A multisite audit to assess how women with complex social factors access and engage with maternity services

Objectiveto audit women with socially complex lives’ documented access to and engagement with antenatal care provided by three inner city, UK maternity services in relation to birth and neonatal outcomes, and referral processes.Backgroundwomen living socially complex lives, including young mothers, recently arrived immigrants, non-English speaking, and those experiencing domestic violence, poor mental health, drug and alcohol abuse, and poverty experience high rates of morbidity, mortality and poor birth outcomes. This is associated with late access to and poor engagement with antenatal care.Methoddata was collected from three separate NHS trusts data management systems for a total of 182 women living socially complex lives, between January and December 2015. Data was presented by individual trust and compared to standards derived from NICE guidelines, local trust policy and national statistic using Excel and SPSS Version 22. Tests of correlation were carried out to minimise risks of confounding factors in characteristic differences.Findingsnon-English speaking women were much less likely to have accessed care within the recommended timeframes, with over 70% of the sample not booked for maternity care by 12 weeks gestation. On average 89% primiparous women across all samples had less than the recommended number of antenatal appointments. No sample met the audit criteria in terms of number of antenatal appointments attended. Data held on the perinatal data management systems for a number of outcomes and processes was largely incomplete and appeared unreliable.Conclusionthis data forms a baseline against which to assess the impact of future service developments aimed at improving access and engagement with services for women living with complex social factors. The audit identified issues with the completeness and reliability of data on the perinatal data management system.     

Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation

Serogroup B is the only major disease-associated capsular group of Neisseria meningitidis for which no protein-polysaccharide conjugate vaccine is available. This has led to the development of multi-component protein-based vaccines that target serogroup B invasive meningococcal disease (IMD), including Bexsero®, which was implemented for UK infants in 2015, and Trumenba®. Given the diversity of meningococcal protein antigens, post-implementation surveillance of IMD isolates, including characterisation of vaccine antigens, is essential for assessing the effectiveness of such vaccines. Whole genome sequencing (WGS), as realised in the Meningitis Research Foundation Meningococcus Genome Library (MRF-MGL), provides a rapid, comprehensive, and cost-effective approach to this. To facilitate the surveillance of the antigen targets included in Bexsero® (fHbp, PorA, NHBA and NadA) for protective immunity, a Bexsero® Antigen Sequence Type (BAST) scheme, based on deduced peptide sequence variants, was implemented in the PubMLST.org/neisseria database, which includes the MRF-MGL and other isolate collections. This scheme enabled the characterisation of vaccine antigen variants and here the invasive meningococci isolated in Great Britain and Ireland in the epidemiological years 2010/11 to 2013/14 are analysed. Many unique BASTs (647) were present, but nine of these accounted for 39% (775/1966) of isolates, with some temporal and geographic differences in BAST distribution. BASTs were strongly associated with other characteristics, such as serogroup and clonal complex (cc), and a significant increase in BAST-2 was associated with increased prevalence of serogroup W clonal complex 11 meningococci. Potential coverage was assessed by the examination of the antigen peptide sequences present in the vaccine and epidemiological dataset. There were 22.8–30.8% exact peptide matches to Bexsero® components and predicted coverage of 66.1%, based on genotype-phenotype modelling for 63.7% of serogroup B isolates from 2010/14 in UK and Ireland. While there are many caveats to this estimate, it lies within the range of other published estimates.     

Novel mutations associated with carnitine-acylcarnitine translocase and carnitine palmitoyl transferase 2 deficiencies in Malaysia

ObjectiveCarnitine-acylcarnitine Translocase (CACT) deficiency (OMIM 212138) and carnitine palmitoyl transferase 2 (CPT2) deficiency (OMIM 60065050) are rare inherited disorders of mitochondrial long chain fatty acid oxidation. The aim of our study is to review the clinical, biochemical and molecular characteristics in children diagnosed with CACT and CPT2 deficiencies in Malaysia.Design and methodsThis is a retrospective study. We reviewed medical records of six patients diagnosed with CACT and CPT2 deficiencies. They were identified from a selective high-risk screening of 50,579 patients from January 2010 until Jun 2020.ResultsAll six patients had either elevation of the long chain acylcarnitines and/or an elevated (C16 + C18:1)/C2 acylcarnitine ratio. SLC25A20 gene sequencing of patient 1 and 6 showed a homozygous splice site mutation at c.199–10 T > G in intron 2. Two novel mutations at c.109C > T p. (Arg37*) in exon 2 and at c.706C > T p. (Arg236*) in exon 7 of SLC25A20 gene were found in patient 2. Patient 3 and 4 (siblings) exhibited a compound heterozygous mutation at c.638A > G p. (Asp213Gly) and novel mutation c.1073 T > G p. (Leu358Arg) in exon 4 of CPT2 gene. A significant combined prevalence at 0.01% of CACT and CPT2 deficiencies was found in the symptomatic Malaysian patients.ConclusionsThe use of the (C16 + C18:1)/C2 acylcarnitine ratio in dried blood spot in our experience improves the diagnostic specificity for CACT/CPT2 deficiencies over long chain acylcarnitine (C16 and C18:1) alone. DNA sequencing for both genes aids in confirming the diagnosis.     

