The preventable productivity burden of sleep apnea in Australia: a lifetime modelling study.

Obstructive sleep apnea (OSA) is a common disorder. OSA is associated with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM) and depression, among other comorbidities. We aim to determine the productivity burden of OSA in Australia using productivity-adjusted life-years (PALYs). Using life table modelling, we built a multistate Markov model to estimate the impact of moderate to severe OSA on the whole working-age Australian population in 2021 (aged 20-65 years) with OSA until retirement (aged 66 years). The model also captured the impact of OSA on CVD, T2DM, depression, and vehicle-related accidents. Data for OSA and comorbidities and Australian specific labour data, were extracted from published sources. A second cohort was then modelled to test the effect of a hypothetical intervention, assuming a 10% reduction in OSA prevalence and a 10% reduction in comorbidities in patients with OSA. The primary outcome of interest were PALYs accrued. All outcomes were discounted 5% annually. Over a lifetime, the Australian population with OSA accrued 193,713,441 years of life lived and 182,737,644 PALYs. A reduction of 10% in OSA prevalence and comorbidities would result in 45,401 extra years of life lived and 150,950 extra PALYs. This resulted in more than AU$25 billion of gained gross domestic product over the lifetime of the working population. Our study highlights the substantial burden of OSA on the Australian population and the need to tailor interventions at the population level to reduce the health and economic impacts.

Inactivated tetanus as an immunological smokescreen: A major step towards harnessing tetanus-based therapeutics.

BACKGROUND AND PURPOSE: Tetanus neurotoxin has many potential therapeutic applications, due to its ability to increase localised muscle tone when injected directly into a muscle. It is a closely related molecule to botulinum neurotoxin (most commonly known as Botox), which has been widely used to release muscle tension for therapeutic and cosmetic applications. However, tetanus toxin has been relegated to the "maybe pile" for protein therapeutics - as most of the population is vaccinated, leading to highly effective antibody-mediated protection against the toxin. The potential for tetanus-based therapeutics remains substantial if the problem of pre-existing immunity can be resolved. EXPERIMENTAL APPROACH: A well-established murine model of localised muscular contraction was utilised. We administered functional tetanus toxin combined with an immunogenic, but functionally inactive, decoy molecule. KEY RESULTS: Incorporation of the decoy molecule greatly reduces the dose of active toxin required to induce a localised increase in muscle tone in mice vaccinated with the human toxoid vaccine. CONCLUSION AND IMPLICATIONS: Our results clearly demonstrate that the barriers to developing a tetanus toxin therapeutic are not insurmountable and the technology presented here is the first major step towards realising the therapeutic potential of this powerful neurotoxin. Opening the therapeutic potential of tetanus toxin will have huge implications for the wide range of diseases caused by low-tone muscle.

The impact of obstructive sleep apnea on motor skill acquisition and consolidation.

STUDY OBJECTIVE: Recent investigations suggest that motor skill learning is impaired in patients with obstructive sleep apnea (OSA) syndrome; however, it is not fully understood at what stages of learning this impairment occurs. The current study aimed to compare motor learning and memory across both daytime acquisition and overnight consolidation. METHODS: Twelve OSA patients and twelve control participants, matched for age and education, were recruited and completed the Karolinska Sleepiness Scale and the sequential finger-tapping task (SFTT), a motor skill learning task, both before and after polysomnographic recorded sleep. RESULTS: During the evening acquisition phase both groups showed significant and equitable improvement in the number of correctly typed sequences across trials. On retesting the following morning, the control patients showed significantly greater improvement overnight (15.35%) compared to OSA patients (1.78%). The post sleep improvement in controls, but lacking in OSA patients, was typical of a sleep dependent enhancement effect. The magnitude of improvement overnight for either group was not significantly correlated with any of the recorded sleep variables. CONCLUSIONS: These results suggest daytime/practice related acquisition of motor skill is largely intact in OSA patients; however, marked impairment in the consolidation phase is evident following a sleep period. This particular pattern of dysfunction may remain unnoticed following single-day learning/memory assessments.

A neurotoxinological approach to the treatment of obstructive sleep apnoea.

Current treatment approaches to the problem of obstructive sleep apnoea (OSA) have limitations. Specifically, invasive anatomical-based surgery and dental appliances typically do not alleviate obstruction at an acceptable rate, and compliance to continuous positive airway pressure (CPAP) devices is frequently suboptimal. Neurotoxinological treatment approaches are widespread in the field of medicine, but as yet have not been evaluated as a treatment for sleep-disordered breathing. In this review, it is argued that despite widespread recognition of the loss of upper airway (UA) muscular tone and/or reflexes in the expression of OSA, most treatment interventions to date have focused on anatomical principles alone. Several hypothesised neurotoxinological interventions aimed at either enhancing UA neuromuscular tone and/or reflexes are proposed, and some preliminary data is presented. Although in its early infancy, with considerable toxicity studies in animals yet to be done, a neurotoxinological approach to the problem of OSA holds promise as a future treatment, with the potential for both high effectiveness and patient compliance.