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PloS One 2024Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining...
BACKGROUND
Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood.
METHODS
The study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data.
RESULTS
Difficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl 'residue' accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use.
CONCLUSION
Our data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipient's tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.
Topics: Fentanyl; Humans; San Francisco; Male; Female; Adult; Smoking; Drug Overdose; Middle Aged; Substance Abuse, Intravenous; Methamphetamine
PubMed: 38776268
DOI: 10.1371/journal.pone.0303403 -
Theranostics 2024Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains...
Methamphetamine (METH) withdrawal anxiety symptom and relapse have been significant challenges for clinical practice, however, the underlying neuronal basis remains unclear. Our recent research has identified a specific subpopulation of choline acetyltransferase (ChAT) neurons localized in the external lateral portion of parabrachial nucleus (eLPB), which modulates METH primed-reinstatement of conditioned place preference (CPP). Here, the anatomical structures and functional roles of eLPB projections in METH withdrawal anxiety and primed reinstatement were further explored. In the present study, a multifaceted approach was employed to dissect the LPB projections in male mice, including anterograde and retrograde tracing, acetylcholine (Ach) indicator combined with fiber photometry recording, photogenetic and chemogenetic regulation, as well as electrophysiological recording. METH withdrawal anxiety-like behaviors and METH-primed reinstatement of conditioned place preference (CPP) were assessed in male mice. We identified that eLPB send projections to PKCδ-positive (PKCδ) neurons in lateral portion of central nucleus of amygdala (lCeA) and oval portion of bed nucleus of the stria terminalis (ovBNST), forming eLPB-lCeA and eLPB-ovBNST pathways. At least in part, the eLPB neurons positively innervate lCeA neurons and ovBNST neurons through regulating synaptic elements of presynaptic Ach release and postsynaptic nicotinic acetylcholine receptors (nAChRs). METH withdrawal anxiety and METH-primed reinstatement of CPP respectively recruit eLPB-lCeA pathway and eLPB-ovBNST pathway in male mice. Our findings put new insights into the complex neural networks, especially focusing on the eLPB projections. The eLPB is a critical node in the neural networks governing METH withdrawal anxiety and primed-reinstatement of CPP through its projections to the lCeA and ovBNST, respectively.
Topics: Animals; Methamphetamine; Male; Mice; Substance Withdrawal Syndrome; Anxiety; Mice, Inbred C57BL; Neurons; Choline O-Acetyltransferase; Septal Nuclei; Behavior, Animal
PubMed: 38773977
DOI: 10.7150/thno.95383 -
Trials May 2024Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several...
BACKGROUND
Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer.
METHODS
Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first.
DISCUSSION
This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness.
TRIAL REGISTRATION
Trial registered on Australian New Zealand Clinical Trials Registry.
REGISTRATION NUMBER
ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.
Topics: Humans; N-Methyl-3,4-methylenedioxyamphetamine; Neoplasms; Anxiety; Double-Blind Method; Randomized Controlled Trials as Topic; Affect; Hallucinogens; Treatment Outcome; Depression; Quality of Life; Methylphenidate; Time Factors; Male; Neoplasm Staging
PubMed: 38773523
DOI: 10.1186/s13063-024-08174-x -
BMJ Paediatrics Open May 2024There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.
BACKGROUND
There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21 July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.
INTERVENTIONS
Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo.
MAIN OUTCOME MEASURES
Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author).
RESULTS
15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment.
CONCLUSIONS
Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.
Topics: Humans; Infant, Newborn; Cardiotonic Agents; Vasoconstrictor Agents; Infant, Premature; Network Meta-Analysis; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Dobutamine
PubMed: 38769048
DOI: 10.1136/bmjpo-2024-002500 -
The Journal of Emergency Medicine May 2024
Topics: Humans; Venlafaxine Hydrochloride; Electrocardiography; Epilepsy; Long QT Syndrome; Antidepressive Agents, Second-Generation; Male; Female; Seizures; Adult
PubMed: 38763732
DOI: 10.1016/j.jemermed.2023.11.027 -
The International Journal on Drug Policy Jun 2024In the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with...
INTRODUCTION
In the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with methamphetamine (either deliberately or inadvertently). We explore risk-mitigating actions taken by people who use drugs to protect their health when using methamphetamine in that context.
METHODS
We conducted qualitative interviews with 48 adults (18+) who used methamphetamine in the past three months at two sites in Nevada, USA and two sites in New Mexico, USA. Interviews were recorded, transcribed, and analyzed using thematic analysis.
RESULTS
Respondents described two rationales for employing harm reduction strategies. First, to prevent harm from methamphetamine containing illicit fentanyl, and second, to maintain their general wellbeing while using methamphetamine. Regarding methamphetamine containing illicit fentanyl, our findings highlight how respondents employ primary strategies like buying from trusted sources and secondary strategies such as spotting and selective use of harm reduction tools (i.e., fentanyl test strips) to reduce risks. To maintain their general wellbeing, participants reduced their use of methamphetamine as reasonably as possible, and used other substances like marijuana and alcohol alongside methamphetamine to counter the unwanted side effects of methamphetamine (i.e., hallucinations and paranoia). Use of these harm reduction strategies varied within situational and social contexts, and respondents usually developed these strategies based on their lived experiences.
CONCLUSION
Our findings uniquely demonstrate that people who use methamphetamine prioritize community driven, trust-based strategies within their social networks to mitigate risks in a fentanyl-contaminated drug environment. Additionally, our results indicate that harm reduction behaviors are influenced by multilevel risk environments, which include social, physical, economic, and political factors. Overall, these results highlight the potential for targeted interventions at the network level, which are responsive to complexities and shifts in drug market dynamics- such as illicit fentanyl in methamphetamine.
