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The Western Journal of Emergency... May 2024Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists....
INTRODUCTION
Bystander provision of naloxone is a key modality to reduce opioid overdose-related death. Naloxone training courses are available, but no standardized program exists. As part of a bystander empowerment course, we created and evaluated a brief naloxone training module.
METHODS
This was a retrospective evaluation of a naloxone training course, which was paired with Stop the Bleed training for hemorrhage control and was offered to administrative staff in an office building. Participants worked in an organization related to healthcare, but none were clinicians. The curriculum included the following topics: 1) background about the opioid epidemic; 2) how to recognize the signs of an opioid overdose; 3) actions not to take when encountering an overdose victim; 4) the correct steps to take when encountering an overdose victim; 5) an overview of naloxone products; and 6) Good Samaritan protection laws. The 20-minute didactic section was followed by a hands-on session with nasal naloxone kits and a simulation mannequin. The course was evaluated with the Opioid Overdose Knowledge (OOKS) and Opioid Overdose Attitudes (OOAS) scales for take-home naloxone training evaluation. We used the paired Wilcoxon signed-rank test to compare scores pre- and post-course.
RESULTS
Twenty-eight participants completed the course. The OOKS, measuring objective knowledge about opioid overdose and naloxone, had improved scores from a median of 73.2% (interquartile range [IQR] 68.3%-79.9%) to 91.5% (IQR 85.4%-95.1%), < 0.001. The three domains on the OOAS score also showed statistically significant results. Competency to manage an overdose improved on a five-point scale from a median of 2.5 (IQR 2.4-2.9) to a median of 3.7 (IQR 3.5-4.1), < 0.001. Concerns about managing an overdose decreased (improved) from a median of 2.3 (IQR 1.9-2.6) to median 1.8 (IQR 1.5-2.1), < 0.001. Readiness to intervene in an opioid overdose improved from a median of 4 (IQR 3.8-4.2) to a median of 4.2 (IQR 4-4.2), < 0.001.
CONCLUSION
A brief course designed to teach bystanders about opioid overdose and naloxone was feasible and effective. We encourage hospitals and other organizations to use and promulgate this model. Furthermore, we suggest the convening of a national consortium to achieve consensus on program content and delivery.
Topics: Naloxone; Humans; Narcotic Antagonists; Retrospective Studies; Male; Female; Drug Overdose; Opiate Overdose; Adult; Program Evaluation; Curriculum; Health Knowledge, Attitudes, Practice; Middle Aged
PubMed: 38801036
DOI: 10.5811/westjem.60409 -
The Western Journal of Emergency... May 2024Emergency departments (ED) are in the unique position to initiate buprenorphine, an evidence-based treatment for opioid use disorder (OUD). However, barriers at the...
INTRODUCTION
Emergency departments (ED) are in the unique position to initiate buprenorphine, an evidence-based treatment for opioid use disorder (OUD). However, barriers at the system and clinician level limit its use. We describe a series of interventions that address these barriers to ED-initiated buprenorphine in one urban ED. We compare post-intervention physician outcomes between the study site and two affiliated sites without the interventions.
METHODS
This was a cross-sectional study conducted at three affiliated urban EDs where the intervention site implemented OUD-related electronic note templates, clinical protocols, a peer navigation program, education, and reminders. Post-intervention, we administered an anonymous, online survey to physicians at all three sites. Survey domains included demographics, buprenorphine experience and knowledge, comfort with addressing OUD, and attitudes toward OUD treatment. Physician outcomes were compared between the intervention site and the control sites with bivariate tests. We used logistic regression controlling for significant demographic differences to compare physicians' buprenorphine experience.
RESULTS
Of 113 (51%) eligible physicians, 58 completed the survey: 27 from the intervention site, and 31 from the control sites. Physicians at the intervention site were more likely to spend <75% of their work week in clinical practice and to be in medical practice for <7 years. Buprenorphine knowledge (including status of buprenorphine prescribing waiver), comfort with addressing OUD, and attitudes toward OUD treatment did not differ significantly between the sites. Physicians were 4.5 times more likely to have administered buprenorphine at the intervention site (odds ratio [OR] 4.5, 95% confidence interval 1.4-14.4, = 0.01), which remained significant after adjusting for clinical time and years in practice, (OR 3.5 and 4.6, respectively).
