Opioid-related deaths between 2019 and 2021 across 9 Canadian provinces and territories.

BACKGROUND: The drug toxicity crisis continues to accelerate across Canada, with rapid increases in opioid-related harms following the onset of the COVID-19 pandemic. We sought to describe trends in the burden of opioid-related deaths across Canada throughout the pandemic, comparing these trends by province or territory, age, and sex. METHODS: We conducted a repeated cross-sectional analysis of accidental opioid-related deaths between Jan. 1, 2019, and Dec. 31, 2021, across 9 Canadian provinces and territories using aggregated national data. Our primary measure was the burden of premature opioid-related death, measured by potential years of life lost. Our secondary measure was the proportion of all deaths attributable to opioids; we used the Cochrane-Armitage test for trend to compare proportions. RESULTS: Between 2019 and 2021, the annual number of opioid-related deaths increased from 3007 to 6222 and years of life lost increased from 126 115 to 256 336 (from 3.5 to 7.0 yr of life lost per 1000 population). In 2021, the highest number of years of life lost was among males (181 525 yr) and people aged 30-39 years (87 045 yr). In 2019, we found that 1.7% of all deaths among those younger than 85 years were related to opioids, rising to 3.2% in 2021. Significant increases in the proportion of deaths related to opioids were observed across all age groups (p < 0.001), representing 29.3% and 29.0% of deaths among people aged 20-29 and 30-39 years in 2021, respectively. INTERPRETATION: Across Canada, the burden of premature opioid-related deaths doubled between 2019 and 2021, representing more than one-quarter of deaths among younger adults. The disproportionate loss of life in this demographic group highlights the critical need for targeted prevention efforts.

Top studies of 2023 relevant to primary care: From the PEER team.

OBJECTIVE: To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians. SELECTING THE EVIDENCE: Articles were chosen and ranked by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health professionals focused on evidence-based medicine. The selection process involved routine surveillance of tables of contents in high-impact medical journals and continuous monitoring of EvidenceAlerts. Articles were prioritized based on their direct applicability to and potential to influence primary care practice. MAIN MESSAGE: Selected articles addressed various clinical areas of primary care. The topics included a comparison of a treat-to-target approach versus a high-intensity statins prescription for lipid management; semaglutide and its impact on cardiovascular outcomes; respiratory syncytial virus vaccine for older adults; chlorthalidone versus hydrochlorothiazide in preventing cardiovascular events; amitriptyline for irritable bowel syndrome; the role of opioids in acute back pain; safety of oral penicillin challenges in patients allergic to penicillin; spironolactone for facial acne; strategies to reverse frailty in older adults; and identifying the provider of chronic disease management. Two "up and coming" medications are also mentioned: retatrutide for weight loss and fezolinetant for vasomotor symptoms of menopause. CONCLUSION: Research published in 2023 yielded several high-quality articles with topics relevant to primary care, including cardiovascular care, irritable bowel syndrome, care of the elderly, and acne management.

Barriers and facilitators for family physicians prescribing opioid agonist therapy in Saskatchewan.

OBJECTIVE: To explore barriers and facilitators for family physicians in Saskatchewan prescribing opioid agonist therapy (OAT). DESIGN: Self-administered postal survey. SETTING: Family medicine practices in Saskatchewan. PARTICIPANTS: A total of 218 Saskatchewan family physicians who were not authorized to prescribe OAT as of June 2022. MAIN OUTCOME MEASURES: Descriptive and inferential statistics of physicians' self-reported barriers to and facilitators of prescribing OAT for opioid use disorder (OUD). RESULTS: Most respondents (84.8%) had some comfort with diagnosing OUD. However, more than half (58.3%) did not feel confident or knowledgeable about prescribing OAT. Barriers to OAT prescribing included lack of time, incomplete training requirements, lack of interest, insufficient funding or support, feeling overwhelmed, and perceiving that OAT does not work and thus is not necessary. Physicians working in core neighbourhoods and those receiving fee-for-service compensation reported the least available time to prescribe OAT. Conversely, physicians working in interdisciplinary team settings had increased time for OAT prescribing compared with physicians in other settings. Having a close personal relationship with someone with OUD was correlated with increased comfort in diagnosing OUD as well as with knowledge about and confidence in prescribing OAT. Themes identified as facilitators to increasing OAT prescribing included the addition of resources and supports, increased training, more awareness about OUD and OAT, enhanced compensation, and altered prescribing regulations. CONCLUSION: Despite the presence of several real and perceived barriers limiting OAT prescribing by Saskatchewan family physicians, there are family physicians interested in providing this therapy. Increased clinical resources and support, including increased interdisciplinary practice, are actionable steps that should be considered by policy decision makers to address this issue. Additionally, increased OUD and OAT education, which includes the perspectives of those with lived experience of OUD, would help address physician confidence, knowledge, and awareness in this area.

