Prevalence, Patterns, and Outcomes of Opioid Use by Injured Workers in Tennessee.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2018

Prevalence and Risk Factors Associated With Long-term Opioid Use After Injury Among Previously Opioid-Free Workers

Importance Using opioids for acute pain can lead to long-term use and associated morbidity and mortality. Injury has been documented as a gateway to long-term opioid use in some populations, but data are limited for injured workers. Objective To evaluate the prevalence and risk factors of long-term opioid use after injury among workers in Tennessee who were opioid free at the time of injury. Design, Setting, and Participants This cohort study identified injured workers aged 15 to 99 years who reported only 1 injury to the Tennessee Bureau of Workers’ Compensation from March 2013 to December 2015 and had no opioid prescription in the 60 days before injury. Participants were matched to their prescription history in Tennessee’s prescription drug monitoring program. Analysis was conducted from November 2017 to March 2018. Logistic regression models were used to calculate adjusted odds ratios (ORs) and 95% CIs for associations of demographic, injury, and opioid use variables with long-term use. Main Outcomes and Measures The primary outcome was long-term opioid use, defined as having an opioid supplied for 45 or more days in the 90 days after injury. Results Among 58 278 injured workers who received opioids after injury (18 977 [32.5%] aged 15-34 years, 27 514 [47.2%] aged 35-54 years, and 11 787 [20.2%] aged 55-99 years; 32 607 [56.0%] men), 46 399 (79.6%) were opioid free at the time of injury. Among opioid-free injured workers, 1843 (4.0%) began long-term opioid use. After controlling for covariates, long-term use was associated with receiving 20 or more days’ supply in the initial opioid prescription compared with receiving less than 5 days’ supply (OR, 28.94; 95% CI, 23.44-35.72) and visiting 3 or more prescribers in the 90 days after injury compared with visiting 1 prescriber (OR, 14.91; 95% CI, 12.15-18.29). However, even just 5 days’ to 9 days’ supply was associated with an increase in the odds of long-term use compared with less than 5 days’ supply (OR, 1.83; 95% CI, 1.56-2.14). Conclusions and Relevance In this study of injured workers, injury was associated with long-term opioid use. The number of days’ supply of the initial opioid prescription was the strongest risk factor of developing long-term use, highlighting the importance of careful prescribing for initial opioid prescriptions

Objective Characterization of Snow Microstructure for Microwave Emission Modeling

Passive microwave (PM) measurements are sensitive to the presence and quantity of snow, a fact that has long been used to monitor snowcover from space. In order to estimate total snow water equivalent (SWE) within PM footprints (on the order of approx 100 sq km), it is prerequisite to understand snow microwave emission at the point scale and how microwave radiation integrates spatially; the former is the topic of this paper. Snow microstructure is one of the fundamental controls on the propagation of microwave radiation through snow. Our goal in this study is to evaluate the prospects for driving the Microwave Emission Model of Layered Snowpacks with objective measurements of snow specific surface area to reproduce measured brightness temperatures when forced with objective measurements of snow specific surface area (S). This eliminates the need to treat the grain size as a free-fit parameter

A Novel Antibacterial Compound Decreases MRSA Biofilm Formation Without the Use of Antibiotics in A Murine Model

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in-vivo safety and antibacterial efficacy of titanium implants treated with a novel broad-spectrum biocidal compound (DBG21) against methicillin-resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21-treated for 44 treated mice. After implantation, 1x107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were sacrificed at day 7 and 14 to determine the number of adherent bacteria (biofilm) on implants and in the peri-implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21-treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU (99.97%) reduction (p<0.001) and 1.9 median log10 CFU (98.7%) reduction (p=0.037), respectively) and peri-implant surrounding tissues (2.7 median log10 CFU/g (99.8%) reduction (p<0.001) and 5.6 median log10 CFU/g (99.9997%) reduction (p<0.001), respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG-21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant-related infections

Protein complexes are under evolutionary selection to assemble via ordered pathways