CONCLUSION
Physicians exposed to interventions addressing system- and clinician-level implementation barriers were at least three times as likely to have administered buprenorphine in the ED. Physicians' buprenorphine knowledge, comfort with addressing and attitudes toward OUD treatment did not differ significantly between sites. Our findings suggest that ED-initiated buprenorphine can be facilitated by addressing implementation barriers, while physician knowledge, comfort, and attitudes may be harder to improve.
Topics: Humans; Buprenorphine; Emergency Service, Hospital; Cross-Sectional Studies; Opioid-Related Disorders; Male; Female; Opiate Substitution Treatment; Practice Patterns, Physicians'; Narcotic Antagonists; Adult; Middle Aged; Surveys and Questionnaires; Attitude of Health Personnel; Physicians
PubMed: 38801034
DOI: 10.5811/westjem.18320 -
Bioorganic Chemistry Jul 2024The number of opioid-related overdose deaths and individuals that have suffered from opioid use disorders have significantly increased over the last 30 years. FDA...
The number of opioid-related overdose deaths and individuals that have suffered from opioid use disorders have significantly increased over the last 30 years. FDA approved maintenance therapies to treat opioid use disorder may successfully curb drug craving and prevent relapse but harbor adverse effects that reduce patient compliance. This has created a need for new chemical entities with improved patient experience. Previously our group reported a novel lead compound, NAT, a mu-opioid receptor antagonist that potently antagonized the antinociception of morphine and showed significant blood-brain barrier permeability. However, NAT belongs to thiophene containing compounds which are known structural alerts for potential oxidative metabolism. To overcome this, 15 NAT derivatives with various substituents at the 5'-position of the thiophene ring were designed and their structure-activity relationships were studied. These derivatives were characterized for their binding affinity, selectivity, and functional activity at the mu opioid receptor and assessed for their ability to antagonize the antinociceptive effects of morphine in vivo. Compound 12 showed retention of the basic pharmacological attributes of NAT while improving the withdrawal effects that were experienced in opioid-dependent mice. Further studies will be conducted to fully characterize compound 12 to examine whether it would serve as a new lead for opioid use disorder treatment and management.
Topics: Animals; Structure-Activity Relationship; Mice; Receptors, Opioid, mu; Humans; Molecular Structure; Thiophenes; Male; Dose-Response Relationship, Drug; Analgesics, Opioid; Narcotic Antagonists; Morphine
PubMed: 38797065
DOI: 10.1016/j.bioorg.2024.107489 -
The International Journal on Drug Policy Jun 2024Expanding public naloxone access is a key strategy to reduce opioid overdose fatalities. We describe tailored community-engaged, data-driven approaches to install and...
BACKGROUND
Expanding public naloxone access is a key strategy to reduce opioid overdose fatalities. We describe tailored community-engaged, data-driven approaches to install and maintain naloxone housing units (naloxone boxes) in New York State and estimate the cost of these approaches.
METHODS
Guided by the Consolidated Framework for Implementation Research, we collected data from administrative records and key informant interviews that documented the unique processes employed by four counties enrolled in the HEALing Communities Study to install and maintain naloxone housing units. We conducted a prospective micro-costing analysis to estimate the cost of each naloxone housing unit strategy from the community perspective.
RESULTS
While all counties used a coalition to guide action planning for naloxone distribution, we identified unique approaches to implementing naloxone housing units: 1) County-led with technology expansion; 2) County-led grassroots; 3) Small-scale rural opioid overdose prevention program (OOPP) contract and 4) Comprehensive OOPP contract including overdose education and naloxone distribution (OEND) to individuals. The first two county-led approaches had lower cost per naloxone dose disbursed ($28-$38) compared to outsourcing to an OOPP ($183-$266); costs depended on services added to installing and maintaining units, such as OEND. Barriers included competing demands on public health resources (i.e., COVID-19) and stigma toward naloxone and opioid use disorder. Geographic access was a barrier in rural areas whereas existing infrastructure was a facilitator in urban counties. The policy landscape in New York State, which provides free naloxone kits and financial support to OOPPs, facilitated implementation in all counties.
CONCLUSIONS
If a community has the resources, installing and maintaining naloxone housing units in-house can be less expensive than contracting with an outside partner. However, contracts that include OEND may be more effective at reaching target populations. Financial support from health departments and legislative authorization are important facilitators to making naloxone available in public settings.