Comparing the Effectiveness of a Clinical Decision Support Tool in Reducing Pediatric Opioid Dose Calculation Errors: PediPain App vs. Traditional Calculators - A Simulation-Based Randomised Controlled Study.

Wrong dose calculation medication errors are widespread in pediatric patients mainly due to weight-based dosing. PediPain app is a clinical decision support tool that provides weight- and age- based dosages for various analgesics. We hypothesized that the use of a clinical decision support tool, the PediPain app versus pocket calculators for calculating pain medication dosages in children reduces the incidence of wrong dosage calculations and shortens the time taken for calculations. The study was a randomised controlled trial comparing the PediPain app vs. pocket calculator for performing eight weight-based calculations for opioids and other analgesics. Participants were healthcare providers routinely administering opioids and other analgesics in their practice. The primary outcome was the incidence of wrong dose calculations. Secondary outcomes were the incidence of wrong dose calculations in simple versus complex calculations; time taken to complete calculations; the occurrence of tenfold; hundredfold errors; and wrong-key presses. A total of 140 residents, fellows and nurses were recruited between June 2018 and November 2019; 70 participants were randomized to control group (pocket calculator) and 70 to the intervention group (PediPain App). After randomization two participants assigned to PediPain group completed the simulation in the control group by mistake. Analysis was by intention-to-treat (PediPain app = 68 participants, pocket calculator = 72 participants). The overall incidence of wrong dose calculation was 178/576 (30.9%) for the control and 23/544 (4.23%) for PediPain App, P < 0·001. The risk difference was - 32.8% [-38.7%, -26.9%] for complex and - 20.5% [-26.3%, -14.8%] for simple calculations. Calculations took longer within control group (median of 69 Sects. [50, 96]) compared to PediPain app group, (median 48 Sects. [38, 63]), P < 0.001. There were no differences in other secondary outcomes. A weight-based clinical decision support tool, the PediPain app reduced the incidence of wrong doses calculation. Clinical decision support tools calculating medications may be valuable instruments for reducing medication errors, especially in the pediatric population.

CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal-glial-immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

In Vitro and In Vivo Pharmacological Profiles of LENART01, a Dermorphin-Ranatensin Hybrid Peptide.

Diverse chemical and pharmacological strategies are currently being explored to minimize the unwanted side effects of currently used opioid analgesics while achieving effective pain relief. The use of multitarget ligands with activity at more than one receptor represents a promising therapeutic approach. We recently reported a bifunctional peptide-based hybrid LENART01 combining dermorphin and ranatensin pharmacophores, which displays activity to the mu-opioid receptor (MOR) and dopamine D2 receptor (D2R) in rat brains and spinal cords. In this study, we investigated the in vitro binding and functional activities to the human MOR and the in vivo pharmacology of LENART01 in mice after subcutaneous administration. In vitro binding assays showed LENART01 to bind and be selective to the human MOR over the other opioid receptor subtypes and delta, kappa and nociceptin receptors. In the [35S]GTPγS binding assay, LENART01 acted as a potent and full agonist to the human MOR. In mice, LENART01 produced dose-dependent antinociceptive effects in formalin-induced inflammatory pain, with increased potency than morphine. Antinociceptive effects were reversed by naloxone, indicating MOR activation in vivo. Behavioral studies also demonstrated LENART01's properties to induce less adverse effects without locomotor dysfunction and withdrawal syndrome compared to conventional opioid analgesics, such as morphine. LENART01 is the first peptide-based MOR-D2R ligand known to date and the first dual MOR-dopamine D2R ligand for which in vivo pharmacology is reported with antinociceptive efficacy and reduced opioid-related side effects. Our current findings may pave the way to new pain therapeutics with limited side effects in acute and chronic use.

