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Faster regulatory approval processes often fail to achieve faster patient access. We seek an approach, using performance-based risk-sharing arrangements, to address uncertainty for payers regarding the relative effectiveness and value for money of products launched through accelerated approval schemes. One important reason for risk sharing is to resolve differences of opinion between innovators and payers about a technology's underlying value. To date, there has been no formal attempt to set out the circumstances in which risk sharing can address these differences. We use a value of information framework to understand what a performance-based risk-sharing arrangements can, in principle, add to a reimbursement scheme, separating payer perspectives on cost-effectiveness and the value of research from those of the innovator. We find 16 scenarios, developing 5 rules to analyze these 16 scenarios, identifying cases in which risk sharing adds value for both parties. We find that risk sharing provides an improved solution in 9 out of 16 combinations of payer and innovator expectations about treatment outcome and the value of further research. Among our assumptions, who pays for research and scheme administration costs are key. Steps should be undertaken to make risk sharing more practical, ensuring that payers consider it an option. This requires additional costs to the health system falling on the innovator in an efficient way that aligns incentives for product development for global markets. Health systems benefits are earlier patient access to cost-effective treatments and payers with higher confidence of not wasting money. Innovators get greater returns while conducting research. • Accelerated regulatory approvals often fail to provide early access because of uncertainty about value. Performance-based risk-sharing arrangements (PBRSAs) have been used in some circumstances to achieve access, but many payers and innovators are resistant to using them. Value of Information approaches allow analysis of when risk sharing may help provide early access but, to date, have not addressed PBRSA use to resolve differences of opinion between innovators and payers about a technology's value. • We use a Value of Information framework to understand what a PBRSA can add to a reimbursement scheme, separating payer perspectives on cost-effectiveness and on the value of research from those of the innovator. We find 16 scenarios, developing 5 rules to analyze these 16 scenarios, identifying situations in which risk sharing adds value for both parties. We show that PBRSAs can address differences of opinion between payers and innovators about underlying value in 9 out of 16 scenarios. • Incentives should be aligned to make PBRSA choices efficient. Key requirements are that (1) innovators pay for both evidence generation costs and for the administration of PBRSAs, (2) prices could go up or down after evidence collection, and (3) innovators face penalties if they do not undertake and complete agreed research. Health systems benefits are earlier patient access to cost-effective treatments and payers having higher confidence of not wasting money. Innovators get greater returns while conducting research. [ABSTRACT FROM AUTHOR]

To assess the hepatic disease-free survival (HDFS) and overall survival (OS) of patients who underwent resection of colorectal cancer liver metastases (CRCLM) in our population, and evaluate what factors are associated with these outcomes. Patients with resected non-mucinous CRCLM between January 2013-February 2020 were retrospectively identified. Dates of diagnosis, surgery, and, if applicable, death were recorded. HDFS and OS were calculated using a census date of 24 September 2022. Separate Cox multivariate regression analyses were performed to evaluate for association between HDFS and OS and the following factors: pre-operative imaging interval (<4 weeks vs. ≥4 weeks); pre-operative imaging modality (CT only vs. MRI+CT); extrahepatic disease at time of hepatectomy (yes vs. no); tumor burden score (TBS, where TBS2 = (largest axial dimension of CRCLM)2 + (number of CRCLM)2); pT and pN; and neoadjuvant chemotherapy. 137 subjects (mean age, 61 ± 11 years, 86 males) were included. Associations with recurrent hepatic disease were found with chemotherapy (HR 2.11[95 % CI = 1.13–3.92]), TBS (HR 1.30[95 % CI = 1.17–1.45]), MRI+CT (HR 2.12[95 % CI = 1.29–3.48]), and extrahepatic disease at hepatectomy (HR 2.16[95 % CI = 1.08–4.35]). For mortality, associations were found with TBS (HR 1.22[95 % CI = 1.09–1.37]), pT (HR 1.45[95 % CI = 1.05–2.00]), and extrahepatic disease at hepatectomy (HR 2.10[95 % CI = 1.31–3.36]). In our population, non-imaging related factors TBS, neoadjuvant chemotherapy, pT and presence of extrahepatic disease at time of hepatectomy were associated with HDFS and/or OS. The preoperative imaging interval and use of preoperative MRI were not associated with improved patient outcomes. [ABSTRACT FROM AUTHOR]

