Strategies used to reduce harms associated with fentanyl exposure among rural people who use drugs: multi-site qualitative findings from the rural opioid initiative
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SUBMITTER: Walters S
PROVIDER: S-EPMC11344336 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:The United States continues to be impacted by decades of an opioid misuse epidemic, worsened by the COVID-19 pandemic and by the growing prevalence of highly potent synthetic opioids (HPSO) such as fentanyl. In instances of a toxicity event, first-response administration of reversal medications such as naloxone can be insufficient to fully counteract the effects of HPSO, particularly when there is co-occurring substance use. In an effort to characterize and study this multi-faceted problem, the Camden Opioid Research Initiative (CORI) has been formed. The CORI study has collected and analyzed post-mortem toxicology data from 42 cases of decedents who expired from opioid-related toxicity in the South New Jersey region to characterize substance use profiles. Co-occurring substance use, whether by intent or through possible contamination of the illicit opioid supply, is pervasive among deaths due to opioid toxicity, and evidence of medication-assisted treatment is scarce. Nearly all (98%) of the toxicology cases show the presence of the HPSO, fentanyl, and very few (7%) results detected evidence of medication-assisted treatment for opioid use disorder, such as buprenorphine or methadone, at the time of death. The opioid toxicity reversal drug, naloxone, was detected in 19% of cases, but 100% of cases expressed one or more stimulants, and sedatives including xylazine were detected in 48% of cases. These results showing complex substance use profiles indicate that efforts at mitigating the opioid misuse epidemic must address the complications presented by co-occurring stimulant and other substance use, and reduce barriers to and stigmas of seeking effective medication-assisted treatments.
| S-EPMC10619848 | biostudies-literature
Project description:ObjectiveEvaluate the postoperative pain management of patients at a single institution following routine thyroid and parathyroid surgery and compare patient opioid use before and after a practice wide quality improvement change.Study designRetrospective chart review with prospective survey administration.SettingUniversity of New Mexico Hospital.MethodsA standardized perioperative pain management protocol was implemented for patients undergoing routine thyroid or parathyroid surgery. Quality assurance surveys about pain and medication use following surgery were given to patients treated after the standardized protocol was introduced. Univariate and multivariate analysis was performed. Descriptive statistics and qualitative thematic analysis of survey responses were used to analyze survey results.ResultsA standardized pain management routine reduced opioid prescriptions by 46.6% for routine thyroid and parathyroid surgery patients (20.2% vs 11.0%, P < .01). On multivariate logistic regression, receiving education about pain at discharge (OR 0.37, P < 0.05) and older age (OR 0.97, P < .01) were associated with fewer opioid prescriptions while anxiety (OR 2.77, P < .05) and drain placement (4.61, P < .001) were associated with more opioid prescriptions. About half of surveyed patients completed at least one postoperative questionnaire, and most patients complained of headache, fatigue, or sore throat as opposed to pain at the surgical site.ConclusionStandardized counseling about postoperative pain, including clear expectations and adjunctive measures, reduces the need for postoperative opioid prescriptions in patients undergoing routine thyroid and parathyroid surgery.
| S-EPMC11881014 | biostudies-literature
Project description:The opioid crisis has escalated during the COVID-19 pandemic. More than half of the overdose-related deaths are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, crystal structures of mOR complexed with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like synthetic opioids remains lacking. Exploiting the X-ray structure of mOR bound to a morphinan ligand and several state-of-the-art simulation techniques, including weighted ensemble and continuous constant pH molecular dynamics, we elucidated the detailed binding mechanism of fentanyl with mOR. Surprisingly, in addition to the orthosteric site common to morphinan opiates, fentanyl can move deeper and bind mOR through hydrogen bonding with a conserved histidine H297, which has been shown to modulate mOR's ligand affinity and pH dependence in mutagenesis experiments, but its precise role remains unclear. Intriguingly, the secondary binding mode is only accessible when H297 adopts a neutral HID tautomer. Alternative binding modes and involvement of tautomer states may represent general mechanisms in G protein-coupled receptor (GPCR)-ligand recognition. Our work provides a starting point for understanding mOR activation by fentanyl analogs that are emerging at a rapid pace and assisting the design of safer analgesics to combat the opioid crisis. Current protein simulation studies employ standard protonation and tautomer states; our work demonstrates the need to move beyond the practice to advance our understanding of protein-ligand recognition.
