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Frontiers in Pharmacology 2024"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and...
BACKGROUND
"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences.
METHODS
We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types.
RESULTS
Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information.
CONCLUSION
As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.
PubMed: 38948457
DOI: 10.3389/fphar.2024.1412397 -
Drug and Alcohol Dependence Reports Jun 2024As the US opioid-involved morbidity and mortality increase, uptake and implementation of evidence-based interventions remain key policy responses. Respond to Prevent was...
Policies, adaptations, and ongoing challenges to naloxone, buprenorphine and nonprescription syringe access across four-states: Findings from an environmental scan and key informant interviews.
BACKGROUND
As the US opioid-involved morbidity and mortality increase, uptake and implementation of evidence-based interventions remain key policy responses. Respond to Prevent was a multi-component, randomized trial implemented in four states and two large pharmacy chains with the aim of improving the pharmacy's capacity to provide naloxone, dispense buprenorphine, and sell nonprescription syringes (NPS). We sought to provide context and assess how policies and organizational practices affect communities and pharmacies across the study states.
METHODS
Using a multi-method approach we: 1) conducted an environmental scan of published literature and online materials spanning January 2015 to June 2021, 2) created timelines of key events pertaining to those policies and practices and 3) conducted semi-structured interviews with stakeholders (key informants) at the state and local levels (N=36) to provide further context for the policies and practices we discovered.
RESULTS
Key informants discussed state policies, pharmacy policies and local practices that facilitated access to naloxone, buprenorphine and NPSs. Interviewees from all states spoke about the impact of naloxone standing orders, active partnerships with community-based harm reduction organizations, and some federal and state policies like Medicaid coverage for naloxone and buprenorphine, and buprenorphine telehealth permissions as key facilitators. They also discussed patient stigma, access in rural settings, and high cost of medications as barriers.
CONCLUSION
Findings underscore the important role harm reduction-related policies play in boosting and institutionalizing interventions in communities and pharmacies while also identifying structural barriers where more focused state and local attention is needed.
PubMed: 38948428
DOI: 10.1016/j.dadr.2024.100243 -
PeerJ 2024Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible...
Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible damage to the myocardium. The number of mitochondria in cardiomyocytes is large, which generate adenosine triphosphate (ATP) to sustain proper cardiac contractile function, and mitochondrial dysfunction plays a crucial role in cell death during myocardial ischemia-reperfusion, leading to an increasing number of studies investigating the impact of mitochondria on ischemia-reperfusion injury. The disarray of mitochondrial dynamics, excessive Ca accumulation, activation of mitochondrial permeable transition pores, swelling of mitochondria, ultimately the death of cardiomyocyte are the consequences of ischemia-reperfusion injury. -opioid receptors can alleviate mitochondrial dysfunction, regulate mitochondrial dynamics, mitigate myocardial ischemia-reperfusion injury, exert protective effects on myocardium. The mechanism of -OR activation during myocardial ischemia-reperfusion to regulate mitochondrial dynamics and reduce myocardial ischemia-reperfusion injury will be discussed, so as to provide theoretical basis for the protection of ischemic myocardium.
PubMed: 38948204
DOI: 10.7717/peerj.17333 -
Substance Abuse and Rehabilitation 2024This study compares substance use, treatment histories, and sociodemographic characteristics of patients presenting to an emergency department (ED) following a heroin...
PURPOSE
This study compares substance use, treatment histories, and sociodemographic characteristics of patients presenting to an emergency department (ED) following a heroin overdose or seeking detoxification services for heroin and examines risk factors for a subsequent return to the ED for a substance-related problem.
METHODS
A convenience sample of patients presenting for an overdose or detoxification at an urban teaching ED was recruited for this study. During their ED visit, patients were interviewed regarding demographics, substance use experiences, and treatment history. Subsequently, a review of patient records for past and subsequent ED use was performed.
