Early Isolates of SARS-CoV-2 Result in Different Pathogenesis in the Transduced Mouse Model of COVID-19.

A transduced mouse model of SARS-CoV-2 infection was established using Balb/c mice. This was achieved through the adenovirus-vectored delivery of the hACE2 gene, to render the mice transiently susceptible to the virus. The model was characterised in terms of the dissemination of hACE2 receptor expression, the dissemination of three SARS-CoV-2 virus variants in vivo up to 10 days following challenge, the resulting histopathology and the clinical signs induced in the mice. In transduced mice, the infection was short-term, with a rapid loss in body weight starting at day 2 with maximum weight loss at day 4, followed by subsequent recovery until day 10. The induced expression of the hACE2 receptor was evident in the lungs, but, upon challenge, the SARS-CoV-2 virus disseminated beyond the lungs to spleen, liver and kidney, peaking at day 2 post infection. However, by day 10 post infection, the virus was undetectable. The lung histopathology was characterised by bronchial and alveolar inflammation, which was still present at day 10 post infection. Transduced mice had differential responses to viral variants ranking CVR-Glasgow 1 > Victoria-1 > England-2 isolates in terms of body weight loss. The transduced mouse model provides a consistent and manipulatable model of SARS-CoV-2 infection to screen viral variants for their relative virulence and possible interventions.

'Tough love': The experiences of midwives giving women sterile water injections for the relief of back pain in labour.

OBJECTIVE: To explore midwives' experiences of administering sterile water injections (SWI) to labouring women as analgesia for back pain in labour. DESIGN: A qualitative study, which generated data through semi-structured focus group interviews with midwives. Data were analysed thematically. SETTING: Two metropolitan maternity units in Queensland, Australia. PARTICIPANTS: Eleven midwives who had administered SWI for back pain in labour in a randomised controlled trial. FINDINGS: Three major themes were identified including: i. SWI, is it an intervention?; ii. Tough love, causing pain to relieve pain; iii. The analgesic effect of SWI and impact on midwifery practice. KEY CONCLUSIONS: Whilst acknowledging the potential benefits of SWI as an analgesic the midwives in this study described a dilemma between inflicting pain to relieve pain and the challenges encountered in their discussions with women when offering SWI. Midwives also faced conflict when women requested SWI in the face of institutional resistance to its use. IMPLICATIONS FOR PRACTICE: The procedural pain associated with SWI may discourage some midwives from offering women the procedure, providing women with accurate information regarding the intensity and the brevity of the injection pain and the expected degree of analgesic would assist in discussion about SWI with women.

ADding negative pRESSure to improve healING (the DRESSING trial): a RCT protocol.

INTRODUCTION: Obese women are more likely to develop a surgical site infection (SSI) following caesarean section (CS) than non-obese women. Negative pressure wound therapy (NPWT) is increasingly being used to reduce SSI with limited evidence for its effectiveness. OBJECTIVES: To determine the clinical and cost-effectiveness of using NPWT in obese women having elective and semiurgent CS. METHODS AND ANALYSIS: A multisite, superiority parallel pragmatic randomised controlled trial with an economic evaluation. Women with a body mass index (BMI) of ≥ 30, booked for elective and semiurgent CS at 4 Australian acute care hospitals will be targeted. A total of 2090 women will be enrolled. A centralised randomisation service will be used with participants block randomised to either NPWT or standard surgical dressings in a 1:1 ratio, stratified by hospital. The primary outcome is SSI; secondary outcomes include type of SSI, length of stay, readmission, wound complications and health-related quality of life. Economic outcomes include direct healthcare costs and cost-effectiveness, which will be evaluated using incremental cost per quality-adjusted life year gained. Data will be collected at baseline, and participants followed up on the second postoperative day and weekly from the day of surgery for 4 weeks. Outcome assessors will be masked to allocation. The primary statistical analysis will be based on intention-to-treat. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the ethics committees of the participating hospitals and universities. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12615000286549; Pre-results.

The maternal and neonatal outcomes for an urban Indigenous population compared with their non-Indigenous counterparts and a trend analysis over four triennia.

BACKGROUND: Indigenous Australians experience significantly disproportionate poorer health outcomes compared to their non-Indigenous counterparts. Despite the recognised importance of maternal infant health (MIH), there is surprisingly little empirical research to guide service redesign that successfully addresses the disparities. This paper reports on a service evaluation that also compared key MIH indicators for Indigenous and non-Indigenous mothers and babies over a 12-year period 1998-2009. METHODS: Trend analysis with logistic regression, using the independent variables of ethnicity and triennia, explored changes over time (1998-2009) between two cohorts: 1,523 births to Indigenous mothers and 43,693 births to non-Indigenous mothers. We included bivariate and multivariate analysis on key indicators (e.g. teenage births, preterm birth, low birth weight, smoking) and report odds ratios (ORs), 95% CIs and logistic regression adjusting for important confounders. We excluded transfers in from other areas which are identified within the database. RESULTS: Bivariate analysis revealed Indigenous women were statistically more likely to have spontaneous onset of labour and a non-instrumental vaginal birth. They were less likely to take epidurals for pain relief in labour, have assisted births, caesarean sections or perineal trauma. Despite better labour outcomes, Indigenous babies were more likely to be born preterm (< 37 weeks) and be low birth weight (< 2500 g); these differences remained significant in multivariate analysis. The trend analysis revealed relatively stable rates for teenage pregnancy, small for gestational age, low birth weight babies, and perinatal mortality for both cohorts, with the gap between cohorts consistent over time. A statistical widening of the gap in preterm birth and smoking rates was found with preterm birth demonstrating a relative increase of 51% over this period. CONCLUSIONS: The comprehensive database from a large urban hospital allowed a thorough examination of outcomes and contributing factors. The gap between both cohorts remains static in several areas but in some cases worsened. Alternative models for delivering care to Indigenous women and their babies have shown improved outcomes, including preterm birth, though not all have been sustained over time and none are available Australia-wide. New models of care, which recognise the heterogeneity of Indigenous communities, incorporate a multiagency approach, and are set within a research framework, are urgently needed.