Is the order in which proteins assemble into complexes important for biological function? Here, we seek to address this by searching for evidence of evolutionary selection for ordered protein complex assembly. First, we experimentally characterize the assembly pathways of several heteromeric complexes and show that they can be simply predicted from their three-dimensional structures. Then, by mapping gene fusion events identified from fully sequenced genomes onto protein complex assembly pathways, we demonstrate evolutionary selection for conservation of assembly order. Furthermore, using structural and high-throughput interaction data, we show that fusion tends to optimize assembly by simplifying protein complex topologies. Finally, we observe protein structural constraints on the gene order of fusion that impact the potential for fusion to affect assembly. Together, these results reveal the intimate relationships among protein assembly, quaternary structure, and evolution and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Épidémiologie, facteurs et complications associée à l’utilisation de noradrénaline en chirurgie cardiaque avec circulation extracorporelle : une étude observationnelle française multicentrique et prospective

International audienceBackgroundThe present study was designed to describe the prevalence of norepinephrine use, the factors associated with its use, and the incidence of postoperative complications according to norepinephrine use, in patients undergoing cardiac surgery with cardiopulmonary bypass.MethodWe performed a prospective, multicenter, observational study in 4 University-affiliated medico-surgical cardiovascular units. We analyzed all patients treated with cardiac surgery after excluding pre-ECMO surgery, LVAD implantation, heart transplantation and intraoperative hemorrhage.ResultsOf 9316 patients screened during the study period, 2862 were included and 2510 were analyzed. Among them, 1549 (61%) were treated with norepinephrine with a median maximal dose of 0.11 [0.06–0.2] μg/kg/min–1 and a median duration of 10 h [2–24]. Norepinephrine was most often started in the operating room before cardiopulmonary bypass. The multiple regression logistic analysis identified several modifiable (haematocrit, maintenance of beta-blocker, cardiopulmonary bypass time, glucose-insulin-potassium, Custodiol cardioplegia, Delnido cardioplegia, and fibrinogen transfusion) and non-modifiable factors (age, ASA score, chronic high blood pressure, coronary disease, dyslipidemia, right ventricular dysfunction, left ventricular dysfunction, active endocarditis, and valvular aortic surgery) associated with norepinephrine use. Mortality, morbidity (neurological and renal complications, death) and length of stay in the ICU were higher in patients treated with norepinephrine.ConclusionNorepinephrine is often used in cardiac surgical patients but for < 24 h with a low dose. Many preoperative and surgical factors are associated with norepinephrine use. Patients supported by norepinephrine have a higher incidence of major postoperative events.ContexteL’objectif de cette étude était de décrire la prévalence de l’utilisation de la noradrénaline, les facteurs associés à son utilisation, et l’incidence des complications postopératoires en fonction de son utilisation ou non, chez les patients opérés d’une chirurgie cardiaque avec circulation extracorporelle (CEC).MéthodeNous avons réalisé une étude prospective, multicentrique et observationnelle dans 4 unités médicochirurgicales cardiovasculaires de CHU. Nous avons analysé tous les patients de chirurgie cardiaque après avoir exclu les patients avec une ECMO avant la chirurgie, l’implantation d’un LVAD (définir), la transplantation cardiaque et l’hémorragie peropératoire.RésultatsSur les 9316 patients éligibles pendant la période de l’étude, 2862 ont été inclus et 2510 ont été analysés. La noradrénaline a été utilisée chez 1549 (61 %) patients avec une dose maximale médiane de 0,11 (0,06–0,2) μg/kg–1 min–1 et une durée médiane de 10 heures (2–24). La noradrénaline a le plus souvent été administrée au bloc opératoire, avant la CEC. L’analyse par régression logistique multiple a identifié plusieurs facteurs modifiables (hématocrite, maintien du bêta-bloquant, durée de CEC, glucose-insuline-potassium, la cardioplégie Custodiol, la cardioplégie Delnido et la transfusion de fibrinogène) et non modifiables (âge, score ASA, hypertension artérielle chronique, maladie coronarienne, dyslipidémie, insuffisance cardiaque droite, insuffisance cardiaque gauche, endocardite active et chirurgie valvulaire aortique) associés à l’utilisation de la noradrénaline. La mortalité, la morbidité (complications neurologiques et rénales, décès) et la durée du séjour en unité de soins intensifs étaient plus élevées chez les patients traités par noradrénaline.ConclusionLa noradrénaline est souvent utilisée chez les patients en chirurgie cardiaque, mais à faible dose pendant moins de 24 heures. De nombreux facteurs préopératoires et chirurgicaux sont associés à l’utilisation de la noradrénaline. Les patients traités par noradrénaline présentaient une incidence plus élevée d’événements postopératoires majeurs