RESULTS
Patients requesting detox and those with an overdose were similar in terms of prior treatment. Both groups had similar extensive polysubstance histories. As a group, however, patients presenting for detox were more likely to report use of each of three substances (benzodiazepines, opioid pain medications, and heroin) more than three times per week, compared to those presenting for overdose. Detox patients had higher scores on the 3-item Alcohol Use Disorder Identification Test-C and the drug problems scale compared to overdose patients. Overall, 28% of the patients returned to the ED within 90 days for a drug-related issue, including 8% that returned for an overdose. Factors predictive of a return ED visit included ED visits for substance use in the previous year and recent frequent heroin use.
CONCLUSION
Patients requesting detox were similar in most domains to those presenting following an overdose. Notably, overdose patients were less likely to use heroin more than three times per week compared to detox patients. Both groups were equally likely to return for an SUD reason within 3-months, however for both groups, previous ED visits and recent frequent heroin use predicted a return visit.
PubMed: 38948167
DOI: 10.2147/SAR.S461521 -
Cureus May 2024In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was...
Lateness of Acetaminophen and Non-steroidal Anti-inflammatory Drug Administrations in a Retrospective Cohort of Medication Administration Records Among Patients After Cesarean Delivery.
INTRODUCTION
In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was associated with a substantial reduction in total postoperative opioid use. This likely pharmacodynamic effect may differ if the times when nurses administer acetaminophen and non-steroidal anti-inflammatory drugs often differ substantively from when they are due. We examined the "lateness" of analgesic dose administration times, the positive difference if administered late, and the negative value if early.
METHODS
The retrospective cohort study used all 67,900 medication administration records for scheduled (i.e., not "as needed") acetaminophen, ibuprofen, and ketorolac among all 3,163 cesarean delivery cases at the University of Iowa between January 2021 and December 2023. Barcode scanning at the patient's bedside was used right before each medication administration.
RESULTS
There were 95% of doses administered over a 4.8-hour window, from 108 minutes early (97.5% one-sided upper confidence limit 105 minutes early) to 181 minutes late (97.5% one-sided lower limit 179 minutes late). Fewer than half of doses (46%, P <0.0001) were administered ±30 minutes of the due time. The intraclass correlation coefficient was approximately 0.11, showing that there were small systematic differences among patients. There likewise were small to no systematic differences in lateness based on concurrent administrations of acetaminophen and ibuprofen or ketorolac, time of the day that medications were due, weekday, year, or number of medications to be administered among all such patients within 15 minutes.
DISCUSSION
Other hospitals should check the lateness of medication administration when that would change their ability to perform or apply the results of analgesic clinical trials (e.g., simultaneous versus alternating administration).
PubMed: 38947679
DOI: 10.7759/cureus.61433 -
IScience Jun 2024The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and...
The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and cost-effectiveness of traditional drug development approaches are extremely low. Utilizing large sample genome-wide association study data for drug repurposing has shown promise in many diseases but has not yet been explored in CKD. Herein, we investigated actionable druggable targets to improve renal function using large-scale Mendelian randomization and colocalization analyses. We combined two population-scale independent genetic datasets and validated findings with cell-type-dependent eQTL data of kidney tubular and glomerular samples. We ultimately prioritized two drug targets, opioid receptor-like 1 and F12, with potential genetic support for restoring renal function and subsequent treatment of CKD. Our findings explore the potential pathological mechanisms of CKD, bridge the gap between the molecular mechanisms of pathogenesis and clinical intervention, and provide new strategies in future clinical trials of CKD.
PubMed: 38947510
DOI: 10.1016/j.isci.2024.109953 -
MedRxiv : the Preprint Server For... Jun 2024Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative....
IMPORTANCE
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
OBJECTIVE
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
DESIGN
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
SETTING
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
PARTICIPANTS
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
INTERVENTION
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
MAIN OUTCOMES AND MEASURES
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
RESULTS
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1- p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=- 0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
CONCLUSIONS AND RELEVANCE
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
KEY POINTS
Does white matter (WM) microstructure change with medication-assisted treatment in individuals with heroin use disorder (iHUD)? In this longitudinal cohort study, diffusion MRI was acquired in 34 inpatient iHUD and 25 healthy controls (CTL) twice, separated by a mean of 13.9 weeks. We found HUD- specific WM microstructure changes with time, characterized by increased anisotropy and decreased diffusivity in fronto-striatal WM pathways. These changes were correlated with decreased baseline drug craving with treatment. Frontal WM changes and associated drug craving decreases suggest brain-behavior recovery with inpatient treatment in iHUD, potentially contributing to reduced drug use and sustained abstinence.
