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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 -
Harm Reduction Journal May 2024Individuals with opioid use disorder (OUD) often have concurrent use of non-opioid substances. When patients enter opioid maintenance treatment (OMT), less is known...
BACKGROUND
Individuals with opioid use disorder (OUD) often have concurrent use of non-opioid substances. When patients enter opioid maintenance treatment (OMT), less is known about outcomes regarding the use of other types of drugs. Here we aimed to investigate changes in substance use among patients entering outpatient OMT, from treatment initiation to 1-year follow-up.
METHODS
We used data from the prospective Norwegian Cohort of Patient in OMT and Other Drug Treatment Study (NorComt). Among 283 patients who entered OMT at participating facilities across Norway, 179 were assessed at follow-up. Of these patients, 131 were in a non-controlled environment, and were included in the present analysis. The main outcome was change in substance use. Logistic regression analysis was applied to identify factors associated with abstinence from all substances (other than agonist medication) at follow-up.
RESULTS
Along with opioid use, most patients reported polysubstance use prior to entering treatment. No significant differences were found in baseline characteristics between the included and non-included groups when examining attrition. At the 1-year follow-up, reduced substance use was reported. While in treatment, around two-thirds of patients continued using other drugs to varying degrees. At follow-up, about one-third of patients reported abstinence from all drugs, apart from the agonist medication. Factors related to abstinence included a goal of abstinence at baseline (OR = 5.26; 95% CI 1.14-19.55; p = 0.013) and increasing age (OR = 1.05; 95% CI 1.00-1.09; p = 0.034).
CONCLUSIONS
The majority of patients entering OMT used other substances in addition to opioids. About one-third of patients reported abstinence at the 1-year follow up. Although the majority of patients continued co-use of other drugs while in treatment, for most substances, less than 10% reported daily use at follow-up, with the exception of cannabis which was used daily/almost daily by about 2 in 10. Higher age and treatment goal at the start of OMT were important factors related to reducing concomitant substance use during treatment. These findings suggest that many patients entering OMT are in need of treatment and support related to the use of other substances, to further improve prognosis.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered).
Topics: Humans; Male; Female; Opioid-Related Disorders; Adult; Opiate Substitution Treatment; Norway; Follow-Up Studies; Middle Aged; Prospective Studies; Substance-Related Disorders; Analgesics, Opioid
PubMed: 38790008
DOI: 10.1186/s12954-024-01005-x -
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 -
Addiction Science & Clinical Practice May 2024Norway has a growing proportion of ageing opioid agonist treatment (OAT) patients, with 42% of the 8300 Norwegian OAT patients aged over 50 in 2022. This study aims to...
BACKGROUND
Norway has a growing proportion of ageing opioid agonist treatment (OAT) patients, with 42% of the 8300 Norwegian OAT patients aged over 50 in 2022. This study aims to explore practitioners' views and experiences from treatment of ageing OAT patients.
METHODS
Data were collected as a series of semi-structured interviews with treatment staff (roles interviewed: doctor, psychologist, social worker, nurse, and learning disability nurse). Participants were recruited from three OAT outpatient clinics, one with an urban catchment area and two with a mix of urban and rural. The interviews incorporated questions on patients' somatic and mental health, strengths and weaknesses of the service for this group, and patients' quality of life.
RESULTS
Older patients were perceived to be more often stable in terms of substance use and housing situation, but also experiencing some key challenges in terms of cognitive impairment, loneliness and isolation, and comorbidities. Both the practitioner-patient relationship and healthcare interactions outside OAT had the potential to impact treatment quality positively or negatively depending on how they were managed.
CONCLUSIONS
Treating older patients in a way that respects and enhances their dignity is important. We argue that this requires better services for those whose functioning is impacted by cognitive impairment/dementia, an age-informed treatment model for this patient group, along with urgent work to improve municipal-level services given practitioners describe them as unacceptable in certain areas.
Topics: Humans; Norway; Middle Aged; Male; Female; Opiate Substitution Treatment; Quality of Life; Opioid-Related Disorders; Aged; Attitude of Health Personnel; Interviews as Topic; Cognitive Dysfunction; Comorbidity; Analgesics, Opioid; Loneliness; Professional-Patient Relations
PubMed: 38783382
DOI: 10.1186/s13722-024-00473-7 -
Addiction Science & Clinical Practice May 2024Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in...
BACKGROUND
Delivering methadone treatment in community health facilities by primary care providers is a task-shifting strategy to expand access to drug use treatment, especially in rural mountainous areas. This study aims to investigate factors related to confidence in providing methadone treatment among primary care providers in Vietnam to inform good practice development.
METHODS
We conducted a cross-sectional survey with 276 primary care providers who were physicians, physician assistants, nurses, pharmacists or dispensing staff from 67 communes in a mountainous province in Northern Vietnam. Using self-report scales, we measured providers' confidence in providing methadone treatment, beliefs in harm reduction, perceived work-related support, perceived stigma and risk in working with drug-using patients, and empathy towards this population. We used multiple linear regression analyses to explore factors associated with providers' confidence in providing methadone treatment in the whole sample and to compare two groups of providers who did and did not have experience providing methadone. Potential associated factors were measured at facility and provider levels.
