Vaginal matrix metalloproteinase-9 (MMP-9) as a potential early predictor of preterm birth.

OBJECTIVES: To evaluate the differences in vaginal matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMPs) in pregnant patients with a history of prior preterm birth compared with controls. METHODS: A prospective cohort pilot study recruited patients during prenatal care with history of prior spontaneous preterm birth (high-risk group) or no history of preterm birth (low-risk/controls). Inclusion criteria were singleton gestation at 11-16 weeks and between 18 and 55 years of age. Exclusion criteria were diabetes mellitus, hypertension, diseases affecting the immune response or acute vaginitis. A vaginal wash was performed at time of enrollment, and patients were followed through delivery. Samples were analyzed using semi-quantitative analysis of MMPS and TIMPS. The study was approved by the IRB and a p-value <0.05 was considered significant. RESULTS: A total of 48 pregnant patients were recruited: 16 with a history of preterm birth (high-risk group) and 32 with no history of preterm birth (low-risk group/controls). Groups were similar in age, race, BMI, and delivery mode. The high-risk group had more multiparous women (100 vs. 68.8 %; p=0.02), a greater preterm birth rate (31.2 vs. 6.3 %; p=0.02), and a lower birth weight (2,885 ± 898 g vs. 3,480 ± 473 g; p=0.02). Levels of vaginal MMP-9 were greater in high-risk patients than low-risk patients (74.9 % ± 27.0 vs. 49.4 % ± 31.1; p=0.01). When dividing the cohort into patients that had a spontaneous preterm birth (7/48, 14.6 %) vs. those with a term delivery (41/48, 85.4 %), the vaginal MMP-9 remained elevated in the cohort that experienced a preterm birth (85.46 %+19.79 vs. 53.20 %+31.47; p=0.01). There were no differences in the other MMPS and in TIMPs between high and low-risk groups. CONCLUSIONS: There was an increase in vaginal MMP-9 during early pregnancy in those at high risk for preterm birth and in those who delivered preterm, regardless of prior pregnancy outcome. Vaginal MMP-9 may have potential as a marker of increased risk of preterm birth.

Missingness patterns in a comprehensive instrument identifying psychosocial and substance use risk in antenatal care.

BACKGROUND: Psychosocial vulnerabilities (e.g. inadequate social support, financial insecurity, stress) and substance use elevate risks for adverse perinatal outcomes and maternal mental health morbidities. However, various barriers, including paucity of validated, simple and usable comprehensive instruments, impede execution of the recommendations to screen for such vulnerabilities in the first antenatal care visit. The current study presents findings from a newly implemented self-report tool created to overcome screening barriers in outpatient antenatal clinics. METHODS: This was a retrospective chart-review of 904 women who completed the Profile for Maternal & Obstetric Treatment Effectiveness (PROMOTE) during their first antenatal visit between June and December 2019. The PROMOTE includes the 4-item NIDA Quick Screen and 15 additional items that each assess a different psychosocial vulnerability. Statistical analysis included evaluation of missing data, and exploration of missing data patterns using univariate correlations and hierarchical clustering. RESULTS: Three quarters of women (70.0%) had no missing items. In the entire sample, all but four PROMOTE items (opioid use, planned pregnancy, educational level, and financial state) had < 5% missing values, suggesting good acceptability and feasibility. Several respondent-related characteristics such as lower education, less family support, and greater stress were associated with greater likelihood of missing items. Instrument-related characteristics associated with missing values were completing the PROMOTE in Spanish or question positioning at the end of the instrument. CONCLUSIONS AND IMPLICATIONS: Conducting a comprehensive screening of theoretically and clinically meaningful vulnerabilities in an outpatient setting is feasible. Study findings will inform modifications of the PROMOTE and subsequent digitisation.

Applying machine learning methods to psychosocial screening data to improve identification of prenatal depression: Implications for clinical practice and research.