PubMed: 38946983
DOI: 10.1101/2024.06.10.24308719 -
Orthopaedic Surgery Jul 2024The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to...
OBJECTIVES
The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population.
METHODS
Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test.
RESULTS
Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission.
CONCLUSION
Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.
PubMed: 38946692
DOI: 10.1111/os.14150 -
Progress in Community Health... 2024Recent data indicate rising opioid overdose deaths among African American residents of Washington, DC.
BACKGROUND
Recent data indicate rising opioid overdose deaths among African American residents of Washington, DC.
OBJECTIVES
We highlight a community-informed approach to assessing attitudes toward opioid use disorder treatment among DC residents (February 2019 to March 2020).
METHODS
A listening tour with trusted community leaders led to the formation of a Community Advisory Board (CAB). When the COVID-19 pandemic commenced in March 2020, community dialogues became exclusively virtual. The CAB partnered with academic leaders to co-create project mission and values and center the community's concerns related to opioid use and its causes, treatment structure, and facilitators of effective engagement.
RESULTS
Interview guides were created for the engagement of community members, using values highlighted by the CAB. The CAB underscored that in addition to opioid problems, effective engagement must address community experience, collective strengths/resilience, and the role of indigenous leadership.
CONCLUSIONS
Engaging community prior to project implementation and maintaining alignment with community values facilitated opioid use disorder assessments. Community-informed assessments may be critical to building community trust.
Topics: Humans; Black or African American; Opioid-Related Disorders; District of Columbia; COVID-19; Community-Based Participatory Research; Female; Male; SARS-CoV-2; Community Participation; Adult
PubMed: 38946568
DOI: No ID Found -
Clinical Toxicology (Philadelphia, Pa.) Jul 2024The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim...
INTRODUCTION
The opioid receptor mu1 is a protein coding gene that can have different codes for a protein and may have variations (polymorphisms) affecting how opioids work. The aim of this study was to investigate the prevalence of the most common opioid receptor mu1 polymorphism () and any relationship between this polymorphism and features following tramadol overdose.
MATERIALS AND METHODS
This was a cross-sectional study of patients admitted with tramadol poisoning to an Iranian hospital. These patients were not taking any other drugs or medications and had no history of seizures.
RESULTS
The results showed that among the 83 patients included in the study, 57 (69 per cent) had the AA genotype, 25 (30 per cent) had the AG genotype, and one (1 per cent) had the GG genotype for the opioid receptor mu1 polymorphism. Nausea and/or vomiting occurred in nine (11 per cent) patients and dizziness in 38 (46 per cent) patients. Serious adverse events included seizures in 51 (60 per cent) patients and respiratory failure requiring mechanical ventilation in 21 (25 per cent) patients. However, there was no significant association between the opioid receptor mu1 polymorphism and these adverse events.
DISCUSSION
In our study, the frequency of the A allele was greater than the G allele, and the AA genotype was more prevalent than AG. The GG genotype was the least common among the polymorphisms of opioid receptor mu1 . There was no significant association between the opioid receptor mu1 polymorphism and symptoms in tramadol-poisoned patients. Although these allele proportions are similar to the results reported in other Caucasian populations, they are dissimilar to the findings in Chinese and Singaporean populations. In these Asian studies, the predominant allele was the G allele. It has been suggested that a mutated G allele will decrease the production of opioid receptor mu1-related messenger ribonucleic acid and related proteins, leading to fewer mu-opioid receptors in the brain.
CONCLUSIONS
This study found no significant association between the opioid receptor mu1 polymorphism and adverse outcomes in tramadol-poisoned patients. However, more research is needed to draw more definitive conclusions due to the limited evidence and variability of opioid receptor mu1 polymorphisms in different populations.
PubMed: 38946467
DOI: 10.1080/15563650.2024.2366921