the group not meeting criteria of normality, even if cases with low STV are excluded. Cases not meeting criteria should be followed up closely, unless the STV is ≥8 ms. Stillbirths still occurred in the group meeting criteria, but the rate was lower than in the general population.

Prevention of psychosocial distress consequences in somatic hospital inpatients via a stepped and collaborative care model: protocol of SomPsyNet, a stepped wedge cluster randomised trial.

INTRODUCTION: Approximately 30% of somatic hospital inpatients experience psychosocial distress, contributing to increased (re-)hospitalisation rates, treatment resistance, morbidity, and direct and indirect costs. However, such distress often remains unrecognised and unaddressed. We established 'SomPsyNet', a 'stepped and collaborative care model' (SCCM) for somatic hospital inpatients, aiming at alleviating this issue through early identification of distress and provision of appropriate care, providing problem-focused pathways and strengthening collaborative care. We report the protocol of the 'SomPsyNet' study, aiming to evaluate implementation and impact of the SCCM on distressed patients' health-related quality of life. Secondary objectives include assessing efficacy of the screening procedures, influence of SCCM on other health outcomes and associated costs. METHODS AND ANALYSIS: Our stepped wedge cluster randomised trial conducted at three tertiary hospitals comprises three conditions: treatment as usual (TAU) without screening for distress (phase 0), TAU with screening but without consequences (phase I, main comparator) and TAU with screening and psychosomatic-psychiatric consultations for those distressed (phase II). The time-of-transition between phases I and II was randomised. Sample size target is N=2200-2500 participants, with 6 month follow-up for distressed (anticipated n=640-700) and a subsample of non-distressed (anticipated n=200) patients. Primary outcome is mental health-related quality of life (SF-36 'Mental Health Component Summary score'); secondary outcomes include psychosocial distress, anxiety, depressive and somatic symptoms, symptom burden and distress, resilience, social support and qualitative of life, assessed by internationally accepted instruments, with good psychometric properties. Further, health claims data will be used to assess SCCM's impact on direct and indirect costs. ETHICS AND DISSEMINATION: SomPsyNet adheres to the Helsinki Declaration and is approved by the 'Ethikkommission Nordwest- und Zentralschweiz' (2019-01724). Findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: Swiss National Clinical Trials Portal; ClinicalTrials.gov (NCT04269005, updated 19.09.2023).

Is mid-gestational uterine artery Doppler still useful in a setting with routine first-trimester pre-eclampsia screening? A cohort study.

OBJECTIVE: To evaluate whether routine mid-gestational uterine artery Doppler (UtAD) modifies the risk for preterm pre-eclampsia after first-trimester combined pre-eclampsia screening. DESIGN: Retrospective cohort study. SETTING: London Tertiary Hospital. POPULATION: A cohort of 7793 women with singleton pregnancies, first-trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and UtAD pulsatility index (PI) assessment at the mid-gestation ultrasound. METHODS: Pregnancies were divided into four groups: high risk in both trimesters (H1 H2 ), high risk in the first but not in the second trimester (H1 L2 ), low risk in the first but high risk in the second trimester (L1 H2 ) and low risk in both trimesters (L1 L2 ). MAIN OUTCOME MEASURES: Small for gestational age (SGA), hypertensive disorders of pregnancy (HDP) and stillbirth. RESULTS: In this cohort, 600 (7.7%) and 620 (7.9%) women were designated as being at high risk in the first and second trimesters, respectively. Preterm pre-eclampsia was more prevalent in the H1 L2 group (4.5%) than in women considered at low risk in the first trimester (0.4%, p < 0.0001). The prevalence of preterm pre-eclampsia in the L1 H2 group (3.3%) was significantly lower than that in women considered at high risk in the first trimester (7.0%, p = 0.0076), and was higher than that observed in the L1 L2 group (0.2%, p < 0.0001). The prevalence of SGA and term HDP followed similar trends. CONCLUSIONS: Pre-eclampsia risk after first-trimester FMF pre-eclampsia screening may be stratified through mid-gestational routine UtAD assessment. Pregnancy care should not be de-escalated for low mid-gestational UtAD resistance in women classified as being at high risk in the first trimester. The escalation of care may be justified in women at low risk but with high mid-gestational UtAD resistance.

