Quality-improvement program for ultrasound-based fetal anatomy screening using large-scale clinical audit.

OBJECTIVE: A large-scale audit and peer review of ultrasound images may improve sonographer performance, but is rarely performed consistently as it is time-consuming and expensive. The aim of this study was to perform a large-scale audit of routine fetal anatomy scans to assess if a full clinical audit cycle can improve clinical image-acquisition standards. METHODS: A large-scale, clinical, retrospective audit was conducted of ultrasound images obtained during all routine anomaly scans performed from 18 + 0 to 22 + 6 weeks' gestation at a UK hospital during 2013 (Cycle 1), to build a baseline understanding of the performance of sonographers. Targeted actions were undertaken in response to the findings with the aim of improving departmental performance. A second full-year audit was then performed of fetal anatomy ultrasound images obtained during the following year (Cycle 2). An independent pool of experienced sonographers used an online tool to assess all scans in terms of two parameters: scan completeness (i.e. were all images archived?) and image quality using objective scoring (i.e. were images of high quality?). Both were assessed in each audit at the departmental level and at the individual sonographer level. A random sample of 10% of scans was used to assess interobserver reproducibility. RESULTS: In Cycle 1 of the audit, 103 501 ultrasound images from 6257 anomaly examinations performed by 22 sonographers were assessed; in Cycle 2, 153 557 images from 6406 scans performed by 25 sonographers were evaluated. The analysis was performed including the images obtained by the 20 sonographers who participated in both cycles. Departmental median scan completeness improved from 72% in the first year to 78% at the second assessment (P < 0.001); median image-quality score for all fetal views improved from 0.83 to 0.86 (P < 0.001). The improvement was greatest for those sonographers who performed poorest in the first audit; with regards to scan completeness, the poorest performing 15% of sonographers in Cycle 1 improved by more than 30 percentage points, and with regards to image quality, the poorest performing 11% in Cycle 1 showed a more than 10% improvement. Interobserver repeatability of scan completeness and image-quality scores across different fetal views were similar to those in the published literature. CONCLUSIONS: A clinical audit and a set of targeted actions helped improve sonographer scan-acquisition completeness and scan quality. Such adherence to recommended clinical acquisition standards may increase the likelihood of correct measurement and thereby fetal growth assessment, and should allow better detection of abnormalities. As such a large-scale audit is time consuming, further advantages would be achieved if this process could be automated. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology

Effect of life skills building education and micronutrient supplements provided from preconception versus the standard of care on low birth weight births among adolescent and young Pakistani women (15–24 years): A prospective, population-based cluster-randomized trial

Background: Risk factors known to impact maternal and newborn nutrition and health can exist from adolescence. If an undernourished adolescent girl becomes pregnant, her own health and pregnancy are at an increased risk for adverse outcomes. Offering preconception carefrom adolescence could provide an opportunity for health and nutrition promotion to improve one\u27s own well-being, as well as future pregnancy outcomes and the health of the next generation.Methods: The Matiari emPowerment and Preconception Supplementation (MaPPS) Trial is a population-based two-arm, cluster-randomized, controlled trial of life skills building education and multiple micronutrient supplementation provided in a programmatic context to evaluate the impact on pre-identified nutrition and health outcomes among adolescent and young women (15-24 years) in Matiari district Pakistan, and the infants born to them within the context of the trial. The primary aim is to assess the effect of the intervention on the prevalence of low birth weight births (\u3c 2500 g). The intervention includes bi-monthly life skills building education provided from preconception, and supplementation with multiple micronutrients during preconception (twice-weekly), pregnancy (daily), and post-partum (daily to 6 months). The standard of care includes non-regulated community-based health sessions and daily iron and folic acid supplementation during pregnancy. Additional outcome information will also be collected at set time periods. Among participants, these relate to nutrition (anthropometry, nutritional status), morbidity, and mortality. Among infants, these include birth outcomes (stillbirth, preterm birth, length of gestation, small for gestational age, birth defects), anthropometry, morbidity, and mortality.Discussion: Preconception care from adolescence that includes interventions targeting life skills development and nutrition is suggested to be important to improving the health and nutrition of adolescent and young women and their future offspring. This study is expected to offer insight into providing such an intervention both within a programmatic context and with an extended exposure period prior to conception

Characterizing micronutrient status and risk factors among late adolescent and young women in rural Pakistan: A cross-sectional assessment of the MaPPS trial