Intermedin alleviates the inflammatory response and stabilizes the endothelial barrier in LPS-induced ARDS through the PI3K/Akt/eNOS signaling pathway

Inflammatory storms and endothelial barrier dysfunction are the central pathophysiological features of acute respiratory distress syndrome (ARDS). Intermedin (IMD), a member of the calcitonin gene-related peptide (CGRP) family, has been reported to alleviate inflammation and protect endothelial cell (EC) integrity. However, the effects of IMD on ARDS have not been clearly elucidated. In the present study, clinical ARDS data were used to explore the relationship between serum IMD levels and disease severity and prognosis, and we then established a model to predict the possibility of hospital survival. Mouse models of ARDS and LPS-challenged endothelial cells were used to analyze the protective effect and underlying mechanism of IMD. We found that in patients with ARDS, increased serum IMD levels were associated with reduced disease severity and increased rates of hospital survival. IMD alleviated the LPS-induced inflammatory response by decreasing proinflammatory cytokines, NF-κB p65 expression and NF-κB p65 nuclear translocation. In addition, IMD stabilized the endothelial barrier by repairing adherens junctions (AJs), cytoskeleton and capillary leakage. IMD exerted protective effects against ARDS on pulmonary endothelial cells, at least partly, through PI3K/Akt/eNOS signaling, while IMD’s anti-inflammation effect was mediated through an eNOS-independent mechanism. Our study may provide new therapeutic insight for ARDS treatment.     

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study

BackgroundThe MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks–15 months of age).MethodsFive schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined.ResultsTenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91–100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not.ConclusionMenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines.Clinical trial registryNCT01049035.     

Accuracy of home enteral feed preparation for children with inherited metabolic disorders

Background: Many children with rare chronic disorders require home enteral tube feeds (HETF) consisting of multiple modular ingredients. Feeds are often complex and the risk of errors during their preparation is high. The consequences of over‐ or under‐concentration can be critical. The aim of the present prospective observation study was to assess the accuracy, skills and technique of caregivers when preparing and administering HETF. Methods: Fifty‐two HETF patients (median age 7.5 years, range 0.7–18.0 years) with inherited metabolic disorders (IMD) requiring special feeds were recruited. Using observation and a structured questionnaire, a practical assessment of feed preparation and storage by the main caregiver was undertaken by an independent dietitian and nurse in the child’s home, including hygiene practices, accuracy of measuring recipe ingredients, and storage of both ingredients and prepared feeds. Results: The majority (85%; n = 44) of feeds were based on >1 ingredient (median 3; range 1–6). Almost half (48%; n = 25) of caregivers measured feed ingredients inaccurately. Of the 31% (n = 16) using scoops, 31% used incorrect measuring spoons and 25% did not level scoops appropriately. Some 45% (n = 20/44) of carers measured liquid ingredients inaccurately. Hygiene practices during feed preparation were poor, including a lack of hand washing (31%: n = 16) and incorrect storage procedures for unused feed ingredients (56%; n = 29). Conclusions: Practices in the preparation of modular HETF for children with IMD were not ideal. A combination of inaccuracy, poor hygiene, inappropriate storage, and long feed hanging times increases both metabolic and microbial risk. Better education, regular monitoring and the development of ready‐to‐use or preweighed ingredients would be beneficial.     

