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BACKGROUND: Both increases and decreases in patients prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

OBJECTIVES: There is little understanding of the circumstances behind fatal pediatric opioid poisonings. Our objective was to characterize opioid fatalities according to child, family, and household factors. METHODS: We used data from the National Fatality Review-Case Reporting System to describe the circumstances behind the deaths of children 0 to 17 years of age who died of an opioid poisoning (ie, prescription opioid, heroin, illicit fentanyl) between 2004 and 2020. Decedents were stratified into age groups: 0-4, 5-9, 10-14, and 15-17 years. RESULTS: The majority (65.3%) of the 1696 fatal opioid poisonings occurred in the child's own home. Prescription opioids contributed to 91.8% of deaths, heroin contributed to 5.4%, and illicit fentanyl to 7.7%. Co-poisonings with nonopioid substances occurred in 43.2% of deaths. Among 0- to 4-year-olds, 33.9% died of homicide and 45.0% had a primary caregiver with a history of substance use/abuse. Among 10- to 14-year-olds and 15- to 17-year-olds, respectively, 42.0% and 72.8% of decedents had a history of substance use/abuse. In each age group, at least 25.0% of children were victims of previous child maltreatment. CONCLUSIONS: A history of maltreatment and substance use--whether on the part of the caregiver or the child--are common factors surrounding fatal pediatric opioid poisonings, the majority of which occur in the child's own home. Families with children of all ages would benefit from interventions focused on opioid prescribing, storage, disposal, and misuse. These findings also underscore the urgency of ensuring that access to naloxone becomes universal for families with a history of maltreatment and/or substance use. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin c can relieve the pain after other diseases, but there are no studies on whether vitamin C can relieve the pain after hip replacement. The purpose of this paper is to study whether vitamin C can relieve the pain after total hip replacement. Purpose: In this prospective, double-blind, placebo-controlled, randomized trial, 100 patients receiving THA at our hospital were randomly assigned to vitamin c or control groups. During the operation, the vitamin C group will receive intravenous injection of 3 g vitamin C, and the control group will receive 3 g placebo. If the patient has postoperative pain, 10 ml subcutaneous injection of morphine will be required as a rescue analgesic. The primary outcome was the amount of postoperative injection of morphine as a rescue analgesic and expression of inflammatory factors, and the secondary outcome was postoperative pain and hip recovery as assessed by visual analog scale (VAS). Results: The dosage of subcutaneous injection of morphine was significantly reduced in vitamin C group. VAS pain scores at rest and exercise were lower in the vitamin C group 24 h after surgery, and hip motion was better 24 h after surgery, but there was no significant difference between the two groups 24 h after surgery.Nonetheless, the overall changes in morphine usage and VAS scores did not surpass the established minimal clinically important differences (10 mg for morphine consumption; 1.5 at rest and 1.8 during movement for VAS scores). Conclusion: Adding intravenous vitamin c to multimodal analgesia significantly improved morphine consumption, VAS pain score, and functional recovery. However, it is recommended that single intravenous administration of vitamin C during the perioperative period may achieve better pain relief for patients after THA. [ABSTRACT FROM AUTHOR]

Objectives: The number of drug overdoses and drug-related deaths has increased across the United States in recent years. Reports of suspected opioid drug overdoses identified through emergency medical services (EMS) are valuable sources of information for shaping the public health response to drug overdoses. The objective of this study was to describe trends in the number of EMS-reported suspected opioid drug overdose events in South Carolina from 2019 through 2022. Methods: We included reports of suspected opioid drug overdoses if they met the definition of nonfatal opioid overdose syndrome in our analysis. We analyzed statewide data reported from EMS agencies to biospatial, Inc, from January 2019 through December 2022 to understand demographic trends for a statewide overdose and response program in South Carolina. Results: In 2022, a total of 11 078 suspected opioid drug overdose events, or 216.4 per 100 000 South Carolina residents, were reported by EMS. During the 4-year study period, the number of EMS-reported suspected opioid drug overdoses increased by 82%, with African American people experiencing a 133% increase and White people experiencing a 68% increase. The number of opioid overdoses increased among all age groups during the study period. Approximately 84% of opioid overdoses were reported in urban counties, but rural counties had a higher number of opioid overdose reports per capita than urban counties. Conclusions: Monitoring trends in suspected opioid drug overdoses allows decision makers to adjust resources and programs for overdose response and is essential for local coordinated response. Continued monitoring of trends is needed for an equitable response to prevent opioid drug overdoses. [ABSTRACT FROM AUTHOR]

Background: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z‐hypnotics among school‐aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016–2021. Methods: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID‐19 pandemic. To assess the possible effect of the COVID‐19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14–18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z‐hypnotics. Results: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z‐hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94–1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08–1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z‐hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z‐hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. Conclusions: This study shows that the trend of the nonmedical use of BDZ and Z‐hypnotics among school‐aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents. [ABSTRACT FROM AUTHOR]

Background and aims: Chronic non‐cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long‐term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. Method: A comprehensive systematic literature review and meta‐analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non‐cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case–control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random‐effects multi‐level meta‐analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta‐regressions. Results: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7–14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1–38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4–27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3–30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. Conclusions: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour. [ABSTRACT FROM AUTHOR]

Background and Aims: People with opioid use disorder (OUD) commonly experience pain including chronic pain. Despite the high prevalence, few studies have systematically examined the prevalence and correlates of pain among people seeking or receiving opioid agonist treatment (OAT) for OUD. This review aimed to determine the prevalence of pain in this population globally, and estimate the association between chronic pain and other demographic and clinical characteristics. Methods: Electronic searches were conducted in three databases (Medline, Embase and PsycINFO) from the inception until October 2022. Eligible studies reported prevalence rates of current and/or chronic pain. Meta‐analyses examining the main prevalence estimates were conducted by Stata SE 18.0, and comorbid clinical conditions were analysed by Review Manager 5.4. Results: Fifty‐six studies (n participants = 35 267) from sixty‐seven publications were included. Prevalence estimates of current and chronic pain were reported in 27 (48.2%) and 40 studies (71.4%), respectively. Most studies were conducted in North America (71.4%, n = 40) and used cross‐sectional designs (64.3%, n = 36). Meta‐analyses revealed a pooled prevalence of 60.0% (95% confidence interval [CI]: 52.0–68.0) for current pain and 44.0% [95% CI: 40.0–49.0] for chronic pain. Chronic pain was positively associated with older age (mean deviation of mean age: 2.39 years, 95% CI: 1.40–3.37; I2 = 43%), unemployment (odds ratio [OR] = 0.57, 95% CI: 0.42–0.76; I2 = 78%), more severe mental health symptoms (e.g. more severe depression (standardised mean difference [SMD] of mean scores: 0.45, 95% CI: 0.20–0.70; I2 = 48%) and anxiety symptoms (SMD: 0.52, 95% CI: 0.17–0.88; I2 = 67%), and hepatitis C (OR = 1.41, 95% CI: 1.03–1.94; I2 = 0%). No association was observed between chronic pain and the onset and type of OAT, geographic location, study design, survey year, participant age or use of specific pain assessment tools. Conclusions: There appears to be a high prevalence of pain among people seeking or receiving opioid agonist treatment for opioid use disorder compared with the general population, with positive associations for older age, unemployment, hepatitis C and the severity of some mental health symptoms. [ABSTRACT FROM AUTHOR]

Summary: Background: Opioid analgesic use before total hip or knee arthroplasty has been associated with worse postoperative outcomes. This pilot study aimed to examine the feasibility of a telehealth‐based pharmacist‐partnered opioid tapering intervention before elective primary hip or knee arthroplasty and its potential effectiveness compared with usual care. Methods: This study was conducted at seven hospitals in New South Wales, Australia. Eligible patients were those aged ≥ 18 years, scheduled to undergo primary hip or knee arthroplasty for osteoarthritis and taking opioid analgesics pre‐operatively. The intervention group participated in an opioid tapering telehealth service, a partnership between a pharmacist and general practitioner, for 3 months pre‐operatively up to the day of surgery, while the control group received usual care. The primary outcomes of the study were to investigate the feasibility of the intervention (i.e. adherence to treatment) and potential effectiveness in decreasing baseline daily opioid dose by > 50% before surgery. Results: Between December 2021 and June 2023, 70 patients were recruited and assigned randomly to the intervention group (n = 35) or control group (n = 35). Baseline characteristics were similar between groups. Thirty patients in each group completed their allocated treatment. All patients allocated to the intervention group completed at least one appointment with a pharmacist, with the median (IQR [range]) being 2 (1–4 [1–6]) appointments. The number of patients who successfully decreased their baseline daily opioid dose by ≥ 50% before surgery was 27/30 in the intervention group compared with 5/30 in the usual care group (p < 0.001). Conclusions: The findings of this pilot study support the feasibility of a telehealth‐delivered, pharmacist‐partnered opioid tapering service for patients scheduled for primary hip or knee arthroplasty. A broader multicentre study to examine the effectiveness of this intervention on clinical outcomes is warranted. [ABSTRACT FROM AUTHOR]

