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Transplantation Direct Jul 2024Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living...
BACKGROUND
Enhanced recovery after surgery (ERAS) pathways represent a comprehensive approach to optimizing perioperative management and reducing hospital stay and cost. In living donor kidney transplantation, key impediments to postoperative discharge include pain, and opioid associated complications such as nausea, vomiting, and the return of gastrointestinal function.
METHODS
In this randomized controlled trial, living kidney transplantation donors were assigned to either the ERAS or control group. The ERAS group patients received 15 preoperative, 17 intraoperative, 19 postoperative element intervention. The control group received standard care. The ERAS group received a multimodal opioid sparing pain management including an intraoperative transverse abdominis plane block. Our primary outcome measure was postoperative opioid consumption. The secondary outcome measures were postoperative pain scores, first oral intake, and hospital length of stay.
RESULTS
There were no significant differences in demographics between the 2 groups. The ERAS group had a statistically significant reduction in total postoperative opioid consumption calculated in intravenous morphine equivalents (24.2 ± 20.2 versus 71 ± 39.5 mg, < 0.01). Postoperative pain scores were significantly lower ( < 0.001) from 1 h postoperatively to 48 h. Surgical time was 45 min shorter ( = 0.037). Intraoperative PlasmaLyte administration was lower (PlasmaLyte: 1444 ± 907 versus 2168 ± 1347 mL, = 0.049). Time to tolerating regular diet was shorter by 2 h ( < 0.008), and length of hospital stay was decreased by 10.1 h.
CONCLUSIONS
The ERAS group experienced superior postoperative analgesia and a shorter length of hospital stay compared with controls.
PubMed: 38953038
DOI: 10.1097/TXD.0000000000001663 -
Journal of Pain Research 2024Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA)...
PURPOSE
Joint pain is one of the most commonly reported pain types in the United States. In the case of patients suffering from inflammatory diseases such as osteoarthritis (OA) and gout, persistent inflammation due to long-term overexpression of several key cytokines has been linked to neuronal hypersensitivity and damage within the joints. Ultimately, a subset of patients develop chronic pain. Pharmacologic treatment of joint pain involves the use of analgesics such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, antidepressants, as well as intra-articular injections of corticosteroids and hyaluronic acid. However, NSAIDs are short-acting and fail to alleviate severe pain, opioids are generally ineffective at managing chronic pain, and all therapeutic options involve increased risks of serious side effects.
METHODS
We explored the therapeutic and analgesic effects of transforming growth factor-β-activated kinase 1 (TAK1) inhibition in both the monoiodoacetate (MIA) and monosodium urate (MSU) models of joint pain as an innovative strategy for alleviating chronic inflammatory pain. Mechanical allodynia (Von Frey), weight-bearing and histological changes were measured in separate groups of rats receiving either the selective TAK1 inhibitor, HS-276, gabapentin or vehicle.
RESULTS
Our data support that TAK1 inhibition effectively prevented the development of mechanical allodynia and differential weight-bearing in the MIA model. In the MSU model of gouty arthritis, treatment with HS-276 significantly reduced mechanical allodynia and knee edema in female rats, but not male rats. Histological evaluation of effected joints in both models showed that HS-276 treatment significantly reduced disease-induced degradation of the joint.
CONCLUSION
Our results support that TAK1 is a critical signaling node in inflammatory joint diseases such as OA and gouty arthritis. Selective pharmacological inhibition significantly attenuated several aspects of the disease, including joint degeneration and mechanical pain. Thus, TAK1 is a novel therapeutic target for the treatment of painful inflammatory joint diseases.
PERSPECTIVE
This article reports on the therapeutic potential of TAK1 in the treatment of chronic inflammatory joint diseases such as OA and gout. Using the selective TAK1 inhibitor, HS-276, we show the therapeutic and analgesic effects of TAK1 inhibition in two preclinical murine models of inflammatory joint pain.
PubMed: 38952995
DOI: 10.2147/JPR.S451409 -
Frontiers in Psychiatry 2024Using a validated translational model that quantitatively predicts opioid-induced respiratory depression and cardiac arrest, we compared cardiac arrest events caused by...
Comparison of intranasal naloxone and intranasal nalmefene in a translational model assessing the impact of synthetic opioid overdose on respiratory depression and cardiac arrest.
INTRODUCTION
Using a validated translational model that quantitatively predicts opioid-induced respiratory depression and cardiac arrest, we compared cardiac arrest events caused by synthetic opioids (fentanyl, carfentanil) following rescue by intranasal (IN) administration of the μ-opioid receptor antagonists naloxone and nalmefene.
METHODS
This translational model was originally developed by Mann et al. (Clin Pharmacol Ther 2022) to evaluate the effectiveness of intramuscular (IM) naloxone. We initially implemented this model using published codes, reproducing the effects reported by Mann et al. on the incidence of cardiac arrest events following intravenous doses of fentanyl and carfentanil as well as the reduction in cardiac arrest events following a standard 2 mg IM dose of naloxone. We then expanded the model in terms of pharmacokinetic and µ-opioid receptor binding parameters to simulate effects of 4 mg naloxone hydrochloride IN and 3 mg nalmefene hydrochloride IN, both FDA-approved for the treatment of opioid overdose. Model simulations were conducted to quantify the percentage of cardiac arrest in 2000 virtual patients in both the presence and absence of IN antagonist treatment.