The use of interventional procedures for cancer pain. A brief review.

CONTEXT: Pain is a common experience in people living with cancer. Concerns around opioid prescribing have seen a move toward a multi-modality management approach, which includes interventional pain procedures. PURPOSE: In this paper we discuss the interventional pain procedures used to treat cancer pain at two major tertiary centers in Australia. METHODS AND RESULTS: This expert review provides practical insights on cancer pain management from healthcare providers in different specialties. These insights can be used to guide the management of a wide range of cancer pain types. CONCLUSIONS: Furthermore, this review identifies the need for a systematic and comprehensive approach to the management of cancer pain that is broader than that of a single specialty. With recent advances in pain management procedures, an interdisciplinary approach is essential in order to provide an up to date, patient tailored approach to pain management. This review will help inform the development of a cancer pain intervention registry.

Beyond prediction: unveiling the prognostic power of µ-opioid and cannabinoid receptors, alongside immune mediators, in assessing the severity of SARS-CoV-2 infection.

BACKGROUND: This study aims to explore the potential of utilizing the expression levels of cannabinoid receptor 2 (CB2), µ-opioid receptor (MOR), MCP-1, IL-17, IFN-γ, and osteopontin as predictors for the severity of SARS-CoV-2 infection. The overarching goal is to delineate the pathogenic mechanisms associated with SARS-CoV-2. METHODS: Using quantitative Real-time PCR, we analyzed the gene expression levels of CB2 and MOR in nasopharynx specimens obtained from patients diagnosed with SARS-CoV-2 infection, with 46 individuals classified as having severe symptoms and 46 as non-severe. Additionally, we measured the circulating levels of MCP-1, IL-17, IFN-γ, and osteopontin using an ELISA assay. We examined the predictive capabilities of these variables and explored their correlations across all patient groups. RESULTS: Our results demonstrated a significant increase in MOR gene expression in the epithelium of patients with severe infection. The expression of CB2 receptor was also elevated in both male and female patients with severe symptoms. Furthermore, we observed concurrent rises in MCP-1, IL-17, IFN-γ, and osteopontin levels in patients, which were linked to disease severity. CB2, MOR, MCP-1, IL-17, IFN-γ, and osteopontin showed strong predictive abilities in distinguishing between patients with varying degrees of SARS-CoV-2 severity. Moreover, we identified a significant correlation between CB2 expression and the levels of MOR, MCP-1, osteopontin, and IFN-γ. CONCLUSIONS: These results underline the interconnected nature of molecular mediators in a sequential manner, suggesting that their overexpression may play a role in the development of SARS-CoV-2 infections.

Low-dose ketamine safely reduces acute pain in the ED with a more rapid and shorter effect than morphine.

SOURCE CITATION: Guo J, Zhao F, Bian J, et al. Low-dose ketamine versus morphine in the treatment of acute pain in the emergency department: a meta-analysis of 15 randomized controlled trials. Am J Emerg Med. 2024;76:140-149. 38071883.

Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

[Opioid-free anesthesia : Wrong track or meaningful exit from the era of opioid-based analgesia?] / Opioidfreie Anästhesie : Irrweg oder sinnvoller Ausweg aus der Ära der opioidbasierten Analgesie?