We utilized machine learning (ML) methods on data from the PROMOTE, a novel psychosocial screening tool, to quantify risk for prenatal depression for individual patients and identify contributing factors that impart greater risk for depression. Random forest algorithms were used to predict likelihood for being at high risk for prenatal depression (Edinburgh Postnatal Depression Scale; EPDS ≥ 13 and/or positive self-injury item) using data from 1715 patients who completed the PROMOTE. Performance matrices were calculated to assess the ability of the PROMOTE to accurately classify patients. Probability for depression was calculated for individual patients. Finally, recursive feature elimination was used to evaluate the importance of each PROMOTE item in the classification of depression risk. PROMOTE data were successfully used to predict depression with acceptable performance matrices (accuracy = 0.80; sensitivity = 0.75; specificity = 0.81; positive predictive value = 0.79; negative predictive value = 0.97). Perceived stress, emotional problems, family support, age, major life events, partner support, unplanned pregnancy, current employment, lifetime abuse, and financial state were the most important PROMOTE items in the classification of depression risk. Results affirm the value of the PROMOTE as a psychosocial screening tool for prenatal depression and the benefit of using it in conjunction with ML methods. Using such methods can help detect underreported outcomes and identify what in patients' lives makes them more vulnerable, thus paving the way for effective individually tailored precision medicine.

Compassion within conflict: Toward a computational theory of social groups informed by maternal brain physiology.

Benevolent intersubjectivity developed in parent-infant interactions and compassion toward friend and foe alike are non-violent interventions to group behavior in conflict. Based on a dyadic active inference framework rooted in specific parental brain mechanisms, we suggest that interventions promoting compassion and intersubjectivity can reduce stress, and that compassionate mediation may resolve conflicts.

Considering delay of cholecystectomy in the third trimester of pregnancy.

INTRODUCTION: Current guidelines support laparoscopic cholecystectomy as the treatment of choice for pregnant women with symptomatic gallbladder disease, regardless of the trimester. Early intervention has remained the standard of care, but recent evidence has challenged this practice in pregnant women. We sought to compare surgical and maternal-fetal outcomes of antepartum versus postpartum cholecystectomy in New York State. METHODS: Between 2005 and 2014, the New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for patients who underwent cholecystectomy within 3 months before (antepartum cholecystectomy, APCCY: n = 82) and after (postpartum cholecystectomy, PPCCY: n = 5040) childbirth to approximate third-trimester operations. All patients who underwent cholecystectomy during pregnancy (n = 971) were extracted to evaluate inter-trimester differences. Subgroup analysis compared APCCY patients who were not hospitalized within 1 year before APCCY (n = 80) and PPCCY patients who were hospitalized within 1 year before childbirth (n = 29) for symptomatic biliary disease. Multivariable generalized linear regression models were used to characterize the association between timing of cholecystectomy and several primary outcomes: length of stay (LOS), 30-day non-pregnancy, non-delivery readmission (NPND), bile duct injury (BDI), composite maternal outcome (antepartum hemorrhage, preterm delivery, cesarean section), any complications, and fetal demise. RESULTS: Third-trimester APCCY women had longer LOS (Ratio: 1.44, 95% CI [1.26-1.66], p < 0.0001) and greater incidence of preterm delivery (OR 2.54, 95% CI [1.37-4.43], p = 0.0019). Cholecystectomy timing was not independently associated with differences in composite maternal outcome (p = 0.1480), BDI (p = 0.2578), 30-day NPND readmission (p = 0.7579), any complications (p = 0.2506), and fetal demise (2.44% versus 0.44%, p = 0.0545). Subgroup analysis revealed no differences in any of the seven outcomes. CONCLUSIONS: New York Statewide data suggest that although laparoscopic cholecystectomy is safe in pregnancy, delay of cholecystectomy should be discussed in the third trimester due to an increased risk for preterm delivery.

Pregnant patients requiring appendectomy: comparison between open and laparoscopic approaches in NY State.

