Systems Mapping of the New Zealand Free and Healthy School Lunch Programme: Perspectives from Lunch Providers

As part of the COVID-19 economic recovery package, the Aotearoa New Zealand Government rolled out a universal free and healthy lunch programme to the 25% least advantaged schools nationwide. This study explored experiences of school lunch providers in the Hawke’s Bay region. The aim was to create a systems map identifying points of intervention through which the lunch programme could be improved to meet the goal of reducing child food insecurity. Twelve lunch providers were interviewed to generate casual loop diagrams which were examined and integrated to form a single systems map. Seven themes arose during analysis: teacher support, principal support, nutrition guidelines and government support, supply chain, ingredient suppliers, student feedback and food waste. Teacher support was important for getting students to try new foods and eat the nutritious lunches. Principal support was a strong theme impacting opportunities for broader student engagement. This study employed systems science to highlight the importance of support from different stakeholders within the lunch programme to achieve the goal of reduced child food insecurity. Further work is needed to ensure the programme meets the wider goals of the government and community, and to determine the potential broader benefits of the programme.     

Manufacturing‐dependent change in biological activity of the TLR4 agonist GSK1795091 and implications for lipid A analog development

A phase I trial ({"type":"clinical-trial","attrs":{"text":"NCT03447314","term_id":"NCT03447314"}}NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll‐like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti‐OX40 monoclonal antibody], GSK3359609 [anti‐ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty‐four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid‐study from the original to the modified formulation. Despite the modified formulation demonstrating higher systemic GSK1795091 exposure compared with the original formulation, the transient, dose‐dependent elevations in cytokine and chemokine concentrations were no longer observed (e.g., IP‐10, IL10, IL1‐RA). Most patients (51/54; 94%) experienced ≥1 treatment‐emergent adverse event (TEAE) during the study. Safety profiles were similar between formulations, but a higher incidence of TEAEs associated with immune responses (chills, fatigue, pyrexia, nausea, and vomiting) were observed with the original formulation. No conclusions can be made regarding GSK1795091 anti‐tumor activity due to the limited data collected. Manufacturing changes were hypothesized to have caused the change in biological activity in this study. Structural characterization revealed GSK1795091 aggregate size in the modified formulation to be twice that in the original formulation, suggesting a negative correlation between GSK1795091 aggregate size and PD activity. This may have important clinical implications for future development of structurally similar compounds.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Toll‐like receptor 4 (TLR4) agonists, such as lipopolysaccharide (LPS) and lipid A analogs, have demonstrated anti‐cancer effects in patients. Previous studies offer conflicting evidence on the active form (monomeric vs. aggregates) of LPS/lipid A analogs and suggest that different forms can stimulate different immune pathways.

• WHAT QUESTION DID THIS STUDY ADDRESS?

This phase I study investigated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GSK1795091 with one of three immunotherapies in patients with solid tumors. In addition, the study addressed the effects of a manufacturing change on the biological activity of GSK1795091.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study enables a better understanding of the impact of the manufacturing process on drug aggregate morphology and activity. The formulation change led to the formation of particle aggregates with globular morphology, suggesting the initial dissolution of GSK1795091 in ethanol, instead of initial dissolution using sonication, was the likely contributor to the lowered biological activity of GSK1795091. This could have implications for the development of other lipid A analogs and TLR agonists.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Following manufacturing changes of LPS/other lipid A analogs and chemically manufactured active pharmaceutical ingredients that are prone to structural organization in solution, it is recommended to perform in vitro PD assessments to understand the impact on its biological activity prior to clinical assessment. PK and PD evaluations should be prioritized to ensure no clinically meaningful changes related to the manufacturing occur.     

Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.     

Corrosion Resistance of 3D Printed Ti6Al4V Gyroid Lattices with Varying Porosity

Corrosion of medical implants is a possible failure mode via induced local inflammatory effects, systemic deposition and corrosion related mechanical failure. Cyclic potentiodynamic polarisation (CPP) testing was utilized to evaluate the effect of increased porosity (60% and 80%) and decreased wall thickness in gyroid lattice structures on the electrochemical behaviour of LPBF Ti6Al4V structures. The use of CPP allowed for the landmarks of breakdown potential, resting potential and vertex potential to be analysed, as well as facilitating the construction of Tafel plots and qualitative Goldberg analysis. The results indicated that 60% gyroid samples were most susceptible to the onset of pitting corrosion when compared to 80% gyroid and solid samples. This was shown through decreased breakdown and vertex potentials and were found to correlate to increased lattice surface area to void volume ratio. Tafel plots indicated that despite the earlier onset of pitting corrosion, both gyroid test groups displayed lower rates of corrosion per year, indicating a lower severity of corrosion. This study highlighted inherent tradeoffs between lattice optimisation and corrosion behaviour with a potential parabolic link between void volume, surface area and corrosion being identified. This potential link is supported by 60% gyroid samples having the lowest breakdown potentials, but investigation into other porosity ranges is suggested to support the hypothesis. All 3D printed materials studied here showed breakdown potentials higher than ASTM F2129′s suggestion of 800 mV for evaluation within the physiological environment, indicating that under static conditions pitting and crevice corrosion should not initiate within the body.     

Effect of the Affordable Care Act on healthcare utilization for Veterans with spinal cord injuries and disorders

Context/Objective: Provisions of the Affordable Care Act (ACA) potentially increase insurance options for Veterans with disabilities. We examined Veterans with spinal cord injuries and disorders (SCI/D) to assess whether the ACA was associated with changes in healthcare utilization from Department of Veterans Affairs (VA) healthcare facilities.Design: Using national VA data, we investigated impacts on VA healthcare utilization pre- (2012/13) and post-ACA (2014/15) implementation with negative binomial regression models.Setting: VA healthcare facilities.Participants: 8,591 VA users with SCI/D. Veterans with acute myelitis, Guillain-Barré syndrome, multiple sclerosis, or amyotrophic lateral sclerosis were excluded as were patients who died during the study period.Interventions: We assessed VA healthcare utilization before and after ACA implementation.Outcome Measures: Total numbers of VA visits for SCI/D care, diagnostic care, primary care, specialty care, and mental health care, and VA admissions.Results: The number of VA admissions was 7% higher in the post than pre-ACA implementation period (P < 0.01). The number of VA visits post-implementation increased for SCI/D care (8%; P < 0.01) and specialty care (12%; P < 0.001). Conversely, the number of mental health visits was 17% lower in the post-ACA period (P < 0.001). Veterans with SCI/D who live <5 miles from their nearest VA facility received VA care more frequently than those ≥40 miles from VA (P < 0.001).Conclusion: Counter to expectations, results suggest that Veterans with SCI/D sought more frequent VA care after ACA implementation, indicating Veterans with SCI/D continue to utilize the lifelong, comprehensive care provided at VA.