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Revue Medicale Suisse Jun 2024Sexual health is a key element to the well-being and quality of life of individuals. However, it is rarely incorporated into care delivery for women with an addictive...
Sexual health is a key element to the well-being and quality of life of individuals. However, it is rarely incorporated into care delivery for women with an addictive condition. Female with severe dependence to opiate have their medical and social conditions improved by diacetylmorphine treatment. Which allows them to escape situations of high-risk of sexual violence. However, this pharmacotherapy can also induce adverse effects on the sexual sphere. This paper describes the relevance of integrating psycho-socio-sexological counselling into the care provision for the opiate dependence. The counselling should be oriented to respond to the specific relational and sexual issues faced by these female patients and empowering them on their lives and in recovering a better quality of life.
Topics: Humans; Female; Opioid-Related Disorders; Heroin; Sexual Health; Quality of Life; Narcotics; Counseling; Undertreatment
PubMed: 38836394
DOI: 10.53738/REVMED.2024.20.877.1115 -
Scientific Reports Jun 2024Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease marked by inflammatory cell infiltration and joint damage. The Chinese government has approved the...
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease marked by inflammatory cell infiltration and joint damage. The Chinese government has approved the prescription medication sinomenine (SIN), an effective anti-inflammation drug, for treating RA. This study evaluated the possible anti-inflammatory actions of SIN in RA based on bioinformatics analysis and experiments. Six microarray datasets were acquired from the gene expression omnibus (GEO) database. We used R software to identify differentially expressed genes (DEGs) and perform function evaluations. The CIBERSORT was used to calculate the abundance of 22 infiltrating immune cells. The weighted gene co-expression network analysis (WGCNA) was used to discover genes associated with M1 macrophages. Four public datasets were used to predict the genes of SIN. Following that, function enrichment analysis for hub genes was performed. The cytoHubba and least absolute shrinkage and selection operator (LASSO) were employed to select hub genes, and their diagnostic effectiveness was predicted using the receiver operator characteristic (ROC) curve. Molecular docking was undertaken to confirm the affinity between the SIN and hub gene. Furthermore, the therapeutic efficacy of SIN was validated in LPS-induced RAW264.7 cells line using Western blot and Enzyme-linked immunosorbent assay (ELISA). The matrix metalloproteinase 9 (MMP9) was identified as the hub M1 macrophages-related biomarker in RA using bioinformatic analysis and molecular docking. Our study indicated that MMP9 took part in IL-17 and TNF signaling pathways. Furthermore, we found that SIN suppresses the MMP9 protein overexpression and pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the LPS-induced RAW264.7 cell line. In conclusion, our work sheds new light on the pathophysiology of RA and identifies MMP9 as a possible RA key gene. In conclusion, the above findings demonstrate that SIN, from an emerging research perspective, might be a potential cost-effective anti-inflammatory medication for treating RA.
Topics: Morphinans; Arthritis, Rheumatoid; Matrix Metalloproteinase 9; Mice; Animals; RAW 264.7 Cells; Computational Biology; Cytokines; Humans; Molecular Docking Simulation; Gene Expression Regulation; Macrophages; Anti-Inflammatory Agents
PubMed: 38834626
DOI: 10.1038/s41598-024-61769-x -
Computers in Biology and Medicine Jul 2024Buprenorphine is an effective evidence-based medication for opioid use disorder (OUD). Yet premature discontinuation undermines treatment effectiveness, increasing the...
An explainable machine learning framework for predicting the risk of buprenorphine treatment discontinuation for opioid use disorder among commercially insured individuals.
OBJECTIVES
Buprenorphine is an effective evidence-based medication for opioid use disorder (OUD). Yet premature discontinuation undermines treatment effectiveness, increasing the risk of mortality and overdose. We developed and evaluated a machine learning (ML) framework for predicting buprenorphine care discontinuity within 12 months following treatment initiation.
METHODS
This retrospective study used United States (US) 2018-2021 MarketScan commercial claims data of insured individuals aged 18-64 who initiated buprenorphine between July 2018 and December 2020 with no buprenorphine prescriptions in the previous six months. We measured buprenorphine prescription discontinuation gaps of ≥30 days within 12 months of initiating treatment. We developed predictive models employing logistic regression, decision tree classifier, random forest, extreme gradient boosting, Adaboost, and random forest-extreme gradient boosting ensemble. We applied recursive feature elimination with cross-validation to reduce dimensionality and identify the most predictive features while maintaining model robustness. For model validation, we used several statistics to evaluate performance, such as C-statistics and precision-recall curves. We focused on two distinct treatment stages: at the time of treatment initiation and one and three months after treatment initiation. We employed SHapley Additive exPlanations (SHAP) analysis that helped us explain the contributions of different features in predicting buprenorphine discontinuation. We stratified patients into risk subgroups based on their predicted likelihood of treatment discontinuation, dividing them into decile subgroups. Additionally, we used a calibration plot to analyze the reliability of the models.