Background: Although substance use rates among adolescents have decreased, drug overdose deaths among adolescents have increased since 2020, driven largely by illegally made fentanyl (IMF). This study explores substance use patterns and characteristics of adolescents who were assessed for substance use disorder (SUD) treatment to inform prevention and response strategies. Methods: A convenience sample of adolescents aged 10–18 years assessed for SUD treatment from September 2017 to December 2021 was analyzed using the Comprehensive Health Assessment for Teens. The percentage of lifetime and past 30-day substance use was examined. Adolescent characteristics (e.g., demographics, history of overdoses or hospital visits due to drug/alcohol use) were analyzed by lifetime substances used. Results: Among 5,377 assessments, most were male (58.7%), aged 16–18 years (50.5%), non-Hispanic White (43.1%), enrolled in school (87.3%), and living with their parent(s) (72.4%). The most commonly reported lifetime substances used were marijuana (68.0%), alcohol (54.2%), and prescription opioid misuse (13.6%). The most common past 30-day substance use combination was alcohol and marijuana (35.6%). The percentage of assessments indicating past-year overdoses or hospital visits due to drug/alcohol use was greatest among those who reported lifetime use of IMF (24.0%), followed by heroin (21.4%) and cocaine (15.3%). Overall, 2.3% reported lifetime IMF use and 0.6% thought IMF was causing them the most problems. Conclusions: Findings inform opportunities to address substance use and increased IMF-involved overdose among adolescents. Continued overdose prevention and response strategies such as evidence-based education campaigns, naloxone distribution and harm reduction efforts, and evidence-based SUD treatment expansion are needed. [ABSTRACT FROM AUTHOR]

BACKGROUND: Opioids are known to cause respiratory depression, aspiration, and to suppress the immune system. This study aimed to investigate the relationship between short- and long-term opioid use and the occurrence and clinical outcomes of pneumonia in South Korea. METHODS: The data for this population-based retrospective cohort analysis were obtained from the South Korean National Health Insurance Service. The opioid user group consisted of those prescribed opioids in 2016, while the non-user group, who did not receive opioid prescriptions that year, was selected using a 1:1 stratified random sampling method. The opioid users were categorized into short-term (1-89 d) and long-term (≥90 d) users. The primary end point was pneumonia incidence from January 1, 2017-December 31, 2021, with secondary end points including pneumonia-related hospitalizations and mortality rates during the study period. RESULTS: In total, 4,556,606 adults were enrolled (opioid group, 2,070,039). Opioid users had a 3% higher risk of pneumonia and an 11% higher risk of pneumonia requiring hospitalization compared to non-users. Short-term users had a 3% higher risk of pneumonia, and long-term users had a 4% higher risk compared to non-users (P < .001). Additionally, short-term users had an 8% higher risk of hospital-treated pneumonia, and long-term users had a 17% higher risk compared to non-users (P < .001). CONCLUSIONS: Both short- and long-term opioid prescriptions were associated with higher incidences of pneumonia and hospital-treated pneumonia. In addition, long-term opioid prescriptions were linked to higher mortality rates due to pneumonia. [ABSTRACT FROM AUTHOR]

Background: The primary aim of our study was to determine which patient characteristics were associated with opioid consumption following cesarean delivery. Methods: The Baylor Scott & White Research Institute institutional review board approved this study (024-178). Patients who underwent cesarean delivery at Baylor Scott & White Medical Center – Temple with single injection or combined spinal epidural anesthesia in 2023 were eligible for inclusion. We examined the medical records of 300 patients, calculated the 24-hour opioid consumption for each, and compared the top third to the low group in a bivariate analysis and then performed a multivariate logistic regression. Results: One hundred thirty-one patients had no opioid consumption in the first 24 postoperative hours, and 100 patients had a morphine milligram consumption of 30 to 117.5 mg. A multivariate logistic regression determined that patients in the higher opioid consumption cohort were more likely to have received combined spinal epidural anesthesia (odds ratio 2.079; 95% confidence interval 1.149, 3.762; P = 0.02) and administration of intravenous dexmedetomidine in the intraoperative period (odds ratio 2.542; 95% confidence interval 1.038, 6.224; P = 0.04). Conclusion: Intraoperative administration of intravenous dexmedetomidine and combined spinal epidural anesthesia was associated with increased postoperative opioid consumption following cesarean delivery. [ABSTRACT FROM AUTHOR]

Background & Objective: HSG was performed to determine tubal patency of nulliparous and primiparous patients without contraception who underwent a pregnancy program. The contrast used can cause allergies, although the incidence of post-HSG allergy is rare. The clinicians need to be aware of this to remain vigilant. Case Presentation: The Presented case is report of a patient P1A0 who had an allergy after HSG. Hysterosalpingography was performed as the patient wanted another pregnancy, after a long wait without contraception, while the first child was 12 years old. A P1A0 woman with a 12-year-old first child wanted a second pregnancy, who was diagnosed bronchial asthma without regularly taking asthma medications. The patient received analgesic drugs and underwent an HSG examination on the 10th day of menstruation. Thirty minutes later, she complained of itching that started on the face and spread to the whole body, including the arms and legs. The whole body then appeared to be bumped. An hour later, an asthma attack occurred in the form of short breaths. HSG examination was a routine examination carried out in patients undergoing a pregnancy program. Incidence of allergies after HSG is a rare thing. Thus, this case report needs to be submitted to consider that allergic events such as those in this case report can occur. Conclusion: Allergic reactions after HSG are rare. HSG examination is performed on patients with bronchial asthma, and drug allergy (antalgin) must be noted carefully. The two allergy risk factors can trigger an allergic reaction to the contrast used during HSG examination. [ABSTRACT FROM AUTHOR]

Opioid receptors belonging to the class A G‐protein coupled receptors (GPCRs) are the targets of choice in the treatment of acute and chronic pain. However, their on‐target side effects such as respiratory depression, tolerance and addiction have led to the advent of the 'opioid crisis'. In the search for safer analgesics, bivalent and more recently, bitopic ligands have emerged as valuable tool compounds to probe these receptors. The activity of bivalent and bitopic ligands rely greatly on the allosteric nature of the GPCRs. Bivalent ligands consist of two pharmacophores, each binding to the individual orthosteric binding site (OBS) of the monomers within a dimer. Bitopic or dualsteric ligands bridge the gap between the OBS and the spatially distinct, less conserved allosteric binding site (ABS) through the simultaneous occupation of these two sites. Bivalent and bitopic ligands stabilize distinct conformations of the receptors which ultimately translates into unique signalling and pharmacological profiles. Some of the interesting properties shown by these ligands include improved affinity and/or efficacy, subtype and/or functional selectivity and reduced side effects. This review aims at providing an overview of some of the bivalent and bitopic ligands of the opioid receptors and, their pharmacology in the hope of inspiring the design and discovery of the next generation of opioid analgesics. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the clinical evidence for performing total knee arthroplasty (TKA) without a tourniquet, a shift from the near-universal use in 2009 to current trends towards tourniquet-less TKA in Norway and Sweden. This change is set against a backdrop of conflicting evidence regarding the positive and negative effects of tourniquet use. Questions/purposes: The aims were to determine if the tourniquet has an impact on [1] Forgotten Joint Score-12 (FJS-12) at 8 weeks after surgery; [2] postoperative strength and function; [3] postoperative pain and opioid analgesic use; and [4] operative time, bleeding, and length of stay (LOS). Methods: Eighty-one patients were randomised to TKA with or without a tourniquet. The outcome measures, FJS-12, muscle strength, functional test, pain, estimated blood loss, haemoglobin (Hb) loss, knee circumference, opioid consumption, and LOS were assessed preoperatively and at 1 day, 8 weeks, and 1 year after surgery. Results: No significant difference in FJS-12 scores was found between the two groups at postoperative 8 weeks. However, the tourniquet group showed statistically significant better knee extension strength at 8 weeks (p = 0.045). There were no differences in other outcomes, except for a greater decrease in haemoglobin levels (p = 0.02) and higher estimated perioperative blood loss (p < 0.001) in the no tourniquet group than the torniquet group. Conclusions: Our study indicates that tourniquet use during TKA causes no significant differences in FJS-12 at 8 weeks, significantly reduces bleeding and postoperative Hb loss, and improves quadriceps strength at 8 weeks. Trial registration: Clinicaltrails.gov. Registry Number: NCT03666598. Registered 30 August 2018. [ABSTRACT FROM AUTHOR]