The limitations and disadvantages of opioids in anesthesia are very well known but the advantages combined with a lack of effective alternatives even now still prevents refraining from using opioids as part of an adequate pain therapy. For decades, pain research has had the declared goal of replacing opioids with new substances which have no serious side effects; however, currently this goal seems to be a long way off. Due to the media coverage of the "opioid crisis" in North America, the use of opioids for pain management is also increasingly being questioned by the patients. Measures to contain this crisis are only slowly taking effect in view of the increasing number of deaths, which is why the triggers are still being sought. The perioperative administration of opioids is not only a possible gateway to addiction and abuse but it can also cause outcome-relevant complications, such as respiratory depression, postoperative nausea and vomiting and an increase in postoperative pain. Therefore, these considerations gave rise to the idea of an opioid-free anesthesia (OFA), i.e., opioids are not administered as part of anesthesia to carry out surgical procedures. Although this idea may make sense at first glance, a rapid introduction of this concept appears to be risky as it entails significant changes for the entire anesthesiological management. Based on relatively robust data from clinical studies, this concept can now be evaluated and discussed not only emotionally but also objectively. This review article presents arguments for or against the complete avoidance of intraoperative or even perioperative opioids. The current conditions in Germany are primarily taken into account, so that the perioperative pain therapy is transferable to the established standards. The results from current clinical studies on the implementation of an opioid-free anesthesia are summarized and discussed.

Substance use patterns, quantities, and associated risk factors in women with polysubstance misuse.

Polysubstance use (PSU), the use of two or more substances proximally, is highly prevalent and has amplified the risk for morbidity and mortality. However, PSU patterns and associated risk factors are not well characterized. This may be especially relevant to women who are known to be vulnerable to stress/trauma, craving, pain, and anxious and depressive symptoms as associated risk factors for PSU. A cross-sectional observational study was conducted to characterize substance use patterns in women who regularly used cocaine, opioids, marijuana, alcohol, benzodiazepines and/or nicotine and were being assessed for a placebo-controlled study of guanfacine treatment (n = 94; ages 19-65). Data on stress/traumatic life events, drug cravings for each substance, pain ratings, and anxiety and depressive symptoms were also obtained using standardized well-validated surveys. High use per day of two or more drugs was observed (72.7% ± 33.3%) and opioid amounts were high relative to other drug amounts (p's < 0.001). Notably, higher stress/trauma events and higher cravings are each associated with cumulative PSU days, amounts and probability of an individual PSU day (p's < 0.02). This remained when PSU versus single substance use was compared. Pain, anxiety and depressive symptoms were not associated with PSU metrics. These findings characterize specific patterns of PSU in women and show that average drug craving and stress/trauma events are associated with PSU. Interventions that focus on stress/trauma and craving management could be of benefit in reducing PSU risk in women.

Prescribing Benzodiazepines and Opioids and Clinical Characteristics Associated With 30-Day Hospital Return in Patients Aged ≥75 Years: Secondary Data Analysis.

PURPOSE: The current study compared prevalence of opioid or benzodiazepine (BZD) prescription and co-prescription of opioids and BZD at discharge and return to a community hospital within 30 days, as well as identified clinical characteristics associated with hospital return in patients aged ≥75 years. METHOD: A secondary analysis of a database created during implementation of the Safe Transitions for At Risk Patients program at a 400-bed community teaching hospital in south Florida was conducted. Multivariable logistic regression analyses were performed to identify significant demographic and clinical characteristics associated with return to the hospital within 30 days of discharge. RESULTS: A total of 24,262 participants (52.6% women) with a mean age of 85.3 (SD = 6.42) years were included. More than 20% in each central nervous system prescription group (i.e., opioids only, BZD only, opioids and BZD) returned to the hospital within 30 days of discharge. Demographic and chronic conditions (e.g., congestive heart failure, chronic obstructive pulmonary disease, diabetes) and poly-pharmacy were significant factors of a 30-day return to the hospital. CONCLUSION: Findings highlight the importance of hospital nurses' role in identifying high-risk patients, educating patients and caregivers, monitoring them closely, communicating with primary care physicians and specialists, and conducting intensive follow up via telephone to avoid 30-day rehospitalization. [Journal of Gerontological Nursing, 50(4), 25-33.].