INTRODUCTION: Even though acute appendicitis is the most common general surgical condition encountered during pregnancy, the preferred approach to appendectomy in pregnant patients remains controversial. Current guidelines support laparoscopic appendectomy as the treatment of choice for pregnant women with appendicitis, regardless of trimester. However, recent published data suggests that the laparoscopic approach contributes to higher rates of fetal demise. Our study aims to compare laparoscopic and open appendectomy in pregnancy at a statewide population level. METHODS: ICD-9 codes were used to extract 1006 pregnant patients undergoing appendectomy between 2005 and 2014 from the NY Statewide Planning and Research Cooperative System (SPARCS) database. Surgical outcomes (any complications, 30-day readmission rate, length of stay (LOS)) and obstetrical outcomes (antepartum hemorrhage, preterm delivery, cesarean section, sepsis, chorioamnionitis) were compared between open and laparoscopic appendectomy. Multivariable generalized linear regression models were used to compare different outcomes between two surgical approaches after adjusting for possible confounders. RESULTS: The laparoscopic cohort (n = 547, 54.4%) had significantly shorter LOS than the open group (median ± IQR: 2.00 ± 2.00 days versus 3.00 ± 2.00 days, p value < 0.0001, ratio = 0.789, 95% CI 0.727-0.856). Patients with complicated appendicitis had longer LOS than those with simple appendicitis (p value < 0.0001, ratio = 1.660, 95% CI 1.501-1.835). Obstetrical outcomes (p value = 0.097, OR 1.254, 95% CI 0.961-1.638), 30-day non-delivery readmission (p value = 0.762, OR 1.117, 95% CI 0.538-2.319), and any complications (p value = 0.753, OR 0.924, 95% CI 0.564-1.517) were not statistically significant between the laparoscopic versus open appendectomy groups. Three cases of fetal demise occurred, all within the laparoscopic appendectomy group. CONCLUSIONS: The laparoscopic approach resulted in a shorter LOS. Although fetal demise only occurred in the laparoscopic group, these results were not significant (p value = 0.255). Our large population-based study further supports current guidelines that laparoscopic appendectomy may offer benefits over open surgery for pregnant patients in any trimester due to reduced time in the hospital and fetal and maternal outcomes comparable to open appendectomy.

Risk of metformin failure in the treatment of women with gestational diabetes.

OBJECTIVES: To estimate the metformin failure rate in women with gestational diabetes. METHODS: The study was designed as a retrospective cohort of women diagnosed with gestational diabetes by the 75 g 2 h oral glucose tolerance test. Women were placed into two groups: metformin success (107 patients not requiring insulin therapy) or metformin failure (15 patients requiring the addition of, or, transition to insulin). Primary outcome: rate of metformin failure. Secondary outcomes: maternal and neonatal factors. RESULTS: The failure rate of metformin was 15% (19/122 women) in the study. The failure group was more likely to have 3 abnormal values on a 2-h 75 g oral glucose tolerance test (37% (n=7/19) vs. 15% (n=15/103), p=0.02). Patients who failed had higher average fasting blood glucose levels on the glucose tolerance test as well as on pretreatment fasting finger stick values. Those who failed metformin were diagnosed with gestational diabetes and started on metformin earlier in gestation. CONCLUSIONS: Overall low rate of metformin failure in treatment of gestational diabetes.

Effects of opioids on the parental brain in health and disease.

The epidemic of opioid use disorder (OUD) directly affects millions of women of child-bearing age. Unfortunately, parenting behaviors - among the most important processes for human survival - are vulnerable to the effects of OUD. The standard of care for pregnant women with OUD is opioid maintenance therapy (OMT), of which the primary objective is to mitigate addiction-related stress. The aim of this review is to synthesize current information specific to pregnancy and parenting that may be affected by OUD. We first summarize a model of the parental brain supported by animal research and human neuroimaging. We then review animal models of exogenous opioid effects on parental brain and behavior. We also present preliminary data for a unifying hypothesis that may link different effects of exogenous opioids on parenting across species and in the context of OMT. Finally, we discuss future directions that may inform research and clinical decision making for peripartum women with OUD.

Assisted reproductive technologies (ART) and placental abnormalities.

Objectives Assisted reproductive technologies (ART) may be associated with placental abnormalities including placenta previa, umbilical cord abnormalities, and placental abruption. Our study evaluates the relationship between ART and placental abnormalities compared with spontaneously conceived controls. Methods An IRB-approved cohort study was conducted including women who delivered between January 2013 and December 2018. We excluded delivery prior to 23 weeks and known fetal anomalies. Patients were matched with controls (2:1) for parity, age, and mode of delivery. Controls were women who had spontaneously conceived and delivered immediately preceding and following the index delivery. The primary outcome was placental abnormalities found on both antenatal ultrasound and pathology in ART gestations compared with spontaneously conceived gestations. Results There were 120 ART pregnancies and 240 matched control pregnancies identified. The groups were similar for parity, BMI, comorbidities, number of multiples, mode of delivery, and female newborns. The ART group had a higher maternal age (37.1±5 y vs. 30.0±5 y; p<0.001), greater preterm birth (29 vs. 6%; p<0.001), and lower BW (2,928±803 g vs. 3,273±586 g; p<0.001). The ART group had a higher incidence of placenta previa on ultrasound (4.0 vs. 0.4%, p=0.01), adherent placentas at delivery (3 vs. 0% p=0.014), placental abruption (2 vs. 0%; p=0.04), as well as an increased rate of velamentous cord insertion (12 vs. 3%, p<0.001) and marginal cord insertion (28 vs. 15%, p=0.002). ART demonstrated a two-fold likelihood of abnormal placental pathology. Conclusions ART is associated with increased rate of placental abnormalities, including abnormal umbilical cord insertion and increased rates of adherent placentation. This information may be beneficial in planning and surveillance in patients with ART pregnancies.