Background: Practice facilitation (PF) is an evidence-based multicomponent in-person implementation strategy. COVID-19-related lockdowns caused many implementation initiatives to rapidly shift to virtual settings, but there is limited evidence on PF deployed exclusively using virtual meeting platforms. Our objective was to assess the feasibility and acceptability of virtual PF used in a primary care setting to implement interdisciplinary opioid safety committees (OSCs) to improve care for patients using opioid medicines for persistent pain and reduce high-dose opioid prescribing. We also describe alignment of virtual PF with the core functions of PF and fidelity of participating clinics to the OSC intervention. Methods: We applied qualitative and quantitative methods to evaluate virtual PF used to implement a quality improvement project at Kaiser Permanente Washington, an integrated health system in Washington State. We established interdisciplinary OSCs in primary care clinics using virtual PF. OSCs were tasked with promoting opioid safety and high-quality pain care through population management and chart reviews. We used administrative data to calculate feasibility measures including attendance and retention. Acceptability data came from interviews with OSC members conducted by evaluators. Measures of fidelity to the OSC intervention were abstracted from meeting notes and administrative data. We used qualitative methods to assess the adherence of virtual PF to the core functions of PF. Results: Facilitators carried out a comprehensive PF approach virtually and demonstrated adherence to the core functions of PF. We established OSCs in eight clinics and conducted an average of 17.5 virtual PF meetings over eight months of PF for each clinic. Average attendance was 75% and we had 84% retention. OSC members were highly satisfied with virtual PF. Facilitators effectively supported teams through implementation and technical challenges and OSC members gained skills through virtual PF. We implemented OSCs with high fidelity, suggesting virtual PF is an effective implementation strategy. Conclusions: We found virtual PF is a feasible and acceptable implementation strategy for this intervention and identified strategies to support care teams through challenges. Our findings can help inform future implementation efforts, especially those hoping to engage geographically dispersed clinics or remote clinical staff. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

The opioid epidemic continues to have a staggering impact on millions of individuals and families across all socioeconomic levels and communities. Recent studies suggest high numbers of patients presenting for surgery with reported opioid misuse and/or opioid use disorder (OUD). Anesthesiologists often lack basic education to treat patients suffering with OUD or patients in recovery from this treatable disease. This manuscript will provide a review of the American Society of Anesthesiology and Pain Medicine Multisociety Working Group Practice Advisory recommendations on existing OUD treatment barriers and perioperative management best practices; it will also demonstrate the benefits that greater involvement of the anesthesiologist can have in managing patients with OUD perioperatively. [ABSTRACT FROM AUTHOR]

Purpose: Despite their dangerous side effects, opioid drugs remain a standard of care for moderate to severe pain with few alternatives. Strategies to maintain the analgesic effects of opioids while minimizing the associated risks are needed. Pre-clinical studies have shown using a dopamine 3 receptor (D3R) agonist as an adjuvant to morphine provides superior analgesia against painful stimuli compared to morphine alone. Our objective was to test if adjunct treatment with a D3R agonist can lead to a reduction in opioid use while maintaining effective analgesia. Patients and methods: This study was set up as a double-blinded, placebocontrolled randomized trial. Enrollment included acute renal colic patients presenting to the emergency department, from which patients were randomized to either the "control" or "study arm". The control group received standard treatment of care (morphine, 0.1 mg/kg; i.v.) and an oral placebo pill. The experimental group received half-dosed morphine and oral pramipexole pill (0.25 mg). Pain measurements including a numerical pain scale and visual analog scale were collected from enrollees at baseline and every subsequent 15 min. Results: A total of 19 patients completed the study, 10 in the experimental arm and 9 in the control arm. During the study period, effective analgesia (50% decrease from baseline) was achieved in 80% of patients in the experimental arm vs. 33.3% in the control arm. Conclusion: Our pilot clinical trial demonstrated that D3R recruitment can serve as an effective adjuvant to low-dose morphine for control of renal colic pain and potentially other acute pain conditions. [ABSTRACT FROM AUTHOR]

Background: The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown. Methods: This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days. Results: The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age. Conclusions: The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain. Trial registration: The study used national health registry data from the period 2010–2019. A pre-registered analysis plan is available at Open Science Framework. [ABSTRACT FROM AUTHOR]

Introduction: Intestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare. Case presentation: We report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient's symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction. Conclusions: This case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Opioid analgesics can alleviate ischaemia/reperfusion (I/R) injury in chronic heart failure. However, the underlying mechanisms and targets remain unknown. Here, we investigate if caveolin‐3 (Cav3) interacts with μ opioid receptors and if Cav3–μ receptor interactions play a role in morphine‐induced cardioprotection in failing hearts.Cav3 and μ receptor proteins in human and rat heart tissue were determined by western blot, immunofluorescence and co‐immunoprecipitation. Methyl‐β‐cyclodextrin (MβCD), a destroyer of caveolae, and AAV‐Cav3 shRNA were used to reduce Cav3 expression in failing rat hearts. CTOP, a specific μ antagonist, was administrated before morphine preconditioning in perfused failing heart models of myocardial I/R injury.Levels of Cav3 and μ receptor proteins were significantly higher in human and rat myocardial tissues with heart failure than in control tissues. Cav3 and μ receptor expression levels were positively correlated with disease severity. The signal of the cardiac Cav3 protein was colocalized with μ receptor in both the human and rat heart sections. Disruption of caveolae in the failing heart by either MβCD or AAV‐Cav3 shRNA significantly inhibits morphine‐induced phosphorylation of ERK1/2 and cardioprotection. Administration of CTOP substantially reduced Cav3 expression and morphine‐induced cardioprotective effect in heart failure.Our data suggest that up‐regulation of the Cav3/μ receptor complex is critical for morphine protection of the failing heart against I/R injury by regulating the ERK1/2 pathway. The activated Cav3/μ receptor complex is an understudied therapeutic target for opioid treatment of heart failure and ischaemic insult. [ABSTRACT FROM AUTHOR]

We recently demonstrated that transient attenuation of Toll-like receptor 4 (TLR4) in dorsal root ganglion (DRG) neurons, can both prevent and reverse pain associated with chemotherapy-induced peripheral neuropathy (CIPN), a severe side effect of cancer chemotherapy, for which treatment options are limited. Given the reduced efficacy of opioid analgesics to treat neuropathic, compared with inflammatory pain, the cross talk between nociceptor TLR4 and mu-opioid receptors (MORs), and that MOR and TLR4 agonists induce hyperalgesic priming (priming), which also occurs in CIPN, we determined, using male rats, whether (1) antisense knockdown of nociceptor MOR attenuates CIPN, (2) and attenuates the priming associated with CIPN, and (3) CIPN also produces opioid-induced hyperalgesia (OIH). We found that intrathecal MOR antisense prevents and reverses hyperalgesia induced by oxaliplatin and paclitaxel, two common clinical chemotherapy agents. Oxaliplatin-induced priming was also markedly attenuated by MOR antisense. Additionally, intradermal morphine, at a dose that does not affect nociceptive threshold in controls, exacerbates mechanical hyperalgesia (OIH) in rats with CIPN, suggesting the presence of OIH. This OIH associated with CIPN is inhibited by interventions that reverse Type II priming [the combination of an inhibitor of Src and mitogen-activated protein kinase (MAPK)], an MOR antagonist, as well as a TLR4 antagonist. Our findings support a role of nociceptor MOR in oxaliplatin-induced pain and priming. We propose that priming and OIH are central to the symptom burden in CIPN, contributing to its chronicity and the limited efficacy of opioid analgesics to treat neuropathic pain. [ABSTRACT FROM AUTHOR]