Impact on caesarean section rates following injections of sterile water (ICARIS): a multicentre randomised controlled trial.

BACKGROUND: Sterile water injections have been used as an effective intervention for the management of back pain during labour. The objective of the current research is to determine if sterile water injections, as an intervention for back pain in labour, will reduce the intrapartum caesarean section rate. DESIGN: A double blind randomised placebo controlled trialSetting: Maternity hospitals in AustraliaParticipants: 1866 women in labour, ≥18 years of age who have a singleton pregnancy with a fetus in a cephalic presentation at term (between 37 + 0 and 41 + 6 weeks gestation), who assess their back pain as equal to or greater than seven on a visual analogue scale when requesting analgesia and able to provide informed consent. INTERVENTION: Participants will be randomised to receive either 0.1 to 0.3 millilitres of sterile water or a normal saline placebo via four intradermal injections into four anatomical points surrounding the Michaelis' rhomboid over the sacral area. Two injections will be administered over the posterior superior iliac spine (PSIS) and the remaining two at two centimetres posterior, and one centimetre medial to the PSIS respectively. MAIN OUTCOME MEASURE: Proportion of women who have a caesarean section in labour.Randomisation: Permuted blocks stratified by research site.Blinding (masking):Double-blind trial in which participants, clinicians and research staff blinded to group assignment. FUNDING: Funded by the National Health and Medical Research CouncilTrial registration:Australian New Zealand Clinical Trials Registry (No ACTRN12611000221954). DISCUSSION: Sterile water injections, which may have a positive effect on reducing the CS rate, have been shown to be a safe and simple analgesic suitable for most maternity settings. A procedure that could reduce intervention rates without adversely affecting safety for mother and baby would benefit Australian families and taxpayers and would reduce requirements for maternal operating theatre time. Results will have external validity, as the technique may be easily applied to maternity populations outside Australia. In summary, the results of this trial will contribute High level evidence on the impact of SWI on intrapartum CS rates and provide evidence of the analgesic effect of SWI on back pain.

The peer-professional interface in a community-based, breast feeding peer-support project.

OBJECTIVE: to explore key elements of the peer-professional interface within one breast feeding peer-support project. DESIGN: a descriptive, qualitative study design. Data were generated through focus-group discussions with volunteer peer supporters and health professionals. SETTING: the Breastfriends scheme was a community-based, peer-support project located in Doncaster, a town in the North of England. PARTICIPANTS: all of the volunteer peer supporters who were involved in the scheme at the time of data collection (n=7). In addition, a convenience sample of health professionals (community midwives and health visitors [n=9]) was also generated. ANALYSIS: thematic analysis of the data was undertaken. Two key themes that have relevance to understanding the peer-professional interface were derived: benefits of working together, and constraints on enabling working relationships. FINDINGS: benefits associated with participating in the breast feeding peer-support scheme were highlighted by volunteers and health professionals. Volunteers experienced enhanced social support and increased self-esteem and personal development. Health professionals benefited from being able to 'spread the load' of breast feeding support. Some health professionals were also able to learn from volunteers' specialist experiential and cultural knowledge. Health professionals were concerned about volunteers transgressing (poorly defined) boundaries. Both volunteers and health professionals described gate-keeping activities and surveillance behaviours practised by health professionals in an effort to control aspects of volunteers' access to, and work with, breast feeding women. DISCUSSION: as a cohort of peer supporters develops, members may derive benefits from their participation that extend beyond those predicted and planned for in the project. They may also exert a proactive influence upon the evolution of the peer-support project and upon the relationships between volunteers and health professionals. However, midwives and health professionals may also seek to exert influence over the work of peer supporters, preferring the volunteers to work for, rather than with, them as health professionals. It is at the peer-professional interface that any disjuncture between the project ideal and the reality of the group may be most evident and most problematic. CONCLUSION AND IMPLICATIONS FOR PRACTICE: in order to reduce tension at the peer-professional interface, and optimise relationships between volunteers and health professionals, an ongoing process of development involving volunteers and health professionals is essential. Such a process would need to proactively identify and diffuse professionals' concerns while addressing both volunteers' vulnerabilities and their potential for semi-autonomous development within and beyond the context of the peer-support scheme.