Estimating the value of repositioning timing to streamline pressure injury prevention efforts in nursing homes: A cost-effectiveness analysis of the 'TEAM-UP' clinical trial.

Pressure injury (PrI) prevention guidelines recommend 2-h repositioning intervals in healthcare settings, requiring significant nursing time investment. We analysed the cost-effectiveness of PrI prevention protocols with 2-, 3- and 4-h repositioning intervals in US nursing homes according to 'Turn Everyone and Move for Ulcer Prevention' (TEAM-UP) randomized controlled trial findings. Markov modelling compared 2-, 3- and 4-h repositioning intervals, controlling for other practice guidelines, to prevent PrIs in nursing home residents from a US health sector perspective over one year using TEAM-UP trial data for model structure, sampling and parameterization. Costs, captured in 2020 US dollars, and quality-adjusted life years (QALYs) were used to derive an incremental cost-effectiveness ratio and net monetary benefit (NMB) at $50 000/QALY-$150 000/QALY cost-effectiveness thresholds. Sensitivity analyses tested model uncertainty. Repositioning intervals between 3 and 4 h were cost-effective based on reduced costs at slightly lower QALYs than 2 h at a $50 000/QALY threshold, and the NMB of 4-h repositioning was also more efficient than at 3 h ($9610). Repositioning labour cost and prevention routines were among the most sensitive parameters. Sensitivity analyses demonstrated that 3- and 4-h intervals were cost-effective in over 65% of simulations at any cost-effectiveness threshold. Repositioning intervals of 3 to 4 h have potential to reduce nursing time costs without significant decrements in clinical benefits to nursing home residents. Clinical guidelines for PrI prevention should be updated to reflect TEAM-UP clinical and economic findings. Facilities can use cost-savings recuperated from nursing time to deploy to other patient safety priorities without seriously jeopardizing PrI safety.

Microglia produce the amyloidogenic ABri peptide in familial British dementia.

Mutations in ITM2B cause familial British, Danish, Chinese and Korean dementias. In familial British dementia (FBD) a mutation in the stop codon of the ITM2B gene (also known as BRI2 ) causes a C-terminal cleavage fragment of the ITM2B/BRI2 protein to be extended by 11 amino acids. This fragment, termed amyloid-Bri (ABri), is highly insoluble and forms extracellular plaques in the brain. ABri plaques are accompanied by tau pathology, neuronal cell death and progressive dementia, with striking parallels to the aetiology and pathogenesis of Alzheimer's disease. The molecular mechanisms underpinning FBD are ill-defined. Using patient-derived induced pluripotent stem cells, we show that expression of ITM2B/BRI2 is 34-fold higher in microglia than neurons, and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. Consequently, the ABri peptide was detected in patient iPSC-derived microglial lysates and conditioned media but was undetectable in patient-derived neurons and control microglia. Pathological examination of post-mortem tissue support ABri expression in microglia that are in proximity to pre-amyloid deposits. Finally, gene co-expression analysis supports a role for ITM2B/BRI2 in disease-associated microglial responses. These data demonstrate that microglia are the major contributors to the production of amyloid forming peptides in FBD, potentially acting as instigators of neurodegeneration. Additionally, these data also suggest ITM2B/BRI2 may be part of a microglial response to disease, motivating further investigations of its role in microglial activation. This has implications for our understanding of the role of microglia and the innate immune response in the pathogenesis of FBD and other neurodegenerative dementias including Alzheimer's disease.

Microsimulation to compare activity-related bleed risks between pharmacokinetic-guided rurioctocog alfa pegol prophylaxis and emicizumab.

BACKGROUND: Owing to a lack of clinical study data, computational modeling was used to estimate activity-related bleed risk during prophylaxis with either rurioctocog alfa pegol or emicizumab. RESEARCH DESIGN AND METHODS: A pharmacokinetic (PK)-based computational model was used to estimate factor VIII (FVIII) levels for individual patients in the PROPEL study who were treated with PK-guided rurioctocog alfa pegol prophylaxis targeting FVIII trough levels of 1-3% or 8-12%. Emicizumab was assumed to have 20% FVIII equivalency. Six hypothetical patient activity profiles were created using the National Hemophilia Foundation's physical activity risk ratings scale. For each profile and treatment regimen combination, the total bleed risk over a 2-week period was estimated relative to a patient who was participating in a low-risk activity with 0% FVIII, and the overall relative bleed risks were compared. RESULTS: For all evaluated activity profiles, rurioctocog alfa pegol prophylaxis targeting either 1-3% or 8-12% FVIII trough levels was associated with a lower estimated bleed risk compared with emicizumab prophylaxis with assumed 20% FVIII equivalency (P < 0.001). CONCLUSION: Although this model does not reflect actual patient outcomes, it suggests that PK-guided rurioctocog alfa pegol prophylaxis may reduce the bleed risk during physical activities.