Objective: This study compared the efficacy of ultrasound-guided erector spinae plane block (ESPB) and wound infiltration (WI) for postoperative analgesia in patients who underwent lumbar spinal surgery with instrumentation. Methods: In this randomized controlled trial, 80 patients were divided into two groups: ESPB (n = 40) and WI (n = 40). Postoperative pain intensity was assessed via the visual analog scale (VAS) at multiple time points within 24 h. Additionally, opioid consumption, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), and patient satisfaction were evaluated. Results: Both ESPB and WI provided effective postoperative pain management, with no significant differences in VAS scores. However, the ESPB group demonstrated a significantly longer duration of analgesia, a shorter time to first rescue analgesia, and lower total tramadol consumption (50 ± 60 mg vs. 100 ± 75 mg; p = 0.010) than did the WI group. Furthermore, a trend toward reduced PONV incidence was observed in the ESPB group, likely due to its opioid-sparing effect. Conclusion: While both ESPB and WI provided effective postoperative pain management, ESPB demonstrated a distinct advantage by offering a longer duration of analgesia and significantly reducing opioid consumption. These findings suggest that ESPB is more effective than WI for postoperative analgesia in lumbar spinal surgeries, providing prolonged pain relief and improving patient outcomes. Further studies are warranted to explore its long-term benefits and cost-effectiveness. Trial Registration: ClinicalTrials.govPRS: NCT06567964 Date: 08/21/2024 Retrospectively registered. Key Points: 1. Study Objective: This study aimed to compare the efficacy of ultrasound-guided erector spinae plane block (ESPB) with that of wound infiltration (WI) for postoperative analgesia in lumbar spinal surgeries involving instrumentation. 2. Primary outcome: Postoperative pain intensity was measured via the visual analog scale (VAS) at multiple time points. The VAS scores were comparable between ESPB and WI at all assessed time points, indicating no significant differences in pain scores. However, both techniques still played a role in postoperative pain management. 3. Opioid consumption: ESPB was associated with a significant reduction in total tramadol consumption compared with WI, indicating that an opioid-sparing effect that could reduce the risk of opioid-related side effects. 4. Duration of Analgesia: Patients in the ESPB group experienced a longer duration before requiring rescue analgesia, suggesting that ESPB provides more prolonged pain relief than WI does. 5. Side Effects and Patient Satisfaction: The incidence of postoperative nausea and vomiting (PONV) was lower in the ESPB group, potentially due to reduced opioid consumption. These findings suggest that ESPB may increase patient satisfaction and comfort during the postoperative period. 6. Clinical Implications: These findings support the integration of ESPB into multimodal analgesia protocols for lumbar spinal surgeries, given its potential advantages in reducing opioid consumption and providing extended pain relief. 7. Limitations: This study has several limitations. First, although the sample size was calculated based on a power analysis and was sufficient to detect significant differences in the primary outcomes, a larger sample size might provide more robust insights into secondary outcomes or less common side effects. Additionally, the study was conducted at a single center, which may limit the generalizability of the findings. Future multicenter studies are needed to validate these results across diverse patient populations and clinical practices. Lastly, the follow-up period was limited to 24 h, which does not allow for the assessment of long-term outcomes such as chronic pain development or functional recovery. 8. Future research: Further studies are recommended to explore the long-term benefits of ESPB, its cost-effectiveness, and its potential integration into enhanced recovery protocols (ERASs) for surgical patients. [ABSTRACT FROM AUTHOR]

Objective: Currently, the primary surgical treatment for pseudomyxoma peritonei (PMP) is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The perioperative period is frequently accompanied by severe pain. Erector spinae plane block (ESPB) can enhance analgesia for abdominal surgery. The purpose of this study was to compare the analgesic effects of bilateral multiple-injection ESPB in patients with PMP. Methods: Fifty patients with PMP were randomly divided into two groups: the ESPB combined with general anesthesia group (Group E) and the general anesthesia alone group (Group C). Prior to the induction, patients in Group E underwent ESPB at the T7 and T11 levels. The primary outcome was the visual analog scale (VAS) scores during rest at 6 h post-extubation. Secondary outcomes included intraoperative and postoperative opioid consumption, time for first rescue analgesia, frequency distribution of rescue analgesia, incidence of nausea and vomiting, adverse events associated with ESPB. Results: The Visual Analogue Scale (VAS) scores in Group E were significantly lower compared to Group C at immediate post-extubation (1.6 ± 0.9 vs. 2.4 ± 1.2, P = 0.008), and at 2 (1.9 ± 1.2 vs. 3.2 ± 1.1, P < 0.001), 4 (2.4 ± 1.5 vs. 3.7 ± 1.0, P = 0.001), and 6 h (2.7 ± 1.1 vs. 3.8 ± 1.4, P = 0.004) post-extubation during rest. Similarly, the VAS scores in Group E were significantly lower than those in Group C at immediate post-extubation (3.0 ± 1.4 vs. 4.6 ± 1.2, P < 0.001), and at 2 (3.8 ± 1.7 vs. 4.9 ± 1.4, P = 0.019), 4 (3.5 ± 1.3 vs. 5.3 ± 1.5, P < 0.001), and 6 h (3.9 ± 1.8 vs. 4.9 ± 1.3, P = 0.004) post-extubation during movement. In Group E, the intraoperative remifentanil administration (2319.3 ± 1089.5 vs. 2984.6 ± 796.1, P = 0.017) and the amount of rescue analgesia within 2 h post-extubation (0 vs. 4, P = 0.037) were significantly less than in Group C, and the first rescue analgesia time was shorter as well (231.4 ± 147.5 vs. 668.8 ± 416.7, P < 0.001). Conclusion: Compared to general anesthesia alone, bilateral multiple-injection ESPB with 0.2% ropivacaine can enhance analgesia and reduce opioid administration in patients with PMP. However, the duration of analgesia with ESPB is relatively short due to the low concentration of the local anesthetic used. Trial registration: Chinese Clinical Trial Registry, ChiCTR2300069504, 20/03/2023. [ABSTRACT FROM AUTHOR]

Xylazine is a potent sedative used in veterinary medicine. Recently, recreational drugs such as fentanyl have been found to contain xylazine, increasing the risk of respiratory depression and death. Despite a similar presentation to opioid overdose, patients who ingest xylazine do not respond to treatment with Narcan. Therefore, rapid detection of xylazine could improve patient management and prevent adverse outcomes.We evaluated the XYL500 one-step xylazine drug of abuse test for its ability to detect xylazine in 152 urine samples from patients on chronic opioid therapy for pain management or in treatment for substance use disorder. Results were compared to LC-MS/MS as the reference method. Precision, cross-reactivity, interference and stability studies were performed.Pooled patient samples were consistently negative or positive when tested five times on the same day and over three days of testing. The diagnostic sensitivity, specificity and accuracy of the XYL500 assay were 74, 98, and 82 % respectively, as compared with LC-MS/MS. XYL500 detected 77 of the 104 LC-MS/MS positive samples identified in our initial evaluation, including some that contained low levels of xylazine (n=8), <10 ng/mL. Minimal cross-reactivity with other opioid analgesics and commonly encountered drugs was seen with only one false positive result. Interferences by common urine contaminants were negligible. Specimens were stable up to 160 days refrigerated and up to 80 days at room temperature.XYL500 allows for rapid detection of xylazine, illustrating its utility in monitoring patients who ingested recreational drugs containing the additive, xylazine, and its potential to improve patient management. [ABSTRACT FROM AUTHOR]

AbstractTramadol is a synthetic opioid with a central effect from the aminocyclohexanol group, which has two main mechanisms of action, including as a weak agonist of opioid receptors and as a norepinephrine and serotonin reuptake inhibitor. The present study presents a review based on clinical trials designed in 2023. In July 2023, six international databases, including Medline/PubMed, ProQuest, Scopus, EMBASE, Google Scholar, and ISI (Web of Science), were searched and 58 articles were included in the study. The results of most studies showed that tramadol can be used as an analgesic drug, although in some studies it was shown that tramadol is not therapeutically superior in reducing pain compared to other treatments. Also, complications related to this treatment have been reported in some studies. Physicians should consider these factors to prevent drug toxicity, poor pain relief, use disorder in patients, and unpredictable complications. It should be noted that there is not enough evidence to support the long-term effectiveness of tramadol, but this argument also extends to nonopioid and other types of opioid analgesics, and the lack of long-term trials is due to regulatory and ethical issues. Although opioids can cause addiction when used for a long time, tramadol has a reasonable safety profile. According to the patient’s condition and the clinical judgment of the medical professional, tramadol can be prescribed for patients, but the consequences of its use must be considered and a personalized treatment algorithm should be selected if the benefits outweigh the risks of the drug. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionsThe increasing presence of counterfeit opioid drugs in the United States can contaminate data collection systems and confound estimates derived from surveillance of the opioid epidemic. Data sources and analyses that can quantify the contribution of counterfeit opioid products are needed to provide accurate and timely data to inform public health responses. We describe a novel approach to identify and quantify intentional abuse and misuse exposures involving suspected counterfeit opioid products in United States poison center data.An ecological study was performed using data, including narrative case notes, reported to participating United States Poison Centers of the Researched Abuse, Diversion and Addiction Related Surveillance System between 2009-Quarter 1 and 2021-Quarter 4. A machine learning natural language processing approach was used to develop a predictive model.Sensitivity for detecting suspected non-counterfeit-involved exposures by the predictive model was 92%, specificity was 73%, and the area under the receiver operating characteristic curve was 92%. Overall, only 2.1% of intentional abuse and misuse exposure calls were predicted to be suspected counterfeit-involved during 2009–2021; however, we observed an exponential increase in suspected counterfeit exposures over this time period. There was a 7-fold increase in the estimated number of suspected counterfeit exposures from 2009 to 2021, and 23.7% of all opioid analgesic intentional abuse and misuse exposures were suspected counterfeit-involved in 2021.We demonstrate the feasibility and reliability of using machine learning natural language processing to identify exposures involving suspected counterfeit opioid products in United States poison center data. Results suggest that suspected counterfeits have had a meaningful influence on rates of intentional abuse exposures to opioid analgesics in more recent years.The increasing presence of counterfeit opioid drugs can contaminate data collection systems and compromise the reliability of the data. [ABSTRACT FROM AUTHOR]