Nutritional deficiencies are a leading underlying risk factor contributing to the global burden of disease. In Pakistan, late adolescence is considered a nutritionally vulnerable period, as micronutrient requirements are increased to support maturation, and dietary staples are nutrient poor. However, there has been limited evaluation of micronutrient status beyond anemia and its determinants. Using cross-sectional data from late adolescent and young women (15-23 years) at enrolment in the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial, we aimed to describe the prevalence of key micronutrient deficiencies of public health concern, and generate hierarchical models to examine associations with proxies for social determinants of health (SDoH). The prevalence of micronutrient deficiencies was high: 53.6% (95% confidence interval (CI): 53.0-54.3%) had anemia; 38.0% (95% CI: 36.4-39.6%) iron deficiency anemia; 31.8% (95% CI: 30.2-33.3%) vitamin A deficiency; and 81.1% (95% CI: 79.8-82.4%) vitamin D deficiency. At least one deficiency was experienced by 91.0% (95% CI: 90.1-92.0%). Few SDoH were maintained in the final hierarchical models, although those maintained were often related to socioeconomic status (e.g., education, occupation). To improve the micronutrient status of late adolescent and young women in Pakistan, a direct micronutrient intervention is warranted, and should be paired with broader poverty alleviation methods

Dietary diversity and social determinants of nutrition among late adolescent girls in rural Pakistan

The conditions in which adolescent girls mature shape their health, development and nutrition. Nutrient requirements increase to support growth during adolescence, but gaps between consumption and requirements exist in low- and middle-income countries. We aimed to identify and quantify the relationship between dietary intake and diverse social determinants of nutrition (SDN) among a subset of adolescent girls 15-18.9 years (n = 390) enrolled within the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial. The primary outcome, dietary diversity score (DDS), was derived by applying the Minimum Dietary Diversity for Women 10-item scale to 24-h dietary recall data collected three times per participant. To examine the associations between the SDN-related explanatory variables and DDS, we generated a hierarchical, causal model using mixed effects linear regression to account for the cluster-randomized trial design. Using all data, diets lacked diversity (DDS mean ± SD: 3.35 ± 1.03 [range: 1-7; n = 1170]), and the minimum cut-off for dietary diversity was infrequently achieved (13.5%; 95% CI: 11.6-15.6%). Consumption of starches was reported in all recalls, but micronutrient-rich food consumption was less common. Of the SDN considered, wealth quintile had the strongest association with DDS (P \u3c 0.0001). The diets of the sampled Pakistani adolescent girls were insufficient to meet micronutrient requirements. Poverty was the most important predictor of a diet lacking in diversity, indicating limited purchasing power or access to nutritious foods. Dietary diversification and nutrition education strategies alone are unlikely to lead to improved diets without steps to tackle this barrier, for example, through fortification of staple foods and provision of supplements

International standards for fetal brain structures based on serial ultrasound measurements from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured by ultrasound, from healthy, well-nourished women, at low risk of impaired fetal growth and poor perinatal outcomes, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicentre, longitudinal study. We measured, in planes reconstructed from 3-dimensional (3D) ultrasound volumes of the fetal head at different time points in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle (AV), atrium of the posterior ventricle (PV) and cisterna magna (CM). The sample analysed was randomly selected from the overall FGLS population, ensuring an equal distribution amongst the eight diverse participating sites and of 3D ultrasound volumes across pregnancy (range: 15 - 36 weeks' gestation). Fractional polynomials were used to the construct standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were randomly selected. After exclusions, 3D ultrasound volumes from 442 fetuses born without congenital malformations were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures showed increasing size with gestation and increasing variability for the POF, SF, PV and CM. The 3rd , 5th , 50th , 95th and 97th smoothed centile are presented. The 5th centile of POF and SF were 2.8 and 4.3 at 22 weeks and 4.2 and 9.4mm at 32 weeks respectively. The 95th centile of PV and CM were 8.5 and 7.4 at 22 weeks and 8.5 and 9.4mm at 32 weeks respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcomes. We recommend these as international standards for the assessment of measurements obtained by ultrasound from fetal brain structures

Co-activation of Gi and Gq proteins exerts synergistic effect on human platelet aggregation through activation of phospholipase C and Ca2+ signalling pathways

Our previous studies have shown that subthreshold concentrations of two platelet agonists exert synergistic effects on platelet aggregation. Here we studied the mechanism of synergistic interaction of 5-hydroxytryptamine (5-HT) and epinephrine mediated platelet aggregation. We show that 5-HT had no or little effect on aggregation but it did potentiate the aggregation response of epinephrine. The synergistic interaction of 5-HT (1-5 microM) and epinephrine (0.5-2 microM) was inhibited by alpha2-adrenoceptor blocker (yohimbine; IC50= 0.4 microM), calcium channel blockers (verapamil and diltiazem with IC50 of 10 and 48 mM, respectively), PLC inhibitor (U73122; IC50=6 microM) and nitric oxide (NO) donor, SNAP (IC50=1.6 microM)). The data suggest that synergistic effects of platelet agonists are receptor-mediated and occur through multiple signalling pathways including the activation PLC/Ca2+ signalling cascades

PET imaging of putative microglial activation in individuals at ultra-high risk for psychosis, recently diagnosed and chronically ill with schizophrenia

