Impact of neurofibromatosis type 1 with plexiform neurofibromas on the health-related quality of life and work productivity of adult patients and caregivers in the UK: a cross-sectional survey.

BACKGROUND: Plexiform neurofibromas (PN) are complex, benign nerve-sheath tumours that occur in 30-50% of patients with neurofibromatosis type 1 (NF1), a rare, genetic disorder. PN are associated with substantial, heterogeneous morbidities that impact health-related quality of life (HRQoL), including affecting motor function and causing pain, though HRQoL and work productivity data are scarce. This UK cross-sectional study explored HRQoL and work productivity in adult patients with NF1 PN and caregivers of paediatric patients. METHODS: Adult patients and caregivers of paediatric patients self-enrolled in an online survey (March-April 2021). Outcomes included EQ-5D-5L, PROMIS® GH and INF1-QOL (adult patients only), and EQ-5D-5L, CarerQol and WPAI (caregivers only). Utilities were estimated from EQ-5D-5L responses using the UK crosswalk value set. Linear regression models explored univariable associations between adult patient characteristics and HRQoL. RESULTS: Mean (± standard deviation) EQ-5D utility in adult patients with NF1 PN was 0.65 (± 0.29; n = 35; age-/sex-matched norm: 0.89 [± 0.04]). Moderate-extreme pain/discomfort and anxiety/depression were reported by 14/35 (40.0%) and 18/35 (51.4%) patients, respectively. Mean PROMIS® GH physical and mental health scores were 43.6 (± 9.19) and 41.7 (± 11.5; n = 35; matched norm: 50.0 [± 10.0]). Mean INF1-QOL score was 11.03 (± 6.02; n = 33). Chronic itching, at least one symptom, at least one comorbidity, PN location at extremities (arms/legs) and pain were associated with worse HRQoL scores. Mean caregiver EQ-5D utility was 0.72 (± 0.24; n = 8; age-/sex-matched norm: 0.88 [± 0.03]). Moderate pain/discomfort and moderate-severe anxiety/depression were reported by 4/8 (50.0%) and 2/8 (25.0%) caregivers, respectively. Mean CarerQol score was 69.3 (± 13.9; n = 8). Mean WPAI regular activity productivity loss was 36.3% (± 31.6%; n = 8). CONCLUSIONS: NF1 PN worsens adult patient and caregiver HRQoL compared to the general population, notably affecting pain and discomfort, anxiety and depression and caregiver productivity.

An Economic Model to Establish the Costs Associated With Routes to Presentation for Patients With Multiple Myeloma in the United Kingdom.

OBJECTIVES: Patients with myeloma often face significant diagnostic delay, with up to one-third of UK patients diagnosed after an emergency presentation (EP). Compared with other routes, patients presenting as an emergency have more advanced disease, increased complications, and poorer prognosis. METHODS: An economic model was developed using a decision-tree framework and lifetime time horizon to estimate costs related to different presentation routes (EP, general practitioner [GP] 2-week wait, GP urgent, GP routine, and consultant to consultant) for UK patients diagnosed as having myeloma. After diagnosis, patients received one of 3 first-line management options (observation, active treatment, or end-of-life care). Inputs were derived from UK health technology assessments and targeted literature reviews, or based on authors' clinical experience where data were unavailable. Active treatment, complication, and end-of-life care costs were included. RESULTS: The average per-patient cost of treating myeloma (across all routes) was estimated at £146 261. The average per-patient cost associated with EP (£152 677) was the highest; differences were minimal compared with GP 2-week wait (£149 631) and consultant to consultant (£147 237). GP urgent (£140 025) and GP routine (£130 212) were associated with marginally lower costs. Complication (£42 252) and end-of-life care (£11 273) costs were numerically higher for EP than other routes (£25 021-£38 170 and £9772-£10 458, respectively). CONCLUSIONS: An economic benefit may be associated with earlier diagnosis, gained via reduced complication and end-of-life care costs. Strategies to expedite myeloma diagnosis and minimize EPs have the potential to improve patient outcomes and may result in long-term savings that could offset any upfront costs associated with their implementation.