Background: Maternal opioid use (MOU) remains a public health concern. Studies have demonstrated significant increases in MOU, but estimates using ICD-10-CM or stratified by sociodemographic variables are limited. Objectives: Using a statewide, population-based dataset of Florida resident deliveries from 2000 to 2019, we examined the trend of MOU by age, race/ethnicity, education level, and insurance. Methods: Florida administrative data was used to conduct a retrospective cohort study. MOU was identified using opioid-related hospital discharge diagnoses documented prenatally or at delivery. Maternal sociodemographic variables were obtained from Florida vital statistics. Joinpoint regression was used to identify statistically significant changes in the trends overall and stratified by sociodemographic variables. Results are presented as annual percentage changes (APC) and 95% confidence intervals. Results: Our sample included over 3.6 million Florida resident mothers; of which, MOU was identified in 1% (n = 22,828) of the sample. From 2000 to 2019, MOU increased over ten-fold from 8.7 to 94.7 per 10,000 live birth deliveries. MOU increased significantly from 2000 to 2011 (APC: 32.8; 95% CI: 29.4, 36.2), remained stable from 2011 to 2016, and decreased significantly from 2016 to 2019 (APC: 3.9; 95% CI: −6.6, −1.0). However, from 2016 to 2019, MOU increased among non-Hispanic Black mothers (APC: 9.2; 95% CI: 7.5, 11.0), and those ages 30–34 (APC: 2.9; 95% CI: 1.2, 4.6) and 35–39 (APC: 6.4; 95% CI: 4.3, 8.4). Conclusions: Accurate prevalence estimates of MOU by sociodemographic factors are necessary to fully understand prevalence trends, describe the burden among sub-populations, and develop targeted interventions. [ABSTRACT FROM AUTHOR]

Introduction: Buprenorphine is used to treat opioid use disorder (OUD). However, therapy is often disrupted during acute pain episodes, and re-initiation is often deferred due to intolerable interruption in opioid analgesics. This case report describes a unique strategy for inducing buprenorphine without stopping opioid analgesics. Case: One patient with OUD and acute pain was initiated on buprenorphine using intravenous microdosing without precipitated withdrawal or pain exacerbation. Full agonist opioids were successfully weaned after discharge and the patient was linked with a community-based treatment program. Conclusion: This case describes use of intravenous buprenorphine to treat OUD and acute pain without adverse consequences. [ABSTRACT FROM AUTHOR]

Background: Opioid use disorder (OUD) remains a significant public health challenge with high recurrence rates and varied long-term outcomes. Affective temperament and emotion regulation have been identified as influencing addictive behaviors and treatment outcomes in OUD. However, limited research has explored their association with reversion over an extended period. Objectives: The EDATOUD (Emotion Dysregulation and Affective Temperaments in Opioid Use Disorder) study aimed to evaluate the effects of affective temperament and emotion regulation characteristics on recurrence over a 1-year follow-up period. The study aimed to compare the baseline characteristics of patients who achieved remission versus those who did not and identify potential predictors of recurrence risk. Methods: The study included 63 patients with OUD who were assessed monthly for return-to-use through self-report, psychiatric examination, and urine analysis. Sociodemographic data, affective temperament, difficulties in emotion regulation, anxiety, and depression were measured at baseline. Statistical analyses were performed to compare the recurrent and remission groups and determine the predictive value of these clinical features on recurrence. Results: Within the one-year, 77.8% of patients returned to use. Affective temperament characteristics did not differ between the groups. However, the recurrent group patients exhibited significantly more difficulties in emotion regulation. Conclusions: Difficulties in emotion regulation are associated with an increased risk of recurrence in patients with OUD. Understanding these factors can inform the development of tailored treatment strategies to improve long-term outcomes. Further research is needed to explore additional factors contributing to reversion and enhance intervention and support systems for sustained recovery in OUD. [ABSTRACT FROM AUTHOR]

In many countries, the consumption of illicit opioids is rising, becoming a major public health issue called the "opioid crisis". Many reasons contribute to this phenomenon. One of them is opioid misuse, defined as the use of legally prescribed opioids for a purpose different than pain treatment. This matter has not been well studied in Poland, where the opioid crisis has not been identified so far. This study was conducted among patients admitted for elective surgery with opioid-based postoperative pain treatment. The frequency of opioid misuse was found to be 10.8% in a sample comprising 92 patients. The group of individuals with potential opioid use disorder had a more frequent history of inadequately controlled postoperative pain compared to the group of non-misusers (p = 0.023). Furthermore, this group asked to receive additional pain treatment almost six times more often than the control group (p < 0.000). Also, patients declaring opioid misuse reported substantial differences concerning their knowledge and opinions about pain treatment and opioid analgesics: supporting the administration of opioids for pain when needed, finding opioids less harmful, and supporting messages that opioids are safe, effective, well-tolerated, easy to cutoff more often than control. There is an urgent need for the education of patients to avoid the spreading of the opioid crisis. [ABSTRACT FROM AUTHOR]

Objectives: To describe the use of buprenorphine/naloxone micro-inductions in hospitalized patients and characterize the success rate of these inductions. Methods: We conducted a retrospective chart review of hospitalized patients receiving a buprenorphine/naloxone micro-induction for opioid use disorder in a tertiary care hospital from Jan 2020–Dec 2020. The primary outcome was a description of the micro-induction prescribing patterns used. The secondary outcomes were a description of the demographic characteristics of patients, the estimated frequency of withdrawal symptoms experienced by patients undergoing a micro-induction, and the overall success rate of the micro-inductions defined as retention on buprenorphine/naloxone therapy with no precipitated withdrawal experienced. Results: Thirty-three patients were included in the analysis. Three main micro-induction regimens were identified, including rapid micro-inductions (8 patients), 0.5 mg SL BID initiations (6 patients), and 0.5 mg SL daily initiations (19 patients). Twenty-four patients (73%) met the criteria for a successful micro-induction, defined as being retained in buprenorphine/naloxone therapy with no precipitated withdrawal experienced. The most common reason for micro-induction failure was patient request to discontinue buprenorphine/naloxone therapy due to perceived adverse effects or personal preference. Conclusion: Buprenorphine/naloxone micro-induction in hospitalized patients resulted in a majority of patients being successfully initiated on buprenorphine/naloxone therapy without requiring opioid abstinence prior to induction. Dosing regimens were variable, and the ideal regimen remains unclear. [ABSTRACT FROM AUTHOR]

Aging is a global reality that is accompanied by an increase in polypharmacy. In this vital stage, caregivers emerge as relevant actors since their intervention impacts on the safety of the medication use process and on the quality of life of the patient they assist. As the knowledge about the treatments that caregivers supervise for the patient under their care conditions the health outcomes of the medications, the main objective of this study is to characterize the caregivers of patients who use opioid analgesics and to identify factors that increase the risk of the appearance of Medication Related Problems (DRP). The results reveal that the caregiver profile affects the health outcomes of this therapeutic group in both the prevalence and type of DRP. Of the 63 patients using opioid analgesics under pharmacotherapeutic follow-up during this study, 17 (27%) had caregivers. The caregiver in this study was predominantly female (61.1%). Considering DRP and kinship, a higher prevalence of DRP was observed when the caregivers were children or external personnel. Analyzing the pharmacotherapy of these caregivers, 4.8% have started antidepressant treatment, 3.2% hypnotic treatment after becoming caregivers of these patients. The Zarit Test reveals that 29.4% of the caregivers of these patients manifest overload. We conclude that Pharmaceutical Care should consider the opportunity and relevance of designing and implementing intervention and education protocols focused on caregivers. [ABSTRACT FROM AUTHOR]