Chemistry of Singlet Oxygen with a Cadmium-Sulfur Cluster: Physical Quenching versus Photooxidation.

We investigated the chemistry of singlet oxygen with a cadmium-sulfur cluster, (Me4N)2[Cd4(SPh)10]. This cluster was used as a model for cadmium-sulfur nanoparticles. Such nanoparticles are often used in conjunction with photosensitizers (for singlet oxygen generation or dye-sensitized solar cells), and hence, it is important to determine if cadmium-sulfur moieties physically quench and/or chemically react with singlet oxygen. We found that (Me4N)2[Cd4(SPh)10] is indeed a very strong quencher of singlet oxygen with total rate constants for 1O2 removal of (5.8 ± 1.3) × 108 M-1 s-1 in acetonitrile and (1.2 ± 0.5) × 108 M-1 s-1 in CD3OD. Physical quenching predominates, but chemical reaction leading to decomposition of the cluster and formation of sulfinate is also significant, with a rate constant of (4.1 ± 0.6) × 106 M-1 s-1 in methanol. Commercially available cadmium-sulfur quantum dots ("lumidots") show similar singlet oxygen quenching rate constants, based on the molar concentration of the quantum dots.

Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines.

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical-chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were toxic in all cell types. TiO2 and SiO2 MNMs also triggered toxicity in some, but not all, cell types and the cell type-specific effects were influenced by the specific coating and surface modification. CeO2 MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type-specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.

Internalization of nanopolymeric tracers does not alter characteristics of placental cells.

In the cell therapy scenario, efficient tracing of transplanted cells is essential for investigating cell migration and interactions with host tissues. This is fundamental to provide mechanistic insights which altogether allow for the understanding of the translational potential of placental cell therapy in the clinical setting. Mesenchymal stem/stromal cells (MSC) from human placenta are increasingly being investigated for their potential in treating patients with a variety of diseases. In this study, we investigated the feasibility of using poly (methyl methacrylate) nanoparticles (PMMA-NPs) to trace placental MSC, namely those from the amniotic membrane (hAMSC) and early chorionic villi (hCV-MSC). We report that PMMP-NPs are efficiently internalized and retained in both populations, and do not alter cell morphofunctional parameters. We observed that PMMP-NP incorporation does not alter in vitro immune modulatory capability of placental MSC, a characteristic central to their reparative/therapeutic effects in vitro. We also show that in vitro, PMMP-NP uptake is not affected by hypoxia. Interestingly, after in vivo brain ischaemia and reperfusion injury achieved by transient middle cerebral artery occlusion (tMCAo) in mice, iv hAMSC treatment resulted in significant improvement in cognitive function compared to PBS-treated tMCAo mice. Our study provides evidence that tracing placental MSC with PMMP-NPs does not alter their in vitro and in vivo functions. These observations are grounds for the use of PMMP-NPs as tools to investigate the therapeutic mechanisms of hAMSC and hCV-MSC in preclinical models of inflammatory-driven diseases.

Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder.

BACKGROUND: Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size. METHODS: Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells. RESULTS: Quartz crystals were grown in the submicron (n-Qz-syn) or micron (µ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (µ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface. CONCLUSIONS: Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz.

Nanomaterials: impact on cells and cell organelles.