RESULTS
Following simulated overdoses with both fentanyl and carfentanil in chronic opioid users, IN nalmefene produced a substantially greater reduction in the incidence of cardiac arrest compared to IN naloxone. For example, following a dose of fentanyl (1.63 mg) producing cardiac arrest in 52.1% (95% confidence interval, 47.3-56.8) of simulated patients, IN nalmefene reduced this rate to 2.2% (1.0-3.8) compared to 19.2% (15.5-23.3) for IN naloxone. Nalmefene also produced large and clinically meaningful reductions in the incidence of cardiac arrests in opioid naïve subjects. Across dosing scenarios, simultaneous administration of four doses of IN naloxone were needed to reduce the percentage of cardiac arrest events to levels that approached those produced by a single dose of IN nalmefene.
CONCLUSION
Simulations using this validated translational model of opioid overdose demonstrate that a single dose of IN nalmefene produces clinically meaningful reductions in the incidence of cardiac arrest compared to IN naloxone following a synthetic opioid overdose. These findings are especially impactful in an era when >90% of all opioid overdose deaths are linked to synthetic opioids such as fentanyl.
PubMed: 38952632
DOI: 10.3389/fpsyt.2024.1399803 -
Journal of Biochemical and Molecular... Jul 2024Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human...
Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 μM, and the IC50 of Tilianin for H1299 cells was 44.6 μM. Functionally, 0.5 nM sufentanil and 10 μM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 μM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 μM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 μM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Sufentanil; Lung Neoplasms; Animals; Mice; Apoptosis; Xenograft Model Antitumor Assays; A549 Cells; Mice, Nude; Drug Synergism; Cell Line, Tumor; Mice, Inbred BALB C; Antineoplastic Agents; Chondroitin Sulfates; Amphibian Venoms
PubMed: 38952040
DOI: 10.1002/jbt.23761 -
BMC Pharmacology & Toxicology Jul 2024We investigated acute poisonings resulting from medications affecting the nervous system and illicit substances at Loghman Hakim Hospital in Tehran.
BACKGROUND
We investigated acute poisonings resulting from medications affecting the nervous system and illicit substances at Loghman Hakim Hospital in Tehran.
METHODS
We retrospectively reviewed patient records at Iran's largest tertiary toxicology referral center between January 2010 and December 2015. We analyzed the prevalence, trend, age and gender distribution of acute poisoning caused by nervous system agents.
RESULTS
The present study included 16,657 (57.27%) males and 12,426 (42.73%) females, resulting in 29,083 patients. The median age of men and women was 29 and 26 years, respectively (p < 0.0001). There were 12,071 (72.47%) men and 10,326 (83.10%) women under the age of 40 (p < 0.001). Most cases were intentional (69.38% in men and 79.00% in women, p < 0.001) and 44.10% had a history of poisoning. The proportions of men and women varied significantly between different age groups and nervous system agents. For women, the most common agent was alprazolam, whereas for men, methadone. The overall trend of acute poisoning with drug used in addictive disorders, opioids and alcohol was increasing but decreasing with benzodiazepines and antidepressants. Acute poisoning by nervous system agents led to more deaths in men (1.95% vs. 0.56%; p < 0.001).
CONCLUSIONS
Methadone intoxication was common especially among young men and most of these intoxications were intentional. Women and men aged 20-29 most frequently suffer poisoning from alprazolam and clonazepam, respectively. Women over 60 and men over 30 used opium. Illicit drugs caused more than half of the deaths, and opium dominated. This study may create awareness and develop educational and preventive gender and age-specific local programs.
Topics: Humans; Female; Adult; Male; Middle Aged; Young Adult; Iran; Adolescent; Poisoning; Retrospective Studies; Aged; Age Factors; Child; Sex Factors; Child, Preschool; Infant; Prevalence
PubMed: 38951926
DOI: 10.1186/s40360-024-00759-1 -
Current Pain and Headache Reports Jul 2024With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This... (Review)
Review
PURPOSE OF THE REVIEW
With the increasing prevalence of cesarean section globally, the importance of perioperative analgesia for cesarean section is becoming increasingly evident. This article provides an overview and update on the current status of cesarean section worldwide and associated analgesic regimens.
RECENT FINDINGS
Some recent studies unveiled potential association of neuraxial analgesia might be associated with children's autism, pharmacologic analgesia in obstetric will potentially gain some more attention. Various commonly used techniques and medications for analgesia in cesarean section are highlighted. While neuraxial administration of opioid remains the most classic method, the use of multimodal analgesia, particularly integration of nonsteroidal anti-inflammatory drugs, acetaminophen, peripheral nerve blocks has provided additional and better options for patients who are not suitable for intrathecal and neuraxial techniques and those experiencing severe pain postoperatively. Optimal pain management is crucial for achieving better clinical outcomes and optimal recovery, and with the continuous development of medications, more and better pharmacologic regimen will be available in the future.