Background: Neuromodulation has provided promising results in chronic pain management. Sacral neurostimulation (SNS) is a neuromodulatory technique, where the sacral nerve roots are electrically stimulated. Objective: Evaluate the efficacy of the trial phase to control severe cancer pain in pelvic organs. Design: Pilot study. Methods: Chronic pelvic cancer pain patients were managed with morphine ≥ 60 mg daily, duloxetine 30 mg, and celecoxib 200 mg twice daily. Twenty‑two adults were divided randomly into two equal groups: the SNS group (N = 11), received a sacral neurostimulator device and opioid analgesics, and the opioid group (N = 11), received increased opioid analgesics to control pain. Results: Visual analog scale scores were decreased in the SNS group at 24 h, 4 days, 1, and 2 weeks in SNS compared to the opioid group, medians (IQR) [4 (3–5) vs 6 (5–7), 3 (3–4) vs 5 (5–6), 3 (3–4) vs 5 (5–6), and 3 (3–3) vs 5 (4–6) P < 0.001], daily morphine consumption was reduced in the SNS group compared to the opioid group, median (IQR) [90 (60–90) mg vs 120 (120–150) mg, P < 0.001] and [30 (30–60) mg vs 150 (120–180) mg] during the first and second weeks. The SNS group had a better life quality compared to the opioid group after 2 weeks, median (IQR) was (123 (122.5–124) vs 117 (117–118.5) P < 0.001), respectively. Conclusion: The SNS trial device showed effectiveness in managing severe chronic pelvic cancer pain. [ABSTRACT FROM AUTHOR]

Background: Naldemedine, a peripherally acting opioid μ receptor antagonist, is effective for prevention of opioid-induced constipation (OIC); however, evidence on its use in children is limited. Objective: To evaluate the efficacy and safety of naldemedine in pediatric patients with OIC. Design, Setting/Subjects: Retrospective analysis of 32 pediatric patients with OIC treated with naldemedine in a single institution in Japan from June 2017 to March 2021. Measurements: Efficacy was evaluated in 13 evaluable patients with bowel movement (BM) response, defined as those with at least three BMs in the first 7 days after naldemedine initiation and an increase of at least one BM from baseline. Safety was evaluated by examining adverse events (AEs) based on the Common Terminology Criteria for AEs (v5.0). Results: BM response was recorded in 11 of the 13 patients (85%), and the number BMs per day significantly increased from 0.43 before naldemedine to 1.00 after naldemedine (p = 0.025). The most common AE was diarrhea, observed in 16 of the 32 patients (50%), and all instances were grade 1 or 2. In three of the 16 patients, naldemedine was discontinued owing to worsening diarrhea. Conclusions: In pediatric patients, naldemedine resulted in a high rate of BM response and increased the BM frequency, indicating its efficacy. In some patients, grade 2 diarrhea required naldemedine discontinuation, suggesting that it should be used with caution in pediatric patients. Further studies are warranted to determine the optimal naldemedine dose in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: The use of opioids occasionally causes tinnitus. However, there is a paucity of data regarding the use of peripherally acting μ-opioid receptor antagonists for opioid-associated tinnitus in patients with cancer. Actual case: A 74-year-old male with pancreatic cancer complained of abdominal pain. Two days after initiating oxycodone therapy, the patient experienced tinnitus during body movements. Although peripheral tinnitus disappeared after discontinuing oxycodone, it reappeared with hydromorphone or tapentadol administration. Possible courses of action: Drug cessation is a preferred intervention for drug-induced tinnitus; however, the cessation of opioids may not be feasible in patients with cancer who are already taking opioids. Formulation of a plan: Based on the presumed mechanism of peripheral tinnitus, the use of peripherally acting μ-opioid receptor antagonists was planned, and 200 μg/day of naldemedine was prescribed for tinnitus relief. Outcome: Tinnitus disappeared immediately after initiating naldemedine, and the pain was well-controlled. The effect was preserved after increasing or switching opioids. Lessons: The use of peripherally acting μ-opioid receptor antagonists may be an option to treat opioid-associated tinnitus without compromising the analgesic effects. View: Further clinical data regarding the secondary effect of peripherally acting μ-opioid receptor antagonists on opioid-associated complications other than constipation are required. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluated the impact of intraoperative opioid use and anesthesia type on outcomes for patients undergoing radical cystectomy for bladder cancer. Data from 508 patients treated between 2015 and 2022 were analyzed. Most (82%) received combined intravenous and epidural anesthesia, while the rest received intravenous-only anesthesia. Results showed that combined anesthesia was linked to better overall survival and fewer intensive care unit admissions. However, opioid dosage and type did not significantly affect survival, recurrence rates, or major perioperative outcomes. The findings are limited by the study's single-center, retrospective nature, and further research is needed to confirm the safety of opioids in patients undergoing radical cystectomy. Background: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. Methods: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. Results: A total of 508 patients with a median age of 73 years (IQR: 64–78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98–808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4–0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31–0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. Conclusion: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC. [ABSTRACT FROM AUTHOR]

Background: The opioid crisis caused a huge health concern in the United States. Despite this, few studies have examined the influence of opioid-related disorders (OD) on outcomes after bariatric surgery. The major goal of this study is to determine the impact of OD on in-hospital outcomes for patients undergoing bariatric surgery. Method: The National Inpatient Sample (NIS) database from 2016 to 2020 was used to evaluate patients with OD who underwent bariatric operations including sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion with duodenal switch. The non-OD comparison group was created using a propensity score match (1:1). Weighted analysis was carried out utilizing NIS-provided weights. The odds ratios were obtained using multivariate logistic regression. Results: A total of 159,455 patients who underwent bariatric surgery were evaluated. Propensity score matching and weighted analysis were used to compare 11,025 in the OD group and 11,025 in the non-OD group. OD was an independent predictor for postoperative complications (odds ratio: 1.29, 95% confidence interval: 1.19–1.39, p < 0.001). Among complications, OD was a predictor for bleeding complications, postoperative nausea and vomiting, anastomotic leak, and mechanical ventilation. In addition, the OD group experienced significantly longer lengths of stay (LOS) and a higher total hospital charges. Conclusion: In patients undergoing bariatric surgery, OD is associated with a significantly higher risk of postoperative complications, as well as increased LOS and total hospital charges. These patients may benefit from further preoperative optimization, including decreasing the opioid dose and closer postoperative monitoring. [ABSTRACT FROM AUTHOR]

Introduction: Currently there are few opioid prescribing guidelines for orthopaedic fractures. Long-term post-surgical analgesia requirements, understandably, vary between orthopaedic cases. Our study aims to provide detailed information to clinicians and policy makers, on the opioid requirement associations for patients sustaining tibial fractures. Methods: This study reviewed all patients sustaining an isolated tibial fracture at a major trauma centre that were operated on within 1 month of injury, from 2015 to 2022. The total opioid dosage used each month in morphine milligrams equivalents (MME) and the number of days opioids were used each month, within the first-year post-surgery were collected, representing the strength and coverage of opioid analgesia in the post-operative stage, respectively. We compared opioid strength and coverage requirements with types of definitive fracture fixations, location, fracture type and concurrent patient medical comorbidities to assess for any trends. Results: A total of 1814 patients sustaining a combined of 1970 fractures were included in the study. Tibial plateau fractures had the highest opioid strength and coverage requirements in each month and the entire year (p <.05). Across all fracture locations, Ex Fix frame showed higher opioid strength and coverage requirements compared to both IM nailing and plate ORIF. With regard to opioid coverage in the presence of specific comorbidities, only chronic kidney disease (quotient: 1.37, 95% Confidence interval [95%CI] = 1.19–1.55, p =.002) and hypertension (quotient: 1.34, 95%CI = 1.14–1.53, p =.009) showed significance at the 1-year overall level. For opioid strength, Chronic Kidney Disease (quotient: 1.72, 95%CI = 1.41–2.03 p =.005) and COPD (quotient: 1.90, 95%CI = 1.44–2.36, p =.014), show significance at the 1-year overall level. Conclusion: Our study details opioid requirements post-surgery amongst tibial fractures with subgroup analysis assessing opioid needs amongst specific fracture locations, types, surgical techniques and medical comorbidities. This framework aids clinicians in anticipating rehabilitation and assists in risk stratifying patients at injury onset. [ABSTRACT FROM AUTHOR]