Colloidal nanoparticles designed for the interactions with cells are very small, nanoscale objects usually consisting of inorganic cores and organic shells that are dispersed in a buffer or biological medium. By tuning the material properties of the nanoparticles a number of different biological applications of nanomaterials are enabled i.e. targeting, labelling, drug delivery, use as diagnostic tools or therapy. For all biological applications of nanoparticles, it is important to understand their interactions with the surrounding biological environment in order to predict their biological impact, in particular when designing the nanoparticles for diagnostic and therapeutic purpose. Due to the high surface-to-volume ratio, the surface of nanomaterials is very reactive. When exposed to biological fluids, the proteins and biomolecules present therein tend to associate with the nanoparticles' surface. This phenomenon is defined as biomolecular corona formation. The biomolecular corona plays a key role in the interaction between nanoparticles and biological systems, impacting on how these particles interact with biological systems on a cellular and molecular level. This book chapter describes the nature of the interactions at the bio-nano interface, shows the design strategy of nanoparticles for nanomedicine, and defines the concepts of biomolecular corona and biological identity of nanoparticles. Moreover, it describes the interaction of functionalised nanomaterials with cell organelles and intracellular fate of nanoparticles and it shows therapeutic application of gold nanoparticles as dose enhancers in radiotherapy.

Racial and ethnic identity in nursing research.

Nurse researchers need to be able to identify the race and ethnicity of participants in their studies for several reasons including addressing health disparities, ensuring adequate representation from under-represented minorities, and making sure other nurses can understand how findings may or may not pertain to their own patient population. However, obtaining accurate information about race and ethnicity requires careful attention to norms of study participants. Race and ethnicity are not always viewed as 2 separate constructs and the definition of both changes over time. In fact, a random sample of 100 patients in 1 hospital found an 11% discrepancy between patients' self-identification of race using 2 different methodologies of self-identification. To optimize accuracy of self-identification of race and ethnicity, this paper discusses techniques learned in practice and in the literature for improving self-identification of these 2 constructs.

Serial image interpretation tasks improve accuracy and increase confidence in Level 1 echocardiography reporting: a pilot study.

BACKGROUND: Focused echocardiography is increasingly used in acute and emergency care, with point-of-care ultrasound integrated into several specialist training curricula (e.g. Emergency Medicine, Cardiology, Critical Care). Multiple accreditation pathways support development of this skill but there is scant empirical evidence to inform selection of teaching methods, accreditation requirements or quality assurance of education in focussed echocardiography. It has also been noted that access to in-person teaching can be a barrier to completing accreditation programmes, and that this may affect learners disproportionately depending on the location or nature of their institution. The purpose of the study was to determine whether serial image interpretation tasks as a distinct learning tool improved novice echocardiographers' ability to accurately identify potentially life-threatening pathology from focused scans. We also aimed to describe the relationship between accuracy of reporting and participants' confidence in those reports, and to assess users' satisfaction with a learning pathway that could potentially be delivered remotely. METHODS: 27 participants from a variety of healthcare roles completed a program of remote lectures and 2 in-person study days. During the program they undertook 4 'packets' of 10 focused echocardiography reporting tasks (total = 40) based on images from a standardised dataset. Participants were randomized to view the scans in varying orders. Reporting accuracy was compared with consensus reports from a panel of expert echocardiographers, and participants self-reported confidence in their image interpretation and their satisfaction with the learning experience. RESULTS: There was a stepwise improvement in reporting accuracy with each set of images reported, from an average reporting score of 66% for the 1st packet to 78% for the 4th packet. Participants felt more confident in identifying common life-threatening pathologies as they reported more echocardiograms. The correlation between report accuracy and confidence in the report was weak and did not increase during the study (rs = 0.394 for the 1st packet, rs = 0.321 for the 4th packet). Attrition during the study related primarily to logistical issues. There were high levels of satisfaction amongst participants, with most reporting that they would use and / or recommend a similar teaching package to colleagues. CONCLUSIONS: Healthcare professionals undertaking remote training with recorded lectures, followed by multiple reporting tasks were capable of interpreting focused echocardiograms. Reporting accuracy and confidence in identifying life-threatening pathology increased with the number of scans interpreted. The correlation between accuracy and confidence for any given report was weak (and this relationship should be explored further given the potential safety considerations). All components of this package could be delivered via distance learning to enhance the flexibility of echocardiography education.

Building a Covid-19 secure intensive care unit: A human-centred design approach.

