Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.939
Filtrar
Mais filtros








Intervalo de ano de publicação
1.
Front Psychiatry ; 15: 1409284, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962056

RESUMO

Background: Little is known about recovery from opioid use disorder (OUD) or outcomes of detoxification and drug-free treatment of chronic opioid therapy (COT). Harm reduction with medications for opioid use disorder (MOUD) is regarded as the only legitimate treatment. Methods: The Institutional Review Board (IRB) approved reporting deidentified outcomes. Patients seen over a 10-year period whose records suggested recovery were called and interviewed. Results: Overall, 69/86 (80%) confirmed that they had been sober for at least a year, including 41 patients with OUD (75%) and 28 COT patients (90%). 91% were drug-free, and 9% were on MOUD. 79% preferred a psychotherapy approach. 21% preferred MOUD. Coming for more treatment and abstinence from tobacco were significantly correlated with recovery. Conclusion: This is the first report that we are aware of regarding the frequency of recovery from OUD and COT. We have complicated the discussion about what is the best treatment for patients with OUD and patients on COT. Advising that maintenance is the only legitimate treatment for patients who suffer from OUD or who are on COT seems both premature and jeopardizes the ability of treaters to individualize treatment recommendations.

2.
Front Pain Res (Lausanne) ; 5: 1390322, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962712

RESUMO

Background: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch. Objective: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses. Study design: This is a randomized experimental study with a Latin square design. Methods: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 µg h-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (TailTDP), metacarpus region (MetacarpusTDP), or gaskin region (GaskinTDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables. Results: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml-1 when applied to the ventral aspect of the tail base. In the TailTDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml-1 from 2 to 32 h. The highest group mean was 0.25 ng ml-1 noted at 4 h. Conclusions: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.

3.
Laryngoscope ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967426

RESUMO

OBJECTIVES: The opioid crisis has prompted consideration of analgesic prescriptions. This study explored the value of preoperative acetaminophen for pain control following microsuspension laryngoscopy (MSL) and compared the results with a previous study of pain and opioid use following MSL (Tsang et al.). METHODS: A prospective open-label clinical trial was conducted in patients undergoing MSL. All patients were administered preoperative acetaminophen. Short-form McGill Pain Questionnaire (SF-MPQ), pain visual analogue scale (VAS), and present pain intensity (PPI) scores were collected preoperatively and on postoperative days (PODs) 1, 3, 7, and 14. Statistical analysis identified variables associated with opioid use or increased pain scores, and compared outcomes with Tsang et al. RESULTS: Eighty-nine patients were included (mean age 52.8 ± 17.3 years, 40 males). All patients received preoperative 1 g acetaminophen (77 (86.5%) orally) with no adverse effects. On POD1, opioid usage was 10%. Median [IQR] pain scores were 5 [2-11], 21 [12.3-56.8], and 3 [2-3.3] on SF-MPQ, VAS, and PPI, respectively. Post-Anesthesia Care Unit (PACU) opioid requirements significantly correlated with POD1 opioid consumption (τb = 0.214; p ≤ 0.05), and significant associations with PACU opioid administration were found for total anesthesia time (OR (95%CI) = 1.271 (1.043-1.548), p = 0.017) and total laryngoscope suspension time (OR (95%CI) = 0.791 (0.651-0.962, p = 0.019)). This cohort demonstrated reduced opioid usage on POD1 compared with Tsang et al (23%). CONCLUSIONS: Preoperative acetaminophen is a safe intervention, resulting in decreased postoperative opioid use following MSL. Anesthesia time correlated with need for postoperative opioids. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

