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JAMA Network Open May 2024Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors.
IMPORTANCE
Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors.
OBJECTIVES
To evaluate the potential impact of increased naloxone availability on opioid overdose deaths (OODs) and explore strategies to enhance this impact by integrating interventions to address solitary drug use.
DESIGN, SETTING, AND PARTICIPANTS
This decision analytical modeling study used PROFOUND (Prevention and Rescue of Fentanyl and Other Opioid Overdoses Using Optimized Naloxone Distribution Strategies), a previously published simulation model, to forecast annual OODs between January 2023 and December 2025. The simulated study population included individuals from Rhode Island who misused opioids and stimulants and were at risk for opioid overdose.
EXPOSURES
The study modeled expanded naloxone distribution supported by the state's opioid settlement (50 000 naloxone nasal spray kits each year). Two approaches to expanding naloxone distribution were evaluated: one based on historical spatial patterns of naloxone distribution (supply-based approach) and one based on the spatial distribution of individuals at risk (demand-based approach). In addition, hypothetical interventions to enhance the likelihood of witnessed overdoses in private or semiprivate settings were considered.
MAIN OUTCOMES AND MEASURES
Annual number of OODs and ratio of fatal to nonfatal opioid overdoses.
RESULTS
Modeling results indicated that distributing more naloxone supported by the state's opioid settlement could reduce OODs by 6.3% (95% simulation interval [SI], 0.3%-13.7%) and 8.8% (95% SI, 1.8%-17.5%) in 2025 with the supply-based and demand-based approaches, respectively. However, increasing witnessed overdoses by 20% to 60% demonstrated greater potential for reducing OODs, ranging from 8.5% (95% SI, 0.0%-20.3%) to 24.1% (95% SI, 8.6%-39.3%). Notably, synergistic associations were observed when combining both interventions: increased naloxone distribution with the 2 approaches and a 60% increase in witnessed overdoses could reduce OODs in 2025 by 33.5% (95% SI, 17.1%-50.4%) and 37.4% (95% SI, 19.6%-56.3%), respectively.
CONCLUSIONS AND RELEVANCE
These findings suggest that interventions to address solitary drug use are needed to maximize the impact of continued efforts to increase community-based naloxone distribution, which may be particularly important for jurisdictions that have strong community-based naloxone distribution programs.
Topics: Naloxone; Humans; Narcotic Antagonists; Rhode Island; Opiate Overdose; Analgesics, Opioid; Opioid-Related Disorders; Drug Overdose
PubMed: 38814644
DOI: 10.1001/jamanetworkopen.2024.13861 -
Harm Reduction Journal May 2024People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in...
BACKGROUND
People in Connecticut are now more likely to die of a drug-related overdose than a traffic accident. While Connecticut has had some success in slowing the rise in overdose death rates, substantial additional progress is necessary.
METHODS
We developed, verified, and calibrated a mechanistic simulation of alternative overdose prevention policy options, including scaling up naloxone (NLX) distribution in the community and medications for opioid use disorder (OUD) among people who are incarcerated (MOUD-INC) and in the community (MOUD-COM) in a simulated cohort of people with OUD in Connecticut. We estimated how maximally scaling up each option individually and in combinations would impact 5-year overdose deaths, life-years, and quality-adjusted life-years. All costs were assessed in 2021 USD, employing a health sector perspective in base-case analyses and a societal perspective in sensitivity analyses, using a 3% discount rate and 5-year and lifetime time horizons.
RESULTS
Maximally scaling NLX alone reduces overdose deaths 20% in the next 5 years at a favorable incremental cost-effectiveness ratio (ICER); if injectable rather than intranasal NLX was distributed, 240 additional overdose deaths could be prevented. Maximally scaling MOUD-COM and MOUD-INC alone reduce overdose deaths by 14% and 6% respectively at favorable ICERS. Considering all permutations of scaling up policies, scaling NLX and MOUD-COM together is the cost-effective choice, reducing overdose deaths 32% at ICER $19,000/QALY. In sensitivity analyses using a societal perspective, all policy options were cost saving and overdose deaths reduced 33% over 5 years while saving society $338,000 per capita over the simulated cohort lifetime.
CONCLUSIONS
Maximally scaling access to naloxone and MOUD in the community can reduce 5-year overdose deaths by 32% among people with OUD in Connecticut under realistic budget scenarios. If societal cost savings due to increased productivity and reduced crime costs are considered, one-third of overdose deaths can be reduced by maximally scaling all three policy options, while saving money.