RESULTS
A total of 30,373 patients initiated buprenorphine and 14.98% (4551) discontinued treatment. C-statistic varied between 0.56 and 0.76 for the first-stage models including patient-level demographic and clinical variables. Inclusion of proportion of days covered (PDC) measured after one month and three months following treatment initiation significantly increased the models' discriminative power (C-statistics: 0.60 to 0.82). Random forest (C-statistics: 0.76, 0.79 and 0.82 with baseline predictors, one-month PDC and three-months PDC, respectively) outperformed other ML models in discriminative performance in all stages (C-statistics: 0.56 to 0.77). Most influential risk factors of discontinuation included early stage medication adherence, age, and initial days of supply.
CONCLUSION
ML algorithms demonstrated a good discriminative power in identifying patients at higher risk of buprenorphine care discontinuity. The proposed framework may help healthcare providers optimize treatment strategies and deliver targeted interventions to improve buprenorphine care continuity.
Topics: Humans; Buprenorphine; Opioid-Related Disorders; Machine Learning; Adult; Female; Male; Retrospective Studies; Middle Aged; Adolescent; United States; Young Adult; Opiate Substitution Treatment; Analgesics, Opioid
PubMed: 38833799
DOI: 10.1016/j.compbiomed.2024.108493 -
Journal of Addiction MedicineOverdose mortality has risen most rapidly among racial and ethnic minority groups while buprenorphine prescribing has increased disproportionately in predominantly...
OBJECTIVES
Overdose mortality has risen most rapidly among racial and ethnic minority groups while buprenorphine prescribing has increased disproportionately in predominantly non-Hispanic White urban areas. To identify whether buprenorphine availability equitably meets the needs of diverse populations, we examined the differential geographic availability of buprenorphine in areas with greater concentrations of racial and ethnic minority groups.
METHODS
Using IQVIA longitudinal prescription data, IQVIA OneKey data, and Microsoft Bing Maps, we calculated 2 outcome measures across the continental United States: the number of buprenorphine prescribers per 1000 residents within a 30-minute drive of a ZIP code, and the number of buprenorphine prescriptions dispensed per capita at retail pharmacies among nearby buprenorphine prescribers. We then estimated differences in these outcomes by ZIP codes' racial and ethnic minority composition and rurality with t tests.
RESULTS
Buprenorphine prescribers per 1000 residents within a 30-minute drive decreased by 3.8 prescribers per 1000 residents in urban ZIP codes (95% confidence interval = -4.9 to -2.7) and 2.6 in rural ZIP codes (95% confidence interval = -3.0 to -2.2) whose populations consisted of ≥5% racial and ethnic minority groups. There were 45% to 55% fewer prescribers in urban areas and 62% to 79% fewer prescribers in rural areas as minority composition increased. Differences in dispensed buprenorphine per capita were similar but larger in magnitude.
CONCLUSIONS
Achieving more equitable buprenorphine access requires not only increasing the number of buprenorphine-prescribing clinicians; in urban areas with higher racial and ethnic minority group populations, it also requires efforts to promote greater buprenorphine prescribing among already prescribing clinicians.
Topics: Buprenorphine; Humans; United States; Healthcare Disparities; Health Services Accessibility; Narcotic Antagonists; Urban Population; Rural Population; Opiate Substitution Treatment; Opioid-Related Disorders; Ethnic and Racial Minorities; Ethnicity
PubMed: 38833558
DOI: 10.1097/ADM.0000000000001287 -
PloS One 2024In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences...
BACKGROUND
In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences short-term clinician prescribing practices. We sought to understand the long-term impact on postoperative opioid prescribing habits after an opioid default pill count reduction.
MATERIALS AND METHODS
A retrospective electronic medical record system (EMRS) review was conducted in a healthcare system comprised of seven affiliated hospitals. Patients who underwent a surgical procedure and were prescribed an opioid on discharge between 2017-2021 were evaluated. All prescriptions were converted into morphine equivalents (MME). Analyses were performed with the chi-square test and Bonferonni adjusted t-test.