Effect of crude lipopolysaccharide from Escherichia coli O127:B8 on the amebocyte-producing organ of Biomphalaria glabrata (Mollusca)

Lipopolysaccharide (LPS) is a pathogen associated molecular pattern (PAMP) to which the internal defense system (IDS) of both vertebrates and invertebrates responds. We measured the mitotic response of the hematopoietic tissue of the schistosome-transmitting snail, Biomphalaria glabrata, to crude LPS from Escherichia coli 0127:B8. In a dose-response study, snails were injected with a range of concentrations of crude LPS, and mitotic figures were enumerated in histological sections of amebocyte-producing organ (APO) fixed at 24 h post-injection (PI) following a 6 h treatment with 0.1% colchicine. In APOs from Salvador strain snails, which are genetically resistant to infection with Schistosoma mansoni, LPS concentrations of 0.01 mg/ml and above triggered a large increase in mitotic activity, whereas in APOs from schistosome-susceptible NIH albino snails, concentrations of 0.1 mg/ml elicited a much smaller, but statistically significant increase. A time course study, without colchicine treatment, revealed that in Salvador APOs the mitotic response to 0.1 mg/ml occurred by 18 h PI, peaked at 24 h, and returned to control levels by 72 h; NIH albino APOs showed no detectible response. When Salvador APOs were exposed to crude LPS in vitro, no increase in mitotic activity occurred, a result suggesting the possible requirement for a peripheral tissue or hemolymph factor. The increased cell proliferation induced by crude LPS represents a novel systemic response of an invertebrate IDS to one or more PAMPs from a Gram-negative bacterium.     

糖尿病大鼠血浆中介素的水平变化及其对胃动力的影响

目的 观察糖尿病大鼠血浆中介素(IMD)的水平变化及其对胃动力的影响.方法 将60只雄性Wistar大鼠按照随机数字表法分为糖尿病2 w组(DM-1),正常对照2 w组(NC-1),糖尿病20 w组(DM-2),正常对照20 w组(NC-2),每组15只.糖尿病组大鼠饲喂高脂高糖饲料以诱导出胰岛素抵抗,腹腔注射小剂量链脲佐菌素(STZ,30 mg/kg)复制2型糖尿病大鼠模型.造模成功后,分别于第2周和第20周行SPECT胃排空功能测定,得出半排空时间(GET1/2)和55 min胃内核素残留率;酶联免疫法测定血浆IMD含量.结果 ①DM-1组大鼠胃排空半排时间少于NC-1组(P＜0.05);DM-2组半排时间多于NC-2组(P<0.05);DM-1组与DM-2组比较差异显著(P<0.001);NC-1组与NC-2组比较无差异.②DM-1组大鼠血浆IMD含量低于NC-1组(P<0.05);DM-2组血浆IMD含量高于NC-2组(P<0.05);DM-1组与DM-2组比较差异显著(P<0.001);NC-1组与NC-2组比较无差异.③血浆IMD水平与胃排空半排时间呈正的直线相关.结论 IMD参与了糖尿病大鼠胃动力异常的病理生理过程,可能对胃运动具有调节作用.     

A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults

Background

Neisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis and septicemia in adolescents and young adults. No currently licensed and available vaccine has been shown to provide broad protection against endemic MnB disease. A bivalent rLP2086 vaccine based on two factor H-binding proteins (fHBPs) has been developed to provide broad protection against MnB disease-causing strains.

Methods

This study assessed the safety and immunogenicity of the final formulation of a bivalent rLP2086 vaccine in 60 healthy adults (18–40 years of age) receiving 120 μg doses at 0, 1, and 6 months. Safety was assessed by collecting solicited reactogenicity data and participant-reporting of adverse events. Immunogenicity was evaluated by human serum bactericidal assay (hSBA) against 5 MnB strains expressing distinct fHBP variants and fHBP-specific immunoglobulin G titre.

Results

After each immunisation, local reactions such as pain at the injection site and erythema were generally mild or moderate. The most common vaccine-related adverse event was upper respiratory tract infection, which was reported by two participants. Seroprotection (hSBA titres ≥ 1:4) was achieved in 94.3% of participants against a MnB strain expressing the vaccine-homologous fHBP variant A05 and 70.0%–94.7% against MnB strains expressing the heterologous fHBP variants B02, A22, B44, and B24. Seroconversion rates (≥4-fold rise in hSBA titres) ranged from 70.0% to 94.7% across the five MnB test strains following the 3-dose vaccination regimen. Immunogenicity responses tended to increase upon subsequent vaccine doses.

Conclusions

Bivalent rLP2086 is a promising vaccine candidate for broad protection against MnB disease-causing strains.