Estimating the Health-Related Quality of Life Benefit of Prophylactic Treatment for COVID-19 in Immunocompromised People: A Multimethod Valuation Study.

Background: Pre-exposure prophylaxis (PrEP) for COVID-19 provides additional protection, beyond vaccines alone, for individuals who are immunocompromised (IC). This may reduce the need for preventative behavioral modification, such as shielding-a behavioral restriction limiting an IC individual to minimize face-to-face interactions and/or crowded places. Therefore, PrEP may improve psychosocial well-being and health-related quality of life (HRQoL) for individuals with IC conditions. Objective: To estimate the potential HRQoL and utility benefit of PrEP for prevention of COVID-19 in individuals with IC conditions who may not have an adequate response of full vaccination (and therefore are at "highest risk" of severe COVID-19) that can be used in future economic evaluations of preventative therapies against COVID-19. Methods: Vignettes describing HRQoL associated with 2 pre-PrEP states (shielding and semi-shielding behavioral restrictions) and a post-PrEP state were developed from a literature review and tested through interviews with clinicians (n = 4) and individuals with IC conditions (n = 10). Vignettes were valued by a general population sample (N = 100) using a visual analog scale (VAS), time trade-off (TTO), and EQ-5D-5L. A sample of individuals with IC conditions (n = 48) valued their current HRQoL and a post-PrEP vignette using VAS and EQ-5D-5L. Results: Individuals with IC conditions reported a mean current EQ-5D-5L score of 0.574, and 0.656 for post-PrEP based on the vignette. PrEP would lead to behavior changes for 75% (30/40) of individuals with IC conditions and an emotional benefit for 93% (37/40) of individuals with IC conditions. Mean values from the general population valuation based on EQ-5D-5L ranged from 0.606 ("shielding") to 0.932 ("post-PrEP"). Conclusion: This study quantified the expected health state utility benefit of reduced psychosocial burden and behavioral restriction. PrEP would potentially result in a utility gain between 0.082 and 0.326, dependent on valuation approach and expected change in behavioral restrictions, leading to improvements in daily activities and emotional well-being.

Cost-Utility Analysis of Lurasidone Versus Aripiprazole in Adults with Schizophrenia.

BACKGROUND: In 2014, lurasidone, an atypical antipsychotic, was approved for the treatment of schizophrenia in adults. It is an alternative treatment option to aripiprazole, and when compared with aripiprazole, lurasidone was associated with improved symptom reduction and reduced risk of weight gain and relapse. We conducted a cost-utility analysis of lurasidone versus aripiprazole from the perspective of healthcare services, using Scotland and Wales as specific case studies. METHODS: A 10-year Markov model, incorporating a 6-week acute phase and a maintenance phase across three health states (discontinuation, relapse, death) was constructed. Six-week probabilities of discontinuation and adverse events were based on a published independent mixed-treatment comparison; long-term risks of relapse and discontinuation were from an indirect comparison. Costs included drug therapy, relapse, and outpatient, primary and residential care. Costs and benefits were discounted at 3.5 %. Utility estimates were taken from published literature, and cost effectiveness was expressed as total 10-year incremental costs and quality-adjusted life-years (QALYs). RESULTS: Lurasidone yielded a cost saving of £3383 and an improvement of 0.005 QALYs versus aripiprazole, in Scotland. Deterministic sensitivity analysis demonstrated that results were sensitive to relapse rates, while probabilistic sensitivity analysis suggested that lurasidone had the highest expected net benefit at willingness-to-pay thresholds of £20,000-30,000 per QALY. The probability that lurasidone was a cost-effective treatment strategy was approximately 75 % at all willingness-to-pay thresholds, with similar results being obtained for the Welsh analysis. CONCLUSIONS: Our analysis suggests that lurasidone would provide an effective, cost-saving alternative for the healthcare service in the treatment of adult patients with schizophrenia.

Phase-locking of bursting neuronal firing to dominant LFP frequency components.

Neuronal firing in the hippocampal formation relative to the phase of local field potentials (LFP) has a key role in memory processing and spatial navigation. Firing can be in either tonic or burst mode. Although bursting neurons are common in the hippocampal formation, the characteristics of their locking to LFP phase are not completely understood. We investigated phase-locking properties of bursting neurons using simulations generated by a dual compartmental model of a pyramidal neuron adapted to match the bursting activity in the subiculum of a rat. The model was driven with stochastic input signals containing a power spectral profile consistent with physiologically relevant frequencies observed in LFP. The single spikes and spike bursts fired by the model were locked to a preferred phase of the predominant frequency band where there was a peak in the power of the driving signal. Moreover, the preferred phase of locking shifted with increasing burst size, providing evidence that LFP phase can be encoded by burst size. We also provide initial support for the model results by analysing example data of spontaneous LFP and spiking activity recorded from the subiculum of a single urethane-anaesthetised rat. Subicular neurons fired single spikes, two-spike bursts and larger bursts that locked to a preferred phase of either dominant slow oscillations or theta rhythms within the LFP, according to the model prediction. Both power-modulated phase-locking and gradual shift in the preferred phase of locking as a function of burst size suggest that neurons can use bursts to encode timing information contained in LFP phase into a spike-count code.