Topics: Naloxone; Humans; Narcotic Antagonists; New York; Opiate Overdose; Opioid-Related Disorders; Health Services Accessibility; Prospective Studies; Drug Overdose; Community Participation
PubMed: 38795466
DOI: 10.1016/j.drugpo.2024.104462 -
Medicina (Kaunas, Lithuania) May 2024: The aim of this study was to compare the effectiveness of pericapsular nerve group (PENG) and lumbar erector spinae plane (L-ESP) blocks, both administered with a high... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
: The aim of this study was to compare the effectiveness of pericapsular nerve group (PENG) and lumbar erector spinae plane (L-ESP) blocks, both administered with a high volume (40 mL) of local anesthetic (LA), for multimodal postoperative analgesia in patients undergoing hip surgery. : This was a prospective, double-blind, randomized study that included 75 adult patients who were divided into three equal groups: control, PENG, and L-ESP. The study compared pain intensity, morphine consumption, time to first morphine request, and postoperative satisfaction between the control group, which received standard multimodal analgesia, and the block groups, which received PENG or L-ESP block in addition to multimodal analgesia. The numerical rating scale (NRS) was used to measure pain intensity. : The results showed that the block groups had lower pain intensity scores and morphine consumption, a longer time to the first morphine request, and higher postoperative satisfaction compared to the control group. The median maximum NRS score during the first 12 h was four in the control group, two in the PENG group, and three in the L-ESP group. The control group (21.52 ± 9.63 mg) consumed more morphine than the two block groups (PENG, 11.20 ± 7.55 mg; L-ESP, 12.88 ± 8.87 mg) and requested morphine 6.8 h earlier and 5 h earlier than the PENG and L-ESP groups, respectively. The control group (median 3) had the lowest Likert satisfaction scores, while the PENG group (median 4) had the lowest NRS scores (L-ESP, median 4). : The application of PENG or L-ESP blocks with high-volume LA in patients undergoing hip surgery reduces the need for postoperative analgesia and improves the quality of multimodal analgesia.
Topics: Humans; Nerve Block; Male; Female; Double-Blind Method; Prospective Studies; Middle Aged; Pain, Postoperative; Pain Measurement; Adult; Aged; Elective Surgical Procedures; Hip; Pain Management; Anesthetics, Local; Morphine; Analgesia
PubMed: 38792981
DOI: 10.3390/medicina60050799 -
The International Journal on Drug Policy Jun 2024British Columbia (BC) Canada has a large take-home naloxone (THN) program, implemented as part of the provincial response to the ongoing toxic unregulated drug supply...
BACKGROUND
British Columbia (BC) Canada has a large take-home naloxone (THN) program, implemented as part of the provincial response to the ongoing toxic unregulated drug supply emergency. Ascertaining the rate of use of THN kits is vital to understanding the full impact of the program. However, this is a challenging problem due to under-reporting of kit distribution. This study aims to estimate the total number of THN kits used based on the number of THN kits shipped, the number of THN kits reported as distributed, and the number of THN kits reported as used.
METHODS
We used BC THN shipment and distribution records (February 2015 to August 2023) to inform a simple Bayesian model of naloxone kit distribution and use. A logistic regression term by health region and distribution site type was incorporated to account for variable under-reporting, and a convolution term was incorporated to account for kit distribution.
RESULTS
We find the number of THN kits reported as used, and the number of total THN kits distributed, are largely under-reported. An estimated 1,500 (95 % CrI: 1,430 - 1,590) THN kits per 10,000 BC population were used, of which 288 per 10,000 had been reported as used. Of all the THN kits shipped, the model estimated that 43 % (95 % CrI: 41-45 %) of kits were used. We also found variation in both distribution and use by distribution site type, with kits distributed from overdose prevention sites having the highest rate of use (56 %; 95 % CrI: 53-59 %).
CONCLUSION
Across all sites, kit use is approximately five times higher than has been reported. Our framework can also be applied to other localities where THN programs operate, in order to better estimate the true reach and impact of take home naloxone distribution.
Topics: Humans; Naloxone; Bayes Theorem; British Columbia; Narcotic Antagonists; Drug Overdose
PubMed: 38788389
DOI: 10.1016/j.drugpo.2024.104454 -
Chemical Communications (Cambridge,... Jun 2024The enantioselective synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using...
The enantioselective synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors were measured.