A Cost-Utility Analysis of Remote Pulse-Oximetry Monitoring of Patients With COVID-19.

OBJECTIVES: Since 2020, COVID-19 has infected tens of millions and caused hundreds of thousands of fatalities in the United States. Infection waves lead to increased emergency department utilization and critical care admission for patients with respiratory distress. Although many individuals develop symptoms necessitating a ventilator, some patients with COVID-19 can remain at home to mitigate hospital overcrowding. Remote pulse-oximetry (pulse-ox) monitoring of moderately ill patients with COVID-19 can be used to monitor symptom escalation and trigger hospital visits, as needed. METHODS: We analyzed the cost-utility of remote pulse-ox monitoring using a Markov model with a 3-week time horizon and daily cycles from a US health sector perspective. Costs (US dollar 2020) and outcomes were derived from the University Hospitals' real-world evidence and published literature. Costs and quality-adjusted life-years (QALYs) were used to determine the incremental cost-effectiveness ratio at a cost-effectiveness threshold of $100 000 per QALY. We assessed model uncertainty using univariate and probabilistic sensitivity analyses. RESULTS: Model results demonstrated that remote monitoring dominates current standard care, by reducing costs ($11 472 saved) and improving outcomes (0.013 QALYs gained). There were 87% fewer hospitalizations and 77% fewer deaths among patients with access to remote pulse-ox monitoring. The incremental cost-effectiveness ratio was not sensitive to uncertainty ranges in the model. CONCLUSIONS: Patient with COVID-19 remote pulse-ox monitoring increases the specificity of those requiring follow-up care for escalating symptoms. We recommend remote monitoring adoption across health systems to economically manage COVID-19 volume surges, maintain patients' comfort, reduce community infection spread, and carefully monitor needs of multiple individuals from one location by trained experts.

Diagnosing newborns with suspected mitochondrial disorders: an economic evaluation comparing early exome sequencing to current typical care.

PURPOSE: To determine the value of early exome sequencing (eES) relative to the current typical care (TC) in the diagnosis of newborns with suspected severe mitochondrial disorders (MitD). METHODS: We used a decision tree-Markov hybrid to model neonatal intensive care unit (NICU)-related outcomes and costs, lifetime costs and quality-adjusted life-years among patients with MitD. Probabilities, costs, and utilities were populated using published literature, expert opinion, and the Pediatric Health Information System database. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were calculated from lifetime costs and quality-adjusted life-years for singleton and trio eES, and TC. Robustness was assessed using univariate and probabilistic sensitivity analyses (PSA). Scenario analyses were also conducted. RESULTS: Findings indicate trio eES is a cost-minimizing and cost-effective alternative to current TC. Diagnostic probabilities and NICU length-of-stay were the most sensitive model parameters. Base case analysis demonstrates trio eES has the highest incremental NMB, and PSA demonstrates trio eES had the highest likelihood of being cost-effective at a willingness-to-pay (WTP) of $200,000 relative to TC, singleton eES, and no ES. CONCLUSION: Trio and singleton eES are cost-effective and cost-minimizing alternatives to current TC in diagnosing newborns suspected of having a severe MitD.

A US Population Health Survey on the Impact of COVID-19 Using the EQ-5D-5L.