Background: Postoperative neurocognitive disorders (PNDs) frequently occur following orthopedic surgery and are closely associated with adverse prognosis. PNDs are an emerging concept that includes both postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). The prevention of combined use of peripheral nerve block (PNB) and general anesthesia (GA) on POCD and/or POD incidence following orthopedic surgery remains unknown. We aimed to investigate the effect of this combined anesthesia method on POCD/POD incidence after orthopedic surgery, compared with GA. Methods: The databases of PubMed, Web of Science, Embase via Ovid, and the Cochrane Central Register of Controlled Trials were searched for all available randomized controlled trials (RCTs). The incidence of POD/POCD was the primary outcome. Continuous and dichotomous outcomes are represented as standardized mean differences [SMD, 95% confidence interval (CI)] and risk ratios [RR, 95%CI], respectively. Results: Meta-analysis of twelve RCTs with a total of 1488 patients revealed that compared with GA, PNB plus GA decreased the incidence of POCD (RR: 0.58, 95%CI: 0.35 to 0.95, P = 0.03, I2 = 0%), while the incidence of POD had no significant difference (RR: 0.87, 95%CI: 0.54 to 1.40, P = 0.57, I2 = 67%). Compared with GA alone, a significant decrease of intraoperative and postoperative opioid consumption (SMD: -1.54, 95%CI: -2.26 to -0.82, P < 0.0001, I2 = 89%; SMD: -7.00, 95%CI: -9.89 to -4.11, P < 0.00001, I2 = 99%) and postoperative nausea and vomiting incidence (RR: 0.16, 95%CI: 0.06 to 0.44, P = 0.0004, I2 = 0%) was found with PNB plus GA. Conclusions: The combined use of PNB and GA decreases the incidence of POCD but not POD following orthopedic surgery. Trial registration: The protocol of this study was registered with PROSPERO (Registration Number: CRD42022366454). [ABSTRACT FROM AUTHOR]

The number of low back pain (LBP) cases is projected to increase to more than 800 million by 2050. To address the substantial burden of disease associated with this rise in prevalence, effective treatments are needed. While clinical practice guidelines (CPG) consistently recommend non-pharmacological therapies as first-line treatments, recommendations regarding manual therapy (MT) in treating low back pain vary. The goal of this narrative review was to critically summarize the available evidence for MT behind these recommendations, to scrutinize its mechanisms of action, and propose some actionable steps for clinicians on how this knowledge can be integrated into a person-centered approach. Despite disparate recommendations from CPG, MT is as effective as other available treatments and may be offered to patients with LBP, especially as part of a treatment package with exercise and education. Most of the effects of MT are not specific to the technique. MT and other interventions share several mechanisms of action that mediate treatment success. These mechanisms can encompass patients' expectations, prior experiences, beliefs and convictions, epistemic trust, and nonspecific contextual effects. Although MT is safer than opioids for patients with LBP, this alone is insufficient. Our goal is to encourage clinicians to shift away from outdated and refuted ideas in MT and embrace a person-centered approach rooted in a comprehensive biopsychosocial framework while incorporating patients' beliefs, addressing illness behaviors, and seeking to understand each patient's journey. [ABSTRACT FROM AUTHOR]

Objective: The state of Illinois' Opioid Alternative Pilot Program (OAPP) is the first and only official harm-reduction program in the US to address the opioid crisis via facilitation of safe and legal access to medical cannabis. This study evaluates the association of medical cannabis use with pain level and frequency of opioid use in the first cohort of OAPP participants in 2019. Methods: A survey was sent OAPP enrollees between February and July 2019. Cannabis users (n = 626) were compared to non-users (n = 234) to determine whether there was an association between cannabis use and self-reported (a) pain level and (b) frequency of opioid use. Backward stepwise regression models were used. Results: A total of 860 participants was included in the analysis. Overall, 75% of the study sample reported pain as their primary medical symptom, and 67% of cannabis users reported having a disability. The mean difference in pain level between cannabis users and non-users was 4.5 units (on a 100-point scale) higher among cannabis users than non-users (p = 0.03); and cannabis use was statistically associated with pain level. High-frequency opioid users had lower odds of reporting cannabis use within the past year than low/no opioid users. Conclusions: Although there was a statistical association between cannabis use and pain, the difference of 4.5 points in pain level between users and non-users was too small to reflect a clinically meaningful relative difference. This study may provide useful information to providers and clinicians about how the OAPP and similar programs may reduce opioid use and improve health outcomes. [ABSTRACT FROM AUTHOR]

Background: Older adults, an increasingly diverse segment of the United States population, are a priority population for prescription painkiller misuse. This study documents trends and correlates of prescription painkiller misuse among Hispanic and non-Hispanic adults ages 50 and older. Methods: A secondary analysis of adults 50 years and older across 5 cohorts using the 2015–2019 National Survey on Drug Use and Health (unweighted n = 16,181, 8.5% Hispanic, and 54% female). Logistic regression modeling with complex survey design was used to examine trends in prescription painkiller misuse. Results: Over time, the prevalence of past year painkiller misuse significantly decreased for Hispanic respondents (56.1% relative decrease, p = 0.02); elevated proportions were observed across strata of demographic characteristics. Conclusions: Variability in the prevalence of painkiller misuse may be explained by demographic characteristics. Further, these results emphasize the importance of addressing comorbid recreational marijuana use when designing interventions to address painkiller misuse for older adults. [ABSTRACT FROM AUTHOR]

Background: Transcarotid artery revascularization (TCAR) is growing in popularity. Although major clinical end-points such as stroke rate and mortality are well-known, patient reported outcomes such as pain, and length of stay are among the purported benefits that are as yet untested. We sought to determine if there are differences in pain and other clinical outcomes when comparing carotid endarterectomy (CEA) and TCAR. Methods: We performed a retrospective review of 326 patients undergoing TCAR (n = 50) or CEA (n = 276) from 2019-2023. Primary outcomes of interest were maximum pain numeric rating scales (NRS) reported in the post-anesthesia care unit (PACU) and on postoperative days (POD) zero and 1, and oral morphine milligram equivalents (OMMEs) received intraoperatively through POD1. Secondary outcomes included length of stay (LOS), complications, and 30-day emergency department (ED) returns/readmissions. Results: Fifty TCAR and 150 CEA patients were included in the propensity score matched cohorts. TCAR patients reported lower pain-NRS in PACU (P <.001) and on POD0 (P =.002), but similar pain scores on POD1 (P =.112). Postoperatively, TCAR patients were less likely to receive opioids (52% vs 75.3%, P =.003) and received less OMME from PACU through POD1 (12.8 ± 16.2 vs 23.2 ± 27.2, P =.001). After adjusting for age, sex, BMI, prior chronic opioid use, and prior carotid surgery, TCAR patients were approximately 70% less likely to receive post-operative opioids. No significant differences in LOS, 30-day ED returns/readmissions, or complications were observed between groups. Conclusions: Compared with CEA, patients undergoing TCAR reported lower pain scores and consumed fewer narcotics overall. However, the absolute difference was modest, and pain scores were low in both cohorts. Differences in pain and post-operative narcotic use may be of less importance when deciding between TCAR and CEA. Total non-opioid protocols may be feasible in both approaches. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to estimate the absolute (incidence) and relative (hazard ratio; HR) risk of agranulocytosis associated with metamizole in comparison with non-steroidal antiinflammatory drugs (NSAIDs). Methods: A cohort study of new users of metamizole versus NSAIDs was performed with BIFAP (Pharmacoepidemiologic Research Database in Public Health Systems; Spain). Patients aged ≥ 2 years in 2005–2022 were followed up from the day after their first metamizole or NSAID dispensation till the end of the treatment period to identify patients hospitalized due to idiosyncratic agranulocytosis. Incidence rate (IR) and adjusted HR of agranulocytosis with metamizole versus NSAID were estimated assuming the onset date of agranulocytosis was the date of hospitalization sensitivity analysis or 7 days before (main analysis). In secondary analyses, we used (1) opioids-paracetamol as negative control and (2) any hospitalized neutropenia as outcome (assuming the onset was 7 days before). Results: The cohorts included 444,972 new users of metamizole, 3,814,367 NSAID, and 3,129,221 opioids-paracetamol on continuous treatment during a median of 37–40 days. Overall, 26 hospitalized agranulocytosis occurred, 5 in the first week (and so removed in main analysis) and 21 thereafter. IR of agranulocytosis was 14.20 (N = 5 cases) and 8.52 (N = 3), 1.95 (N = 6) and 1.62 (N = 5), and 4.29 (N = 15) and 3.72 (N = 13)/107 person-weeks of continuous treatment using the date of hospitalization or 7 days before, respectively. Two, 0 and 2 of cases identified in both analyses had neoplasia in every cohort, respectively. HR of agranulocytosis associated with metamizole was 7.20 [95% CI: 1.92–26.99] and 4.40 [0.90–21.57] versus NSAID, and 3.31 [1.17–9.34] and 2.45 [0.68–8.83] versus opioid-paracetamol, respectively. HR of neutropenia with metamizole was 2.98 [1.57–5.65] versus NSAID. Conclusions: Agranulocytosis was very rare but more common (above 4 times more) with metamizole than other analgesics. The impact of the drug-induced agranulocytosis was less precise with metamizole than the comparators due to its lower use, which precluded to find statistical differences in main analysis. The increased risk of hospitalized neutropenias with metamizole supports the link with its severity although triggers unavailable during the follow-up (ex. cytotoxic medication) can not be discarded. [ABSTRACT FROM AUTHOR]