Topics: Stereoisomerism; Morphinans; Naltrexone; Molecular Structure; Narcotic Antagonists; Receptors, Opioid
PubMed: 38787679
DOI: 10.1039/d4cc01788a -
Cells May 2024In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been...
In recent decades, there has been a dramatic rise in the rates of children being born after in utero exposure to drugs of abuse, particularly opioids. Opioids have been shown to have detrimental effects on neurons and glia in the central nervous system (CNS), but the impact of prenatal opioid exposure (POE) on still-developing synaptic circuitry is largely unknown. Astrocytes exert a powerful influence on synaptic development, secreting factors to either promote or inhibit synapse formation and neuronal maturation in the developing CNS. Here, we investigated the effects of the partial µ-opioid receptor agonist buprenorphine on astrocyte synaptogenic signaling and morphological development in cortical cell culture. Acute buprenorphine treatment had no effect on the excitatory synapse number in astrocyte-free neuron cultures. In conditions where neurons shared culture media with astrocytes, buprenorphine attenuated the synaptogenic capabilities of astrocyte-secreted factors. Neurons cultured from drug-naïve mice showed no change in synapses when treated with factors secreted by astrocytes from POE mice. However, this same treatment was synaptogenic when applied to neurons from POE mice, indicating a complex neuroadaptive response in the event of impaired astrocyte signaling. In addition to promoting morphological and connectivity changes in neurons, POE exerted a strong influence on astrocyte development, disrupting their structural maturation and promoting the accumulation of lipid droplets (LDs), suggestive of a maladaptive stress response in the developing CNS.
Topics: Astrocytes; Animals; Synapses; Female; Pregnancy; Mice; Analgesics, Opioid; Prenatal Exposure Delayed Effects; Neurons; Signal Transduction; Buprenorphine; Cells, Cultured; Mice, Inbred C57BL
PubMed: 38786059
DOI: 10.3390/cells13100837 -
The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.Pharmacoepidemiology and Drug Safety Jun 2024To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on...
PURPOSE
To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old).
METHODS
Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs.
RESULTS
Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease.
CONCLUSIONS
Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.
Topics: Humans; Hydrocodone; Analgesics, Opioid; Child, Preschool; Oxycodone; Poison Control Centers; United States; Emergency Service, Hospital; Drug and Narcotic Control; Codeine; Infant; Interrupted Time Series Analysis; Child; Drug Combinations
PubMed: 38783553
DOI: 10.1002/pds.5793 -
Behavioural Brain Research Jul 2024Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect....
Acetaminophen (paracetamol) is one of the most popular analgesics for the management of fever and pain but few reports have investigated its antidepressant-like effect. Moreover, the role of the opioidergic pathway has been indicated in depression pathophysiology. This study aimed to examine the involvement of the opioid receptors in the antidepressant-like effect of acetaminophen after acute and sub-chronic administration using mice forced swimming test (FST). Our finding showed that administration of acetaminophen (50 and 100 mg/kg, i.p.) 30 min before the FST produced an antidepressant effect which was reduced by naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). Moreover, we observed that acetaminophen in higher doses (200 and 400 mg/kg) was ineffective. Also, the response of the non-effective dose of acetaminophen (25 mg/kg) was potentiated by the non-effective dose of morphine (0.1 mg/kg) in the FST that was antagonized by naloxone. Also, in contrast to morphine (10 mg/kg), acetaminophen (100 mg/kg, i.p.) induced neither tolerance to the anti-immobility behavior nor withdrawal syndrome after repeated administration. In addition, RT-PCR showed that hippocampal mu- and kappa-opioid receptor mRNA expression increased in mice after repeated administration of acetaminophen; however, morphine therapy for 6 days did not affect kappa-opioid receptor expression. Our findings demonstrated that acetaminophen in lower doses but not high doses revealed an antidepressant-like activity without inducing tolerance and withdrawal syndromes. Moreover, the observed effect of acetaminophen may be via altering the opioid system, particularly hippocampal mu- and kappa-receptors.
Topics: Animals; Acetaminophen; Male; Mice; Antidepressive Agents; Naloxone; Narcotic Antagonists; Dose-Response Relationship, Drug; Swimming; Depression; Morphine; Hippocampus; Disease Models, Animal; Analgesics, Opioid; Analgesics, Non-Narcotic; Receptors, Opioid; Receptors, Opioid, mu
PubMed: 38782097
DOI: 10.1016/j.bbr.2024.115065