Implementing a pragmatic clinical trial to tailor opioids for acute pain on behalf of the IGNITE ADOPT PGx investigators.

Opioid prescribing for postoperative pain management is challenging because of inter-patient variability in opioid response and concern about opioid addiction. Tramadol, hydrocodone, and codeine depend on the cytochrome P450 2D6 (CYP2D6) enzyme for formation of highly potent metabolites. Individuals with reduced or absent CYP2D6 activity (i.e., intermediate metabolizers [IMs] or poor metabolizers [PMs], respectively) have lower concentrations of potent opioid metabolites and potentially inadequate pain control. The primary objective of this prospective, multicenter, randomized pragmatic trial is to determine the effect of postoperative CYP2D6-guided opioid prescribing on pain control and opioid usage. Up to 2020 participants, age ≥8 years, scheduled to undergo a surgical procedure will be enrolled and randomized to immediate pharmacogenetic testing with clinical decision support (CDS) for CYP2D6 phenotype-guided postoperative pain management (intervention arm) or delayed testing without CDS (control arm). CDS is provided through medical record alerts and/or a pharmacist consult note. For IMs and PM in the intervention arm, CDS includes recommendations to avoid hydrocodone, tramadol, and codeine. Patient-reported pain-related outcomes are collected 10 days and 1, 3, and 6 months after surgery. The primary outcome, a composite of pain intensity and opioid usage at 10 days postsurgery, will be compared in the subgroup of IMs and PMs in the intervention (n = 152) versus the control (n = 152) arm. Secondary end points include prescription pain medication misuse scores and opioid persistence at 6 months. This trial will provide data on the clinical utility of CYP2D6 phenotype-guided opioid selection for improving postoperative pain control and reducing opioid-related risks.

Urban scaling of opioid analgesic sales in the United States.

Opioid misuse is a public health crisis in the United States. The origin of this crisis is associated with a sharp increase in opioid analgesic prescribing. We used the urban scaling framework to analyze opioid prescribing patterns in US commuting zones (CZs), i.e., groups of counties based on commuting patterns. The urban scaling framework postulates that a set of scaling relations can be used to predict health outcomes and behaviors in cities. We used data from the Drug Enforcement Administration's Automated Reports and Consolidated Ordering System (ARCOS) to calculate counts of oxycodone/hydrocodone pills distributed to 607 CZs in the continental US from 2006 to 2014. We estimated the scaling coefficient of opioid pill counts by regressing log(pills) on log(population) using a piecewise linear spline with a single knot at 82,363. Our results show that CZs with populations below the knot scaled superlinearly (ß = 1.36), i.e., larger CZs had disproportionally larger pill counts compared to smaller CZs. On the other hand, CZs with populations above the knot scaled sublinearly (ß = 0.92), i.e., larger CZs had disproportionally smaller pill counts compared to smaller CZs. This dual scaling pattern was consistent across US census regions. For CZs with population below the knot, the superlinear scaling of pills is consistent with the explanation that an increased number of successful matches between prescribers and users will lead to higher prescribing rates. The non-linear scaling behavior observed could be the result of a combination of factors, including stronger health care systems and prescribing regulation in largely populated commuting zones, as well as high availability of other opioids such as heroin in these commuting zones. Future research should explore potential mechanisms for the non-linearity of prescription opioid pills.

Patient-Centered Decision-making for Postoperative Narcotic-Free Endocrine Surgery: A Randomized Clinical Trial.

Importance: Historically, opioid pain medications have been overprescribed following thyroid and parathyroid surgery. Many narcotic prescriptions are incompletely consumed, creating waste and opportunities for abuse. Objective: To determine whether limiting opioid prescriptions after outpatient thyroid and parathyroid surgery to patients who opt in to narcotic treatment reduces opioid consumption without increasing postoperative pain compared with usual care (routine narcotic prescriptions). Design, Setting, and Participants: A randomized clinical trial of Postoperative Opt-In Narcotic Treatment (POINT) or routine narcotic prescription (control) was conducted at a single tertiary referral center from June 1 to December 30, 2020. A total of 180 adults undergoing ambulatory cervical endocrine surgery, excluding patients currently receiving opioids, were assessed for eligibility. POINT patients received perioperative pain management counseling and were prescribed opioids only on patient request. Patients reported pain scores (0-10) and medication use through 7 daily postoperative surveys. Logistic regression was used to determine factors associated with opioid consumption. Interventions: Patients in the POINT group were able to opt in or out of receiving prescriptions for opioid pain medication on discharge. Control patients received routine opioid prescriptions on discharge. Main Outcomes and Measures: Daily peak pain score through postoperative day 7 was the primary outcome. Noninferiority was defined as a difference less than 2 on an 11-point numeric rating scale from 0 to 10. Analysis was conducted on the evaluable population. Results: Of the 180 patients assessed for eligibility, the final study cohort comprised 102 patients: 48 randomized to POINT and 54 to control. Of these, 79 patients (77.5%) were women and median age was 52 (interquartile range, 43-62) years. A total of 550 opioid tablets were prescribed to the control group, and 230 tablets were prescribed to the POINT group, in which 23 patients (47.9%) opted in for an opioid prescription. None who opted out subsequently required rescue opioids. In the first postoperative week, 17 POINT patients (35.4% of survey responders in the POINT group) reported consuming opioids compared with 27 (50.0%) control patients (P = .16). Median peak outpatient pain scores were 6 (interquartile range, 4-8) in the control group vs 6 (interquartile range, 5-7) in the POINT group (P = .71). In multivariate analysis, patients with a history of narcotic use were 7.5 times more likely to opt in (95% CI, 1.61-50.11; P = .02) and 4.8 times more likely to consume opioids (95% CI, 1.04-1.52; P = .01). Higher body mass index (odds ratio, 1.11; 95% CI, 1.01-1.23; P = .03) and highest inpatient postoperative pain score (odds ratio, 1.24; 95% CI, 1.04-1.52; P = .02) were also associated with opioid consumption. Conclusions and Relevance: In this trial, an opt-in strategy for postoperative narcotics reduced opioid prescription without increasing pain after cervical endocrine surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04710069.

Pre-exposure of adolescent mice to morphine results in stronger sensitization and reinstatement of conditioned place preference than pre-exposure to hydrocodone.

BACKGROUND: Opioids are commonly prescribed to treat moderate-to-severe pain. However, their use can trigger the development of opioid use disorder. A major problem in treating opioid use disorder remains the high rate of relapse. AIM: The purpose of this study was to determine whether there are differences among opioids in their ability to trigger relapse after pre-exposure during adolescence. METHODS: On postnatal day 33, mice were examined for the acute locomotor response to saline, morphine, or hydrocodone (5 mg/kg). They were administered with the corresponding opioid or saline during postnatal days 34-38 (20 mg/kg) and 40-44 (40 mg/kg). On postnatal day 45, they were recorded for the development of locomotor sensitization (5 mg/kg). Starting on postnatal day 55, mice were examined for the acquisition (1, 5, 10, 20, and 40 mg/kg), extinction, and drug-induced reinstatement (1, 2.5, and 5 mg/kg) of conditioned place preference. RESULTS: There were no significant differences in the acute locomotor response to morphine and hydrocodone. Morphine induced significantly stronger locomotor sensitization as compared to hydrocodone. Pre-exposure to morphine, but not hydrocodone, sensitized the acquisition of conditioned place preference. There were no significant differences in extinction rates. Mice pre-exposed to morphine reinstate conditioned place preference after priming with a 1 mg/kg dose. In contrast, higher priming doses were required for reinstatement in all other experimental groups. CONCLUSIONS: Adolescent mice administered with morphine develop greater sensitization to its effects and subsequently reinstate conditioned place preference more readily than mice administered with hydrocodone. This suggests higher risk for relapse after pre-exposure to morphine during adolescence as compared to hydrocodone.

Prospective Study of Acute Opioid Use After Adolescent Anterior Cruciate Ligament Reconstruction Shows No Effect From Patient- or Surgical-Related Factors.

INTRODUCTION: Patient-reported pain scores and opioid use have not been quantified after outpatient adolescent anterior cruciate ligament reconstruction (ACLR). METHODS: Patients aged 12 to 18 years undergoing primary isolated ACLR, with or without meniscal treatment, were prospectively recruited. Patients actively taking opioids or with previous extended use of opioids were excluded. Two orthopaedic surgeons performed ACLR and determined the use of a hamstring or bone-patellar tendon-bone autograft. For postoperative pain management, patients were prescribed 40 tablets of hydrocodone/acetaminophen 5/325 mg. Patients were instructed to document daily pill consumption and side effects through a daily log for 6 weeks. Patients completed the American Pain Society Patient Outcome Questionnaire at the end of weeks 1 and 6. RESULTS: One hundred three patients were enrolled, with age: 12.5 to 18.9 years (mean 16.2 y ± 1.3), weight: 41.3 to 113.6 kg (mean 72.4 kg ± 17.2), and body mass index: 17.8 to 40.1 (mean 25.9 ± 4.9). Sixty-nine patients received a hamstring autograft, and 34 received a bone-patellar tendon-bone autograft. Fifty-six received additional meniscal procedures. The median number of postoperative opioids taken by patients was 17 (range 0 to 40). No notable differences were found in total pill consumption with regard to age, weight, body mass index, sex, block type, autograft type, or meniscal treatment at 1 week post-op or 6 weeks post-op. No correlation was found between the self-reported "worst pain in the past 24 hours" at the end of the first postoperative week or after 6 weeks (r = 0.112, P = 0.26, and r = 0.093, P = 0.36). No correlation was found between the level of satisfaction with pain treatment and total number of pills taken during the first postoperative week or at the end of 6 weeks (r = -0.090, P = 0.37, and r = -0.172, P = 0.08). CONCLUSION: Patients take most pain medication during the first postoperative week after adolescent ACLR, although patient and surgical variables had no notable influence on pill consumption. LEVEL OF EVIDENCE: Level IV, case series.

Drug Enforcement Agency 2014 Hydrocodone Rescheduling Rule and Opioid Dispensing after Surgery.

BACKGROUND: In 2014, the U.S. Drug Enforcement Agency reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in new restrictions on refills. The authors hypothesized that hydrocodone rescheduling led to decreases in total opioid dispensing within 30 days of surgery and reduced new long-term opioid dispensing among surgical patients. METHODS: The authors studied privately insured, opioid-naïve adults undergoing 10 general or orthopedic surgeries between 2011 and 2015. The authors conducted a differences-in-differences analysis that compared overall opioid dispensing before versus after the rescheduling rule for patients treated by surgeons who frequently prescribed hydrocodone before rescheduling (i.e., patients who were functionally exposed to rescheduling's impact) while adjusting for secular trends via a comparison group of patients treated by surgeons who rarely prescribed hydrocodone (i.e., unexposed patients). The primary outcome was any filled opioid prescription between 90 and 180 days after surgery; secondary outcomes included the 30-day refill rate and the amount of opioids dispensed initially and at 30 days postoperatively. RESULTS: The sample included 65,136 patients. The percentage of patients filling a prescription beyond 90 days was similar after versus before rescheduling (absolute risk difference, -1.1%; 95% CI, -2.3% to 0.1%; P = 0.084). The authors estimated the rescheduling rule to be associated with a 45.4-mg oral morphine equivalent increase (difference-in-differences estimate; 95% CI, 34.2-56.7 mg; P < 0.001) in initial opioid dispensing, a 4.1% absolute decrease (95% CI, -5.5% to -2.7%; P < 0.001) in refills within 30 days, and a 37.7-mg oral morphine equivalent increase (95% CI, 20.6-54.8 mg; P = 0.008) in opioids dispensed within 30 days. CONCLUSIONS: Among patients treated by surgeons who frequently prescribed hydrocodone before the Drug Enforcement Agency 2014 hydrocodone rescheduling rule, rescheduling did not impact long-term opioid receipt, although it was associated with an increase in opioid dispensing within 30 days of surgery.

Assessment of the Utility of the Oral Fluid and Plasma Proteomes for Hydrocodone Exposure.

INTRODUCTION: Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in 20 subjects. METHODS: The global proteomic profile was determined for samples taken at four time points per subject: pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between baseline and response time points than was observed with blood plasma, at least partially due to significant person-to-person relative variability in the plasma proteome. RESULTS: A total of 399 proteins were identified from oral fluid samples, and the abundance of 118 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hours). CONCLUSIONS: We present an assessment of the oral fluid and plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a noninvasive sample that may reveal features of hydrocodone in opioid use, and with additional study, may be useful for other opioids and in settings of misuse.

Implementation of a Quality Improvement Initiative to Decrease Opioid Prescribing in General Surgery.

BACKGROUND: There is increasing need to avoid excess opioid prescribing after surgery. We prospectively assessed overprescription in our hospital system and used these data to design a quality improvement intervention to reduce overprescription. MATERIALS AND METHODS: Beginning in January 2017, an e-mail-based survey to assess the quantity of opioids used postoperatively as well as patient-reported pain control was sent to all surgical patients in a 23-hospital system. In January 2018, as a quality improvement initiative, guidelines were given to surgeons based on patient consumption data. Prescription and consumption were then tracked prospectively. Wilcoxon signed-rank, analysis of variance, and Cuzick trend tests were used to assess for overprescription and changes over time in opioid prescribing and consumption. RESULTS: We included 2239 patients in our cohort. The amount prescribed (median [IQR]: 30 [24-45] versus 18 [12-30], P < 0.001) and consumed (median [IQR]: 12 [7-20] versus 8 [3-15], P < 0.001) each decreased between the first and last quarter studied. Academic hospitals prescribed fewer opioids than nonacademic hospitals (median [IQR]: 24[15-40] versus median [IQR]: 30 [20-45], P < 0.001). There was no difference in the quantity of opioids consumed between patients treated at academic and nonacademic facilities (median [IQR]: 10[3-19] versus 10.5 [4-20], P = 0.08). Patients consumed a median of 42% of the opioids prescribed, and there was no significant trend in the percent consumed over time (P = 0.8). CONCLUSIONS: Patients used far fewer opioids than prescribed after common adult general surgery procedures. When surgeons were provided with patient consumption data, the number of opioids prescribed decreased significantly.

Opioid Prescribing Among Adults With Disabilities in the United States After the 2014 Federal Hydrocodone Rescheduling Regulation.

OBJECTIVES: Deaths from prescription opioid overdoses have reached an epidemic level in the United States, particularly among persons with disabilities. The 2014 federal rescheduling regulation is associated with reduced opioid prescribing in the general US population; however, to date, no data have been published on this regulation's effect on persons with disabilities. We examined whether the 2014 hydrocodone rescheduling change was associated with reduced opioid prescribing among adult Medicare beneficiaries with disabilities. METHODS: We identified 680 876 Medicare beneficiaries with disabilities aged 21-64 in 2013 and 657 687 in 2015 from a 20% national sample. We examined changes in the monthly opioid-prescribing rates from January 1, 2013, through December 31, 2015. We also compared opioid-prescribing rates in 2013 with rates in 2015. RESULTS: In 2014, the percentage of Medicare beneficiaries with disabilities who received hydrocodone prescriptions decreased by 0.154% per month (95% confidence interval [CI], -0.186 to -0.121, P < .001). The percentage of Medicare beneficiaries with disabilities who received hydrocodone prescriptions decreased from 32.2% in 2013 to 27.7% in 2015, whereas rates of any opioid prescribing, prolonged prescribing (≥90-day supply), and high-dose prescribing (≥100 morphine milligram equivalents per day for >30 days) decreased only modestly, from 50.2% to 49.0%, from 27.4% to 26.5%, and from 7.5% to 7.0%, respectively. CONCLUSIONS: The 2014 federal rescheduling of hydrocodone was associated with only minor changes in overall and potentially high-risk opioid-prescribing rates. Neither state variation in long-term prescribing nor beneficiary characteristics explained the changes in persistently high opioid-prescribing rates among adults with disabilities after the 2014 regulation. Future studies should examine patient and provider characteristics underlying the persistent high-risk prescribing patterns in this population.

Long-term use of hydrocodone vs. oxycodone in primary care.

BACKGROUND: Hydrocodone and oxycodone are the Schedule II opioids most often prescribed in primary care. Notwithstanding the dangers of prescription opioid use, the likelihood of long-term use with either drug is presently unknown. METHODS: Using a retrospective cohort design and data from a commerical healthcare claims repository, we compared the likelihood of long-term use of hydrocodone and oxycodone in primary care patients presenting with acute back pain. Treatment was categorized as long-term if the prescription dates spanned ≥90 days from initial prescription to the run-out date of the last prescription, and included ≥120 days' supply or ≥10 fills. Instrumental variable methods and probit regression were used to model the effect of drug choice on long-term use, estimate the average treatment effect, and correct for confounding by indication. RESULTS: A total of 3,983 patients who were prescribed only hydrocodone or only oxycodone were followed for 270 days in 2016. Long-term opioid use was observed in 320 patients (8%). Controlling for potential confounders including morphine milligram equivalents and dosage, an estimated 12% (95 CI, 10%-14%) treated with hydrocodone transitioned to long-term use vs. 2% (95 CI, 1%-3%) on oxycodone. Among patients who received more than one prescription (n = 1,866), an estimated 23% (95 CI, 19%-26%) treated with hydrocodone transitioned to long-term use vs. 5% (95 CI, 3%-7%) on oxycodone. The difference between drugs was supported in sensitivity and subgroup analyses. Sample selection bias was not detected. CONCLUSIONS: Long-term use was substantially greater for patients treated with hydrocodone than oxycodone, despite equianalgesia.

Drug Enforcement Administration Rescheduling of Hydrocodone Combination Products Is Associated With Changes in Physician Pain Management Prescribing Preferences.

Due to rising misuse, the Drug Enforcement Administration (DEA) moved hydrocodone combination products (HCPs) from DEA Schedule III to DEA Schedule II in October 2014. Aside from increasing regulatory scrutiny, rescheduling may have increased the administrative burden surrounding HCP prescribing. This study explored how HCP rescheduling and associated administrative barriers may have affected physician treatment of acute (aNCP) and chronic (cNCP) noncancer pain. To this end, physician members of the Texas Medical Association completed a self-administered online questionnaire. Pharmacotherapy treatment plan was measured with two questions asking physicians whether they were more likely to recommend HCPs, acetaminophen/codeine (APAP/codeine), nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, or other agents for the treatment of aNCP and cNCP. Two Likert-scaled items were used to assess administrative burden. In total, 1365 physicians responded (response rate = 15.39%). Physicians more frequently selected APAP/codeine (37%) for aNCP and tramadol (44%) for cNCP. A majority (78.8%) of physicians agreed that rescheduling led to modified prescribing, and those in agreement were significantly less likely than those who disagreed to prescribe HCPs for aNCP (24.2% vs. 56.4%; χ2 = 68.6, P < .001) and cNCP (16.9% vs. 37%; χ2 = 36.1, P < .001). Rescheduling and associated administrative burden are both associated with modified physician HCP prescribing in both aNCP and cNCP.

Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose.

OBJECTIVE: Data regarding opioid effects on esophageal function are limited. We previously demonstrated an association between chronic opioid use and esophageal motor dysfunction characterized by esophagogastric junction outflow obstruction, distal esophageal spasm, achalasia type III, and possibly Jackhammer esophagus. Our aim was to characterize the influence of different opioids and doses on esophageal dysfunction. METHODS: Retrospective review of 225 patients prescribed oxycodone, hydrocodone, or tramadol for >3 months, who completed high-resolution manometry from 2012 to 2017. Demographic and manometric data were extracted from a prospectively maintained motility database. Frequency of opioid-induced esophageal dysfunction (OIED, defined as distal esophageal spasm, esophagogastric junction outflow obstruction, achalasia type III, or Jackhammer esophagus on high-resolution manometry, was compared among different opioids. The total 24-hour opioid doses for oxycodone, hydrocodone, and tramadol were converted to a morphine equivalent for dose effect analysis. RESULTS: OIED was present in 24% (55 of 225) of opioid users. OIED was significantly more prevalent with oxycodone or hydrocodone use compared with tramadol (31% vs 28% vs 12%, P = 0.0162), and for oxycodone alone vs oxycodone with acetaminophen (43% vs 21%, P = 0.0482). There was no difference in OIED for patients taking hydrocodone alone vs hydrocodone with acetaminophen. Patients with OIED were taking a higher median 24-hour opioid dose than those without OIED (45 vs 30 mg, P = 0.058). DISCUSSION: OIED is more prevalent in patients taking oxycodone or hydrocodone compared with tramadol. There is greater likelihood of OIED developing with higher doses. Reducing the opioid dose or changing to tramadol may reduce OIED in opioid users.

Race and ethnicity: Not factors in the prescribing of hydrocodone and codeine-containing products in two pediatric emergency departments.

OBJECTIVE: To describe the prescription of hydrocodone-containing products (HCPs) and codeine-containing products (CCPs) by patient and provider race and ethnicity at two pediatric emergency departments (EDs) before and after the US Drug Enforcement Administration (DEA) rescheduling of HCPs in 2014. DESIGN AND SETTING: The authors performed a secondary analysis of data describing the prescription of HCPs and CCPs for 6 months before and after the DEA rescheduling of HCPs in two academic, urban pediatric EDs. PATIENTS, PARTICIPANTS: The authors included all children for whom race and ethnicity data were available and who were prescribed HCPs or CCPs at the time of discharge from the ED during a 12-month period (n = 1,246). The authors sent a three-question survey soliciting name, race, and ethnicity to all providers who prescribed an HCP or a CCP during the study period. MAIN OUTCOME MEASURES: Chi-square comparisons were made between the number of HCP and CCP prescriptions for primary ED diagnosis and patient ethnicity or race. The number of HCP and CCP prescriptions before and after the DEA rescheduling were compared to patient and provider race and ethnicity using the Breslow-Day test for homogeneity. RESULTS: There were no significant differences in the number of HCP and CCP prescriptions between the pre- and post-DEA rescheduling periods across all racial and ethnic groups. When comparing the number of HCP and CCP prescriptions to patient race, Caucasian patients (84.4 percent) were prescribed more HCPs and CCPs than African Americans (15.6 percent) for abdominal pain (p value = 0.02). Non-Hispanic providers prescribed CCPs more often (n = 38, 55.2 percent) than Hispanic providers (n = 0, 0.0 percent) after DEA rescheduling (Breslow-Day p value = 0.01). Providers of all races wrote similar numbers of HCP and CCP prescriptions before and after the DEA rescheduling (Breslow-Day p value = 0.99). CONCLUSIONS: Pediatric patients of all races and ethnicities received fewer HCP prescriptions after the 2014 DEA rescheduling of HCPs. However, Caucasian patients were prescribed HCPs and CCPs for abdominal pain more frequently than African American patients. There were no significant differences in the number of prescriptions of HCPs and CCPs by provider race.

Predicting inadequate postoperative pain management in depressed patients: A machine learning approach.

Widely-prescribed prodrug opioids (e.g., hydrocodone) require conversion by liver enzyme CYP-2D6 to exert their analgesic effects. The most commonly prescribed antidepressant, selective serotonin reuptake inhibitors (SSRIs), inhibits CYP-2D6 activity and therefore may reduce the effectiveness of prodrug opioids. We used a machine learning approach to identify patients prescribed a combination of SSRIs and prodrug opioids postoperatively and to examine the effect of this combination on postoperative pain control. Using EHR data from an academic medical center, we identified patients receiving surgery over a 9-year period. We developed and validated natural language processing (NLP) algorithms to extract depression-related information (diagnosis, SSRI use, symptoms) from structured and unstructured data elements. The primary outcome was the difference between preoperative pain score and postoperative pain at discharge, 3-week and 8-week time points. We developed computational models to predict the increase or decrease in the postoperative pain across the 3 time points by using the patient's EHR data (e.g. medications, vitals, demographics) captured before surgery. We evaluate the generalizability of the model using 10-fold cross-validation method where the holdout test method is repeated 10 times and mean area-under-the-curve (AUC) is considered as evaluation metrics for the prediction performance. We identified 4,306 surgical patients with symptoms of depression. A total of 14.1% were prescribed both an SSRI and a prodrug opioid, 29.4% were prescribed an SSRI and a non-prodrug opioid, 18.6% were prescribed a prodrug opioid but were not on SSRIs, and 37.5% were prescribed a non-prodrug opioid but were not on SSRIs. Our NLP algorithm identified depression with a F1 score of 0.95 against manual annotation of 300 randomly sampled clinical notes. On average, patients receiving prodrug opioids had lower average pain scores (p<0.05), with the exception of the SSRI+ group at 3-weeks postoperative follow-up. However, SSRI+/Prodrug+ had significantly worse pain control at discharge, 3 and 8-week follow-up (p < .01) compared to SSRI+/Prodrug- patients, whereas there was no difference in pain control among the SSRI- patients by prodrug opioid (p>0.05). The machine learning algorithm accurately predicted the increase or decrease of the discharge, 3-week and 8-week follow-up pain scores when compared to the pre-operative pain score using 10-fold cross validation (mean area under the receiver operating characteristic curve 0.87, 0.81, and 0.69, respectively). Preoperative pain, surgery type, and opioid tolerance were the strongest predictors of postoperative pain control. We provide the first direct clinical evidence that the known ability of SSRIs to inhibit prodrug opioid effectiveness is associated with worse pain control among depressed patients. Current prescribing patterns indicate that prescribers may not account for this interaction when choosing an opioid. The study results imply that prescribers might instead choose direct acting opioids (e.g. oxycodone or morphine) in depressed patients on SSRIs.

Prescription Opioid Type and the Likelihood of Prolonged Opioid Use After Orthopaedic Surgery.

INTRODUCTION: A common belief is that some narcotic medications have a higher association with prolonged use. We assessed whether the initial opiate type prescribed to postoperative, opiate-naive orthopaedic trauma patients was associated with prolonged opioid use. METHODS: We studied 17,961 adult, opiate-naive patients treated for a surgical musculoskeletal injury. Discharge prescription in morphine milligram equivalents (MMEs, a standardized dosing unit that allows for comparison across opioid types) was calculated. Opioid prescribing beyond 90 days after injury was defined as prolonged use. RESULTS: Initial analysis demonstrated a higher likelihood of prolonged use for patients discharged on hydromorphone or morphine versus hydrocodone. However, when we adjusted for discharge MME, only opioid quantity was predictive of prolonged use (P < 0.001). In addition, discharge MME was associated with opioid type (P < 0.01). DISCUSSION: Persistent opiate use was associated with discharge opioid quantity, not the opioid type. These results highlight the importance of calculating equivalence doses when selecting opioid types and considering amount of narcotics prescribed. LEVEL OF EVIDENCE: Level III.

Opioid Prescribing Practices of Orthopaedic Surgeons: Results of a National Survey.

INTRODUCTION: Opioids are widely used after orthopaedic procedures. Nonmedical opioid use is a growing public health issue. METHODS: An anonymous online survey was distributed by e-mail to the orthopaedic societies of all 50 states and several large private practices to assess practicing orthopaedic surgeons' opioid prescribing practices. RESULTS: A total of 555 orthopaedic surgeons practicing in 37 states responded. The most commonly prescribed opioid for both teenagers and adults was hydrocodone/acetaminophen. Of note, 42.3% reported that a patient they have prescribed opioids for developed an opioid dependency, whereas 35.3% do not believe that opioid use is a problem in their practice. Of note, 30.3% reported prescribing refills, and factors significantly associated with increased prescribing of refills included a greater number of years in practice (P < 0.001) and practicing in a suburban rather than an urban or rural environment (P = 0.03). CONCLUSION: Orthopaedic surgeons rarely prescribe any refills, tend to prescribe less opioids to teenagers than adults, and prescribe fairly uniformly for patients who are treated nonsurgically or undergo minor or arthroscopic surgery. They exhibit considerable variation in prescribing for fractures and major procedures.

Prospective Evaluation of Opioid Consumption Following Cubital Tunnel Decompression Surgery.

BACKGROUND: Managing postoperative pain is important for patients and surgeons. However, there is concern over opioid dependency. Cubital tunnel decompression is among the most common upper extremity surgeries. Our study aimed to analyze opioid use after cubital tunnel decompression to guide postoperative opioid prescribing. METHODS: We prospectively collected opioid consumption for 16 consecutive months (February 2016 to June 2017) for cubital tunnel decompression patients. Data on demographics, insurance type, surgery performed, functional questionnaires (Quick Disabilities of the Arm, Shoulder and Hand [QuickDASH]), and electrodiagnostics (electromyography) were collected. Opioid consumption was reported at first postoperative visits. RESULTS: One hundred patients consumed a mean of 50 morphine equivalent units (MEUs) (range, 0-300), or 7 oxycodone 5-mg pills, postoperatively. Cubital tunnel release (CuTR) patients consumed fewer than ulnar nerve transposition (UNT) patients (40.4 vs 62.5 MEUs or 5.4 vs 8.3 pills, P = .08). Patients undergoing submuscular UNT consumed more than CuTR (115.0 vs 40.4 MEUs or 15.3 vs 5.4 pills, p = 0.003) and more than subcutaneous UNT patients (37.8 MEU or 5.0 pills, p = 0.03). Medicare patients consumed less than privately insured (42.7 vs 54.1 MEUs, 5.7 vs 7.2 pills, P = .02) and less than workers' compensation patients (76.8 MEU or 10.2 pills, P = .04). Older patients consumed fewer than younger patients ( P = .03). Postoperative QuickDASH score was positively related to opioid intake ( P = .009). CONCLUSIONS: Patients consumed 7 oxycodone 5-mg pills after cubital tunnel decompression. Younger, privately insured, and workers' compensation patients, and those with worse functional scores and those undergoing UNT (specifically the submuscular technique) consumed more opioids.

Prescribers' perceptions on the impact of hydrocodone rescheduling on geriatric pain management: A qualitative study.

OBJECTIVE: To qualitatively assess prescribers) perceptions regarding the consequences associated with hydrocodone rescheduling among geriatric patients being discharged from inpatient settings. DESIGN: This was a cross-sectional study. SETTING: Two focus groups were conducted by a trained facilitator in a metropolitan academic medical center in January 2016. PARTICIPANTS: Prescribers who manage noncancer pain for geriatric patients were recruited. Focus groups were recorded, transcribed, and then analyzed using ATLAS.ti Qualitative Data Analysis software. Codes were derived from six primary research questions and results were summarized into key themes regarding the impact of rescheduling. MAIN OUTCOME MEASURES: Prescribers) perceptions regarding hydrocodone rescheduling. RESULTS: Prescribers mentioned that they review the prescription monitoring program (PMP) more often before prescribing opioids after rescheduling. They expressed concern regarding the required special serialized prescription forms needed to issue schedule II prescriptions. This led to substituting hydrocodone with potentially less effective pain medications, the inability to issue refills on hydrocodone prescriptions, and an ethical concern over prescribing hydrocodone to patients not under their direct care. Additionally, rescheduling has affected the coordination of care upon discharge, as patients moving to long-term care or skilled nursing facilities may not have adequate pain management when transferred. CONCLUSIONS: The majority of physicians felt rescheduling negatively impacted both practical and ethical aspects of patient care related to pain management after discharge. Rescheduling has changed physicians) hydrocodone prescribing patterns, leading to more caution when prescribing hydrocodone and greater use of the PMP. Future studies should assess geriatric patients) satisfaction and quality of life regarding pain management since hydrocodone was rescheduled.