Biological sex is associated with heterogeneous responses to IL-6 receptor inhibitor treatment in COVID-19-A retrospective cohort study.

COVID-19 is associated with higher inflammatory markers, illness severity and mortality in males compared to females. Differences in immune responses to COVID-19 may underpin sex- specific outcome differences. We hypothesised that anti-IL-6 receptor monoclonal antibodies are associated with heterogenous treatment effects between male and female patients.

Dying, death and bereavement: developing a national survey of bereaved relatives.

Background: Assessing and measuring the experience and quality of care provided is central to the improvement of care delivery of all healthcare systems. This paper reports on the development of a survey instrument to capture the experiences of care at end of life from the perspective of bereaved relatives in the Republic of Ireland.

Methods: A multi-method, multi-stakeholder, sequential approach was adopted for this study.

Generating actionable insights from free-text care experience survey data using qualitative and computational text analysis: A study protocol.

The National Care Experience Programme (NCEP) conducts national surveys that ask people about their experiences of care in order to improve the quality of health and social care services in Ireland. Each survey contains open-ended questions, which allow respondents to comment on their experiences. While these comments provide important and valuable information about what matters most to service users, there is to date no unified approach to the analysis and integration of this detailed feedback.

Women's experiences of initiating feeding shortly after birth in Ireland: A secondary analysis of quantitative and qualitative data from the National Maternity Experience Survey.

Objective: To explore women's experiences of initiating and continuing breast or formula feeding shortly after birth in Ireland's maternity hospitals and units, as well as at home after birth.

Design: Mixed methods secondary analysis of qualitative and quantitative data from the Irish National Maternity Experience Survey 2020.

Setting: All 19 maternity hospitals and units in the Republic of Ireland and the national home births service.

Care Experiences of Older People in the Emergency Department: A Concurrent Mixed-Methods Study.

The growing population of older people has increased demand to meet their complex healthcare needs, including in emergency departments (EDs). This study explored the experiences of people aged 65+ in Irish EDs, involving secondary analysis of quantitative and qualitative data from the 2019 National Inpatient Experience Survey (NIES). Experiences in the ED and overall hospital experiences were dichotomized as poor to fair or good to very good.

Development of a survey instrument to evaluate women's experiences of their maternity care.

Background: The process of developing a survey instrument to evaluate women's experiences of their maternity care is complex given that maternity care encapsulates various contexts, services, professions and professionals across the antenatal, intranatal and postnatal periods.

Aim: To identify and prioritise items for inclusion in the National Maternity Experience Survey, a survey instrument to evaluate women's experiences of their maternity care in the Republic of Ireland.

Methods: This study used an adapted two-phase exploratory sequential mixed methods design.

Variation in resource allocation in urgent and emergency Care Systems in Ireland.

Background: A key challenge for most systems is how to provide effective access to urgent and emergency care across rural and urban populations. Tensions about the placement and scope of hospital emergency services are longstanding in Irish political life and there has been recent reform to centralise hospital services in some regions. The focus of this paper is a system approach to examine the geographic variation in resourcing and utilisation of such care across GP practices, out-of-hours care, ambulance services, Emergency Departments and Local Injury Units in Ireland.

Understanding the impetus for major systems change: A multiple case study of decisions and non-decisions to reconfigure emergency and urgent care services.

Objective: The optimal organisation of emergency and urgent care services (EUCS) is a perennial problem internationally. Similar to other countries, the Health Service Executive in Ireland pursued EUCS reconfiguration in response to quality and safety concerns, unsustainable costs and workforce issues. However, the implementation of reconfiguration has been inconsistent at a regional level.

Case fatality ratios for serious emergency conditions in the Republic of Ireland: a longitudinal investigation of trends over the period 2002-2014 using joinpoint analysis.

Background: In the past decade, the Republic of Ireland has undertaken significant reconfiguration programmes to improve emergency services. During this time the public healthcare system experienced a large real decrease in resources. This study assesses national and regional population outcomes over the period 2002-2014, and whether changes coincide with system reconfiguration and the financial restrictions imposed by the 2008 recession.

Understanding perspectives on major system change: A comparative case study of public engagement and the implementation of urgent and emergency care system reconfiguration.

Objectives: Major changes have been made to how emergency care services are configured in several regions in the Republic of Ireland. This study investigated the hypothesis that engagement activities undertaken prior to these changes influenced stakeholder perspectives on the proposed changes and impacted on the success of implementation.

Methods: A comparative case-study approach was used to explore the changes in three regions.

