ABSTRACT
Spurred in part by literature published in the immediate aftermath of the severe acute respiratory syndrome epidemic in 2003, powered air-purifying respirators have seen increased use worldwide during the COVID-19 pandemic. Whereas these devices provide excellent protection of the user, there is an added element of risk during doffing and cleaning of the device. An additional layer of barrier protection, in the form of a polypropylene gown, to be worn over the hood and motor belt, can be used to minimise this risk. However, the device entrains air perpendicular to the lie of the gown, resulting in the impermeable material being sucked into the air intake, and partial occlusion of flow. In this report, we describe a clinical-academic partnership whereby a bespoke filter guard was designed to disrupt airflow and prevent gown entrainment, thereby enabling full barrier protection of both the device and user. This intervention was simple, cheap, scalable and able to be mass produced.
ABSTRACT
UNLABELLED: Antiplatelet therapy is given to millions of patients and has saved numerous lives. However, it is also associated with complications including fatal bleedings. Clinically used antiplatelet drugs seem to follow the rule of an inherent link of improved anti-thrombotic potency with increased risk of bleeding complications. Therefore, there is an ongoing quest to develop drugs that are able to break this link that has prevented many patients from receiving antiplatelet protection and has resulted in substantial mortality and morbidity. We describe a new antiplatelet approach that is based on an recombinant antibody protein, a drug format that has recently attracted major interest. Two unique components are genetically combined in this molecule: 1) The ecto-nucleoside triphosphate diphosphohydrolase NTPDase CD39, which enzymatically degrades ATP and ADP to AMP, which is then further degraded to adenosine by the endothelially expressed CD73. Thereby, the platelet activating ADP is reduced and replaced by the platelet inhibiting adenosine resulting in a strong antiplatelet effect. 2) A single-chain antibody (scFv) that specifically binds to the activated GPIIb/IIIa receptor and thus allows targeting to activated platelets. The described fusion protein results in strong enrichment of CD39's antiplatelet effect, resulting in potent inhibition of platelet adhesion and aggregation and thrombosis in mice. The activated platelet targeting allows using a low systemic concentration that does not interfere with normal haemostasis and thus does not cause bleeding time prolongation in mice. CONCLUSION: We describe a new antiplatelet approach that promises to deliver strong localized antithrombotic effects without associated bleeding problems.