National Trends and Predictors of Opioid Administration in Patients Presenting With Abdominal Pain to the Emergency Department (2010-2018).

Given the current opioid crisis, in this study, we assess the national trend and factors associated with opioid administration for patients presenting to the emergency department with abdominal pain. This is a retrospective cross-sectional study conducted using the National Hospital Ambulatory Medical Care Survey from 2010 to 2018. Weighted multiple logistic regression was applied to assess the independent factors associated with opioid administration in the emergency department. Trends of opioid administration were evaluated using the linear trend analysis. There were an estimated total of 100,925,982 emergency department visits for abdominal pain. Overall, opioid was administered in 16.8% of visits. Age less than 25 years was associated with lower odds of receiving opioids. Patients living in the Northeast had the lower odds of receiving opioids (odds ratio [OR] = 0.82, p = .006) than patients living in the Midwest. Patients in the West had the highest odds of receiving opioids (OR = 1.16, p = .01). Non-Hispanic White patients had higher odds of opioid administration (OR = 1.29, p < .001). Trend analysis demonstrated a statistically significant reduction in opioid administration. From 2010 to 2018, opioid administration has approximately decreased in half. Living in the West and the non-Hispanic White racial group were the significant factors associated with a higher risk of opioid administration.

Challenges of acute pain management in older patients.

Adequate management of acute pain in the older population is crucial. However, it is inherently complex because of multiple physiological changes that significantly impact both the pharmacokinetics and pharmacodynamics of medications. Current guidelines promote paracetamol as the first-line analgesic for acute pain in older adults, whereas opioids are advised cautiously for moderate to severe acute pain. However, opioids come with a significant array of side effects, which can be more pronounced in older individuals. Ketamine administered via intranasal (IN) and nebulised inhalation in the emergency department for managing acute pain in older patients shows promising potential for improving pain management and reducing opioid reliance Kampan, Thong-on, Sri-on (2024, Age Ageing, 53, afad255). Nebulised ketamine appears superior in terms of adverse event incidence. However, the adoption of IN or nebulised ketamine in older adult acute pain management remains unclear because of the lack of definitive conclusions and clear guidelines. Nevertheless, these modalities can be valuable options for patients where opioid analgesics are contraindicated or when intravenous morphine titration is impractical or contraindicated. Here, we review these concepts, the latest evidence and propose avenues for research.

Evaluation of erector spinae plane block in patients undergoing percutaneous nephrolithotomy in terms of postoperative pain reduction and patient satisfaction.

OBJECTIVES: Intravenous opioids and local anesthetic infiltrations are traditionally used to relieve postoperative pain. With developments in the field of regional anesthesia, several methods are now available for postoperative analgesia. This study aimed to investigate the efficacy of the erector spinae plane block (ESPB) in reducing both intraoperative opioid consumption and postoperative analgesic use in patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: A total of 60 patients who underwent PCNL were divided into two groups: 30 patients who received ESPB (Group I) and 30 patients in the control group (Group II). Intraoperative and postoperative opioid usage were recorded for both groups. The pain levels of the patients were evaluated using visual analog scale (VAS) scores obtained at 1, 3, 6, 12, and 24 hours postoperatively. Postoperative satisfaction of the patients in both groups was also questioned and compared. RESULTS: A significant difference was detected between Group I and Group II patients in terms of intraoperative opioid require-ments (p=0.00), analgesic requirements in the first 24 hours postoperatively (p=0.00), patient satisfaction status (p=0.00), and VAS scores obtained at 0, 3, 6, and 12 hours postoperatively. No significant difference was found in VAS scores at the 24th postoperative hour. CONCLUSION: ESPB is a simple, convenient technique that can be performed under ultrasound guidance. It provides remarkable postoperative analgesia and satisfaction in patients undergoing PCNL.