Assessing cyanobacterial frequency and abundance at surface waters near drinking water intakes across the United States.

This study presents the first large-scale assessment of cyanobacterial frequency and abundance of surface water near drinking water intakes across the United States. Public water systems serve drinking water to nearly 90% of the United States population. Cyanobacteria and their toxins may degrade the quality of finished drinking water and can lead to negative health consequences. Satellite imagery can serve as a cost-effective and consistent monitoring technique for surface cyanobacterial blooms in source waters and can provide drinking water treatment operators information for managing their systems. This study uses satellite imagery from the European Space Agency's Ocean and Land Colour Instrument (OLCI) spanning June 2016 through April 2020. At 300-m spatial resolution, OLCI imagery can be used to monitor cyanobacteria in 685 drinking water sources across 285 lakes in 44 states, referred to here as resolvable drinking water sources. First, a subset of satellite data was compared to a subset of responses (n = 84) submitted as part of the U.S. Environmental Protection Agency's fourth Unregulated Contaminant Monitoring Rule (UCMR 4). These UCMR 4 qualitative responses included visual observations of algal bloom presence and absence near drinking water intakes from March 2018 through November 2019. Overall agreement between satellite imagery and UCMR 4 qualitative responses was 94% with a Kappa coefficient of 0.70. Next, temporal frequency of cyanobacterial blooms at all resolvable drinking water sources was assessed. In 2019, bloom frequency averaged 2% and peaked at 100%, where 100% indicated a bloom was always present at the source waters when satellite imagery was available. Monthly cyanobacterial abundances were used to assess short-term trends across all resolvable drinking water sources and effect size was computed to provide insight on the number of years of data that must be obtained to increase confidence in an observed change. Generally, 2016 through 2020 was an insufficient time period for confidently observing changes at these source waters; on average, a decade of satellite imagery would be required for observed environmental trends to outweigh variability in the data. However, five source waters did demonstrate a sustained short-term trend, with one increasing in cyanobacterial abundance from June 2016 to April 2020 and four decreasing.

Cost-Utility Analysis of Anterior Vertebral Body Tethering versus Spinal Fusion in Idiopathic Scoliosis from a US Integrated Healthcare Delivery System Perspective.

PURPOSE: Anterior vertebral body tethering (VBT) is a non-fusion, minimally invasive, growth-modulating procedure with some early positive clinical outcomes reported in pediatric patients with idiopathic scoliosis (IS). VBT offers potential health-related quality of life (HRQoL) benefits over spinal fusion in allowing patients to retain a greater range of motion after surgery. We conducted an early cost-utility analysis (CUA) to compare VBT with fusion as a first-choice surgical treatment for skeletally immature patients (age >10 years) with moderate to severe IS, who have failed nonoperative management, from a US integrated healthcare delivery system perspective. PATIENTS AND METHODS: The CUA uses a Markov state transition model, capturing a 15-year period following index surgery. Transition probabilities, including revision risk and subsequent fusion, were based on published surgical outcomes and an ongoing VBT observational study (NCT02897453). Patients were assigned utilities derived from published patient-reported outcomes (PROs; SRS-22r mapped to EQ-5D) following fusion and the above VBT study. Index and revision procedure costs were included. Probabilistic (PSA) and deterministic sensitivity analyses (DSA) were performed. RESULTS: VBT was associated with higher costs but also higher quality-adjusted life years (QALYs) than fusion (incremental costs: $45,546; QALYs gained: 0.54). The subsequent incremental cost-effectiveness ratio for VBT vs fusion was $84,391/QALY gained. Mean PSA results were similar to the base case, indicating that results were generally robust to uncertainty. The DSA indicated that results were most sensitive to variations in utility values. CONCLUSION: This is the first CUA comparing VBT with fusion in pediatric patients with IS and suggests that VBT may be a cost-effective alternative to fusion in the US, given recommended willingness-to-pay thresholds ($100,000-$150,000). The results rely on HRQoL benefits for VBT compared with fusion. For improved model accuracy, further analyses with longer-term PROs for VBT, and comparative effectiveness studies, would be needed.