RESULT
114 (41.3%) participants had previously experience in providing methadone treatment. Providers with methadone treatment experiences had higher confidence in and more accurate knowledge of methadone treatment, perceived less stigma of working with drug-using patients, and reported more work-related support than those without experiences. Higher medical education is associated with lower confidence in providing methadone treatment among providers without methadone experiences, but higher confidence among providers with methadone experiences. Better methadone knowledge was associated with greater confidence in providing methadone treatment among inexperienced providers but not among those with experiences. Receiving work-related support was associated with greater confidence in providing treatment in both groups, regardless of their past methadone experiences.
CONCLUSION
In rural provinces where methadone treatment has been expanded to primary care clinics, interventions to improve primary care providers' confidence should benefit professionals with diverse experiences in providing methadone treatment. Continued training and support at work for providers is essential to ensuring quality in decentralized methadone treatment.
Topics: Humans; Methadone; Vietnam; Cross-Sectional Studies; Female; Male; Primary Health Care; Opiate Substitution Treatment; Adult; Attitude of Health Personnel; Middle Aged; Health Personnel; Opioid-Related Disorders; Social Stigma; Harm Reduction; Health Knowledge, Attitudes, Practice
PubMed: 38778428
DOI: 10.1186/s13722-023-00419-5 -
Journal of Neuroscience Methods Aug 2024Although the effects on neural activation and glucose consumption caused by opiates such as morphine are known, the metabolic machinery underlying opioid use and misuse...
BACKGROUND
Although the effects on neural activation and glucose consumption caused by opiates such as morphine are known, the metabolic machinery underlying opioid use and misuse is not fully explored. Multiphoton microscopy (MPM) techniques have been developed for optical imaging at high spatial resolution. Despite the increased use of MPM for neural imaging, the use of intrinsic optical contrast has seen minimal use in neuroscience.
NEW METHOD
We present a label-free, multimodal microscopy technique for metabolic profiling of murine brain tissue following incubation with morphine sulfate (MSO). We evaluate two- and three-photon excited autofluorescence, and second and third harmonic generation to determine meaningful intrinsic contrast mechanisms in brain tissue using simultaneous label-free, autofluorescence multi-harmonic (SLAM) microscopy.
RESULTS
Regional differences quantified in the cortex, caudate, and thalamus of the brain demonstrate region-specific changes to metabolic profiles measured from FAD intensity, along with brain-wide quantification. While the overall intensity of FAD signal significantly decreased after morphine incubation, this metabolic molecule accumulated near the nucleus accumbens.
COMPARISON WITH EXISTING METHODS
Histopathology requires tissue fixation and staining to determine cell type and morphology, lacking information about cellular metabolism. Tools such as fMRI or PET imaging have been widely used, but lack cellular resolution. SLAM microscopy obviates the need for tissue preparation, permitting immediate use and imaging of tissue with subcellular resolution in its native environment.
CONCLUSIONS
This study demonstrates the utility of SLAM microscopy for label-free investigations of neural metabolism, especially the intensity changes in FAD autofluorescence and structural morphology from third-harmonic generation.
Topics: Animals; Morphine; Microscopy, Fluorescence, Multiphoton; Brain; Mice, Inbred C57BL; Mice; Male; Analgesics, Opioid; Narcotics
PubMed: 38777156
DOI: 10.1016/j.jneumeth.2024.110171 -
Cureus Apr 2024Coma blisters, or coma bullae, are lesions often seen in the setting of impaired consciousness. Most commonly associated with drug-induced comas, coma bullae have been...
Coma blisters, or coma bullae, are lesions often seen in the setting of impaired consciousness. Most commonly associated with drug-induced comas, coma bullae have been repeatedly linked to central nervous system (CNS) depressing agents, such as opiates. These lesions are believed to develop due to a complex multifactorial process involving external pressure on the skin, which leads to hypoxia and eventual death of eccrine sweat glands. In addition, the vasoactive and inflammatory properties of CNS depressing agents may play a role in this process. Come bullae usually develop on pressure points 48-72 hours after the onset of impaired consciousness and are self-limiting. We present the case of a 68-year-old male who was brought to the emergency department after being found unresponsive on the street. The urine drug screen was positive for cocaine and fentanyl. The initial examination showed several large, non-tender bullae on his scalp that continued to expand over two days. He subsequently developed similar lesions on his thighs, right shoulder, and knuckles. Dermatology was consulted and clinically diagnosed the patient with coma bullae, likely attributed to his altered consciousness and opiate use. Notably, more violaceous bullae were found on the bilateral lower extremities, with dermatology suspecting additional vasculitic features related to concurrent opiate and cocaine use. Skin biopsy and aspiration were deferred to avoid the risk of infection, and the patient was discharged per dermatology's recommendations for no immediate intervention. He continued to follow with wound care for the next six months, with most of the bullae healing. However, eschars developed over the scalp and left lower extremity, requiring debridement by general surgery. This case report underscores a unique manifestation of coma bullae. Unlike typical presentations localized to pressure-dependent areas and appearing after two to three days of unconsciousness, our patient exhibited blisters in atypical sites with associated vasculitic features. Moreover, the development of eschars over time may be linked to ongoing vasoactive drug use, reperfusion injury, and social determinants of health. This case highlights the complex and multifactorial nature of coma bullae, emphasizing the challenges in wound care and management despite their expected self-resolution.
PubMed: 38770478
DOI: 10.7759/cureus.58646 -
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