Prehospital continuous positive airway pressure (CPAP) for acute respiratory distress: a randomised controlled trial.

OBJECTIVE: To compare the efficacy of continuous positive airway pressure (CPAP) versus usual care for prehospital patients with severe respiratory distress. METHODS: We conducted a parallel group, individual patient, non-blinded randomised controlled trial in Western Australia between March 2016 and December 2018. Eligible patients were aged ≥40 years with acute severe respiratory distress of non-traumatic origin and unresponsive to initial treatments by emergency medical service (EMS) paramedics. Patients were randomised (1:1) to usual care or usual care plus CPAP. The primary outcomes were change in dyspnoea score and change in RR at ED arrival, and hospital length of stay. RESULTS: 708 patients were randomly assigned (opaque sealed envelope) to usual care (n=346) or CPAP (n=362). Compared with usual care, patients randomised to CPAP had a greater reduction in dyspnoea scores (usual care -1.0, IQR -3.0 to 0.0 vs CPAP -3.5, IQR -5.2 to -2.0), median difference -2.0 (95% CI -2.5 to -1.6); and RR (usual care -4.0, IQR -9.0 to 0.0 min-1 vs CPAP -8.0, IQR -14.0 to -4.0 min-1), median difference -4.0 (95% CI -5.0 to -4.0) min-1. There was no difference in hospital length of stay (usual care 4.2, IQR 2.1 to 7.8 days vs CPAP 4.8, IQR 2.5 to 7.9 days) for the n=624 cases admitted to hospital, median difference 0.36 (95% CI -0.17 to 0.90). CONCLUSIONS: The use of prehospital CPAP by EMS paramedics reduced dyspnoea and tachypnoea in patients with acute respiratory distress but did not impact hospital length of stay. TRIAL REGISTRATION NUMBER: ACTRN12615001180505.

Low-cost, rapidly deployable emergency mechanical ventilators during the COVID-19 pandemic in a developing country: Comparing development feasibility between bag-valve and positive airway pressure designs.

The COVID-19 pandemic disrupted the world by interrupting most supply chains, including that of the medical supply industry. The threat imposed by export restriction measures and the limitation in the availability of mechanical ventilators posed a higher risk for smaller, developing countries, used to importing most of their technologies. To actively respond to the possible device shortage, the initiative "Ventilators for Panama" was established and was able to develop two different, non-competing, open-source hardware mechanical ventilator models for emergency use in case of shortages: one based on a bag-valve design and another based on positive airway pressure. The aim of this article is to compare both devices in terms of feasibility and functionality. Results from the functional testing show that both devices perform within specification, as the error percentage is lower than 5% for the desired pressure values and a standard deviation of less than 0.5 for all cases.Clinical Relevance- This study shows the feasibility of quickly deploying two different mechanical ventilator designs for emergency use and their effectiveness.

Assisting Visually Impaired People in the Public Transport System through RF-Communication and Embedded Systems †.

For a significant number of people with visual impairments, public transport plays an important role in productivity, community participation, and independence, since it may be the only feasible mobility option to participate in their education, work, medical care, food, and to attend many other places in their community. To use the public bus system safely, effectively, and autonomously, these people need to collect information about their physical environment and visible information at stops and terminals, such as timetables, routes, etc. Unfortunately, most people who are blind or visually impaired experience difficulties in getting on the right bus or getting off at the right destination. These situations usually force them to depend on other people that assist them in activities close to their homes, or settle for simpler jobs, or simply stay at home. Therefore, our efforts should aim to develop a system where technology is used to empower people with visual disabilities, allowing them to navigate autonomously in the public transport system. This paper presents a system based on radio frequency (RF) communication proposed within the framework of the MOVIDIS (Mobility for Visually Disabled People) research project (funded by the National Secretariat of Science, Technology and Innovation-SENACYT, under Grants No. 109-2015-4-FID14-073 and No. 99-2018-4-FID17-031), which provides an alternative to assist people with visual disabilities with their mobility in the public transport system. The various modules of this system communicate with each other by means of radio frequency and allow users to interact with buses and their respective stops. The first experimental results show that RF communication represents a viable option to help people with visual disabilities in public transport services.

Impact of high-dose, chemically modified sulfamidase on pathology in a murine model of MPS IIIA.

Mucopolysaccharidosis type IIIA (MPS IIIA) is a neurodegenerative lysosomal storage disorder that results from a deficiency of sulfamidase (N-sulfoglucosamine sulfohydrolase), with consequential accumulation of its substrate, partially degraded heparan sulfate. Conventional doses (e.g. 1mg/kg) of intravenously delivered recombinant human sulfamidase (rhSGSH) do not improve neuropathology in MPS IIIA mice due to an inability to traverse the blood-brain barrier; however high-dose treatment or administration of enzyme that has been chemically modified to remove mannose-6-phosphate glycans has been shown to reduce neuropathology in related animal models. We have combined these approaches to evaluate the ability of 1, 5, 10 or 20mg/kg of similarly chemically modified or unmodified rhSGSH to reduce neuropathology following repeated intravenous delivery to adult MPS IIIA mice. rhSGSH was detected in brain homogenates from mice treated with all doses of modified rhSGSH and those receiving the two higher doses of unmodified rhSGSH, albeit at significantly lower levels. Immunohistochemically, rhSGSH visualized in the brain was localized to the endothelium, meninges and choroid plexus, with no convincing punctate intra-neuronal staining seen. This presumably underlies the failure of the treatment to reduce the relative level of a heparan sulfate-derived oligosaccharide (GlcNS-UA), or secondarily stored substrates that accumulate in MPS IIIA brain cells. However, modification of rhSGSH significantly increased its effectiveness in degrading GlcNS-UA in non-CNS tissues, potentially as a result of its reduced plasma clearance. If this observation is generally applicable, chemical modification may permit the use of significantly lower doses of lysosomal enzymes in patients currently receiving intravenous enzyme replacement therapy.

Preclinical dose ranging studies for enzyme replacement therapy with idursulfase in a knock-out mouse model of MPS II.

Mucopolysaccharidosis II (MPS II; Hunter syndrome) is an X-linked metabolic disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase (I2S), which catalyzes the catabolism of glycosaminoglycans (GAG) by cleaving the O-linked sulfate from dermatan sulfate and heparan sulfate. Recently, enzyme replacement therapy (ERT) with recombinant human I2S (Elaprase (idursulfase), Shire Human Genetic Therapies, Inc.), has been approved in the US and European Union for the treatment and management of MPS II. The purpose of the studies presented here was to describe some of the preclinical development of idursulfase using the I2S knock-out mouse model of MPS II designed to study the effect of dose and various dosing regimens of idursulfase on urine and tissue GAG levels. Urine and tissue samples were collected prior to idursulfase treatment and periodically throughout each study and analyzed for GAGs. The presence of anti-idursulfase antibodies in the mice serum after idursulfase use was also determined. Results showed that idursulfase, at several doses and at several dosing frequencies, caused a reduction in tissue and urine GAG levels in a dose-dependent manner. These studies also demonstrated that after IV administration, idursulfase is biologically active in the IdS-KO mouse model and is transported to key target tissues, reaching the lysosomes in an active form, and degrading the accumulated GAG. In conclusion, these results indicated that ERT with idursulfase produced in a human cell line could be useful in the treatment and management of MPS II, and were used in the design of clinical studies to evaluate the efficacy of idursulfase in MPS II patients.