4.
J Gen Intern Med ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954321

RESUMO

BACKGROUND: Primary care (PC) offers an opportunity to treat opioid use disorders (OUD). The Substance Use Symptom Checklist ("Checklist") can assess DSM-5 substance use disorder (SUD) symptoms in PC. OBJECTIVE: To test the psychometric properties of the Checklist among PC patients with OUD or long-term opioid therapy (LTOT) in Kaiser Permanente Washington (KPWA). DESIGN: Observational study using item response theory (IRT) and differential item functioning (DIF) analyses of measurement consistency across age, sex, race and ethnicity, and receipt of treatment. PATIENTS: Electronic health records (EHR) data were extracted for all adult PC patients visiting KPWA 3/1/15-8/30/2020 who had ≥ 1 Checklist documented and indication of either (a) clinically-recognized OUD (i.e., documented OUD diagnosis and/or OUD medication treatment) or (b) LTOT in the year prior to the checklist. MAIN MEASURE: The Checklist includes 11 items reflecting DSM-5 criteria for SUD. We described the prevalence of 2 SUD symptoms reported on the Checklist (consistent with mild-severe DSM-5 SUD). Analyses were conducted in the overall sample and in two subsamples (clinically-recognized OUD and LTOT only). KEY RESULTS: Among 2007 eligible patients, 39.9% endorsed ≥ 2 SUD symptoms (74.3% in the clinically-recognized OUD subsample and 13.1% in LTOT subsample). IRT indicated that a unidimensional model for the 11 checklist items had excellent fit (comparative fit index = 0.998) with high item-level discrimination parameters for the overall sample and both subsamples. DIF across age, race and ethnicity, and treatment was observed for one item each, but had minimal impact on expected number of criteria (0-11) patients endorse. CONCLUSIONS: The Substance Use Symptom Checklist measured SUD symptoms consistent with DSM-5 conceptualization (scaled, unidimensional) in patients with clinically-recognized OUD and LTOT and had similar measurement properties across demographic subgroups. The Checklist may support symptom assessment in patients with OUD and diagnosis in patients with LTOT.

5.
Front Nutr ; 11: 1422084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957870

RESUMO

Objective: This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality in long-term prescription opioid users. Methods: The study included 1856 long-term prescription opioid users from the National Health and Nutrition Examination Survey (NHANES, 2001-2018). Mortality status were determined by matching with the National Death Index (NDI) records until December 31, 2019. Multivariable Cox proportional hazard models were constructed to assess the association. Results: Over a median follow-up period of 7.75 years, there were 443 cases of all-cause mortality, including 135 cardiovascular disease (CVD) deaths and 94 cancer deaths. After multivariable adjustment, participants with serum 25(OH)D concentrations within 50.00 to <75.00 nmol/L and ≥ 75 nmol/L had a lower risk of all-cause mortality, with hazard ratios (HRs) of 0.50 (95% confidence interval [CI] 0.29, 0.86) and 0.54 (95% CI 0.32, 0.90), respectively. Nevertheless, no significant association was found between serum 25(OH)D concentrations and the risk of CVD or cancer mortality. The RCS analysis revealed a non-linear association of serum 25(OH)D concentration with all-cause mortality (p for non-linear = 0.01). Per 1-unit increment in those with serum 25(OH)D concentrations <62.17 nmol/L corresponded to a 2% reduction in the risk of all-cause mortality (95% CI 0.97, 1.00), but not changed significantly when 25(OH)D concentrations ≥62.17 nmol/L. Conclusion: In conclusion, a non-linear association existed between serum 25(OH)D concentrations and all-cause mortality in long-term prescription opioid users. Maintaining serum 25(OH)D concentrations ≥62.17 nmol/L may be beneficial in preventing all-cause mortality in this population.

6.
BMC Health Serv Res ; 24(1): 776, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956585

RESUMO

BACKGROUND: While brief duration primary care appointments may improve access, they also limit the time clinicians spend evaluating painful conditions. This study aimed to evaluate whether 15-minute primary care appointments resulted in higher rates of opioid prescribing when compared to ≥ 30-minute appointments. METHODS: We performed a retrospective cohort study using electronic health record (EHR), pharmacy, and administrative scheduling data from five primary care practices in Minnesota. Adult patients seen for acute Evaluation & Management visits between 10/1/2015 and 9/30/2017 scheduled for 15-minute appointments were propensity score matched to those scheduled for ≥ 30-minutes. Sub-groups were analyzed to include patients with acute and chronic pain conditions and prior opioid exposure. Multivariate logistic regression was performed to examine the effects of appointment length on the likelihood of an opioid being prescribed, adjusting for covariates including ethnicity, race, sex, marital status, and prior ED visits and hospitalizations for all conditions. RESULTS: We identified 45,471 eligible acute primary care visits during the study period with 2.7% (N = 1233) of the visits scheduled for 15 min and 98.2% (N = 44,238) scheduled for 30 min or longer. Rates of opioid prescribing were significantly lower for opioid naive patients with acute pain scheduled in 15-minute appointments when compared to appointments of 30 min of longer (OR 0.55, 95% CI 0.35-0.84). There were no significant differences in opioid prescribing among other sub-groups. CONCLUSIONS: For selected indications and for selected patients, shorter duration appointments may not result in greater rates of opioid prescribing for common painful conditions.


