The financial and environmental impact of unopened medical supplies discarded in the emergency department.

BACKGROUND: Inefficient supply chain management within the US healthcare industry results in significant financial and environmental impact. Unopened medical supplies may routinely be discarded in the Emergency Department (ED), contributing as a source of unnecessary medical waste. OBJECTIVES: Quantify the financial and environmental impact of unopened medical supplies that are routinely discarded in two EDs. METHODS: The study utilized a waste audit of collection bins targeting unopened medical supplies that would have otherwise been discarded. Associated financial cost was calculated using data from the purchasing department and from an online search. End-of-life (EOL) environmental impact was calculated using the M+ Wastecare calculator. A lifecycle analysis was performed on a supplier-packaged intubation kit, which the study identified as a significant source of waste. RESULTS: High volumes of unused, unopened supplies (143.48 kg) were collected during the study period with a yearly extrapolated value of 1337 kg. Purchasing costs over 44 days at Hospital A and 37 days at Hospital B for these items amounted to $16,159.71 across both sites with a yearly extrapolated value of $150,631.73. Yearly extrapolated EOL impact yielded 5.79 tons per year of CO2eq. Components from supplier-packaged intubation kits were found to contribute to 45.2% of collected items at one site which purchased them. Lifecycle analysis of an intubation kit yields 23.6 kg of CO2eq. CONCLUSION: This study demonstrates that the disposal of unopened medical supplies contributes a significant source of financial and environmental waste in the ED setting. The results continue to support the trend of procedure kits generating significant environmental and financial waste.

Therapeutic targeting of TRAIL death receptors.

The discovery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) along with its potent and selective antitumor effects initiated a decades-long search for therapeutic strategies to target the TRAIL pathway. First-generation approaches were focused on the development of TRAIL receptor agonists (TRAs), including recombinant human TRAIL (rhTRAIL) and TRAIL receptor-targeted agonistic antibodies. While such TRAIL pathway-targeted therapies showed promise in preclinical data and clinical trials have been conducted, none have advanced to FDA approval. Subsequent second-generation approaches focused on improving upon the specific limitations of first-generation approaches by ameliorating the pharmacokinetic profiles and agonistic abilities of TRAs as well as through combinatorial approaches to circumvent resistance. In this review, we summarize the successes and shortcomings of first- and second-generation TRAIL pathway-based therapies, concluding with an overview of the discovery and clinical introduction of ONC201, a compound with a unique mechanism of action that represents a new generation of TRAIL pathway-based approaches. We discuss preclinical and clinical findings in different tumor types and provide a unique perspective on translational directions of the field.

Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA.

Recent studies have highlighted the importance of immune sensing of cytosolic DNA of both pathogen and host origin. We aimed to examine the role of DNA sensors interferon-γ-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) in responding to cytosolic DNA. We show IFI16 and cGAS can synergistically induce IFNb transcriptional activity in response to cytoplasmic DNA. We also examined the role of polyglutamine binding protein 1 (PQBP1), a protein predominantly expressed in lymphoid and myeloid cells that has been shown to lead to type I interferon production in response to retroviral infection. We show PQBP1 associates with cGAS and IFI16 in THP-1 cells. Unexpectedly, knockout of PQBP1 in THP-1 cells causes significantly increased type I IFN production in response to transfected cytosolic nucleic acids or DNA damage, unlike what is seen in response to retroviral infection. Overexpression of PQBP1 in HEK293 T cells impairs IFI16/cGAS-induced IFNb transcriptional activity. In human cancer patients, low expression of PQBP1 is correlated with improved survival, the opposite correlation of that seen with cGAS or IFI16 expression. Our findings suggest that PQBP1 inhibits IFI16/cGAS-induced signaling in response to cytosolic DNA, in contrast to the role of this protein in response to retroviral infection.