RESULTS
191,379 surgical procedures were studied. The average quantity of opioids prescribed decreased from 32 oxycodone 5 mg tablets in 2017 to 21 oxycodone 5 mg tablets in 2021 (236 MME to 154 MME, p<0.001). The percentage of patients obtaining a refill within 90 days of surgery varied between 18.3% and 19.9% (p<0.001). Patients with a pre-existing opioid prescription and opioid-naïve patients both had significant reductions in prescription quantities above the default MME (79.7% to 60.6% vs. 65.3% to 36.9%, p<0.001). There was no significant change in refills for both groups (pre-existing 36.7% to 38.3% (p = 0.1) vs naïve 15.0% to 15.3% (p = 0.29)).
CONCLUSIONS
The benefits of decreasing the default opioid pill count continue to accumulate long after the original change. Physician uptake of small changes to default EMRS practices represents a sustainable and effective intervention to reduce the quantities of postoperative opioids prescribed without deleterious effects on outpatient opiate requirements.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Retrospective Studies; Pain, Postoperative; Drug Prescriptions; Practice Patterns, Physicians'; Adult; Aged; Electronic Health Records; Oxycodone
PubMed: 38833500
DOI: 10.1371/journal.pone.0304100 -
South African Family Practice :... May 2024Pharmacy professionals working in community pharmacies frequently provide pharmacist-initiated therapy, including codeine-containing medicines. Codeine is an opioid...
BACKGROUND
Pharmacy professionals working in community pharmacies frequently provide pharmacist-initiated therapy, including codeine-containing medicines. Codeine is an opioid with great potential for misuse, adding to the global opioid epidemic burden. Professional pharmacy personnel are the first intervention point in relation to management of codeine use. This study highlights the importance of pharmacy professionals' perceptions and behaviours in combatting the opioid epidemic.
METHODS
A descriptive cross-sectional study was conducted. Simple random sampling included pharmacy professionals in the metropolitan city of Johannesburg. An electronic questionnaire was distributed via e-mail and data analysed descriptively.
RESULTS
Findings indicate that pharmacy personnel routinely ask patients about codeine use (n = 48; 53.9%), avoid dispensing over-the-counter (OTC) codeine as an initial treatment (n = 61; 69%) and express confidence to identify and manage codeine misuse (n = 69; 77.5%). Despite this, increased patient demands for OTC codeine (n = 69; 77.5%) were concerning, highlighting the ease of availability from internet sources (n = 76; 85.4%) and multiple pharmacies (n = 84; 94.4%). Apprehension about the lack of patient awareness on adverse health consequences (n = 66; 74.2%) and the risk of codeine dependence (n = 79; 88.8%) was expressed.
CONCLUSION
Growing concern regarding availability and accessibility of codeine-containing medicines within the community pharmacy sector is highlighted. Adverse health consequences of codeine misuse and dependence are not understood by customers and the ineffective information provided by pharmacy personnel was highlighted as a concern.Contribution: The results of this study give insight to the influence of dispensing personnel's attitude towards the growing challenges with respect to codeine containing medication abuse.
Topics: Humans; Codeine; Cross-Sectional Studies; Female; Male; Adult; Surveys and Questionnaires; Analgesics, Opioid; Pharmacists; Nonprescription Drugs; South Africa; Attitude of Health Personnel; Middle Aged; Opioid-Related Disorders; Community Pharmacy Services; Health Knowledge, Attitudes, Practice
PubMed: 38832385
DOI: 10.4102/safp.v66i1.5862 -
Journal of Addictions Nursing
Topics: Humans; Naloxone; Narcotic Antagonists; Pulmonary Edema; Edema; Male; Adult
PubMed: 38830001
DOI: 10.1097/JAN.0000000000000579 -
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
International Journal of Nanomedicine 2024Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side...
BACKGROUND
Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia.
METHODS
To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA.
RESULTS
Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine ( < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group ( < 0.0001).
CONCLUSION
Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.
Topics: Animals; Morphine; Ganglia, Spinal; Nanoparticles; Rats; PC12 Cells; Analgesics, Opioid; Male; Neuralgia; Mice; Lipids; Proto-Oncogene Proteins; Peripheral Nerves; Mixed Function Oxygenases; DNA-Binding Proteins; Liposomes
PubMed: 38828199
DOI: 10.2147/IJN.S453608 -
Drug Design, Development and Therapy 2024Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
PURPOSE
Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery.
METHODS
In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1.
RESULTS
All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; =0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; =0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups.
CONCLUSION
For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100052085).
Topics: Humans; Oxycodone; Double-Blind Method; Middle Aged; Male; Female; Laparoscopy; Pain, Postoperative; Visceral Pain; Aged; Analgesics, Opioid; Adult; Digestive System Surgical Procedures; Dexmedetomidine; Sufentanil; Analgesia, Patient-Controlled; Flurbiprofen
PubMed: 38828025
DOI: 10.2147/DDDT.S464518