Assuntos
Analgésicos Opioides , Agendamento de Consultas , Padrões de Prática Médica , Atenção Primária à Saúde , Humanos , Analgésicos Opioides/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Minnesota , Padrões de Prática Médica/estatística & dados numéricos , Fatores de Tempo , Idoso , Dor Crônica/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos
7.
Clin Exp Dent Res ; 10(4): e913, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38973213

RESUMO

OBJECTIVES: After the shutdown of most dental services during the COVID-19 lockdown, the oral health community was concerned about an increase in prescribing opioids and antibiotics by dentists due to patients' limited access to dental offices. Therefore, the objective of this study was to investigate the impact of COVID-19 pandemic on the pattern of antibiotic and opioid prescriptions by dentists in Alberta, Canada. METHODS: Data obtained from the Tracked Prescription Program were divided into antibiotics and opioids. Time periods were outlined as pre-, during-, and postlockdown (phase 1 and 2). For the number of prescriptions and average supply, each monthly average was compared to the corresponding prelockdown monthly average, using descriptive analysis. Time series analyses were conducted using regression analyses with an autoregressive error model. Data were trained and tested on monthly observations before lockdown and predicted for during- and postlockdown. RESULTS: A total of 1.1 million antibiotics and 400,000 opioids dispense were tracked. Decreases in the number of prescriptions during lockdown presented for antibiotics (n = 24,933 vs. 18,884) and opioids (n = 8892 vs. 6051). Average supplies (days) for the antibiotics (n = 7.10 vs. 7.55) and opioids (n = 3.92 vs. 4.05) were higher during the lockdown period. In the trend analyses, the monthly number of antibiotic and opioid prescriptions showed the same pattern and decreased during lockdown. CONCLUSION: The COVID-19 pandemic altered the trends of prescribing antibiotics and opioids by dentists. The full impact of COVID-19 pandemic on the population's oral health in light of changes in prescribing practices by dentists during and after lockdown warrants further investigation.


Assuntos
Analgésicos Opioides , Antibacterianos , COVID-19 , Prescrições de Medicamentos , Padrões de Prática Odontológica , Humanos , COVID-19/epidemiologia , Analgésicos Opioides/uso terapêutico , Padrões de Prática Odontológica/estatística & dados numéricos , Antibacterianos/uso terapêutico , Alberta/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Pandemias , SARS-CoV-2 , Odontólogos/estatística & dados numéricos
8.
Radiol Case Rep ; 19(9): 3643-3647, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38983293

RESUMO

We present a case of a 29-year-old male who was brought into the hospital due to unresponsiveness and found to have heroin inhalational leukoencephalopathy (HLE). HLE is one component of a broad spectrum of opioid encephalopathies that is associated with heroin inhalation and other opioids. There is considerable overlap of HLE with other toxic and hypoxic-ischemic encephalopathies; however, the specific territories of brain involvement help distinguish it from other cerebral insults. The goal of this study is to help elucidate the findings of HLE and compare these findings to other toxic and hypoxic-ischemic encephalopathies.

9.
Orthop Surg ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946692

RESUMO

OBJECTIVES: The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. METHODS: Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. RESULTS: Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. CONCLUSION: Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.