Epidemiology, risk factors and outcomes of norepinephrine use in cardiac surgery with cardiopulmonary bypass: a multicentric prospective study

Background: The present study was designed to describe the prevalence of norepinephrine use, the factors associated with its use, and the incidence of postoperative complications according to norepinephrine use, in patients undergoing cardiac surgery with cardiopulmonary bypass.Method: We performed a prospective, multicenter, observational study in 4 University-affiliated medico-surgical cardiovascular units. We analyzed all patients treated with cardiac surgery after excluding pre-ECMO surgery, LVAD implantation, heart transplantation and intra-operative hemorrhage.Results: Of 9316 patients screened during the study period, 2862 were included and 2510 were analyzed. Among them, 1549 (61%) were treated with norepinephrine with a median maximal dose of 0.11 [0.06-0.2] µg. kg-1. min-1 and a median duration of 10 hours 2-24. Norepinephrine was most often started in the operating room before cardiopulmonary bypass. The multiple regression logistic analysis identified several modifiable (haematocrit, maintenance of beta-blocker, cardiopulmonary bypass time, glucose-insulin-potassium, Custodiol cardioplegia, Delnido cardioplegia, and fibrinogen transfusion) and non-modifiable factors (age, ASA score, chronic high blood pressure, coronary disease, dyslipidemia, right ventricular dysfunction, left ventricular dysfunction, active endocarditis, and valvular aortic surgery) associated with norepinephrine use. Mortality, morbidity (neurological and renal complications, death) and length of stay in the ICU were higher in patients treated with norepinephrine.Conclusion: Norepinephrine is often used in cardiac surgical patients but for less than 24 hours with a low dose. Many preoperative and surgical factors are associated with norepinephrine use. Patients supported by norepinephrine have a higher incidence of major postoperative events

Epidemiology, risk factors and outcomes of norepinephrine use in cardiac surgery with cardiopulmonary bypass: a multicentric prospective study

Background: The present study was designed to describe the prevalence of norepinephrine use, the factors associated with its use, and the incidence of postoperative complications according to norepinephrine use, in patients undergoing cardiac surgery with cardiopulmonary bypass.Method: We performed a prospective, multicenter, observational study in 4 University-affiliated medico-surgical cardiovascular units. We analyzed all patients treated with cardiac surgery after excluding pre-ECMO surgery, LVAD implantation, heart transplantation and intra-operative hemorrhage.Results: Of 9316 patients screened during the study period, 2862 were included and 2510 were analyzed. Among them, 1549 (61%) were treated with norepinephrine with a median maximal dose of 0.11 [0.06-0.2] µg. kg-1. min-1 and a median duration of 10 hours 2-24. Norepinephrine was most often started in the operating room before cardiopulmonary bypass. The multiple regression logistic analysis identified several modifiable (haematocrit, maintenance of beta-blocker, cardiopulmonary bypass time, glucose-insulin-potassium, Custodiol cardioplegia, Delnido cardioplegia, and fibrinogen transfusion) and non-modifiable factors (age, ASA score, chronic high blood pressure, coronary disease, dyslipidemia, right ventricular dysfunction, left ventricular dysfunction, active endocarditis, and valvular aortic surgery) associated with norepinephrine use. Mortality, morbidity (neurological and renal complications, death) and length of stay in the ICU were higher in patients treated with norepinephrine.Conclusion: Norepinephrine is often used in cardiac surgical patients but for less than 24 hours with a low dose. Many preoperative and surgical factors are associated with norepinephrine use. Patients supported by norepinephrine have a higher incidence of major postoperative events

CAESAR: a new tool to assess relatives' experience of dying and death in the ICU

International audienc