Topics: Humans; Fentanyl; Methamphetamine; Harm Reduction; Adult; Female; Male; Amphetamine-Related Disorders; Drug Contamination; Middle Aged; Young Adult; New Mexico; Nevada; Illicit Drugs; Qualitative Research; Interviews as Topic
PubMed: 38761461
DOI: 10.1016/j.drugpo.2024.104456 -
Medical Care Jul 2024Methamphetamine detoxification before entering formal and longer term treatment may have a positive impact on treatment retention and success. Understanding geographic...
INTRODUCTION
Methamphetamine detoxification before entering formal and longer term treatment may have a positive impact on treatment retention and success. Understanding geographic distribution of methamphetamine specialty detox services and differential access by race/ethnicity is critical for establishing policies that ensure equitable access across populations.
METHODS
We used the Mental health and Addiction Treatment Tracking Repository to identify treatment facilities that offered any substance use detoxification in 2021 (N=2346) as well as the census block group in which they were located. We sourced data from the US Census Bureau to identify the percentage of a census block group that was White, Black, and Hispanic. We used logistic regression to model the availability of methamphetamine-specific detox, predicted by the percentage of a block group that was Black and Hispanic. We adjusted for relevant covariates and defined state as a random effect. We calculated model-based predicted probabilities.
RESULTS
Over half (60%) of detox facilities offered additional detox services specifically for methamphetamine. Sixteen states had <10 methamphetamine-specific detox facilities. The predicted probability of methamphetamine-specific detox availability was 60% in census block groups with 0%-9% Black residents versus only 46% in census block groups with 90%-100% Black residents, and was 61% in census block groups with 0%-9% Hispanic residents versus 30% in census block groups with 90%-100% Hispanic residents.
CONCLUSIONS
During an unprecedented national methamphetamine crisis, access to a critical health care service was disproportionately lower in communities that were predominately Black and Hispanic. We orient our findings around a discussion of health disparities, residential segregation, and the upstream causes of the systematic exclusion of minoritized communities from health care.
Topics: Humans; United States; Methamphetamine; Health Services Accessibility; Amphetamine-Related Disorders; Hispanic or Latino; Substance Abuse Treatment Centers; Ethnicity; Black or African American; White People; Racial Groups; Male; Female
PubMed: 38761164
DOI: 10.1097/MLR.0000000000002013 -
Journal of Environmental Management Jun 2024Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely...
Efficient degradation of venlafaxine using intimately coupled high-active crystal facets exposed TiO and biodegradation system: Kinetic studies, biofilm stress behavior and transformation mechanism.
Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF-TiO exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO crystal surface was modified with NaF, resulting in the formation of NaF-TiO with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h was increased by 33.2%. Next, NaF-TiO was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF-TiO based ICPB system would be lucrative for the future degradation of venlafaxine.
Topics: Venlafaxine Hydrochloride; Biofilms; Titanium; Biodegradation, Environmental; Kinetics; Water Pollutants, Chemical; Wastewater; Catalysis
PubMed: 38759549
DOI: 10.1016/j.jenvman.2024.121159 -
Applied Health Economics and Health... Jul 2024This study evaluated, in a Swedish setting, the cost effectiveness of fenfluramine (FFA) as an add-on to standard of care (SoC) for reducing seizure frequency in Dravet...
OBJECTIVE
This study evaluated, in a Swedish setting, the cost effectiveness of fenfluramine (FFA) as an add-on to standard of care (SoC) for reducing seizure frequency in Dravet syndrome, a severe developmental epileptic encephalopathy.
METHODS
Cost effectiveness of FFA+SoC compared with SoC only was evaluated using a patient-level simulation model with a lifetime horizon. Patient characteristics and treatment effects, including convulsive seizures, seizure-free days and mortality, were derived from FFA clinical trials. Resource use and costs included cost of drug acquisition, routine care and monitoring, as well as ongoing and emergency resources. Quality of life (QoL) estimates for patients and their caregivers were derived from clinical trial data. Robustness was evaluated by one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analyses.
RESULTS
Lifetime cost of FFA+SoC was ~3 million SEK per patient compared with ~1.5 million SEK for SoC only. FFA+SoC generated 15% more QALYs than SoC only (21.2 vs 18.5 over a lifetime), resulting in an incremental cost-effectiveness ratio (ICER) of ~540,000 SEK. Moreover, FFA+SoC had a higher probability of being cost effective than SoC only from a willingness-to-pay threshold of 710,000 SEK. Results remained generally consistent across scenario analyses, with only few exceptions (exclusions of carer utility or FFA effect on sudden unexpected death in epilepsy).
CONCLUSION
Due to better seizure control, FFA is a clinically meaningful add-on therapy and was estimated to be a cost-effective addition to current SoC for patients with this rare disease in Sweden at a willingness-to-pay threshold of 1,000,000 SEK.
Topics: Humans; Sweden; Epilepsies, Myoclonic; Cost-Benefit Analysis; Fenfluramine; Female; Male; Standard of Care; Quality-Adjusted Life Years; Anticonvulsants; Adult; Adolescent; Child; Quality of Life; Young Adult; Cost-Effectiveness Analysis
PubMed: 38758509
DOI: 10.1007/s40258-024-00886-0 -
Ecotoxicology and Environmental Safety Jul 2024Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest...
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
Topics: Animals; Methamphetamine; Male; Gastrointestinal Microbiome; Mice; Testis; Reproduction; Spermatozoa; Mice, Inbred C57BL; Central Nervous System Stimulants; Fecal Microbiota Transplantation
PubMed: 38754198
DOI: 10.1016/j.ecoenv.2024.116457