10.
World Neurosurg ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950648

RESUMO

BACKGROUND: Preoperative opioid use has been well-studied in elective spinal surgery and correlated with numerous postoperative complications including increases in immediate postoperative opioid demand (POD), continued opioid use postoperatively, prolonged length of stay (LOS), readmissions, and disability. There is a paucity of data available on the use of preoperative opioids in surgery for spine trauma, possibly because there are minimal options for opioid reduction prior to emergent spinal surgery. Nevertheless, patients with traumatic spinal injuries are at a high risk for adverse postoperative outcomes. This study investigated the effects of preoperative opioid use on POD and LOS in spine trauma patients. METHODS: 130 patients were grouped into two groups for primary comparison: Group 1 (Preoperative Opioid Use, N=16) and Group 2 (No Opioid Use, N=114). Two subgroups of Group 2 were used for secondary analysis against Group 1: Group 3 (No Substance Abuse, N=95) and Group 4 (Other Substance Abuse, N=19). Multivariable analysis was used to determine if there were significant differences in POD and LOS. RESULTS: Primary analysis demonstrated that preoperative opioid users required an estimated 97.5 mg/day more opioid medications compared to non-opioid users (p<0.001). Neither primary nor secondary analysis showed a difference in LOS in any of the comparisons. CONCLUSIONS: Preoperative opioid users had increased POD compared to non-opioid users and patients abusing other substances, but there was no difference in LOS. We theorize the lack of difference in LOS may be due to the enhanced perioperative recovery protocol used, which has been demonstrated to reduce LOS.

11.
Br J Community Nurs ; 29(7): 348-350, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38963266

RESUMO

Chronic constipation, which is common and often difficult to treat, has numerous origins, including neurological and other conditions, and adverse reactions to drugs, especially opioids. Chronic functional constipation lacks a clear underlying cause. Increasing evidence suggests that transanal irrigation (TAI) aids faecal evacuation and is well tolerated in many people with bowel dysfunction who do not adequately respond to first-line treatments. Recent papers offer insights that help nurses and other healthcare professionals implement best practice in the community, including discussing any need for assistance before starting TAI, agreeing the most appropriate device with patients and optimising the irrigation protocol. Training, careful follow-up and ongoing supervision improve adherence and success. Further studies are needed, however, and patients who do not respond adequately or are unable to tolerate TAI should be referred to a specialist service.


Assuntos
Constipação Intestinal , Irrigação Terapêutica , Humanos , Constipação Intestinal/enfermagem , Constipação Intestinal/terapia , Irrigação Terapêutica/métodos , Irrigação Terapêutica/enfermagem , Doença Crônica , Enfermagem em Saúde Comunitária , Canal Anal , Guias de Prática Clínica como Assunto
12.
Artigo em Inglês | MEDLINE | ID: mdl-38964427

RESUMO

CONTEXT: Most cancer-associated pain is experienced in low- and middle-income countries (LMICs) due to inequitable access to opioids. OBJECTIVE: To determine opioid access as estimated by both patients and providers and to understand patient and facility-level factors influencing access among patients with advanced cancer in LMICs in Asia using the Behavioral Model of Health Services Use. METHODS: The APPROACH cross-sectional study was conducted in seven LMICs in Asia, involving in-depth surveys with providers and advanced cancer patients. A hierarchical logistic regression model was used to assess predisposing (i.e. individual factors), enabling (i.e. health care system and facility-level resources) and need (i.e. pain severity) factors predicting opioid access. RESULTS: Among patient participants (n=1,933), approximately 40% reported opioid use. Meanwhile 80% of facilities, as reported by providers, indicated at least half of their advanced cancer patients receive oral morphine prescriptions. Predisposing characteristics factored in the least in the model, with patient education positively associated with access (Odds ratio (OR): 1.01; 95% CI=1.00, 1.03). Facility-level enabling resources, factoring the most, included oral morphine prescription duration >14 days (OR: 1.27; 95% CI=1.05, 1.53) and the extent of physician palliative care training (extensive (>160 hours) OR: 3.95; CI=3.19, 4.88; basic (up to 40 hours) OR: 1.03; CI=1.03, 1.04). Patient need as indicated by greater pain severity predicted access (OR: 1.55; CI=1.47, 1.64). CONCLUSION: Study findings emphasize the importance of palliative care training-even a minimal amount-in supporting access to opioids for advanced cancer patients. This study also highlights pragmatic site-level policies, such as extended morphine prescription durations, enabling access.