PubMed: 38951467
DOI: 10.1007/s11916-024-01278-8 -
Journal of General Internal Medicine Jun 2024A novel Oregon Medicaid policy guiding back pain management combined opioid restrictions with emphasis on non-opioid and non-pharmacologic therapies.
BACKGROUND
A novel Oregon Medicaid policy guiding back pain management combined opioid restrictions with emphasis on non-opioid and non-pharmacologic therapies.
OBJECTIVE
To examine the effect of the policy on prescribing, health outcomes, and health service utilization.
DESIGN
Using Medicaid enrollment, medical and prescription claims, prescription drug monitoring program, and vital statistics files, we analyzed the policy's association with selected outcomes using interrupted time series models.
SUBJECTS
Adult Medicaid patients with back pain enrolled between 2014 and 2018.
INTERVENTION
The Oregon Medicaid back pain policy.
MAIN MEASURES
Opioid and non-opioid medication prescribing, procedural care, substance use and mental health conditions, and outpatient and inpatient healthcare utilization.
KEY RESULTS
The policy was associated with decreases in the percentage of Medicaid enrollees with back pain receiving any opioids (- 2.68 percentage points [95% CI - 3.14, - 2.23] level, - 1.01 pp [95% CI - 1.1, - 0.92] slope), days of short-acting opioid use (- 0.4 days [95% CI - 0.53, - 0.26] slope), receipt of more than 7 days of short-acting opioids (- 2.36 pp [95% CI - 2.76, - 1.95] level, - 0.91 pp [95% CI - 1, - 0.83] slope), chronic opioid use (- 1.27 pp [95% CI - 1.59, - 0.94] level, - 0.46 [95% CI - 0.53, - 0.39 slope), and spinal surgeries and procedures. Among secondary outcomes, we found no increase in opioid overdose and a small, statistically significant trend decrease in opioid use disorders. There were small increases in non-opioid substance use and mental health diagnoses and visits but no increase in self-harm.
CONCLUSIONS
A state Medicaid policy emphasizing evidence-based back pain management was associated with decreases in opioid prescribing, spinal surgeries, and opioid use disorder trends, but also short-term increases in mental health encounters and an increase in non-opioid substance use disorder trends. Such policies may help reinforce evidence-based care, but must be designed with consideration of potential harms.
PubMed: 38951321
DOI: 10.1007/s11606-024-08776-w -
Regional Anesthesia and Pain Medicine Jun 2024Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between...
INTRODUCTION
Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery.
METHODS
We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery.
RESULTS
504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery.
DISCUSSION
This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.
PubMed: 38950932
DOI: 10.1136/rapm-2024-105633 -
Journal of Substance Use and Addiction... Jun 2024Telemedicine is a feasible alternative to in-person evaluations for people with opioid use disorder (OUD). The literature on medications for opioid use disorder (MOUD)...
INTRODUCTION
Telemedicine is a feasible alternative to in-person evaluations for people with opioid use disorder (OUD). The literature on medications for opioid use disorder (MOUD) telemedicine has focused on ongoing OUD treatment. Emergency department (ED) visits are an opportunity to initiate MOUD; however, little is known regarding the outcomes of patients following telemedicine referrals for MOUD from emergency settings. The current study describes rates of initial outpatient clinic appointment attendance and 30-day retention in care among patients referred by telemedicine compared to ED referrals.
METHODS
This paper reports a retrospective review of data for patients referred from EDs or telemedicine through the Medication for Addiction Treatment and Electronic Referrals (MATTERS) Network. The MATTERS online platform collects data on patient demographic information (e.g., age, gender, race/ethnicity, and insurance type), reason for visit, prior medical and mental health history, prior OUD treatment history, and past 30-day substance use behaviors. Analyses compared initial visit attendance and 30-day retention among the patients for whom follow-up data were received from clinics by demographic and initial treatment factors.
RESULTS
Between October 2020 and September 2022, the MATTERS Network made 1349 referrals; 39.7 % originated from an ED and 47.8 % originated from telemedicine. For patients with available data, those referred from telemedicine were 1.64 times more likely to attend their initial clinic appointment and 2.59 times more likely be engaged in treatment at 30 days compared to those referred from an ED. More than two-thirds of patients referred from the emergency telemedicine environment followed up at their first clinic visit and more than half of these patients were still retained in treatment 30 days after referral.
CONCLUSIONS
The rates of initial clinic visit and 30-day retention when referred following a telemedicine evaluation are encouraging. Further development of telemedicine programs that offer evaluations, access to medications, and referrals to treatment should be considered.
PubMed: 38950782
DOI: 10.1016/j.josat.2024.209446 -
World Neurosurgery Jun 2024Preoperative opioid use has been well-studied in elective spinal surgery and correlated with numerous postoperative complications including increases in immediate...
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.
PubMed: 38950648
DOI: 10.1016/j.wneu.2024.06.054