Reducing health inequality in Black, Asian and other minority ethnic pregnant women: impact of first trimester combined screening for placental dysfunction on perinatal mortality.

OBJECTIVE: To assess the impact of the Fetal Medicine Foundation (FMF) first trimester screening algorithm for pre-eclampsia on health disparities in perinatal death among minority ethnic groups. DESIGN: A retrospective cohort study from July 2016 to December 2020. SETTING: A large London teaching hospital. PATIENTS AND METHODS: All women who underwent first trimester pre-eclampsia risk assessment using either the NICE screening checklist or the FMF multimodal approach. Women considered at high-risk in the FMF cohort were offered 150 mg aspirin before 16 weeks' gestation, serial growth scans and elective birth at 40 weeks. MAIN OUTCOME MEASURES: Stillbirth, neonatal death and perinatal death rates stratified by screening method and maternal ethnicity. RESULTS: In the NICE cohort, the perinatal death rate was significantly higher in non-white than white women (7.95 versus 2.63/1000 births, OR 3.035, 95% CI 1.551-5.941). Following the introduction of FMF screening, the perinatal death rate in non-white women fell from 7.95 to 3.22/1000 births (OR 0.403, 95% CI 0.206-0.789), such that it was no longer significantly different from the perinatal mortality rate in white women (3.22 versus 2.55/1000 births, OR 1.261, 95% CI 0.641-2.483). CONCLUSIONS: First trimester combined screening for placental dysfunction is associated with a significant reduction in perinatal death in minority ethnic women. Health disparities in perinatal death among ethnic minority women demand urgent attention from both clinicians and health policy makers. The data of this study suggest that this ethnic health inequality may be avoidable. TWEETABLE ABSTRACT: Multimodal early pregnancy placental dysfunction screening can lead to a significant reduction in perinatal deaths in non-white women.

Advanced maternal age and adverse pregnancy outcomes.

A wide range of adverse pregnancy outcomes are associated with women of advanced maternal age (AMA). These include increased risks for miscarriage, chromosomal abnormalities, stillbirth, foetal growth restriction, preterm birth, pre-eclampsia, gestational diabetes mellitus and caesarean section. While a wide body of literature has reported on these risks, varying definitions in both AMA and reported outcomes can make synthesizing the information difficult when counselling an individual women about her specific risks. In this chapter, we discuss the role of AMA on adverse pregnancy outcomes with a view to clarifying the magnitude of the risks for each outcome in the context to enable more informed clinical counselling and decision-making.

Perceived Need for Psychosocial Support After Aortic Dissection: Cross-Sectional Survey.

BACKGROUND: The gold standard management of aortic dissection, a life-threatening condition, includes multidisciplinary approaches. Although mental distress following aortic dissection is common, evidence-based psychosocial interventions for aortic dissection survivors are lacking. OBJECTIVE: The aim of this study is to identify the perceived psychosocial needs of aortic dissection survivors by surveying patients, their relatives, and health professionals to inform the development of such interventions. METHODS: This study used a cross-sectional survey and collected responses from 41 participants (27 patients with aortic dissection, 8 relatives of patients with aortic dissection, and 6 health professionals) on key topics, types of interventions, best timing, anticipated success, and the intended effects and side effects of psychosocial interventions after aortic dissection. RESULTS: The principal intervention topics were "changes in everyday life" (28/41, 68%, 95% CI 54.5%-82.9%), "anxiety" (25/41, 61%, 95% CI 46.2%-76.2%), "uncertainty" (24/41, 59%, 95% CI 42.9%-73.2%), "tension/distress" (24/41, 59%, 95% CI 43.9%-73.8%), and "trust in the body" (21/41, 51%, 95% CI 35.9%-67.5%). The most commonly indicated intervention types were "family/relative therapy" (21/41, 51%, 95% CI 35%-65.9%) and "anxiety treatment" (21/41, 51%, 95% CI 35%-67.5%). The most recommended intervention timing was "during inpatient rehabilitation" (26/41, 63%, 95% CI 47.6%-77.5%) followed by "shortly after inpatient rehabilitation" (20/41, 49%, 95% CI 32.4%-65%). More than 95% (39/41) of respondents anticipated a benefit from psychosocial interventions following aortic dissection dissection, expecting a probable improvement in 68.6% (95% CI 61.4%-76.2%) of aortic dissection survivors, a worse outcome for 5% (95% CI 2.9%-7.9%), and that 6% (95% CI 1.8%-10.4%) would have negative side effects due to such interventions. CONCLUSIONS: Our findings highlight a substantial need for psychosocial interventions in aortic dissection survivors and indicate that such interventions would be a success. They provide a basis for the development and evaluation of interventions as part of state-of-the-art aortic dissection management.