13.
Perioper Med (Lond) ; 13(1): 68, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970081

RESUMO

BACKGROUND: High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics. METHODS: This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal-proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery. RESULTS: Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) µg in the distal-proximal acupoints group, significantly lower than the sham group, and the mean difference was - 34.9 (- 64.9 to - 4.9) µg, p = 0.023. The consumption of sufentanil was lower in distal-proximal group than regional group (303.9 vs. 339.5), and mean difference was - 35.5 (- 65.6 to - 5.5) µg, p = 0.020. The distal-proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups. CONCLUSION: Transcutaneous electrical acupoint stimulation with distal-proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

14.
Neuropharmacology ; 257: 110060, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960134

RESUMO

The escalating incidence of opioid-related issues among pregnant women in the United States underscores the critical necessity to understand the effects of opioid use and Medication for Opioid Use Disorders (MOUDs) during pregnancy. This research employed a translational rodent model to examine the impact of gestational exposure to buprenorphine (BUP) or morphine on maternal behaviors and offspring well-being. Female rats received BUP or morphine before conception, representing established use, with exposure continuing until postnatal day 2 or discontinued on gestational day 19 to mimic treatment cessation before birth. Maternal behaviors - including care, pup retrieval, and preference - as well as hunting behaviors and brain neurotransmitter levels were assessed. Offspring were evaluated for mortality, weight, length, milk bands, surface righting latency, withdrawal symptoms, and brain neurotransmitter levels. Our results reveal that regardless of exposure length (i.e., continued or discontinued), BUP resulted in reduced maternal care in contrast to morphine-exposed and control dams. Opioid exposure altered brain monoamine levels in the dams and offspring, and was associated with increased neonatal mortality, reduced offspring weight, and elevated withdrawal symptoms compared to controls. These findings underscore BUP's potential disruption of maternal care, contributing to increased pup mortality and altered neurodevelopmental outcomes in the offspring. This study calls for more comprehensive research into prenatal BUP exposure effects on the maternal brain and infant development with the aim to mitigate adverse outcomes in humans exposed to opioids during pregnancy.

15.
Addict Neurosci ; 112024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38957401

RESUMO

Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (µORs). The µOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Oprm1 expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies have revealed that multiple subpopulations of NAc neurons express Oprm1 mRNA, making it unclear which populations mediate diverse behaviors resulting from µOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels of Oprm1 of any NAc cell type. Here, we show that this population is selectively marked by expression of Chst9, a gene encoding a carbohydrate sulfotransferase. Notably, Chst9+ neurons exhibited more abundant expression of Oprm1 as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover, CHST9 mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of Chst9. The abundant expression of Oprm1 in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.

16.
Molecules ; 29(13)2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38998913

RESUMO

This study explored the potential of a series of PZM21 analogues for pain treatment. Specifically, the hydroxyphenyl ring of PZM21 was replaced with a naphthyl ring, the thienyl ring was substituted with either a phenyl ring or furan rings, and the essential dimethylamine and urea groups were retained. These compounds aimed to enhance safety and minimize the adverse effects associated with opioid drugs. The research findings suggest that compound 6a does not induce ß-arrestin recruitment at low-nanomolar concentrations but exhibits significant analgesic effects in established mouse models. Compared to morphine, 6a shows advantages in alleviating respiratory depression and minimizing physical dependence. Molecular docking studies underscore the pivotal role of the D147 amino acid residue in the analgesic mechanism of 6a. Consequently, 6a is a compelling candidate for the development of safer opioid analgesics and warrants further attention.


Assuntos
Analgésicos Opioides , Simulação de Acoplamento Molecular , Receptores Opioides mu , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Animais , Camundongos , Analgésicos Opioides/farmacologia , Analgésicos Opioides/química , Analgésicos Opioides/síntese química , Humanos , Relação Estrutura-Atividade , Dor/tratamento farmacológico , Masculino , Estrutura Molecular , Tiofenos , Ureia/análogos & derivados
17.
Int J Prison Health (2024) ; 20(1): 30-46, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38984552

RESUMO

PURPOSE: Prisonersare at disproportionate risk of suffering substance-related harms. The administration of naloxone is essential to reversing opioid overdose and minimizing substance-related harms in prison and the community. The purpose of this study is to examine how naloxone administration is practiced and perceived in prison settings. DESIGN/METHODOLOGY/APPROACH: The authors conducted surveys with correctional workers in Manitoba, Canada (n = 257) to examine how they understand and feel about the need for and practice of administering naloxone in their everyday work with criminalized populations. FINDINGS: Respondents reported feeling a great need to administer naloxone, but most did not feel adequately trained to administer naloxone, creating the perception that criminalized populations remain at enhanced risk. ORIGINALITY/VALUE: Findings provide emerging evidence of the need for training and accompanying policies and procedures for correctional workers on how to access and administer naloxone.