Topics: Humans; Connecticut; Naloxone; Opioid-Related Disorders; Narcotic Antagonists; Cost-Benefit Analysis; Drug Overdose; Opiate Overdose; Harm Reduction; Adult; Male; Quality-Adjusted Life Years; Female; Prisoners
PubMed: 38807226
DOI: 10.1186/s12954-024-01026-6 -
Scientific Reports May 2024Deep learning neural networks are often described as black boxes, as it is difficult to trace model outputs back to model inputs due to a lack of clarity over the...
Deep learning neural networks are often described as black boxes, as it is difficult to trace model outputs back to model inputs due to a lack of clarity over the internal mechanisms. This is even true for those neural networks designed to emulate mechanistic models, which simply learn a mapping between the inputs and outputs of mechanistic models, ignoring the underlying processes. Using a mechanistic model studying the pharmacological interaction between opioids and naloxone as a proof-of-concept example, we demonstrated that by reorganizing the neural networks' layers to mimic the structure of the mechanistic model, it is possible to achieve better training rates and prediction accuracy relative to the previously proposed black-box neural networks, while maintaining the interpretability of the mechanistic simulations. Our framework can be used to emulate mechanistic models in a large parameter space and offers an example on the utility of increasing the interpretability of deep learning networks.
Topics: Systems Biology; Neural Networks, Computer; Deep Learning; Naloxone; Humans; Pharmacology; Analgesics, Opioid; Computer Simulation
PubMed: 38802422
DOI: 10.1038/s41598-024-59378-9 -
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 -
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 -
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 -
Frontiers in Immunology 2024Recently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker...
INTRODUCTION
Recently, we reported that post COVID-19 condition patients also have Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction, a potential biomarker reported in natural killer (NK) cells from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. As there is no universal treatment for post COVID-19 condition, knowledge of ME/CFS may provide advances to investigate therapeutic targets. Naltrexone hydrochloride (NTX) has been demonstrated to be beneficial as a pharmacological intervention for ME/CFS patients and experimental investigations have shown NTX restored TRPM3 function in NK cells. This research aimed to: i) validate impaired TRPM3 ion channel function in post COVID-19 condition patients compared with ME/CFS; and ii) investigate NTX effects on TRPM3 ion channel activity in post COVID-19 condition patients.
METHODS
Whole-cell patch-clamp was performed to characterize TRPM3 ion channel activity in freshly isolated NK cells of post COVID-19 condition ( = 9; 40.56 ± 11.26 years), ME/CFS ( = 9; 39.33 ± 9.80 years) and healthy controls (HC) ( = 9; 45.22 ± 9.67 years). NTX effects were assessed on post COVID-19 condition ( = 9; 40.56 ± 11.26 years) and HC ( = 7; 45.43 ± 10.50 years) where NK cells were incubated for 24 hours in two protocols: treated with 200 µM NTX, or non-treated; TRPM3 channel function was assessed with patch-clamp protocol.
RESULTS
This investigation confirmed impaired TRPM3 ion channel function in NK cells from post COVID-19 condition and ME/CFS patients. Importantly, PregS-induced TRPM3 currents were significantly restored in NTX-treated NK cells from post COVID-19 condition compared with HC. Furthermore, the sensitivity of NK cells to ononetin was not significantly different between post COVID-19 condition and HC after treatment with NTX.
DISCUSSION
Our findings provide further evidence identifying similarities of TRPM3 ion channel dysfunction between ME/CFS and post COVID-19 condition patients. This study also reports, for the first time, TRPM3 ion channel activity was restored in NK cells isolated from post COVID-19 condition patients after treatment with NTX. The TRPM3 restoration consequently may re-establish TRPM3-dependent calcium (Ca) influx. This investigation proposes NTX as a potential therapeutic intervention and TRPM3 as a treatment biomarker for post COVID-19 condition.
Topics: Humans; TRPM Cation Channels; COVID-19; Killer Cells, Natural; Adult; Male; Middle Aged; Female; Naltrexone; SARS-CoV-2; Fatigue Syndrome, Chronic; Patch-Clamp Techniques; COVID-19 Drug Treatment
PubMed: 38765011
DOI: 10.3389/fimmu.2024.1264702 -
Addiction Science & Clinical Practice May 2024Alcohol-attributable medical disorders are prevalent among individuals with alcohol use disorder (AUD). However, there is a lack of research on prescriptions of...
BACKGROUND
Alcohol-attributable medical disorders are prevalent among individuals with alcohol use disorder (AUD). However, there is a lack of research on prescriptions of pharmacological treatment for AUD in those with comorbid conditions. This study aims to investigate the utilization of pharmacological treatment (acamprosate, disulfiram and naltrexone) in specialist care among patients with AUD and comorbid medical diagnoses.
