Does the socioeconomic background of pregnant women make a difference to their perceptions of antenatal care? A qualitative case study

Socioeconomically deprived women are at greater risk of adverse pregnancy outcomes. To counteract this, attention tends to focus around access (equality) of services. Yet access may not equate with the meaningfulness (equity) of services for women from different socioeconomic backgrounds. Without understanding equity we are not in a position to plan appropriate and equitable care. This study aimed to determine pregnant women's perceptions of the current antenatal provision and to determine if women from the extremes of socioeconomic background perceived their antenatal care differently. Longitudinal interviews were undertaken with multiple, comparative antenatal case studies between January 2007 and April 2009. Cases were primigravida women from ‘least deprived’ (n=9) and ‘most deprived’ (n=12) geographical areas as identified by the Scottish Index of Multiple Deprivation (SIMD 2006). The data were analysed using case study replication analysis. Analysis of categorical data from the sample groups indicated they were less diverse than might have been expected in terms of age and education. However in the key variables of housing tenure, potential income and socioeconomic status based on area of residence, the groups were indicative of the SIMD target populations. The preliminary analysis showed that the sample groups considered the initial General Practitioner contact to be less than adequate and the subsequent utility of antenatal education to be based on self perceived relevance. The substantive analysis showed little difference in access to antenatal services between the ‘least’ and ‘most’ deprived groups but perception of care differed. A key difference concerned the level of ‘engagement’ (defined as personalisation and active involvement in care, power and relationships and health literacy). Using these concepts, engagement was present in most of the ‘least deprived’ group and almost none of the ‘most deprived’ group. In comparison with women from affluent areas, more deprived women described less evidence of: personal connection to their own care; shared decision making; and perceived value in relation to the written educational aspects of antenatal care. In terms of the preliminary analysis, the results suggest that utility of educational material may need to be reviewed to ensure it is relevant to specific needs. Without this relevance, key information may be missed. The substantive analysis suggests that for women from socioeconomically deprived areas, access may be a less useful indicator than engagement when assessing quality of antenatal services. The lack of engagement perceived by those who are most deprived suggests that equity of service has yet to be attained for those who are most in need. Future research needs to be directed to the potential reasons that may undermine equity and engagement in women from lower socioeconomic areas

Prenatal Care in Oregon and Washington: Policy and Utilization for Vulnerable Women

BACKGROUND: In the prenatal period, women can have sustained contact with nurses and other clinicians, forming relationships that are likely to be health enhancing both for the woman and her unborn child. Yet first trimester care use in Oregon dropped noticeably over the past decade. In comparison with Washington State, Oregon has not shown substantial recovery. OBJECTIVE: To explore potential reasons for the declining prenatal trend in Oregon METHODS: We collated county level birth data from all Oregon and Washington counties from 2000-2010. A descriptive, observational, time-series regression analysis for both states assessed the influence of maternal determinants known to impact first trimester care utilization. RESULTS: In Oregon, two factors were significantly associated with declining first trimester care: Medicaid funding (P<.01) and maternal Hispanic ethnicity (P=.016). In Washington, there was no significant association between any assessed determinant and first trimester care. DISCUSSION: In Oregon, over the period of our study, women dependent on Medicaid and women of Hispanic origin were less likely to utilize first trimester care. A similar trend for these variables was not observed in Washington. At the time of our study, both states had different policy approaches which may explain some of the observable patterns. Amid current health care reforms and rising immigration, our findings suggest the need for strong advocacy for those less able to access or utilize care.This is a non-final version of an article. The article is copyrighted by Wolters Kluwer Health, Inc., and published by Lippincott Williams & Wilkins. It can be found as published in final form at: http://journals.lww.com/nursingresearchonline/pages/default.aspxKeywords: Ethnicity, Medicaid, First trimester, Prenatal care, Health disparit

Does the socioeconomic background of pregnant women make a difference to their perceptions of antenatal care? : a qualitative case study

Socioeconomically deprived women are at greater risk of adverse pregnancy outcomes. To counteract this, attention tends to focus around access (equality) of services. Yet access may not equate with the meaningfulness (equity) of services for women from different socioeconomic backgrounds. Without understanding equity we are not in a position to plan appropriate and equitable care. This study aimed to determine pregnant women's perceptions of the current antenatal provision and to determine if women from the extremes of socioeconomic background perceived their antenatal care differently. Longitudinal interviews were undertaken with multiple, comparative antenatal case studies between January 2007 and April 2009. Cases were primigravida women from ‘least deprived’ (n=9) and ‘most deprived’ (n=12) geographical areas as identified by the Scottish Index of Multiple Deprivation (SIMD 2006). The data were analysed using case study replication analysis. Analysis of categorical data from the sample groups indicated they were less diverse than might have been expected in terms of age and education. However in the key variables of housing tenure, potential income and socioeconomic status based on area of residence, the groups were indicative of the SIMD target populations. The preliminary analysis showed that the sample groups considered the initial General Practitioner contact to be less than adequate and the subsequent utility of antenatal education to be based on self perceived relevance. The substantive analysis showed little difference in access to antenatal services between the ‘least’ and ‘most’ deprived groups but perception of care differed. A key difference concerned the level of ‘engagement’ (defined as personalisation and active involvement in care, power and relationships and health literacy). Using these concepts, engagement was present in most of the ‘least deprived’ group and almost none of the ‘most deprived’ group. In comparison with women from affluent areas, more deprived women described less evidence of: personal connection to their own care; shared decision making; and perceived value in relation to the written educational aspects of antenatal care. In terms of the preliminary analysis, the results suggest that utility of educational material may need to be reviewed to ensure it is relevant to specific needs. Without this relevance, key information may be missed. The substantive analysis suggests that for women from socioeconomically deprived areas, access may be a less useful indicator than engagement when assessing quality of antenatal services. The lack of engagement perceived by those who are most deprived suggests that equity of service has yet to be attained for those who are most in need. Future research needs to be directed to the potential reasons that may undermine equity and engagement in women from lower socioeconomic areas.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Viral coinfections in hospitalized coronavirus disease 2019 patients recruited to the international severe acute respiratory and emerging infections consortium WHO clinical characterisation protocol UK study

Background We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged <1 year to 102 years old, recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK study. Comprehensive demographic, clinical, and outcome data were collected prospectively up to 28 days post discharge. Results A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward

Delayed mucosal anti-viral responses despite robust peripheral inflammation in fatal COVID-19

Background While inflammatory and immune responses to SARS-CoV-2 infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished COVID-19 severity categories, and relate these to disease progression and peripheral inflammation. Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalised with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days post-symptom onset) or late (6-20 days post-symptom onset). Results Patients that survived severe COVID-19 showed IFN-dominated mucosal immune responses (IFN-γ, CXCL10 and CXCL13) early in infection. These early mucosal responses were absent in patients that would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by IL-2, IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions Defective early mucosal anti-viral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19

A prenylated dsRNA sensor protects against severe COVID-19

Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

Background The mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure. Results Investigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323. Conclusions These data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely