Opioid utilization after orthopaedic trauma hospitalization among Medicaid-insured adults.

Opioids are vital to pain management and sedation after trauma-related hospitalization. However, there are many confounding clinical, social, and environmental factors that exacerbate pain, post-injury care needs, and receipt of opioid prescriptions following orthopaedic trauma. This retrospective study sought to characterize differences in opioid prescribing and dosing in a national Medicaid eligible sample from 2010-2018. The study population included adults, discharged after orthopaedic trauma hospitalization, and receiving an opioid prescription within 30 days of discharge. Patients were identified using the International Classification of Diseases (ICD-9; ICD-10) codes for inpatient diagnosis and procedure. Filled opioid prescriptions were identified from National Drug Codes and converted to morphine milligram equivalents (MME). Opioid receipt and dosage (e.g., morphine milligram equivalents [MME]) were examined as the main outcomes using regressions and analyzed by year, sex, race/ethnicity, residence rurality-urbanicity, and geographic region. The study population consisted of 86,091 injured Medicaid-enrolled adults; 35.3% received an opioid prescription within 30 days of discharge. Male patients (OR = 1.12, 95% CI: 1.07-1.18) and those between 31-50 years of age (OR = 1.15, 95% CI: 1.08-1.22) were found to have increased odds ratio of receiving an opioid within 30 days of discharge, compared to female and younger patients, respectively. Patients with disabilities (OR = 0.75, 95% CI: 0.71-0.80), prolonged hospitalizations, and both Black (OR = 0.87, 95% CI: 0.83-0.92) and Hispanic patients (OR = 0.72, 95% CI: 0.66-0.77), relative to white patients, had lower odds ratio of receiving an opioid prescription following trauma. Additionally, Black and Hispanic patients received lower prescription doses compared to white patients. Individuals hospitalized in the Southeastern United States and those between the ages of 51-65 age group were found to be prescribed lower average daily MME. There were significant variations in opioid prescribing practices by race, sex, and region. National guidelines for use of opioids and other pain management interventions in adults after trauma hospitalization may help limit practice variation and reduce implicit bias and potential harms in outpatient opioid usage.

In five wastewater treatment plants in Xinjiang, China: Removal processes for illicit drugs, their occurrence in receiving river waters, and ecological risk assessment.

Residues of illicit drugs are frequently detected in wastewater, but data on their removal efficiency by wastewater treatment plants (WWTPs) and the ecological risks to the aquatic environment are lacking in this study. The research evaluates the residues, mass load, drug removal efficiency, and risk assessment of illicit drugs in WWTPs and aquatic environments (lakes) in Xinjiang, China. Initially, the concentration (incidence) and mass load of 10 selected illicit drugs were analyzed through wastewater analysis. The detected substances included methamphetamine (METH), morphine (MOR), 3,4-methylenedioxy methamphetamine (MDMA), methadone (MTD), cocaine (COC), benzoylecgonine (BE), ketamine (KET), and codeine (COD), with concentrations ranging from 0.11 ± 0.01 ng/L (methadone) to 48.26 ± 25.05 ng/L (morphine). Notably, morphine (59.74 ± 5.82 g/day) and methamphetamine (41.81 ± 4.91 g/day) contributed significantly to the WWTPs. Next, the drug removal efficiency by different sewage treatment processes was ranked as follows: Anaerobic-Oxic (A/O) combined Membrane Bio-Reactor (MBR) treatment process > Oxidation ditch treatment process > Anaerobic-Anoxic-Oxic (A2/O) treatment process > Anaerobic-Anoxic-Oxic combined Membrane Bio-Reactor treatment process. Finally, the research reviewed the concentration and toxicity assessments of these substances in the aquatic environment (lakes). The results indicated that Lake1 presented a medium risk level concerning the impact of illicit drugs on the aquatic environment, whereas the other lakes exhibited a low risk level. As a result, it is recommended to conduct long-term monitoring and source analysis of illicit drugs, specifically in Lake1, for further investigation. In conclusion, to enhance the understanding of the effects of illicit drugs on the environment, future research should expand the list of target analytes.

Disease-Modifying Antirheumatic Drug Use and Its Effect on Long-term Opioid Use in Patients With Rheumatoid Arthritis.

BACKGROUND/OBJECTIVES: The prevalence of chronic pain is high in patients with rheumatoid arthritis (RA), increasing the risk for opioid use. The objective of this study was to assess disease-modifying antirheumatic drug (DMARD) use and its effect on long-term opioid use in patients with RA. METHODS: This cohort study included Medicare beneficiaries with diagnosis of RA who received at least 30-day consecutive prescription of opioids in 2017 (n = 23,608). The patients were grouped into non-DMARD and DMARD users, who were further subdivided into regimens set forth by the American College of Rheumatology. The outcome measured was long-term opioid use in 2018 defined as at least 90-day consecutive prescription of opioids. Dose and duration of opioid use were also assessed. A multivariable model identifying factors associated with non-DMARD use was also performed. RESULTS: Compared with non-DMARD users, the odds of long-term opioid use were significantly lower among DMARD users (odds ratio, 0.89; 95% confidence interval, 0.83-0.95). All regimens except non-tumor necrosis factor biologic + methotrexate were associated with lower odds of long-term opioid use relative to non-DMARD users. The mean total morphine milligram equivalent, morphine milligram equivalent per day, and total days of opioid use were lower among DMARD users compared with non-DMARD users. Older age, male sex, Black race, psychiatric and medical comorbidities, and not being seen by a rheumatologist were significantly associated with non-DMARD use. CONCLUSION: Disease-modifying antirheumatic drug use was associated with lower odds of long-term opioid use among RA patients with baseline opioid prescription. Factors associated with non-DMARD use represent a window of opportunity for intervention to improve pain-related quality of life in patients living with RA.

Are There Differences in Postoperative Opioid Prescribing Across Racial and Ethnic Groups? Assessment of an Academic Health System.

BACKGROUND: Previous studies have demonstrated racial disparities in opioid prescribing in emergency departments and after surgical procedures. Orthopaedic surgeons account for a large proportion of dispensed opioid prescriptions, yet there are few data investigating whether racial or ethnic disparities exist in opioid dispensing after orthopaedic procedures. QUESTIONS/PURPOSES: (1) Are Black, Hispanic or Latino, or Asian or Pacific Islander (PI) patients less likely than non-Hispanic White patients to receive an opioid prescription after an orthopaedic procedure in an academic United States health system? (2) Of the patients who do receive a postoperative opioid prescription, do Black, Hispanic or Latino, or Asian or PI patients receive a lower analgesic dose than non-Hispanic White patients when analyzed by type of procedure performed? METHODS: Between January 2017 and March 2021, 60,782 patients underwent an orthopaedic surgical procedure at one of the six Penn Medicine healthcare system hospitals. Of these patients, we considered patients who had not been prescribed an opioid within 1 year eligible for the study, resulting in 61% (36,854) of patients. A total of 40% (24,106) of patients were excluded because they did not undergo one of the top eight most-common orthopaedic procedures studied or their procedure was not performed by a Penn Medicine faculty member. Missing data consisted of 382 patients who had no race or ethnicity listed in their record or declined to provide a race or ethnicity; these patients were excluded. This left 12,366 patients for analysis. Sixty-five percent (8076) of patients identified as non-Hispanic White, 27% (3289) identified as Black, 3% (372) identified as Hispanic or Latino, 3% (318) identified as Asian or PI, and 3% (311) identified as another race ("other"). Prescription dosages were converted to total morphine milligram equivalents for analysis. Statistical differences in receipt of a postoperative opioid prescription were assessed with multivariate logistic regression models within procedure, adjusted for age, gender, and type of healthcare insurance. Kruskal-Wallis tests were used to assess for differences in the total morphine milligram equivalent dosage of the prescription, stratified by procedure. RESULTS: Almost all patients (95% [11,770 of 12,366]) received an opioid prescription. After risk adjustment, we found no differences in the odds of Black (odds ratio 0.94 [95% confidence interval 0.78 to 1.15]; p = 0.68), Hispanic or Latino (OR 0.75 [95% CI 0.47 to 1.20]; p = 0.18), Asian or PI (OR 1.00 [95% CI 0.58 to 1.74]; p = 0.96), or other-race patients (OR 1.33 [95% CI 0.72 to 2.47]; p = 0.26) receiving a postoperative opioid prescription compared with non-Hispanic White patients. There were no race or ethnicity differences in the median morphine milligram equivalent dose of postoperative opioid analgesics prescribed (p > 0.1 for all eight procedures) based on procedure. CONCLUSION: In this academic health system, we did not find any differences in opioid prescribing after common orthopaedic procedures by patient race or ethnicity. A potential explanation is the use of surgical pathways in our orthopaedic department. Formal standardized opioid prescribing guidelines may reduce variability in opioid prescribing. LEVEL OF EVIDENCE: Level III, therapeutic study.

Opioid dispensing 2008-18: a Queensland perspective.

Objective This study provides an overview of opioid dispensing in Queensland from 2008 to 2018 by recipient age, drug, oral morphine equivalent and remoteness. Methods Data were obtained from the Queensland Monitoring of Drugs of Dependence System database for 2008-18 and analysed using data from the Australian Bureau of Statistics to account for population growth. Opioid dispensing by age, drug, oral morphine equivalent and remoteness were assessed. Results The number of prescriptions for Schedule 8 opioid medicines dispensed in Queensland increased from 190 to 430 per 1000 population over the study period (2.3-fold increase). Oxycodone had the largest increase in dispensing over the study period of 3.1-fold, with tapentadol increasing rapidly since initial Pharmaceutical Benefits Scheme listing in 2013 to the third most dispensed opioid by 2018. By 2018, opioid dispensing among the oldest Queenslanders, those aged 85+ years, occurred at triple the rate for those aged 65-84 years. When adjusted to report oral morphine equivalents (OME) in milligrams (mg), there has been an increase of approximately 1.9-fold over the study period. Results were also presented by geographical area, including a heatmap and analysis by remoteness. Prescriptions dispensed per 1000 population were 416 for major cities, 551 for inner regional and 445 for outer regional, and highlight that inner and outer regional areas have higher rates of prescriptions when compared to major cities (32 and 7% higher, respectively). Conclusion This study highlights changes in opioid prescription dispensing by drug and OME, as well as the variation in dispensing rates when accounting for remoteness. Further studies to link statewide databases, and to better understand drivers for differences in dispensing by location, will provide valuable insights to further inform policy and service provision.

Liposomal Bupivacaine Versus Continuous Nerve Block: Liposomal Bupivacaine May be Non-inferior and More Cost Effective.

BACKGROUND: Regional anesthesia with adductor canal block has become the standard of care for pain management after total knee arthroplasty (TKA). We hypothesized that liposomal bupivacaine (LB) may be noninferior to continuous nerve block with a pain pump in terms of average pain scores, 30- and 90-day readmissions, and emergency department (ED) visits while reducing cost. METHODS: A retrospective chart review was performed on primary TKA patients from 2015 to 2020 by 23 orthopaedic surgeons at a single institution. The inclusion criteria was treatment with LB or a pain pump, and exclusion criteria was receipt of both anesthetics and revision surgery. A total of 2,378 patients met the inclusion criteria with 1,640 patients treated with LB and 738 treated with the pain pump. Demographic differences were not statistically significant. Primary outcomes were average pain scores, 30- and 90-day readmissions, and ED visits. Secondary outcomes were average milligram morphine equivalents per admission, hospital lengths of stay , and costs. RESULTS: There was no significant difference in pain scores on postoperative days 0, 1, 2, or 3 (P = .77, .86, 0.08, and 0.40, respectively), 30- or 90- day readmissions (P = .527 and P = .374), ED visits (P = .129 and P = .108), milligram morphine equivalents utilizations (P = .194), or average hospital LOS (P = .348). We estimated a potential cost savings of $95 per patient and $155,800 over the course of the study. CONCLUSION: LB was found to be noninferior to a pain pump, and the transition to this medication was associated with cost savings.

Perioperative Opioid Use in Anterior Cruciate Ligament Reconstruction Patients.

Anterior cruciate ligament reconstruction (ACLR) is one of the most commonly performed outpatient orthopaedic procedures, yet there is little data about perioperative opioid prescribing practices. The purposes of this study were to quantify the perioperative opioid prescriptions filled by patients who underwent ACLR and to identify factors associated with greater postoperative opioid use. Patients who underwent ACLR at a single institution between June 2015 and May 2017 were studied using a regional prescription monitoring database to identify all preoperative and postoperative outpatient opioid prescriptions up to 2 years postoperatively. The number of morphine milligram equivalents of each opioid was calculated to determine total morphine milligram equivalents (TMEs) filled preoperatively, at discharge, and refilled postoperatively. Patients who refilled an opioid prescription postoperatively were compared with those who did not. Ninety-nine of 269 (36.8%) total patients refilled an opioid prescription postoperatively. Thirty-three patients (12.3%) required a refill after 2 weeks postoperatively, and no patients refilled after 21 months postoperatively. Fifty-seven patients (21%) received an opioid prescription in the 2 years following surgery that was unrelated to their ACL reconstruction. Increased age, higher body mass index (BMI), government insurance, current or prior tobacco use history, preoperative opioid use, and greater number of medical comorbidities were significantly associated with refilling a prescription opioid. Higher BMI and government insurance were independent predictors of refilling. Higher preoperative TMEs and surgeon were independent predictor of greater refill TMEs. In the opioid-naïve subgroup of 177 patients, only higher BMI was a predictor of refilling, and only greater comorbidities was a predictor of greater refill TMEs. The results demonstrate that preoperative opioid use was associated with postoperative opioid refills and higher refill TMEs in a dose-dependent fashion. A higher percentage of patients received an opioid prescription for reasons unrelated to the ACL reconstruction than refilled a prescription after the first 2 weeks postoperatively.

Opioid Utility and Hospital Outcomes Among Inpatients Admitted With Osteoarthritis and Spine Disorders.

OBJECTIVE: The aim of the study is to evaluate opioid analgesic utilization and predictors for adverse events during hospitalization and discharge disposition among patients admitted with osteoarthritis or spine disorders. DESIGN: This is a retrospective study of 12,747 adult patients admitted to six private community hospitals from 2017 to 2020. Opioid use during hospitalization and risk factors for hospital-acquired adverse events and nonhome discharge were investigated. RESULTS: The total number of patients using opioids decreased; however, the daily morphine milligram equivalent use for patients on opioids increased from 2017 to 2020. Increased odds of nonhome discharge were associated with older age, Medicaid, Medicare insurance, and increased lengths of stay, increased body mass index, daily morphine milligram equivalent, and electrolyte replacement in the osteoarthritis group. In the spine group, older age, Black race, Medicaid, Medicare, no insurance, increased Charlson Comorbidity Index, lengths of stay, polypharmacy, and heparin use were associated with nonhome discharge. Adverse events were associated with increased age, lengths of stay, Medicare, polypharmacy, antiemetic, and benzodiazepine use in the osteoarthritis group and increased Charlson Comorbidity Index, lengths of stay, and electrolyte replacement in the spine group. CONCLUSIONS: Despite the decreasing number of patients using opioids over the years, patients on opioids had an increased daily morphine milligram equivalent over the same period.

Real-world opioid use among patients with migraine enrolled in US commercial insurance and risk factors associated with migraine progression.

BACKGROUND: Migraineurs may be categorized as having episodic migraine (EM: < 15 headache days/month) or chronic migraine (CM: ≥ 15 days/month for > 3 months with ≥ 8 days/month having features of migraine). Opioid use has been linked to progression from EM to CM. OBJECTIVE: To describe the utilization of opioid prescriptions among patients with migraine, to determine the association between opioid use and migraine progression, and to explore demographic and clinical risk factors for migraine progression. METHODS: This retrospective cohort study used Optum's deidentified Clinformatics Data Mart Database from January 2015 to December 2018. Adult patients with a migraine diagnosis and continuous health plan enrollment were included. Opioid use was measured by average daily morphine equivalent dose, also known as morphine milligram equivalent (MME). Descriptive statistics were used to summarize the opioid use by patient demographic and clinical characteristics. A Cox proportional hazards model with stepwise selection was used to determine the risk factors of new-onset CM. RESULTS: Overall, 35% of patients with migraine (27,331 of 78,134) received prescription opioids (> 0 MME/day) during the 12-month follow-up period. Higher opioid dosage was found in patients who had CM and comorbidities of interest. Compared with patients with EM, patients with CM were twice as likely to receive at least 20 MME/day (CM 3.8% vs EM 1.9%) and had a higher median opioid day supply (CM 20 vs EM 10) during follow-up. About 7% of patients with CM with at least 1 opioid prescription had at least 50 MME/day in any 90-day period during follow-up. A significant association was found between MME level and the likelihood of new-onset CM. Additional significant risk factors of migraine progression included younger age, female sex, South and West regions, and having a diagnosis of medication overuse headache, depression, back pain, or fibromyalgia (all P < 0.05). CONCLUSIONS: Despite guidelines and the availability of more migraine-specific treatments, opioids are still commonly prescribed to patients with migraines in real-world practice, especially for those with CM. In this study population, a higher risk of new-onset CM was associated with receiving higher opioid doses.

Impact of Opioid Restriction Legislation on Prescribing Practices for Outpatient Plastic and Reconstructive Surgery.

BACKGROUND: Overprescription of opioids for acute postoperative pain, plastic surgery procedures included, is contributing to the pervasive opioid epidemic in the United States. This study examines the effect of a statewide legislation limiting postoperative opioids on opioid prescription behavior among providers following outpatient plastic surgery procedures at a high-volume academic center. METHODS: Retrospective review of all outpatient surgical encounters between June 1, 2016, and November 30, 2018, was performed. Encounters were grouped into two cohorts: prepolicy and postpolicy. Primary outcomes included total oral morphine equivalents prescribed on the day of surgery and proportion of patients prescribed greater than 210 oral morphine equivalents. Secondary outcomes included proportion of patients requiring an opioid refill within 30 days following surgery, and number of refills required. RESULTS: The mean oral morphine equivalents prescribed on the day of surgery was reduced from 271.8 to 150.37 oral morphine equivalents ( p < 0.001) following implementation of the legislation, with an associated decrease in the standard deviation of oral morphine equivalents prescribed from 225.35 to 196.71 ( p < 0.001), suggesting a decrease in the variability of prescriber practices. Time series analysis demonstrated the decrease in oral morphine equivalents remained significant when accounting for baseline level of change in opioid prescription patterns. CONCLUSION: This study provides evidence that legislation at the state level restricting postoperative opioid prescriptions is associated with a decrease in opioid prescriptions without an increase in the need for refills in the acute postoperative setting following outpatient plastic surgery procedures.

Enhanced Recovery After Surgery Is Associated With Improved Outcomes and Reduced Racial and Ethnic Disparities After Isolated Coronary Artery Bypass Surgery: A Retrospective Analysis With Propensity-Score Matching.

OBJECTIVES: To evaluate whether enhanced recovery after surgery (ERAS) protocol implementation was associated with improved outcomes and decreased racial and ethnic outcome disparities after isolated coronary artery bypass graft (CABG) surgery. DESIGN: A retrospective analysis of an institutional CABG database with propensity-score matching. SETTING: At a single tertiary care teaching hospital. PARTICIPANTS: One thousand seven hundred thirty-five patients undergoing isolated CABG: 656 patients from 2016 to 2017 (pre-ERAS) and 1,079 patients from 2018 to 2020 (post-ERAS). Each patient cohort was divided into a White subgroup and a racial and ethnic minorities (Minorities) subgroup. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Propensity-matched post-ERAS patients (n = 584) compared to pre-ERAS patients (n = 584) demonstrated reductions in total length of stay (LOS) (median [interquartile range]): (7 [5-10] v 8 [6-11.5] days, p = .006), postoperative LOS (5 [4-7] v 5 [4-7] days, p = .001), total ventilation time (6.1 [4.8-9.5] v 6.6 [5.2-10.9] hours, p = .004), postoperative morphine milligram equivalents (mean ± standard deviation: 68.6 ± 57.5 v 100.0 ± 59.4, p < .001), and increased likelihood of early extubation (48.8% v 42.3%, p = .026); the Minorities subgroup demonstrated reductions in likelihood of intensive care unit (ICU) readmission (1.3% v 8.1%, p = .012) and postoperative morphine milligram equivalents (73.6 ± 64.0 v 107.8 ± 71.9, p < .001). Logistic regression models demonstrated that disparities in ICU readmission and postoperative LOS between White and Minorities patients were eliminated post-ERAS. CONCLUSIONS: ERAS for isolated CABG surgery was associated with reduced total and postoperative LOS, reduced total ventilation time, and increased early extubation for all patients, as well as reduced ICU readmission for the Minorities subgroup. ERAS implementation was associated with reduced disparities between White and racial and ethnic minority patients for ICU readmission and postoperative LOS.

Impact of Palliative Care Clinical Pharmacists in an Inpatient Care Setting on Total Health Care Expenditures.

Background: Inpatient palliative care clinical pharmacy specialists (IPCPS) on multidisciplinary palliative care (PC) teams have expanding roles in the treatment of pain, nausea, and other symptoms for patients with serious illnesses. Objectives: The aim of this study was to assess the clinical and financial outcomes associated with an IPCPS on an inpatient PC team. Setting and Design: This was a retrospective cohort study conducted in Colorado. Adult patients with an inpatient stay and a PC consult between October 1, 2016 and February 28, 2019 were included. Patients were assigned to the observation group if they received PC from a clinical pharmacist and control group if they received usual PC. The primary outcome was the 180-day change in daily total cost-of-care expenditures. Secondary outcomes included length of index hospitalization and 180-day change in daily morphine milligram equivalents (MME), health care utilization, and opioid adverse effects (AE). Results: A total of 1543 patients were included with 228 and 1315 in the IPCPS and usual care groups, respectively. After adjustment, the IPCPS group had a greater median decrease in daily expenditures (-$22 vs. $6, p = 0.003), higher median increase in daily MME (16.5 vs. 9.7 mg, p = 0.007), and fewer patients with a subsequent hospitalization (34.2% vs. 39.2%, p = 0.010) or urgent care visit (10.5% vs. 14.6%, p = 0.024) but longer mean index hospitalization (9.3 vs. 7.7 days, p = 0.003) and no differences in AE during follow-up (all p > 0.05). Conclusion: IPCPS participation on the PC team can be a component of health care cost reduction while contributing to patient-centered quality care.

Factors associated with access to palliative home care in palliative patients at Lampang Hospital.

BACKGROUND: Existing literature has shown the importance of palliative home care to improve quality of life among end-stage patients. However, access to palliative home care remains an issue. This study explores factors associated with successful delivery of palliative home care in palliative patients. METHODS: A retrospective study was conducted among patients who were referred to the palliative care team for consultation at Lampang Hospital from April 2020 to March 2021. Data from electronic medical records, including successful delivery of palliative home care, age, gender, public health insurance, admission department, primary disease (cancer, non-cancer), presenting symptoms (pain, dyspnea), palliative performance scale score and morphine use, were retrieved. Multiple logistic regression analysis was applied to explore the association, adjusting for covariates. RESULTS: A total of 370 patients were identified, with 88 (23.8%) receiving palliative home care. Results showed that being female, having low palliative performance scale score, morphine use, and having Civil Servant Medical Benefit Scheme insurance are associated with a higher chance of having access to palliative home care, compared with their counterparts. CONCLUSIONS: Results of this study pointed out health disparities among palliative patients who required palliative home care. This information can be in part used to redesign palliative home care system with the aim of improving access to care and patients' and caregivers' quality of life as a consequence.

Sex, Race, Insurance, and Pain: Do Patient Sociodemographics Influence Postoperative Opioid Prescriptions Among Hand Surgeons?

BACKGROUND: Social and demographic factors may influence patient treatment by physicians. This study analyzes the influence of patient sociodemographics on prescription practices among hand surgeons. METHODS: We performed a retrospective analysis of all hand surgeries (N = 5278) at a single academic medical center from January 2016 to September 2018. The average morphine milligram equivalent (MME) prescribed following each surgery was calculated and then classified by age, race, sex, type of insurance, and history of substance use or chronic pain. Multivariate linear regression was used to compare MME among groups. RESULTS: Overall, patients with a history of substance abuse were prescribed 31.2 MME more than those without (P < .0001), and patients with a history of chronic pain were prescribed 36.7 MME more than those without (P < .0001). After adjusting for these variables and the type of procedure performed, women were prescribed 11.2 MME less than men (P = .0048), and Hispanics were prescribed 16.6 MME more than whites (P = .0091) overall. Both Hispanic and black patients were also prescribed more than whites following carpal tunnel release (+19.0 and + 20.0 MME, respectively; P < .001). Patients with private insurance were prescribed 24.5 MME more than those with Medicare (P < .0001), but 25.0 MME less than those with Medicaid (P < .0001). There were no differences across age groups. CONCLUSIONS: Numerous sociodemographic factors influenced postoperative opioid prescription among hand surgeons at our institution. These findings highlight the importance of establishing more uniform, evidence-based guidelines for postoperative pain management, which may help minimize subjectivity and prevent the overtreatment or undertreatment of pain in certain patient populations.

Dramatic Reduction in Opioid Prescribing for Common Outpatient Orthopaedic Lower Extremity Surgical Procedures at a Louisiana University-Based Safety-Net Hospital After Enactment of Opioid-Limiting State Legislation.

INTRODUCTION: The opioid epidemic in the United States has been fueled by overprescribing opioids, which is particularly apparent in orthopaedics. Stakeholders, including state legislatures, have attempted to curb opioid overprescribing to reduce related abuse/dependence, overdose deaths, and diversion. OBJECTIVE: To examine trends in opioid prescribing for common outpatient lower extremity orthopaedic surgeries in a population vulnerable to prolonged opioid use before and after the enactment of a 2017 Louisiana state law limiting opioid prescribing for acute pain. METHODS: Eligible patients were adults who underwent one of the five most common outpatient lower extremity orthopaedic surgeries done during 2013 to 2018 at an urban tertiary care academic medical center. Excluded were prisoners and patients who required inpatient hospitalization, had no documented discharge opioid prescription, or filled an opioid prescription unrelated to their orthopaedic procedure within 30 days before surgery. RESULTS: During 2013 to 2018, 655 surgical procedures were done in 655 eligible patients, of whom 49% were Black and 54% were insured by Medicaid. The mean morphine milligram equivalent per discharge prescription decreased by almost 70% from 2014 to 2018. A statistically significant decrease in the mean morphine milligram equivalent per discharge prescription was observed in 2018 versus all previous years (P < 0.0001 for all) and in 2017 versus all previous years (P < 0.0001 for all). Patients receiving at least one new opioid prescription after their discharge prescription declined over time from a high of 50% in 2013 to a low of 19.3% in 2018 with a statistically significant effect over time (P < 0.0001). DISCUSSION: Opioid prescribing for patients undergoing common outpatient lower extremity orthopaedic surgeries who were at high risk for prolonged opioid use markedly declined after the enactment of a state law limiting first-time opioid prescriptions to 7 days, requiring physicians to check the state's Prescription Monitoring Program database and mandating continuing education for opioid prescribers.

Preclinical assessment of utility of M6S for multimodal acute and chronic pain treatment in diabetic neuropathy.

AIMS: Previous reports from our laboratory have established that morphine-6-O-sulfate (M6S) is a mixed µ/δ opioid receptor (OR) agonist and a potential improved alternative to morphine for treatment of chronic multimodal pain in non-diabetic rats. This study extends the antinociceptive effects of M6S and morphine in STZ-induced diabetic rats. MATERIALS AND METHODS: Effects of morphine and M6S were studied across a range of pain modalities, using hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold (PPT) tests. KEY FINDINGS: Acutely, M6S was 3- to 5-fold more potent and 2- to 3-fold more efficacious than morphine in HPT and PST tests. No differences in analgesic drug potency/efficacy were detected in the PPT test. After 7-9days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all three pain tests. Furthermore, morphine-tolerant rats were not cross-tolerant to M6S. The selective δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 62±3% in the HPT test, 93±5% in the PST test, and 30±17% in the PPT test when examined acutely. SIGNIFICANCE: These studies provide additional confirmation for the mixed µ/δ activity of M6S and demonstrate potential improved clinical utility for dual µ/δ agonists relative to morphine in treatment of diabetic neuropathy across multiple pain domains.

[Analysis of the accessibility of short acting oral opioids in Hungary]. / A rövid hatású, szájon át adható morfinszármazékok hazai elérhetoségének elemzése.

Short acting oral formulas make part of optimal opioid analgesia. The use of short acting oral morphine has not widely spread in Hungary, and these drugs completely lacked from the market for three years. Since December 2015 short acting morphine-sulphate has again been commercialised. The causes of the market failure are analysed in this article. The aim of the retrospective analysis is to help the accessibility of the medicine to every patient in need. Prescription morphine use depends on the harmonised cooperation of a number of actors. Besides regulating and financing authorities and professional organisations, patients and the opinion forming media are also responsible for building up the right routine.

Economical synthesis of 13C-labeled opiates, cocaine derivatives and selected urinary metabolites by derivatization of the natural products.

The illegal use of opiates and cocaine is a challenge world-wide, but some derivatives are also valuable pharmaceuticals. Reference samples of the active ingredients and their metabolites are needed both for controlling administration in the clinic and to detect drugs of abuse. Especially, (13)C-labeled compounds are useful for identification and quantification purposes by mass spectroscopic techniques, potentially increasing accuracy by minimizing ion alteration/suppression effects. Thus, the synthesis of [acetyl-(13)C4]heroin, [acetyl-(13)C4-methyl-(13)C]heroin, [acetyl-(13)C2-methyl-(13)C]6-acetylmorphine, [N-methyl-(13)C-O-metyl-(13)C]codeine and phenyl-(13)C6-labeled derivatives of cocaine, benzoylecgonine, norcocaine and cocaethylene was undertaken to provide such reference materials. The synthetic work has focused on identifying (13)C atom-efficient routes towards these derivatives. Therefore, the (13)C-labeled opiates and cocaine derivatives were made from the corresponding natural products.

Internet search and krokodil in the Russian Federation: an infoveillance study.

BACKGROUND: Krokodil is an informal term for a cheap injectable illicit drug domestically prepared from codeine-containing medication (CCM). The method of krokodil preparation may produce desomorphine as well as toxic reactants that cause extensive tissue necrosis. The first confirmed report of krokodil use in Russia took place in 2004. In 2012, reports of krokodil-related injection injuries began to appear beyond Russia in Western Europe and the United States. OBJECTIVE: This exploratory study had two main objectives: (1) to determine if Internet search patterns could detect regularities in behavioral responses to Russian CCM policy at the population level, and (2) to determine if complementary data sources could explain the regularities we observed. METHODS: First, we obtained krokodil-related search pattern data for each Russia subregion (oblast) between 2011 and 2012. Second, we analyzed several complementary data sources included krokodil-related court cases, and related search terms on both Google and Yandex to evaluate the characteristics of terms accompanying krokodil-related search queries. RESULTS: In the 6 months preceding CCM sales restrictions, 21 of Russia's 83 oblasts had search rates higher than the national average (mean) of 16.67 searches per 100,000 population for terms associated with krokodil. In the 6 months following restrictions, mean national searches dropped to 9.65 per 100,000. Further, the number of oblasts recording a higher than average search rate dropped from 30 to 16. Second, we found krokodil-related court appearances were moderately positively correlated (Spearman correlation=.506, P≤.001) with behaviors consistent with an interest in the production and use of krokodil across Russia. Finally, Google Trends and Google and Yandex related terms suggested consistent public interest in the production and use of krokodil as well as for CCM as analgesic medication during the date range covered by this study. CONCLUSIONS: Illicit drug use data are generally regarded as difficult to obtain through traditional survey methods. Our analysis suggests it is plausible that Yandex search behavior served as a proxy for patterns of krokodil production and use during the date range we investigated. More generally, this study demonstrates the application of novel methods recently used by policy makers to both monitor illicit drug use and influence drug policy decision making.

Prevalence of heroin markers in urine for pain management patients.

Surveys of current trends indicate heroin abuse is associated with nonmedical use of pain relievers. Consequently, there is an interest in evaluating the presence of heroin-specific markers in chronic pain patients who are prescribed controlled substances. A total of 926,084 urine specimens from chronic pain patients were tested for heroin/diacetylmorphine (DAM), 6-acetylmorphine (6AM), 6-acetylcodeine (6AC), codeine (COD), and morphine (MOR). Heroin and markers were analyzed using liquid chromatography tandem mass spectrometry (LC-MS-MS). Opiates were analyzed following hydrolysis using LC-MS-MS. The prevalence of heroin use was 0.31%, as 2871 were positive for one or more heroin-specific markers including DAM, 6AM, or 6AC (a known contaminant of illicit heroin). Of these, 1884 were additionally tested for the following markers of illicit drug use: 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), methamphetamine (MAMP), 11-nor-9-carboxy-Δ(9)-tetracannabinol (THCCOOH), and benzoylecgonine (BZE); 654 (34.7%) had positive findings for one or more of these analytes. The overall prevalence of heroin markers were as follows: DAM 1203 (41.9%), 6AM 2570 (89.5%), 6AC 1082 (37.7%). MOR was present in 2194 (76.4%) and absent (