BACKGROUND: The COVID-19 pandemic has resulted in negative impacts on the economy, population health, and health-related quality-of-life (HRQoL). OBJECTIVE: To assess the impact of COVID-19 on US population HRQoL using the EQ-5D-5L. DESIGN: We surveyed respondents on physical and mental health, demographics, socioeconomics, brief medical history, current COVID-19 status, sleep, dietary, financial, and spending changes. Results were compared to online and face-to-face US population norms. Predictors of EQ-5D-5L utility were analyzed using both standard and post-lasso OLS regressions. Robustness of regression coefficients against unmeasured confounding was analyzed using the E-Value sensitivity analysis. SUBJECTS: Amazon MTurk workers (n=2776) in the USA. MAIN MEASURES: EQ-5D-5L utility and VAS scores by age group. KEY RESULTS: We received n=2746 responses. Subjects 18-24 years reported lower mean (SD) health utility (0.752 (0.281)) compared with both online (0.844 (0.184), p=0.001) and face-to-face norms (0.919 (0.127), p<0.001). Among ages 25-34, utility was worse compared to face-to-face norms only (0.825 (0.235) vs. 0.911 (0.111), p<0.001). For ages 35-64, utility was better during pandemic compared to online norms (0.845 (0.195) vs. 0.794 (0.247), p<0.001). At age 65+, utility values (0.827 (0.213)) were similar across all samples. VAS scores were worse for all age groups (p<0.005) except ages 45-54. Increasing age and income were correlated with increased utility, while being Asian, American Indian or Alaska Native, Hispanic, married, living alone, having history of chronic illness or self-reported depression, experiencing COVID-19-like symptoms, having a family member diagnosed with COVID-19, fear of COVID-19, being underweight, and living in California were associated with worse utility scores. Results were robust to unmeasured confounding. CONCLUSIONS: HRQoL decreased during the pandemic compared to US population norms, especially for ages 18-24. The mental health impact of COVID-19 is significant and falls primarily on younger adults whose health outcomes may have been overlooked based on policy initiatives to date.

Medicaid Expansion Increased Preconception Health Counseling, Folic Acid Intake, And Postpartum Contraception.

The period before pregnancy is critically important for the health of a woman and her infant, yet not all women have access to health insurance during this time. We evaluated whether increased access to health insurance under the Affordable Care Act Medicaid expansions affected ten preconception health indicators, including the prevalence of chronic conditions and health behaviors, birth control use and pregnancy intention, and receipt of preconception health services. By comparing changes in outcomes for low-income women in expansion and nonexpansion states, we document greater preconception health counseling, prepregnancy folic acid intake, and postpartum use of effective birth control methods among low-income women associated with Medicaid expansion. We do not find evidence of changes on the other preconception health indicators examined. Our findings indicate that expanding Medicaid led to detectable improvements on a subset of preconception health measures.

Coverage for Adults With Chronic Disease Under the First 5 Years of the Affordable Care Act.

BACKGROUND: A key goal of the Patient Protection and Affordable Care Act (ACA) was to increase health insurance coverage for people with chronic disease. Little is known about progress toward this goal over the first 5 years of ACA implementation. OBJECTIVE: The objective of this study was to assess changes in coverage for nonelderly adults with and without chronic disease over the first 5 years of ACA implementation, and the effects of state-level Medicaid eligibility expansions on coverage for these populations. RESEARCH DESIGN: Multivariable and difference-in-differences regression models. PARTICIPANTS: A total of 2,007,271 adults aged 18-64 years in the nationally representative Behavioral Risk Factor Surveillance System 2011-2018 data. MEASURES: Self-reported insurance coverage. RESULTS: Over the first 5 years of ACA implementation, coverage increased among nonelderly adults with versus without chronic disease by 6.9 versus 5.4 percentage points, respectively (95% confidence interval: 6.1-7.6, P<0.001, and 4.4-6.3, P<0.001, respectively). State-level Medicaid eligibility expansions were associated with a coverage increase among people with chronic disease of 2.8 percentage points (95% confidence interval: 1.7-3.8, P<0.001). After ACA implementation diminished in 2017, coverage gains for people with chronic disease declined by 0.9 percentage points (P<0.001). CONCLUSIONS: Coverage significantly improved for people with chronic disease during the first 5 years of ACA implementation, with ACA Medicaid expansions increasing coverage further. After ACA implementation diminished in 2017, coverage gains decreased.

Impact of nucleation conditions on diameter modulation of GaAs nanowires.