We examined putative microglial activation as a function of illness course in schizophrenia. Microglial activity was quantified using [11C](R)-(1-[2-chrorophynyl]-N-methyl-N-[1-methylpropyl]-3 isoquinoline carboxamide (11C-(R)-PK11195) positron emission tomography (PET) in: (i) 10 individuals at ultra-high risk (UHR) of psychosis; (ii) 18 patients recently diagnosed with schizophrenia; (iii) 15 patients chronically ill with schizophrenia; and, (iv) 27 age-matched healthy controls. Regional-binding potential (BPND) was calculated using the simplified reference-tissue model with four alternative reference inputs. The UHR, recent-onset and chronic patient groups were compared to age-matched healthy control groups to examine between-group BPND differences in 6 regions: dorsal frontal, orbital frontal, anterior cingulate, medial temporal, thalamus and insula. Correlation analysis tested for BPND associations with gray matter volume, peripheral cytokines and clinical variables. The null hypothesis of equality in BPND between patients (UHR, recent-onset and chronic) and respective healthy control groups (younger and older) was not rejected for any group comparison or region. Across all subjects, BPND was positively correlated to age in the thalamus (r=0.43, P=0.008, false discovery rate). No correlations with regional gray matter, peripheral cytokine levels or clinical symptoms were detected. We therefore found no evidence of microglial activation in groups of individuals at high risk, recently diagnosed or chronically ill with schizophrenia. While the possibility of 11C-(R)-PK11195-binding differences in certain patient subgroups remains, the patient cohorts in our study, who also displayed normal peripheral cytokine profiles, do not substantiate the assumption of microglial activation in schizophrenia as a regular and defining feature, as measured by 11C-(R)-PK11195 BPND.M A Di Biase, A Zalesky, G O'keefe, L Laskaris, B T Baune, C S Weickert, J Olver, P D McGorry, G P Amminger, B Nelson, A M Scott, I Hickie, R Banati, F Turkheimer, M Yaqub, I P Everall, C Pantelis and V Crople

Automatic Probe Movement Guidance for Freehand Obstetric Ultrasound

We present the first system that provides real-time probe movement guidance for acquiring standard planes in routine freehand obstetric ultrasound scanning. Such a system can contribute to the worldwide deployment of obstetric ultrasound scanning by lowering the required level of operator expertise. The system employs an artificial neural network that receives the ultrasound video signal and the motion signal of an inertial measurement unit (IMU) that is attached to the probe, and predicts a guidance signal. The network termed US-GuideNet predicts either the movement towards the standard plane position (goal prediction), or the next movement that an expert sonographer would perform (action prediction). While existing models for other ultrasound applications are trained with simulations or phantoms, we train our model with real-world ultrasound video and probe motion data from 464 routine clinical scans by 17 accredited sonographers. Evaluations for 3 standard plane types show that the model provides a useful guidance signal with an accuracy of 88.8% for goal prediction and 90.9% for action prediction.Comment: Accepted at the 23rd International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI 2020

Amyloid-driven disruption of default mode network connectivity in cognitively healthy individuals

Cortical accumulation of amyloid beta is one of the first events of Alzheimer's disease pathophysiology, and has been suggested to follow a consistent spatiotemporal ordering, starting in the posterior cingulate cortex, precuneus and medio-orbitofrontal cortex. These regions overlap with those of the default mode network, a brain network also involved in memory functions. Aberrant default mode network functional connectivity and higher network sparsity have been reported in prodromal and clinical Alzheimer's disease. We investigated the association between amyloid burden and default mode network connectivity in the preclinical stage of Alzheimer's disease and its association with longitudinal memory decline. We included 173 participants, in which amyloid burden was assessed both in CSF by the amyloid beta 42/40 ratio, capturing the soluble part of amyloid pathology, and in dynamic PET scans calculating the non-displaceable binding potential in early-stage regions. The default mode network was identified with resting-state functional MRI. Then, we calculated functional connectivity in the default mode network, derived from independent component analysis, and eigenvector centrality, a graph measure recursively defining important nodes on the base of their connection with other important nodes. Memory was tested at baseline, 2- and 4-year follow-up. We demonstrated that higher amyloid burden as measured by both CSF amyloid beta 42/40 ratio and non-displaceable binding potential in the posterior cingulate cortex was associated with lower functional connectivity in the default mode network. The association between amyloid burden (CSF and non-displaceable binding potential in the posterior cingulate cortex) and aberrant default mode network connectivity was confirmed at the voxel level with both functional connectivity and eigenvector centrality measures, and it was driven by voxel clusters localized in the precuneus, cingulate, angular and left middle temporal gyri. Moreover, we demonstrated that functional connectivity in the default mode network predicts longitudinal memory decline synergistically with regional amyloid burden, as measured by non-displaceable binding potential in the posterior cingulate cortex. Taken together, these results suggest that early amyloid beta deposition is associated with aberrant default mode network connectivity in cognitively healthy individuals and that default mode network connectivity markers can be used to identify subjects at risk of memory decline