METHODS
This was a descriptive register-based Swedish national cohort study including 132,728 adults diagnosed with AUD (N = 270,933) between 2007 and 2015. The exposure was alcohol-attributable categories of comorbid medical diagnoses. Odds ratios (OR) were calculated using mixed-effect logistic regression analyses for any filled prescription of acamprosate, disulfiram or oral naltrexone within 12 months post AUD diagnosis.
RESULTS
Individuals with comorbid alcohol-attributable medical diagnoses had lower odds of filling prescriptions for any type of AUD pharmacotherapy compared to those without such comorbidities. Cardiovascular (OR = 0.41 [95% CI: 0.39-0.43]), neurological (OR = 0.52 [95% CI: 0.48-0.56]) and gastrointestinal (OR = 0.57 [95% CI: 0.54-0.60]) diseases were associated with the lowest rates of prescription receipt. The presence of diagnoses which are contraindications to AUD pharmacotherapy did not fully explain the low prescription rate.
CONCLUSION
There is a substantial underutilization of AUD pharmacotherapy in patients with AUD and comorbid medical disorders in specialist care. Increasing the provision of pharmacotherapy to this group of patients is essential and may prevent morbidity and mortality. There is a need to further understand barriers to medical treatment both from the patient and prescriber perspective.
Topics: Humans; Sweden; Female; Male; Disulfiram; Middle Aged; Alcohol Deterrents; Adult; Comorbidity; Alcoholism; Acamprosate; Naltrexone; Aged; Cohort Studies; Registries; Young Adult
PubMed: 38764075
DOI: 10.1186/s13722-024-00471-9 -
BMC Public Health May 2024Public libraries in the United States have experienced increases in opioid-related substance use in their communities and on their premises. This includes fatal and...
BACKGROUND
Public libraries in the United States have experienced increases in opioid-related substance use in their communities and on their premises. This includes fatal and non-fatal overdose events. Some libraries have adopted response measures in their branches to deter substance use or prevent overdose. A small number of libraries around the nation have decided to stock the opioid antagonist naloxone (Narcan) for staff to administer to patrons who experience overdose. This response measure has generated extensive media attention. Although Ohio ranks fourth in age-adjusted drug mortality rate in the United States, there has been no investigation of whether Ohio libraries are observing opioid-related transactions, consumption, and/or overdose events, or which measures they have adopted in response to these activities. We conducted a multimethod survey with Ohio public library directors to identify the response measures they have adopted. We present descriptive findings from the quantitative and qualitative items in our survey.
METHODS
We conducted a cross-sectional 54-item multimethod survey of public library system directors (one per system) in Ohio. Directors of each of Ohio's public library systems were invited to participate via email.
RESULTS
Of 251 library systems, 56 responded (22.3% response rate), with 34 respondents (60.7%) indicating awareness of opioid-related transactions, consumption, and/or overdose on their premises. Most (n = 43, 76.8%) did not stock naloxone in their buildings. Over half (n = 34, 60.7%) reported implementing one or more non-naloxone response measures. These measures focus on improving security for staff and patrons, deterring opioid-related transactions (purchases and exchanges) and consumption, and providing educational events on substance use. Nearly half (n = 25, 47.2%) partner with community organizations to provide opioid response measures. A similar proportion reported adequate funding to respond to opioid-related substance use (n = 23, 45.1%), and most (n = 38, 74.5%) reported adequate support from their boards and communities. Few respondents have implemented evaluations of their response measures.
CONCLUSIONS
Ohio public libraries are responding to evidence of opioid-related transactions, consumption, and/or overdose on their premises with a range of measures that focus on substance use prevention and deterrence. Most Ohio library systems do not stock naloxone. Respondents indicated they prefer to call 911 and let first responders handle overdose events. The majority of respondents indicated their library systems have political capacity to respond to evidence of opioid-related substance use on their premises, but have limited operational and functional capacity. Findings suggest the need to revisit assumptions that public libraries are willing to stock naloxone to respond to overdose events, and that libraries have the resources to respond robustly to opioid-related transactions, consumption, and/or overdose on their premises.
Topics: Humans; Ohio; Cross-Sectional Studies; Naloxone; Opioid-Related Disorders; Narcotic Antagonists; Libraries; Surveys and Questionnaires; Female; Male; Drug Overdose; Adult
PubMed: 38760681
DOI: 10.1186/s12889-024-18799-x