Effect of Intraoperative infusion Magnesium Sulfate Infusion on Postoperative Quality of Recovery in Patients Undergoing Total Knee Arthroplasty: A Prospective, Double-Blind, Randomized Controlled Trial.

Background: Magnesium sulfate, an intravenous adjuvant, has recently attracted immense attention in multimodal analgesia. Previous studies confirmed the crucial role of magnesium sulfate in postoperative pain and nociceptive hypersensitivity. However, the effect of magnesium sulfate in multimodal analgesia on the quality of recovery (QoR) for elderly patients has not been thoroughly studied. Therefore, the present experiment aimed to investigate the effect of continuous intravenous magnesium sulfate on the quality of postoperative recovery in elderly patients undergoing total knee arthroplasty (TKA). Patients and Methods: In this study, a total of 148 patients scheduled to undergo unilateral total knee arthroplasty were randomized into a magnesium sulfate group (Group M, n=68) and a control group (Group C, n=66) using a double-blind, randomized controlled trial. Before induction of anesthesia, Group M received intravenous magnesium sulfate (40 mg/kg) for 15 min, followed by a continuous infusion (15 mg/kg) until the end of the procedure. In the same manner, Group C received an infusion of the same amount of isotonic saline using the same method as the Group M. Results: Compared with Group C, Group M had significantly better QoR-15 scores on postoperative day 1(POD1) than Group C (P <0.05). Analysis of the dimensions of QoR-15 scores indicated that Group M exhibited notably reduced levels of pain, and higher levels of emotional state and physical comfort than Group C (P <0.05). Furthermore, Group C had significantly higher numerical rating scale (NRS) scores at POD1 than Group M (P <0.05). Conclusion: For elderly patients undergoing knee arthroplasty, magnesium sulfate can be used as an adjuvant in a multimodal analgesic regimen to reduce early postoperative pain and improve the quality of early postoperative recovery.

Development of Opioid Use Disorder After Breast Reconstruction: Effects of Nicotine Exposure.

INTRODUCTION: After undergoing breast reconstructive surgery, patients are typically prescribed opioids. Smoking tobacco increases rate of opioid metabolism and is associated with development of opioid use disorder (OUD). The aim of this study was to determine whether patients who smoke have an increased risk of OUD after breast reconstructive surgery. Given that OUD is a known risk factor for injection drug use and intravenous drug use increases risk of acquiring blood-borne diseases including human immunodeficiency virus (HIV) and hepatitis, the secondary aim was to determine if these patients are also at increased risk of acquiring these communicable diseases associated with OUD. METHODS: A retrospective analysis was conducted using TriNetX, a multi-institutional deidentified database. Individuals included underwent a breast reconstructive surgery and received postoperative opioid treatment. The exposed group included patients who smoke. The control group did not smoke. Risk of developing OUD, hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV from 12 to 36 months after surgery was compared between groups. Patients with preexisting OUD or associated diseases were excluded. Cohorts were matched to control for confounding factors including age, sex, race, mental health history, and concomitant substance use. RESULTS: There were 8648 patients included in the analysis. After matching, 4324 patients comprised the exposure group, and 4324 patients remained in the control group. Preoperative smoking was significantly associated with increased risk of OUD at 12, 24, and 36 months after breast reconstruction (36 months: odds ratio [OR], 2.722; confidence interval [CI], 2.268-6.375). Smoking was also associated with increased risk of HIV and HCV at all time points after surgery (36 months HIV: OR, 2.614; CI, 1.977-3.458; 36 months HCV: OR, 3.718; CI, 2.268-6.375) and increased risk of HBV beginning at 24 months after surgery (36 months HBV: OR, 2.722; CI, 1.502-4.935). CONCLUSIONS: Individuals who smoke have an increased risk of developing OUD, HIV, HCV, and HBV after breast reconstructive surgery. This risk persists for at least 3 years after surgery. Additional research and clinical interventions focusing on early identification of OUD, prevention efforts, and harm reduction strategies for patients who smoke or have nicotine dependence undergoing breast reconstruction are warranted.