LAP proteins are localized at the post-synaptic membrane of neuromuscular junctions and appear to modulate synaptic morphology and transmission.

Erbin, Lano, Scribble, and Densin-180 belong to LAP (leucine-rich repeats and PDZ domain) adaptor proteins involved in cell signaling pathways. Previously, we identified Erbin, Lano, and Scribble, but not Densin-180, in muscle cells, where they are involved in regulating the aggregation of nicotinic acetylcholine receptors in vitro. Here, we analyzed their cellular localization at the neuromuscular junction (NMJ) in skeletal muscles of mice. Erbin, Lano, and Scribble were significantly accumulated at NMJs and localized in different synaptic cells. Moreover, we used mouse mutants to analyze the role of Erbin at the NMJ. We used two Erbin mutant mouse strains that either completely lack Erbin protein (Erbinnull/null ) or express a truncated Erbin mutant where the carboxy-terminal PDZ domain is replaced by ß-galactosidase (ErbinΔC/ΔC ) thereby abolishing its interaction with ErbB receptor tyrosine kinases. Neither the lack of the PDZ domain of Erbin, nor its complete absence interfered with the general localization of LAP proteins at NMJs, but Lano and Scribble transcript levels were up-regulated in homozygous Erbin-null muscles. Furthermore, grip strength was reduced and neural transmission impaired in homozygous aged Erbin-null but not Erbin-ΔC mice. Erbin-null skeletal muscles did not reveal any conspicuous impairment of the muscle fiber. Localization of other NMJ marker proteins was not affected either. Quantitative 3D morphometry showed that NMJs of Erbin-null muscles were significantly smaller and fragmented in the soleus. We speculate that Erbin, Lano, and Scribble act at the post-synaptic membrane of NMJs in a concerted fashion to regulate nicotinic acetylcholine receptors cluster morphology and neural transmission. Cover Image for this issue: doi: 10.1111/jnc.13340.

Contingent Screening for Small by Weight for Gestational Age Neonates.

Effective screening for small for gestational age neonates (SGA), in the absence of preeclampsia, can be accomplished using a contingent screening method. The basis for the contingent model is a combined assessment at 19-24 weeks gestation to stratify patients according to their risk. We can then identify prenatally over 90% of SGA neonates for a false positive rate of 10%.

Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin.

Oxidative stress can be involved in several cellular responses, such as differentiation, apoptosis and necrosis. Dehydrocrotonin (DCTN, diterpene lactone) from Croton cajucara, Brazilian medicinal plant, slightly induced NBT-reducing activity. In presence of protein phosphatase inhibitors significant differentiation of HL60 cells was observed. Flow cytometry analysis demonstrated that apoptosis was induced when the cells were treated with okadaic acid (OKA) and plus trans-dehydrocrotonin (t-DCTN) this effect was two-fold increased. Unlike, when the cells were treated only with t-DCTN, necrosis was observed. On the other hand, the necrosis induced by t-DCTN could be due to oxidative stress, revealed by increase of GSH content. Therefore, this differentiation pathway involves the modulation of protein phosphatases and this inhibition promotes the t-DCTN action on apoptosis induction.