Patient experience of different regional models of urgent and emergency care: a cross-sectional survey study.

Objectives: To compare user experiences of 8 regional urgent and emergency care systems in the Republic of Ireland, and explore potential avenues for improvement.

Design: A cross-sectional survey.

Setting: Several distinct models of urgent and emergency care operate in Ireland, as system reconfiguration has been implemented in some regions but not others.

Intra-arterial delivery of AAV vectors to the mouse brain after mannitol mediated blood brain barrier disruption.

The delivery of therapeutics to neural tissue is greatly hindered by the blood brain barrier (BBB). Direct local delivery via diffusive release from degradable implants or direct intra-cerebral injection can bypass the BBB and obtain high concentrations of the therapeutic in the targeted tissue, however the total volume of tissue that can be treated using these techniques is limited. One treatment modality that can potentially access large volumes of neural tissue in a single treatment is intra-arterial (IA) injection after osmotic blood brain barrier disruption.

Cannulation of the internal carotid artery in mice: a novel technique for intra-arterial delivery of therapeutics.

We have developed a novel minimally invasive technique for the intra-arterial delivery of therapeutics to the mouse brain. CD-1 mice were anesthetized and placed in a lateral decubitus position. A 10mm midline longitudinal incision was made over the thyroid bone.

Orthotopic glioblastoma stem-like cell xenograft model in mice to evaluate intra-arterial delivery of bevacizumab: from bedside to bench.

Bevacizumab (BV), a humanized monocolonal antibody directed against vascular endothelial growth factor (VEGF), is a standard intravenous (IV) treatment for recurrent glioblastoma multiforme (GBM), that has been introduced recently as an intra-arterial (IA) treatment modality in humans. Since preclinical models have not been reported, we sought to develop a tumor stem cell (TSC) xenograft model to investigate IA BV delivery in vivo. Firefly luciferase transduced patient TSC were injected into the cortex of 35 nude mice.

Intra-arterial bevacizumab with blood brain barrier disruption in a glioblastoma xenograft model.

Purpose: In this study we investigated the treatment response and survival of intra-arterial (IA) compared to intra-peritoneal (IP) delivery of bevacizumab (BV) in a glioblastoma (GBM) xenograft mouse model.

Methods: 3x10(5) U87-Luc cells were stereotactically implanted into the cortex of 35 nude mice and grouped for treatment (n = 7 in each group): IP saline (group 1), single IP BV (group 2), biweekly IP BV for 3 weeks (group 3), single intra-arterial (IA) BV alone (group 4) and single IA BV with blood brain barrier disruption (BBBD) (group 5). Tumor growth was monitored every 3 to 4 days using bioluminescence imaging (BLI) and survival was analyzed by the Kaplan Meier method.

Real-time imaging of perivascular transport of nanoparticles during convection-enhanced delivery in the rat cortex.

Convection-enhanced delivery (CED) is a promising technique for administering large therapeutics that do not readily cross the blood brain barrier to neural tissue. It is of vital importance to understand how large drug constructs move through neural tissue during CED to optimize construct and delivery parameters so that drugs are concentrated in the targeted tissue, with minimal leakage outside the targeted zone. Experiments have shown that liposomes, viral vectors, high molecular weight tracers, and nanoparticles infused into neural tissue localize in the perivascular spaces of blood vessels within the brain parenchyma.

Microfluidic probes in the treatment of brain-related diseases.

Many new therapeutic compounds have been developed that target malignancies and other disorders of the brain. However, delivering these compounds to diseased tissue remains a difficult challenge. One option for local drug delivery in the brain is direct infusion of the compounds through a catheter into the brain parenchyma.

Flexible microfluidic devices supported by biodegradable insertion scaffolds for convection-enhanced neural drug delivery.

Convection enhanced delivery (CED) can improve the spatial distribution of drugs delivered directly to the brain. In CED, drugs are infused locally into tissue through a needle or catheter inserted into brain parenchyma. Transport of the infused material is dominated by convection, which enhances drug penetration into tissue compared with diffusion mediated delivery.

Dilation and degradation of the brain extracellular matrix enhances penetration of infused polymer nanoparticles.

This study investigates methods of manipulating the brain extracellular matrix (ECM) to enhance the penetration of nanoparticle drug carriers in convection-enhanced delivery (CED). A probe was fabricated with two independent microfluidic channels to infuse, either simultaneously or sequentially, nanoparticles and ECM-modifying agents. Infusions were performed in the striatum of the normal rat brain.