Ambulatory management of secondary spontaneous pneumothorax: A randomised controlled trial

Secondary spontaneous pneumothorax (SSP) is traditionally managed with an intercostal chest tube attached to an underwater seal. We investigated whether use of a one-way flutter valve shortened patients' length of stay (LoS). This open-label randomised controlled trial enrolled patients presenting with SSP and randomised to either a chest tube and underwater seal (standard care: SC) or ambulatory care (AC) with a flutter valve. The type of flutter valve used depended on whether at randomisation the patient already had a chest tube in place: in those without a chest tube a pleural vent (PV) was used; in those with a chest tube in situ, an Atrium Pneumostat (AP) valve was attached. The primary end-point was LoS. Between March 2017 and March 2020, 41 patients underwent randomisation: 20 to SC and 21 to AC (13=PV, 8=AP). There was no difference in LoS in the first 30 days following treatment intervention: AC (median=6 days, IQR 14.5) and SC (median=6 days, IQR 13.3). In patients treated with PV there was a high rate of early treatment failure (6/13; 46%), compared to patients receiving SC (3/20; 15%) (p=0.11) Patients treated with AP had no (0/8 0%) early treatment failures and a median LoS of 1.5 days (IQR 23.8). There was no difference in LoS between ambulatory and standard care. Pleural Vents had high rates of treatment failure and should not be used in SSP. Atrium Pneumostats are a safer alternative, with a trend towards lower LoS

A systems approach reveals species differences in hepatic stress response capacity

ABSTRACTTo minimise unexpected toxicities in early phase clinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical test species and humans. We have used physiologically-based pharmacokinetic modelling to identify doses of the model hepatotoxin acetaminophen yielding similar hepatic burdens of the reactive metabolite N-acetyl-p-benzoquinoneimine in mice and rats, to enable comparison of tissue adaptive responses under conditions of equivalent chemical insult. Mice exhibited a greater degree of liver injury than rats, despite the equivalent hepatic NAPQI burden. Transcriptomic and proteomic analyses highlighted the stronger activation of stress response pathways (including the Nrf2 oxidative stress response and autophagy) in the livers of rats. Components of these pathways were also found to be expressed at a higher basal level in the livers of rats compared with both mice and humans. Our findings exemplify a systems approach to understanding differential species sensitivity to hepatotoxicity, and have important implications for species selection and human translation in the safety testing of new drug candidates.</jats:p