Co-locating universal welfare advice in health settings for mothers and their families

Childhood deprivation is associated with poor health and social outcomes, limiting childhood development with long-lasting effects into adulthood. Welfare advice services improve financial security but access is often unequal for the most vulnerable. Maternity care offers a unique opportunity to access most pregnant women and may provide a suitable setting to host a universal welfare advice service to improve advice uptake. However, little is known on how to effectively design, implement and evaluate these services to reach those most in need. This thesis aims to understand whether co-location of universal welfare advice in health settings for mothers and their families, as a cost-effective measure to improve health and wellbeing, is acceptable and feasible to deliver and evaluate. The thesis adopts a complex intervention research framework as a methodological approach to the development, implementation and evaluation of this intervention. First, I conducted a narrative systematic review to explore the effectiveness and implementation of co-located welfare services. Secondly, I conducted an analysis of a longitudinal study to explore how financial security changed and impacted the health, wellbeing and socioeconomic security of mothers in Bradford during the COVID-19 pandemic. Third, I conducted a before and after study, exploring the feasibility of evaluating a co-located welfare service in primary care. Finally, I explored the feasibility of utilising financial data linkage to improve evaluations of co-located welfare services. This research presents a theory of change model, depicting how universal welfare services co-located in maternity settings improves health and wellbeing and cost savings to the National Health Service, and demonstrates evidence of promise to support this theory of change. I demonstrate the most appropriate effectiveness and implementation outcomes and report the utility of routine financial data linkage for such evaluations. The thesis culminates with a methodological approach to investigate the effectiveness and implementation of a welfare service co-located in maternity settings

A review of the effectiveness and experiences of welfare advice services co-located in health settings: : A critical narrative systematic review

We conducted a narrative systematic review to assess the health, social and financial impacts of co-located welfare services in the UK and to explore the effectiveness of and facilitators and barriers to successful implementation of these services, in order to guide future policy and practice. We searched Medline, EMBASE and other literature sources, from January 2010 to November 2020, for literature examining the impact of co-located welfare services in the UK on any outcome. The review identified 14 studies employing a range of study designs, including: one non-randomised controlled trial; one pilot randomised controlled trial; one before-and-after-study; three qualitative studies; and eight case studies. A theory of change model, developed a priori, was used as an analytical framework against which to map the evidence on how the services work, why and for whom. All studies demonstrated improved financial security for participants, generating an average of £27 of social, economic and environmental return per £1 invested. Some studies reported improved mental health for individuals accessing services. Several studies attributed subjective improvements in physical health to the service addressing key social determinants of health. Benefits to the health service were also demonstrated through reduced workload for healthcare professionals. Key components of a successful service included co-production during service development and ongoing enhanced multi-disciplinary collaboration. Overall, this review demonstrates improved financial security for participants and for the first time models the wider health and welfare benefits for participants and for health service from these services. However, given the generally poor scientific quality of the studies, care must be taken in drawing firm conclusions. There remains a need for more high quality research, using experimental methods and larger sample sizes, to further build upon this evidence base and to measure the strength of the proposed theoretical pathways in this area

Exploring the feasibility of evaluating a community alliance welfare advice programme co-located in primary care in Bradford : an uncontrolled before and after study

Background: Welfare advice services co-located in health settings are known to improve financial security. However, little is known on how to effectively evaluate these services. This study aims to explore the feasibility of evaluating a welfare advice service co-located in a primary care setting in a deprived and ethnically diverse population. It seeks to investigate whether the proposed evaluation tools and processes are acceptable and feasible to implement and whether they are able to detect any evidence of promise for this intervention on the mental health, wellbeing and financial security of participants. Methods: An uncontrolled before and after study design was utilised. Data on mental health, wellbeing, quality of life and financial outcomes were collected at baseline prior to receiving welfare advice and at three months follow-up. Multiple logistic and linear regression models were used to explore individual differences in self-reported financial security and changes to mental health, wellbeing and quality of life scores before and after the provision of welfare advice. Results: Overall, the majority of key outcome measures were well completed, indicating participant acceptability of the mental health, wellbeing, quality of life and financial outcome measures used in this population. There was evidence suggestive of an improvement in participant financial security and evidence of promise for improvements in measured wellbeing and health-related quality of life for participants accessing services in a highly ethnically diverse population. Overall, the VCS Alliance welfare advice programme generated a total of £21,823.05 for all participants, with participants gaining an average of £389.70 per participant for participants with complete financial outcome data. Conclusions: This research demonstrates the feasibility of evaluating a welfare advice service co-located in primary care in a deprived and ethnically diverse setting utilising the ascribed mental health, wellbeing and quality of life and financial outcome tools. It provides evidence of promise to support the hypothesis that the implementation of a welfare advice service co-located in a health setting can improve health and wellbeing and reduce health inequalities

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival