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.

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.

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.

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.

[Prescription of morphinics in the management of pain in Dakar teaching hospitals]. / La prescription des morphiniques dans la prise en charge de la douleur dans les centres hospitalo-universitaires de Dakar.

The correct management of pain is one of the most frequent problems in a daily medical practice. To achieve this goal physicians have to use many drugs. Among these drugs morphinics represent a special category with specific rules of administration. To assess the use of morphinics in the management of pain in Dakar teaching hospitals and to determine the reasons of under or over prescription, we carried out this study A questionnaire was sent to 200 medical doctors in two teaching hospitals in Dakar between February and April 1999. The response rate was 89.5% (179). According to 73.2% of medical doctors who answered the questionnaire, pain frequently leads to consultation but surprisingly only 14 physicians (7.8%) recognize a regular use of morphinics while 70.1% of them prescribe morphinics exceptionally Morphinics are mainly used to control pain in cancerology (37.2%) and post-operative pain (21.3%). The main reasons to explain the under-use of morphinics were: the fear of respiratory side-effects of morphinics (35.3%), the ignorance of prescription rules (23.5%). The training regarding prescription of morphinics was provided during medical studies and only 10 out of the medical doctors had an adequate postgraduate training in this domain. As expected 51.4% of physicians thought that their training during medical studies was inadequate. To improve the management of pain in our country we recommend a better training of medical doctors during medical studies and the promotion of postgraduate seminars on the use of these molecules. The legislation and rules of administration must be cleared and these drugs should be more available in drugstores and hospital pharmacies. All of these modifications are necessary to help medical doctors to overcome the fear of morphinics for a better management of pain in our country.

[Economic evaluation in a trial of medically controlled prescription of narcotics to dependent users (PROVE)]. / Gesundheitsökonomische Bewertung der Versuche für eine ärztliche Verschreibung von Betäubungsmitteln (PROVE).

In the 1994-1996 trial of medically controlled prescription of narcotics to dependent users, 800 places were ascribed to heroin substitutes and another 200 for methadone and morphine substitutes. The trial was evaluated with the aid of an accompanying research. Among the results demonstrated in the evaluation was an improvement of the health of the participants. The economic assessment was drawn from observations of health effects within a sub-sample of 142 participants from four centers. In a retrospective statistical survey, for each acute illness which could be influenced through the trial, the number of diagnoses was recorded in the first and thirteenth month after study entry. Also, based on a number of representative cases for each of these acute illnesses, the resource use, i.e. the types and numbers of medical products and services rendered to the patients, was recorded. The results showed a clear decline in depressive episodes, skin diseases, digestive system disorders as well as epileptic attacks and intoxication. Treatment costs could be reduced from a total of CHF 94875.--to CHF 21,998.--/month or from CHF 22.27 to CHF 5.15/patient per day. The improvement of somatic and psychic health due to the medically controlled prescription of narcotics resulted in a benefit of CHF 17.11/person per day.

[Postoperative analgesia in France. A study of the prescribing doctor's approach]. / L'analgésie postopératoire en France. Etude sur l'attitude des médecins prescripteurs.

Every year nearly 4 million surgical procedures are carried out in France: about two thirds of the patients will suffer moderate to severe postoperative pain. Beside the obvious philosophical reasons, purely medical arguments also favour good quality postoperative pain relief. In this country, unlike the situation prevailing in many other countries, anaesthetists are in charge of postoperative pain relief. The survey reported here was carried out by questioning the usual prescribers and it reports their attitudes and practices. The results would show a rather good situation: anaesthetists seem to have an interest in the subject, and the approach looks very satisfactory but these points remain to be proved in practice. There is considerable interest in some drugs, but others are in disgrace for unclear reasons. New methods of administration are not very familiar. We may conclude from this study that a greater awareness of the problem is desirable, that general and specific scientific information should be made available, that clearly defined treatment plans should be established and evaluated regularly, and that financial resources must be envisaged.