Diameter-modulated nanowires can be used to impart unique properties to nanowire-based devices. Here, diameter modulation along Au-seeded GaAs nanowires was achieved by varying the flux of the III and V precursors during growth. Furthermore, three different types of [111]B-oriented nanowires were observed to display distinct differences in diameter modulation, growth rate, and cross-sectional shape. These differences are attributed to the presence of multiple distinct Au-Ga seed particle phases at the growth temperature of 420 °C. We show that the diameter modulation behavior can be modified by the growth conditions during nanowire nucleation, including temperature, V/III ratio, substrate orientation, and seed particle size. These results demonstrate the general viability of flow-controlled diameter modulation for compound semiconductors and highlight both opportunities and challenges that can arise from using compound-forming alloys to seed nanowire growth.

From GaN to ZnGa(2)O(4) through a low-temperature process: nanotube and heterostructure arrays.

We demonstrate a method to synthesize GaN-ZnGa2O4 core-shell nanowire and ZnGa2O4 nanotube arrays by a low-temperature hydrothermal process using GaN nanowires as templates. Transmission electron microscopy and X-ray photoelectron spectroscopy results show that a ZnGa2O4 shell forms on the surface of GaN nanowires and that the shell thickness is controlled by the time of the hydrothermal process and thus the concentration of Zn ions in the solution. Furthermore, ZnGa2O4 nanotube arrays were obtained by depleting the GaN core from GaN-ZnGa2O4 core-shell nanowire arrays during the reaction and subsequent etching with HCl. The GaN-ZnGa2O4 core-shell nanowires exhibit photoluminescence peaks centered at 2.60 and 2.90 eV attributed to the ZnGa2O4 shell, as well as peaks centered at 3.35 and 3.50 eV corresponding to the GaN core. We also demonstrate the synthesis of GaN-ZnGa2O4 heterojunction nanowires by a selective formation process as a simple route toward development of heterojunction nanodevices for optoelectronic applications.

Using seed particle composition to control structural and optical properties of GaN nanowires.

The morphology, structure, and optical properties of gallium nitride (GaN) nanowires grown using metal-organic chemical vapor deposition (MOCVD) on r-plane sapphire using gold and nickel seed particles were investigated. We found that different seed particles result in different growth rates and densities of structural defects in MOCVD-grown GaN nanowires. Ni-seeded GaN nanowires grow faster than Au-seeded ones, and they do not contain the basal plane stacking faults that are observed in Au-seeded GaN nanowires. We propose that stacking fault formation is related to the supersaturation and surface energies in different types of seed particles. Room temperature photoluminescence studies revealed a blue-shifted peak in Au-seeded GaN nanowires compared to the GaN near-bandgap emission. The blue-shifted peak evolves as a function of the growth time and originates from the nanowire base, likely due to strain and Al diffusion from the substrate. Our results demonstrate that seed particle composition has a direct impact on the growth, structure, and optical properties of GaN nanowires and reveal some general requirements for seed particle selection for the growth of compound semiconductor nanowires.

Heterojunction photovoltaics using GaAs nanowires and conjugated polymers.

We demonstrate an organic/inorganic solar cell architecture based on a blend of poly(3-hexylthiophene) (P3HT) and narrow bandgap GaAs nanowires. The measured increase of device photocurrent with increased nanowire loading is correlated with structural ordering within the active layer that enhances charge transport. Coating the GaAs nanowires with TiO(x) shells passivates nanowire surface states and further improves the photovoltaic performance. We find that the P3HT/nanowire cells yield power conversion efficiencies of 2.36% under white LED illumination for devices containing 50 wt % of TiO(x)-coated GaAs nanowires. Our results constitute important progress for the use of nanowires in large area solution processed hybrid photovoltaic cells and provide insight into the role of structural ordering in the device performance.

Growth mechanism of GaN nanowires: preferred nucleation site and effect of hydrogen.

The growth mechanism of epitaxial GaN nanowires grown using particle-mediated chemical vapour deposition was investigated. By examining the diameter-dependent growth rate of GaN nanowires, we show that the kinetic reaction-limited growth of GaN nanowires originates from the combination of mono-nuclear and poly-nuclear growth rather than the Gibbs-Thompson effect. We present a generalized nucleation-mediated growth model to describe the diameter dependence of the nanowire growth rate and show that the nucleation of sources occurs at the vapour/liquid/solid three-phase boundary. From the same model, we demonstrate that increased hydrogen concentration in the carrier gas reduces the supersaturation, leading to a reduced GaN nanowire growth rate. Our approach can be applied to other nanowire materials systems, and it allows the determination of the preferred nucleation site during nanowire growth.