Just over 300,000 women give birth in Australia each year. It is important for health care providers, managers, and policy makers know what women want from their care so services can be provided appropriately. This review is a part of the Midwifery Futures Project, which aims to prepare the midwifery workforce to best address the needs of women. The aim of this review was to describe and analyse current literature on the maternity care needs of women in Australia. A scoping review methodology was used, guided by the Joanna Briggs Institute framework. A systematic search of the literature identified 9023 studies, and 59 met inclusion criteria: being peer-reviewed research focusing on maternity care needs, conducted in Australian populations, from 2012 to 2023. The studies were analysed using inductive content analysis. Four themes were developed: Continuity of care , being seen and heard , being safe , and being enabled. Continuity of care, especially a desire for midwifery continuity of care, was the central theme, as it was a tool supporting women to be seen and heard, safe, and enabled. This review highlights that women in Australia consistently want access to midwifery continuity of care as an enabler for addressing their maternity care needs. Transforming Australian maternity care policy and service provision towards continuity would better meet women's needs. [ABSTRACT FROM AUTHOR]

A robust instrument for measuring the educational environment in a pharmacy patient care setting is currently lacking. The authors aimed to develop a person-reported outcome measure to gauge trainee pharmacists' perceptions of their clinical workplace-based educational environment. This paper reports the various sources of validity evidence. A preliminary, three-domain (system, relationship, and personal), 36-item measurement instrument was developed by incorporating results from literature review, focus group interviews, iterative discussions among educators, and cognitive interviews. The preliminary instrument, together with the Dundee Ready Educational Environment Measure (DREEM) and Orientation to Happiness Scale (OHS), were administered to trainee pharmacists recruited from one pharmacy school and one healthcare cluster in Singapore. Rasch analysis was conducted on the overall instrument as well as three domains: System, Relationship, and Personal. The 36-item instrument was administered to 145 learners, of which 66 were trainee pharmacists and 79 undergraduate interns. Upon removal of the middle "neutral" category to resolve poorly functioning categories and removal of five poorly functioning items, the overall instrument and its domains generally showed good fit with the Rasch model. Moreover, the overall 31-item Singapore Pharmacy Educational Environment Questionnaire (SPEEQ) and its three domains showed moderate to high convergent correlation with all the five DREEM domains and low to non-significant divergent correlation with the OHS Pleasure of Life subscale. Among one sample of pharmacy trainees, the 31-item SPEEQ and its three component domains demonstrated notable validity evidence to gauge trainees' perceptions of their learning environment. [ABSTRACT FROM AUTHOR]

Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations. Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy. The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares ∼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days. The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations. • Anti-SARS-CoV-2 neutralizing antibody with ACE2 mimetic binding properties. • Broad-spectrum activity against all past and current SARS-CoV-2 variants of concern. • Mutations escaping mAb activity bind ACE2 poorly and are rare in circulating viruses. • Sterilizing protection from XBB.1.5 infection in an NHP challenge model. [ABSTRACT FROM AUTHOR]

Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity. • Intradermal skin test (IDT) with mRNA COVID-19 vaccines can be used as a surrogate of T cell immunity. • COVID-19 mRNA vaccines induce the trafficking of mainly T cells with a memory profile. • Seronegative immunocompromised patients with T cell immunity are mainly under B cell-depleting therapy. • Seronegative immunocompromised patients without detectable T cell immunity are mainly transplant recipients. [ABSTRACT FROM AUTHOR]