Background: Untreated pain is a source of significant physical and psychosocial distress in patients with cancer. While guidelines for prescribing opioids have improved the treatment of cancer-related pain, all patients who take opioids are at risk for developing opioid-induced respiratory depression (OIRD). The current treatment for OIRD is naloxone although guidelines are highly variable on initial dose and indication. Patients with cancer on chronic opioids are at risk for increased suffering due to naloxone-induced opioid withdrawal and loss of pain control. Aim: A review of the evidence for the safety and benefits of using buprenorphine instead of naloxone for reversal of OIRD in patients prescribed chronic opioids for cancer-related pain. Methods: A realist review of the literature was completed following the RAMSES Framework. An iterative literature search of electronic databases was used to identify appropriate literature relating to buprenorphine and naloxone safety and use as reversal agents in OIRD. Results: While naloxone does reverse OIRD it does have the risk of pulmonary edema and research has consistently shown that naloxone is usually given for the wrong indications and/or at an inappropriate dose for patients on chronic opioids for cancer-related pain. Buprenorphine has been shown to safely reverse OIRD with less incidence and severity of withdrawal and uncontrolled pain when compared to naloxone. Conclusions: Because of the potential for decreased opioid withdrawal-associated symptoms, this review argues that buprenorphine warrants additional study and consideration to replace naloxone as the first-line rescue medication for patients with cancer on chronic opioids who experience OIRD. [ABSTRACT FROM AUTHOR]

Objectives. To examine trends in overdose deaths by intent and drug category to better understand the recent decrease in overdose suicides amid the overdose epidemic. Methods. We examined trends in rates of overdose deaths by intent (unintentional, suicide, or undetermined) across 9 drug categories from 1999 to 2022 using US National Vital Statistics System mortality data. Results. Unintentional overdoses involving synthetic opioids, polydrug toxicity involving synthetic opioids, psychostimulants, and cocaine increased exponentially with annual percentage changes ranging from 15.0% to 104.9% during 2010 to 2022. The death rates also increased for suicides involving these drugs, especially for psychostimulants (annual percentage change = 12.9% for 2010–2022; P <.001). However, these drugs accounted for relatively small percentages of overdose suicides. The leading drug categories among suicides were antidepressants, prescription opioids, and benzodiazepines, though these deaths have decreased or leveled off in recent years. Conclusions. Different drugs commonly involved in suicides and unintentional overdoses may contribute to their divergent trends. Public Health Implications. Amid the overdose epidemic, safe storage of medications remains a crucial strategy to prevent overdose suicides. The large increases in suicides involving psychostimulants warrant monitoring. (Am J Public Health. 2024;114(10):1081–1085. https://doi.org/10.2105/AJPH.2024.307745) [ABSTRACT FROM AUTHOR]

Objectives: Current medical management of osteoarthritis (OA) is mostly palliative with non-steroidal anti-inflammatory drugs (NSAIDs) being the mainstay of therapy. NSAIDs are commonly used despite well-known side effect which may lead to various adverse drug reactions and drug toxicity. Therefore, the objectives of the study are to analyse the prescription pattern of NSAIDs in OA patients and to assess appropriateness of the use of NSAIDs in relation to gastrointestinal and cardiovascular risk. Methods: A cross sectional study was carried out among patients attending orthopaedics out- patient department & provisionally diagnosed as OA. Patients who were prescribed any of the following drugs or their combinations were included in the study: NSAIDs, Glucocorticoids, Opioid analgesics and Symptomatic Slow Acting Drugs for OA (SYSADOA). To assess prescription pattern, ‘WHO core prescribing indicators’ were used Analysis of appropriateness of NSAIDs use by the prescribers in relation to GI & CV risks, the recommendations of the ‘First International Working Party Report on Management of Patients on NSAIDs’ were adopted and categorised as appropriate or inappropriate or uncertain. Data were entered in statistical software ‘EpiInfo’. Data were represented by suitable tables & figures and expressed in frequency and percentage. Results: A total 600 OA patients were included in the study. Out of 600 prescriptions, NSAIDs were prescribed in 547 prescriptions. Total 402 prescriptions were analyzed for appropriateness of NSAIDs therapy. Out of total 402 prescriptions, 222 prescriptions were found appropriate, 127 inappropriate and 53 were found as uncertain. Conclusions: The study showed that NSAIDs should be selected more judiciously for OA patients in relation to GI and CV risk in order to reduce untoward adverse effects of these agents. [ABSTRACT FROM AUTHOR]

Background/Objectives: Precisely selected patients require vitreoretinal surgeries (VRS) performed under general anesthesia (GA) when intravenous rescue opioid analgesics (IROA) are administered intraoperatively, despite a risk of adverse events, to achieve hemodynamic stability and proper antinociception and avoid the possibility of intolerable postoperative pain perception (IPPP). Adequacy of anesthesia guidance (AoA) optimizes the titration of IROA. Preventive analgesia (PA) techniques and intravenous or preoperative peribulbar block (PBB) using different local anesthetics (LAs) are performed prior to GA to optimize IROA. The aim was to analyze the utility of PBBs compared with intravenous paracetamol added to AoA-guided GA on the incidence of IPPP and hemodynamic stability in patients undergoing VRS. Methods: A total of 185 patients undergoing vitreoretinal surgery (VRS) were randomly assigned to one of several anesthesia protocols: general anesthesia (GA) with analgesia optimized through AoA-guided intraoperative remifentanil opioid analgesia (IROA) combined with a preemptive single dose of 1 g of paracetamol (P group), or PBB using one of the following options: 7 mL of an equal mixture of 2% lidocaine and 0.5% bupivacaine (BL group), 7 mL of 0.5% bupivacaine (BPV group), or 7 mL of 0.75% ropivacaine (RPV group). According to the PA used, the primary outcome measure was postoperative pain perception assessed using the numeric pain rating scale (NPRS), whereas the secondary outcome measures were as follows: demand for IROA and values of hemodynamic parameters reflecting quality or analgesia and hemodynamic stability. Results: A total of 175 patients were finally analyzed. No studied PA technique proved superior in terms of rate of incidence of IPPP, when IROA under AoA was administered (p = 0.22). PBB using ropivacaine resulted in an intraoperative reduction in the number of patients requiring IROA (p = 0.002; p < 0.05) with no influence on the dose of IROA (p = 0.97), compared to paracetamol, and little influence on hemodynamic stability of no clinical relevance in patients undergoing VRS under AoA-guided GA. Conclusions: PA using paracetamol or PBBs, regardless of LAs used, in patients undergoing VRS proved no advantage in terms of rate of incidence of IPPP and hemodynamic stability when AoA guidance for IROA administration during GA was utilized. Therefore, PA using them seems no longer justified due to the potential, although rare, side effects. [ABSTRACT FROM AUTHOR]

Background Overuse of medical care is a pervasive problem. Studies using hypothetical scenarios suggest that physicians' risk literacy influences medical decisions; real-world correlations, however, are lacking. We sought to determine the association between physicians' risk literacy and their real-world prescriptions of potentially hazardous drugs, accounting for conflicts of interest and perceptions of benefit--harm ratios in low-value prescribing scenarios. Setting and sample Cross-sectional study--conducted online between June and October 2023 via field panels of Sermo (Hamburg, Germany)--with a convenience sample of 304 English general practitioners (GPs). Methods GPs' survey responses on their treatment-related risk literacy, conflicts of interest and perceptions of the benefit--harm ratio in low-value prescribing scenarios were matched to their UK National Health Service records of prescribing volumes for antibiotics, opioids, gabapentin and benzodiazepines and analysed for differences. Results 204 GPs (67.1%) worked in practices with ≥6 practising GPs and 226 (76.0%) reported 10--39 years of experience. Compared with GPs demonstrating low risk literacy, GPs with high literacy prescribed fewer opioids (mean (M): 60.60 vs 43.88 prescribed volumes/1000 patients/6 months, p=0.016), less gabapentin (M: 23.84 vs 18.34 prescribed volumes/1000 patients/6 months, p=0.023), and fewer benzodiazepines (M: 17.23 vs 13.58 prescribed volumes/1000 patients/6 months, p=0.037), but comparable volumes of antibiotics (M: 48.84 vs 40.61 prescribed volumes/1000 patients/6 months, p=0.076). High-risk literacy was associated with lower conflicts of interest (θ = 0.12, p=0.031) and higher perception of harms outweighing benefits in low-value prescribing scenarios (p=0.007). Conflicts of interest and benefit--harm perceptions were not independently associated with prescribing behaviour (all ps >0.05). Conclusions and relevance The observed association between GPs with higher risk literacy and the prescription of fewer hazardous drugs suggests the importance of risk literacy in enhancing patient safety and quality of care. [ABSTRACT FROM AUTHOR]