Browsing by Subject "opioids"

Now showing 1 - 4 of 4
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    16S Intestinal Microbiome Sequences of Rhesus Macaques Treated with Chronic Morphine for 92 Days, SIV for 21 Days, or in Combination (Morphine for 70 Days then SIV+Morphine for 21 Days)
    (2017-04-10) Sindberg, Gregory M; Roy, Sabita; sind0017@umn.edu; Sindberg, Gregory M
    Rhesus Macaque fecal matter was sequenced at different intervals after receiving Morphine I.V., SIV infection, or in sequence. The intervals are as follows: Morphine for 92 days, SIV for 21 days, or a sequence of morphine for 70 days then SIV+Morphine for 21 days. This was used to look for microbial and metabolic changes due to the treatments.
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    Developing a Respiratory Depression Scorecard for Capnography Monitoring
    (University of Minnesota, College of Pharmacy, 2014) Felhofer, Katie
    Pulse oximetry is the most common way to measure a patient’s respiratory status in the hospital setting; however, capnography monitoring is a more accurate and sensitive technique which can more comprehensively measure respiratory function. Due to the limited number of capnography monitoring equipment at the University of Minnesota Medical Center-Fairview (UMMC-Fairview), we analyzed which patients should preferentially be chosen for capnography monitoring over pulse oximetry based on risk of respiratory depression. We conducted a retrospective chart review of all serious opioid-induced over-sedation events that occurred at UMMCFairview between January 1, 2008 and June 30, 2012. Thirteen risk factors were identified which predispose patients to respiratory depression. The average patient demonstrated 3.75 risk factors. The most commonly occurring risk factor was the concomitant use of multiple opioids or an opioid and a CNS-active sedative, followed by an ASA score ≥ 3. Based on this data, we developed a scorecard for choosing patients at the most risk of developing respiratory depression; these patients are the best candidates for capnography. Although further studies are necessary to corroborate this research, at this time giving extra consideration to patients demonstrating the previously stated risk factors is prudent when assessing those patients most in need of capnography.
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    Disruption of Gut Homeostasis by Opioids in the Early Stages of HIV Infection
    (2014-12) Sindberg, Gregory
    Opioids are a common comorbidity with HIV, with the use of opioids being present in up to 40% of the HIV infected population in some countries. Opioids have been shown to worsen HIV pathogenesis, including increased viral replication and faster progression to AIDS. HIV pathogenesis has been shown to be important in the gastrointestinal tract, where early loss of CD4+ T-cells has been observed in SIV infection and infection with either HIV or SIV show evidence of systemic bacterial translocation which is believed to drive HIV replication. Opioids are believed to worsen this effect and have been shown to increase bacterial translocation in HIV patients. The second chapter study was performed to understand the underlying disruption of gut homeostasis that contributes to bacterial translocation. HIV models were validated to show bacterial translocation, and then look at gut morphology, tight junction localization on gut epithelium, and immune function within the gut at early time points of exposure to HIV infection. Overall, based on the measures examined, opioids enhanced the pathogenesis of HIV in the gut at early infection which likely contributes to the greater replication and faster development of AIDS. While the loss of gut homeostasis is strongly believed to occur at least in part through changes in the host defenses in the gut, namely on immune populations and epithelial barrier integrity, recent evidence suggests that the microbiome of late stage HIV infected individuals is altered and may contribute to the observed disruption. The third chapter investigated the microbiome in early HIV infection to see if dysbiosis occurs, and whether opioids are associated with earlier changes. Using two animals models of infectious HIV, microbial dysbiosis was not observed at early time points of infection in either model. However, this study shows for the first time that morphine induced strong changes in the microbiome, which likely occurs via a combination of constipation and immune mediated effects. Altogether, these findings suggests another mechanism for morphine influencing HIV pathogenesis at early stages of disease. Combined, these studies show the wide ranging effects that opioids and HIV have on gut defenses, including epithelial barrier, immune function, and dysbiosis from the normal microbiome. While mostly descriptive in nature, the results give potential therapeutic opportunities, including potential oral administration of TLR2 and TLR4 antagonists, opioid antagonist naloxone, and bile acids in order to supplement deficiencies in metabolites observed.
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    Measuring chronic pain, non-drug pain therapy, and opioid-related mortality
    (2021-12) Goldsmith, Elizabeth
    Chronic pain comprises three of the top five causes of physical disability in the United States (U.S.) and affects over 60% of U.S. military veterans seen in Veterans Affairs primary care clinics. The opioid epidemic stems in part from health systems’ efforts to treat chronic pain pharmacologically, leading to opioid addiction and opioid-related mortality. Many non-drug therapies are effective for chronic pain but are clinically underused. Managing the widespread problems of chronic pain and opioid-related mortality requires valid and reliable measurement approaches. This dissertation addresses measurement challenges in assessment of chronic pain, non-drug pain therapy use, and opioid-related mortality. The first manuscript examines relationships between physical performance measures and patient-reported outcome measures of pain-related functional interference and pain severity among U.S. military veterans in a 12-month randomized clinical trial of opioid vs. non-opioid medication therapy for chronic musculoskeletal pain. The second manuscript explores patterns of use of non-drug pain therapies among a national cohort of U.S. military veterans prescribed long-term opioid therapy for chronic pain. The third manuscript adapts expert elicitation approaches from Bayesian statistics to incorporate physician opinion into a quantitative bias analysis of potential age-related misclassification in opioid-related mortality data from death certificates in the U.S.