Assuntos
Naloxona , Antagonistas de Entorpecentes , Naloxona/uso terapêutico , Naloxona/administração & dosagem , Humanos , Antagonistas de Entorpecentes/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Masculino , Feminino , Manitoba , Adulto , Prisões , Pessoa de Meia-Idade , Overdose de Drogas/tratamento farmacológico , Overdose de Drogas/prevenção & controle , Overdose de Drogas/epidemiologia , Servidores Penitenciários
19.
Front Pain Res (Lausanne) ; 5: 1388837, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006759

RESUMO

Introduction: This study aimed to assess the percentage of patients treated according to the European Society for Medical Oncology (ESMO) 2018 guidelines for breakthrough cancer pain (BTcP) and the impact of guidelines adherence on patients' quality of life (QoL). Methods: Adult opioid-tolerant patients diagnosed with BTcP and locally advanced or recurrent metastatic cancer with a life expectancy of >3 months prospectively were included. Patients were followed up for 28 days. Results: Of 127 patients included, 37 were excluded due to the impossibility to establish adherence to the ESMO guidelines. Among the evaluable patients [51.1% female; with mean (SD) age of 66.4 (11.8) years], all were adherent. BTcP was diagnosed by the Association for Palliative Medicine algorithm in 47.8% of patients and by clinical experience in 52.2% of patients. The mean number of daily BTcP episodes ranged between 1 and 8, with a mean (95% CI) severity of 7.3 (7.0; 7.6) at week 0 and 6.2 (5.8; 6.6) at week 4. Time to maximum pain intensity was 3-15 min in 52.2% of patients, and BTcP lasted 30-60 min in 14.4% of patients at week 0 and 4.4% of patients at week 4. Mean (95% CI) treatment effectiveness was 6.6 (6.1; 7.1) at week 0 and 7.4 (7.0; 7.8) at week 4. Median (Q1-Q3) patients' global impression of clinical condition was 4.0 (4.0-4.0) at week 0 and 3.0 (2.0-3.0) at week 4. Conclusion: A clear BTcP assessment and strict follow-up could be crucial to guidelines adherence and for patient's QoL.

20.
J Comp Eff Res ; : e230183, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012387

RESUMO

Aim: Explore the safety of Belbuca® (buprenorphine buccal film), buprenorphine transdermal patches and oral opioids for chronic low back pain (cLBP) treatment. Methods: The retrospective analysis of the MarketScan Commercial database (2018-2021) included treatment-naive cLBP adults. The first date of buprenorphine (Belbuca and transdermal patch) or opioid prescription was index date. Cohorts were defined based on the index medication. Observation included a 6-month pre-index period, while post-index lasted until the end of continuous insurance coverage. There were 44 relevant treatment-emergent adverse events (TEAEs) identified in the literature. Incidence rate ratio (IRR) and incidence rate difference (IRD) were used to compare serious TEAE rates (in 1000 person-years) between cohorts. Propensity-score matching minimized the selection bias. Results: Buprenorphine had lower rates of 15 serious TEAEs than oral opioids (all p ≤ 0.037), while higher rates only for serious dizziness (IRR 2.44, p = 0.011; driven by Belbuca), opioid abuse/dependence (IRR 3.13, p = 0.004; driven by patches) and cholecystitis (IRD 20.25, p = 0.044; an outlier). Additionally, a comparison between Belbuca and oral opioids showed lower rates of 13 serious TEAEs (all p ≤ 0.024) and a higher serious dizziness rate (IRR 3.17, p = 0.024). Although the rates of serious opioid abuse/dependence were similar (24.60 vs 26.93, p = 0.921), all Belbuca patients and none of the opioid patients had a positive history of these events. Belbuca also had lower rates of five serious TEAEs than transdermal patches (all p ≤ 0.018), including a serious opioid abuse/dependence (IRR 0.04, p < 0.001), but higher rates of serious cholecystitis (IRD 52.17, p = 0.035; an outlier) and suicidal ideation (IRD 156.50, p < 0.001; an outlier). Conclusion: Buprenorphine had a better safety profile than oral opioids in cLBP treatment. Belbuca showed a more favorable TEAE profile than buprenorphine transdermal patches and oral opioids.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA