ABSTRACT
Background: Serious injection-related infections (SIRIs) in people who inject drugs often lead to prolonged hospitalizations or premature discharges. This may be in part due to provider reluctance to place peripherally inserted central catheters (PICCs) for outpatient parenteral antibiotic therapy in this population. Because internal medicine (IM) residents are often frontline providers in academic centers, understanding their perspectives on SIRI care is important to improve outcomes. Methods: We surveyed IM residents in a large urban multicenter hospital system about SIRI care with a novel case-based survey that elicited preferences, comfort, experience, and stigma. The survey was developed using expert review, cognitive interviewing, and pilot testing. Results are reported with descriptive statistics and linear regression. Results: Of 116 respondents (response rate 34%), most (73%) were uncomfortable discharging a patient with active substance use home with a PICC, but comfortable (87%) with discharge to postacute facilities. Many (â¼40%) endorsed high levels of concern for PICC misuse or secondary line infections, but larger numbers cited concerns about home environment (50%) or loss to follow-up (68%). While overall rates were low, higher stigma was associated with more concerns around PICC use (r = -0.3, P = .002). A majority (58%) believed hospital policies against PICC use in SIRI may act as a barrier to discharge, and 74% felt initiation of medications for opioid use disorder (MOUD) would increase their comfort discharging with a PICC. Conclusions: Most IM residents endorsed high levels of concern about PICC use for SIRI, related to patient outcomes and perceived institutional barriers, but identified MOUD as a mitigating factor.
ABSTRACT
Mutations in copper-zinc superoxide dismutase (SOD1) have been linked to a subset of familial amytrophic lateral sclerosis (fALS), a fatal neurodegenerative disease characterized by progressive motor neuron death. An increasing amount of evidence supports that mitochondrial dysfunction and apoptosis activation play a critical role in the fALS etiology, but little is known about the mechanisms by which SOD1 mutants cause the mitochondrial dysfunction and apoptosis. In this study, we use proteomic approaches to identify the mitochondrial proteins that are altered in the presence of a fALS-causing mutant G93A-SOD1. A comprehensive characterization of mitochondrial proteins from NSC34 cells, a motor neuron-like cell line, was achieved by two independent proteomic approaches. Four hundred seventy unique proteins were identified in the mitochondrial fraction collectively, 75 of which are newly discovered proteins that previously had only been reported at the cDNA level. Two-dimensional gel electrophoresis was subsequently used to analyze the differences between the mitochondrial proteomes of NSC34 cells expressing wild-type and G93A-SOD1. Nine and 36 protein spots displayed elevated and suppressed abundance respectively in G93A-SOD1-expressing cells. The 45 spots were identified by MS, and they include proteins involved in mitochondrial membrane transport, apoptosis, the respiratory chain, and molecular chaperones. In particular, alterations in the post-translational modifications of voltage-dependent anion channel 2 (VDAC2) were found, and its relevance to regulating mitochondrial membrane permeability and activation of apoptotic pathways is discussed. The potential role of other proteins in the mutant SOD1-mediated fALS is also discussed. This study has produced a short list of mitochondrial proteins that may hold the key to the mechanisms by which SOD1 mutants cause mitochondrial dysfunction and neuronal death. It has laid the foundation for further detailed functional studies to elucidate the role of particular mitochondrial proteins, such as VDAC2, in the pathogenesis of familial ALS.