| S-EPMC7491576 | biostudies-literature
Project description:In 2019, drug overdose has claimed over 70,000 lives in the United States. More than half of the deaths are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, the crystal structures of mOR in complex with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like synthetic opioids remains lacking. Exploiting the X-ray structure of mOR bound to a morphinan ligand and several state-of-the-art simulation techniques, including weighted ensemble and continuous constant pH molecular dynamics, we elucidated the detailed binding mechanism of fentanyl with mOR. Surprisingly, in addition to forming a salt-bridge with Asp1473.32 in the orthosteric site common to morphinan opiates, fentanyl can move deeper and bind mOR through hydrogen bonding with a conserved histidine His2976.52, which has been shown to modulate mOR's ligand affinity and pH dependence in mutagenesis experiments, but its precise role remains unclear. Intriguingly, the secondary binding mode is only accessible when His297 adopts a neutral HID tautomer. Alternative binding modes and involvement of tautomer states may represent general mechanisms in G protein-coupled receptor (GPCR)-ligand recognition. Our work provides a starting point for understanding the molecular basis of mOR activation by fentanyl which has many analogs emerging at a rapid pace. The knowledge may also inform the design of safer analgesics to combat the opioid crisis. Current protein simulation studies employ standard protonation and tautomer states; our work demonstrates the need to move beyond the practice to advance our understanding of protein-ligand recognition.
| S-EPMC7444290 | biostudies-literature
Project description:Roughly half of the drug overdose-related deaths in the United States are related to synthetic opioids represented by fentanyl which is a potent agonist of mu-opioid receptor (mOR). In recent years, X-ray crystal structures of mOR in complex with morphine derivatives have been determined; however, structural basis of mOR activation by fentanyl-like opioids remains lacking. Exploiting the X-ray structure of BU72-bound mOR and several molecular simulation techniques, we elucidated the detailed binding mechanism of fentanyl. Surprisingly, in addition to the salt-bridge binding mode common to morphinan opiates, fentanyl can move deeper and form a stable hydrogen bond with the conserved His2976.52, which has been suggested to modulate mOR's ligand affinity and pH dependence by previous mutagenesis experiments. Intriguingly, this secondary binding mode is only accessible when His2976.52 adopts a neutral HID tautomer. Alternative binding modes may represent a general mechanism in G protein-coupled receptor-ligand recognition.
| S-EPMC7881245 | biostudies-literature
Project description:The illicit use of synthetic opioids such as fentanyl has led to a serious public health crisis in the US. People with opioid use disorder are more likely to contract infections such as HIV and viral hepatitis and experience more severe disease. While several drugs of abuse are known to enhance viral replication and to suppress immunologic responses, the effects of synthetic opioids on HIV pathogenesis have not been investigated thoroughly. Thus, we examined the impact of fentanyl on macrophage cell line U937 and monocyte derived macrophage cells and chemokine receptor expression in vitro.
2024-08-28 | GSE241769 | GEO
Project description:BackgroundClinician champions are front-line clinicians who advocate for and influence practice change in their local context. The strategies they use when leading efforts to reduce the use of low-value care have not been well described. The purpose of this study is to identify and describe strategies used by six clinician champions who led a low-value care initiative in their clinical setting.MethodsQualitative data collected during an overuse reduction initiative led by clinician champions were used to identify strategies, guided by the Expert Recommendations for Implementing Change compilation of strategies. Clinician champions were asked to rank the importance of these activities and indicate which one of the six most important activities they would be willing to discuss in an interview. A 30-min semi-structured interview was conducted with each clinician about the activity they selected and thematically analyzed.ResultsTwelve Expert Recommendations for Implementing Change strategies were identified. The top six strategies discussed during interviews were: build a coalition, conduct a local needs assessment, develop a formal implementation blueprint, conduct educational meetings, use facilitation, and develop clinical reminders. Common themes that emerged across all interviews were the use of data to engage clinicians in conversations, including the patient's perspective in designing the interventions, and investing the time upfront to plan and launch the initiative because of the inherent challenges of relinquishing a service.ConclusionsClinician champions identified multiple strategies as important when de-implementing a low-value service. Many were used to engage in conversations with stakeholders, including leadership, providers, and patients, to increase buy-in and support, challenge beliefs, promote behavior change, and gather insights about next steps in their effort. Future work is needed to better understand how prepare clinicians for this role and to understand the mechanisms through which these strategies might be effective.