Background: The Covid-19 pandemic has highlighted weaknesses in the National Health Service critical care provision including both capacity and infrastructure. Traditionally, healthcare workspaces have failed to fully incorporate Human-Centred Design principles resulting in environments that negatively affect the efficacy of task completion, patient safety and staff wellbeing. In the summer of 2020, we received funds for the urgent construction of a Covid-19 secure critical care facility. The aim of this project was to design a pandemic resilient facility centred around both staff and patient requirements and safety, within the available footprint. Methods: We developed a simulation exercise, underpinned by Human-Centred Design principles, to evaluate intensive care designs through Build Mapping, Tasks Analysis and Qualitative data. Build Mapping involved taping out sections of the design and mocking up with equipment. Task Analysis and qualitative data were collected following task completion. Results: 56 participants completed the build simulation exercise generating 141 design suggestions (69 task related, 56 patient and relative related, 16 staff related). Suggestions translated to 18 multilevel design improvements; five significant structural changes (Macro level) including wall moves and lift size change. Minor improvements were made at a Meso and Micro design level. Critical care design drivers identified included functional drivers (visibility, Covid-19 secure environment, workflow, and task efficiency) and behavioural drivers (learning and development, light, humanising intensive care and design consistency). Conclusion: Success of clinical tasks, infection control, patient safety and staff/patient wellbeing are highly dependent on clinical environments. Primarily, we have improved clinical design by focusing on user requirements. Secondly, we developed a replicable approach to exploring healthcare build plans revealing significant design changes, that may have only been identified once built.

Risk Factors for Perinatal Transmission of Hepatitis C Virus.

OBJECTIVE: To estimate the rate of perinatal transmission of hepatitis C virus (HCV) infection, to identify risk factors for perinatal transmission of HCV infection, and to determine the viremic threshold for perinatal transmission. METHODS: This was a prospective, multicenter, observational study of pregnant individuals at less than 24 weeks of gestation screened for HCV infection from 2012 to 2018 in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Individuals found to be HCV antibody-positive were followed throughout pregnancy. Children were followed for evidence of perinatal transmission at 2-6 months (HCV RNA testing) and at 18-24 months (HCV RNA and antibody testing) of life. The primary outcome was perinatal transmission, defined as positive test results at either follow-up time point. RESULTS: A total of 109,379 individuals were screened for HCV infection. Of the 1,224 participants who screened positive, 772 (63.1%) enrolled and 432 of those 772 (56.0%) had data available to assess primary outcome. The overall rate of perinatal transmission was 6.0% (26/432, 95% CI 4.0-8.7%). All children with HCV infection were born to individuals with demonstrable viremia. In viremic participants (n=314), the perinatal transmission rate was 8.0% (95% CI 5.2-11.5%). Risk factors for perinatal transmission included HCV RNA greater than 106 international units/mL (adjusted odds ratio [aOR] 8.22, 95% CI 3.16-21.4) and vaginal bleeding reported at any time before delivery (aOR 3.26, 95% CI 1.32-8.03). A viremic threshold for perinatal transmission could not be established. CONCLUSION: Perinatal transmission of HCV infection was limited to viremic individuals. High viral loads and antepartum bleeding were associated with perinatal transmission.

Rapid and novel prenatal molecular assay for detecting aneuploidies and microdeletion syndromes.

OBJECTIVES: To develop a targeted aneuploidy and microdeletion detection platform for use in the prenatal setting, to assess the integrity of the platform with a robust validation system, and to prospectively determine the performance of the platform under routine clinical conditions. METHODS: To generate proxies for the various disorders assessed by the assay for analytical validation purposes, cells from ten microdeletion syndromes as well as from common aneuploidies were spiked into cleared amniotic fluid. Genomic DNA was isolated, labeled, and hybridized to microbeads that have been coupled to DNA derived from Bacterial Artificial Chromosome (BAC) from the relevant regions targeted by the array. Beads were read using a flow cytometric multiplex bead array detection system. In the prospective part of the study, 104 amniotic fluid samples were collected and analyzed. RESULTS: All microdeletion syndromes and aneuploidies were validated in a blinded fashion. In the prospective study, the total number of readable samples was 101 of 104 (97%). All sample results were confirmed independently. CONCLUSION: The bead array approach is a rapid and reliable test for detecting aneuploidies and microdeletions. This assay has the potential to provide the benefit of expanded molecular cytogenetic testing to pregnant women undergoing invasive prenatal diagnosis. This approach may be especially useful in parts of the world where cytogenetic personnel and facilities may be limited.