| S-EPMC9133862 | biostudies-literature
Project description:W-18 (4-chloro-N-[1-[2-(4-nitrophenyl)ethyl]-2-piperidinylidene]-benzenesulfonamide) and W-15 (4-chloro-N-[1-(2-phenylethyl)-2-piperidinylidene]-benzenesulfonamide) represent two emerging drugs of abuse chemically related to the potent opioid agonist fentanyl (N-(1-(2-phenylethyl)-4-piperidinyl)-N-phenylpropanamide). Here, we describe the comprehensive pharmacological profiles of W-18 and W-15, as examination of their structural features predicted that they might lack opioid activity. We found W-18 and W-15 to be without detectible activity at μ, δ, κ, and nociception opioid receptors in a variety of assays. We also tested W-18 and W-15 for activity as allosteric modulators at opioid receptors and found them devoid of significant positive or negative allosteric modulatory activity. Comprehensive profiling at essentially all the druggable GPCRs in the human genome using the PRESTO-Tango platform revealed no significant activity. Weak activity at the sigma receptors and the peripheral benzodiazepine receptor was found for W-18 (Ki = 271 nM). W-18 showed no activity in either the radiant heat tail-flick or the writhing assays and also did not induce classical opioid behaviors. W-18 is extensively metabolized, but its metabolites also lack opioid activity. Thus, although W-18 and W-15 have been suggested to be potent opioid agonists, our results reveal no significant activity at these or other known targets for psychoactive drugs.
| S-EPMC5752382 | biostudies-literature
Project description:IntroductionEarly-onset sepsis (EOS) and late-onset Sepsis (LOS) are common diagnoses entertained in sick newborns treated in neonatal intensive care units (NICUs), and antibiotics are the medications most prescribed in NICUs. Antibiotic stewardship programs have an important impact on limiting unnecessary antibiotic use.MethodsFollowing the Model for Improvement, between 2/1/16 and 1/31/17, at a level 3 NICU, a multidisciplinary team implemented PDSA cycles to promote antibiotic stewardship practices for newborns at risk of EOS and LOS. The main goal was to decrease the antibiotic usage rate (AUR) safely. Primary strategies included discontinuing antibiotics within 24 hours of life if the newborn was stable, and the blood culture was negative for EOS and implementing an "antibiotic time-out" during rounds.ResultsFor all newborns admitted to our NICU, the AUR decreased, for EOS from 137 to 32 days per 1000 patient days (77% reduction) and for LOS from 277 to 121 days per 1000 patient days (56% reduction). We demonstrated the sustainability of both EOS-AUR and LOS-AUR during the 2 years postcompletion of the intervention period. There were no adverse effects of reducing the AUR.ConclusionInterventions that reduce unnecessary antibiotic use in the NICU are safe and prevent excessive antibiotic exposure.
| S-EPMC10990351 | biostudies-literature
Project description:ObjectivesMore than 2 million people in the United States had an opioid use disorder in 2017. Treatment for opioid use disorder-particularly medication combined with psychosocial support-is effective for reducing opioid use and decreasing overdose risk. However, approximately 50% of people who receive treatment will relapse or drop out. Stress reactivity, defined as the subjective and physiological response to stress, is heightened in people with opioid use disorder and higher stress reactivity is associated with poorer outcomes. Preliminary studies suggest that stress reactivity may be a key mechanistic target for improving outcomes. This article describes the design of an ongoing study examining behavioral strategies for reducing stress reactivity in adults with opioid use disorder. Our objective is to test the efficacy of two behavioral strategies for reducing stress reactivity and enhancing behavioral persistence in the context of stress (distress tolerance).MethodWe will recruit 120 adults with opioid use disorder and randomly assign them to brief training in (a) cognitive reappraisal, (b) affect labeling, or (c) a psychoeducational control. Participants will receive the training intervention followed by a laboratory stressor during which they will be instructed to apply the trained skill.ResultsSubjective and physiological responses to stress will be measured as indices of stress reactivity and the stressor task will include a behavioral persistence component as a measure of distress tolerance.ConclusionsThe ultimate goal of this study is to inform the development of behavioral interventions that can be used as an adjunct to medication-based treatment for opioid use disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
| S-EPMC8352497 | biostudies-literature